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1

DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer  

PubMed Central

AIM: To explore the alteration of DNA methyltransferase expression in gastric cancer and to assess its prognostic value. METHODS: From April 2000 to December 2010, 227 men and 73 women with gastric cancer were enrolled in the study. The expression of DNA methyltransferases (DNMTs), including DNMT1, DNMT3a and DNMT3b, in the 300 cases of gastric carcinoma, of which 85 had paired adjacent normal gastric mucus samples, was evaluated by immunohistochemistry using a tissue microarray. Serum anti-Helicobacter pylori (H. pylori) IgG was detected by enzyme-linked immunosorbent assay (ELISA). The relationships between the above results and the clinicopathological characteristics were analyzed. Their prognostic value was evaluated using the Cox proportional hazards model. RESULTS: In gastric cancer, expression of DNMTs was mainly seen in the nucleus. Weak staining was also observed in the cytoplasm. Expression of DNMT1, DNMT3a and DNMT3b in gastric cancer was significantly higher compared to that in the paired control samples (60.0% vs 37.6%, 61.2% vs 4.7%, and 94.1% vs 71.8%, P < 0.01). The overall survival rate was significantly higher in the DNMT3a negative group than in the DNMT3a positive group in gastric cancer patients (Log-rank test, P = 0.032). No significant correlation was observed between DNMT1 and DNMT3b expression and the overall survival time (Log-rank test, P = 0.289, P = 0.347). Multivariate regression analysis indicated that DNMT3a expression (P = 0.025) and TNM stage (P < 0.001), but not DNMT1 (P = 0.54) or DNMT3b (P = 0.62), were independent prognostic factors in gastric cancer. H. pylori infection did not induce protein expression of DNMTs. CONCLUSION: The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNMT3a might play an important role in gastric carcinogenesis. PMID:25009393

Cao, Xue-Yuan; Ma, Hong-Xi; Shang, Yan-Hong; Jin, Mei-Shan; Kong, Fei; Jia, Zhi-Fang; Cao, Dong-Hui; Wang, Yin-Ping; Suo, Jian; Jiang, Jing

2014-01-01

2

ECL cell tumor and poorly differentiated endocrine carcinoma of the stomach: Prognostic evaluation by pathological analysis  

Microsoft Academic Search

Background & Aims: Gastric endocrine tumors show a wide spectrum of clinical behavior, and prognostic assessement of individual tumors is difficult. The aims of this work were to identify predictors of tumor malignancy and patient outcome and to provide a rationale for treatment guidelines. Methods: Gastric endocrine tumors (86 enterochromaffin-like cell carcinoids and 16 poorly differentiated carcinomas) were investigated for

Guido Rindi; Cinzia Azzoni; Stefano La Rosa; Catherine Klersy; Donatella Paolotti; Sigrid Rappel; Manfred Stolte; Carlo Capella; Cesare Bordi; Enrico Solcia

1999-01-01

3

High DNA Methyltransferase DNMT3B Levels: A Poor Prognostic Marker in Acute Myeloid Leukemia  

PubMed Central

It has been recently shown that DNA methyl transferase overexpression is correlated with unfavourable prognosis in human malignancies while methylation deregulation remains a hallmark that defines acute myeloid leukemia (AML). The oncogenic transcription factor EVI1 is involved in methylation deregulation and its overexpression plays a major role for predicting an adverse outcome. Moreover, the identification of DNMT3A mutations in AML patients has recently been described as a poor prognostic indicator. In order to clarify relationship between these key actors in methylation mechanisms and their potential impact on patient outcomes, we analysed 195 de novo AML patients for the expression of DNMT3A, 3B (and its non-catalytic variant 3BNC) and their correlations with the outcome and the expression of other common prognostic genetic biomarkers (EVI1, NPM1, FLT3ITD/TKD and MLL) in adult AML. The overexpression of DNMT3B/3BNC is (i) significantly correlated with a shorter overall survival, and (ii) inversely significantly correlated with event-free survival and DNMT3A expression level. Moreover, multivariate analysis showed that a high expression level of DNMT3B/3BNC is statistically a significant independent poor prognostic indicator. This study represents the first report showing that the overexpression of DNMT3B/3BNC is an independent predictor of poor survival in AML. Its quantification should be implemented to the genetic profile used to stratify patients for therapeutical strategies and should be useful to identify patients who may benefit from therapy based on demethylating agents. PMID:23251566

Hayette, Sandrine; Thomas, Xavier; Jallades, Laurent; Chabane, Kaddour; Charlot, Carole; Tigaud, Isabelle; Gazzo, Sophie; Morisset, Stéphane; Cornillet-Lefebvre, Pascale; Plesa, Adriana; Huet, Sarah; Renneville, Aline; Salles, Gilles; Nicolini, Franck Emmanuel; Magaud, Jean-Pierre; Michallet, Mauricette

2012-01-01

4

Colorectal signet-ring cell carcinoma: benefit from adjuvant chemotherapy but a poor prognostic factor.  

PubMed

Colorectal signet-ring cell carcinoma (SRCC) has been associated with poor survival compared with mucinous adenocarcinoma (MC) and the more common adenocarcinoma (AC). Efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyzes the prognostic impact of SRCC and determines whether colonic SRCC patients benefit from adjuvant chemotherapy equally compared with MC and AC patients. Data on 196,757 colorectal cancer (CRC) patients in the period 1989-2010 was included in this Dutch nationwide population-based study. Five-year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. SRCC was found in 1,972 (1.0%) patients. SRCC patients presented more frequently with stage III or IV disease than AC patients (75.2% vs. 43.6%, p < 0.0001) and SRCC was more frequently found in the proximal colon (57.7 vs. 32.0%, p < 0.0001). SRCC patients had a poor 5-year relative survival of 30.8% (95% CI 28.1-33.6%) in the colon and 19.5% (95% CI 14.7-24.8%) in the rectum compared with 56.8% (95% CI 56.4-57.1%) and 58.5% (95% CI 57.9-59.1%) for AC. This survival difference was found in stage II, but was most prominent in stage III. Compared with AC, there was no significant interaction between SRCC and adjuvant chemotherapy (RER 1.10, 95% CI 0.81-1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. In conclusion, the prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but adjuvant chemotherapy is associated with improved survival in AC, MC, and SRCC patients. PMID:24841868

Hugen, Niek; Verhoeven, Rob H; Lemmens, Valery E; van Aart, Carola J; Elferink, Marloes A; Radema, Sandra A; Nagtegaal, Iris D; de Wilt, Johannes H

2015-01-15

5

Low serum miR-19a expression as a novel poor prognostic indicator in multiple myeloma.  

PubMed

Multiple myeloma (MM) is the second most common hematologic malignancy characterized by the clonal expansion of plasma cells. Despite continuing advances, novel biomarkers are needed for diagnosis and prognosis of MM. In our study, we characterized the diagnostic and prognostic potential of circulating microRNAs (miRNAs) in MM. Serum miRNA levels were analyzed in 108 newly diagnosed symptomatic MM patients and 56 healthy donors (HDs). Our analysis identified 95 dysregulated miRNAs in newly diagnosed MM patients. Of the 95 dysregulated miRNAs, dysregulation of miR-19a, miR-92a, miR-214-3p, miR-135b-5p, miR-4254, miR-3658 and miR-33b was confirmed by quantitative reverse transcription PCR (RT-qPCR). Receiver operating characteristic analysis revealed that a combination of miR-19a and miR-4254 can distinguish MM from HD with a sensitivity of 91.7% and specificity of 90.5%. Decreased expression of miR-19a was positively correlated with international staging system advancement, del(13q14) and 1q21 amplification. Furthermore, downregulation of miR-19a resulted in significantly decreased progression-free survival (PFS) and overall survival (OS). Our analysis indicated that the poor prognostic correlation of miR-19a expression was independent of genetic abnormalities in MM. Multivariate analysis revealed that miR-19a was a significant predictor of shortened PFS and OS. Interestingly, although miR-19a levels portend a poor prognosis, patients with low miR-19a levels had an improved response to bortezomib compared to those with high miR-19a profile. Patients with downregulated miR-19a experienced a significantly extended survival upon bortezomib-based therapy. These data demonstrate that the expression patterns of serum microRNAs are altered in MM, and miR-19a levels are a valuable prognostic marker to identify high-risk MM. PMID:25220540

Hao, Mu; Zang, Meirong; Wendlandt, Erik; Xu, Yan; An, Gang; Gong, Dasen; Li, Fei; Qi, Fang; Zhang, Yanru; Yang, Ye; Zhan, Fenghuang; Qiu, Lugui

2015-04-15

6

Elevated AKAP12 in Paclitaxel-Resistant Serous Ovarian Cancer Cells Is Prognostic and Predictive of Poor Survival in Patients.  

PubMed

A majority of high-grade (HG) serous ovarian cancer (SOC) patients develop resistant disease despite high initial response rates to platinum/paclitaxel-based chemotherapy. We identified shed/secreted proteins in preclinical models of paclitaxel-resistant human HGSOC models and correlated these candidate proteins with patient outcomes using public data from HGSOC patients. Proteomic analyses of a HGSOC cell line secretome was compared to those from a syngeneic paclitaxel-resistant variant and from a line established from an intrinsically chemorefractory HGSOC patient. Associations between the identified candidate proteins and patient outcome were assessed in a discovery cohort of 545 patients and two validation cohorts totaling 795 independent SOC patients. Among the 81 differentially abundant proteins identified (q < 0.05) from paclitaxel-sensitive vs -resistant HGSOC cell secretomes, AKAP12 was verified to be elevated in all models of paclitaxel-resistant HGSOC. Furthermore, elevated AKAP12 transcript expression was associated with worse progression-free and overall survival. Associations with outcome were observed in three independent cohorts and remained significant after adjusted multivariate modeling. We further provide evidence to support that differential gene methylation status is associated with elevated expression of AKAP12 in taxol-resistant ovarian cancer cells and ovarian cancer patient subsets. Elevated expression and shedding/secretion of AKAP12 is characteristic of paclitaxel-resistant HGSOC cells, and elevated AKAP12 transcript expression is a poor prognostic and predictive marker for progression-free and overall survival in SOC patients. PMID:25748058

Bateman, Nicholas W; Jaworski, Elizabeth; Ao, Wei; Wang, Guisong; Litzi, Tracy; Dubil, Elizabeth; Marcus, Charlotte; Conrads, Kelly A; Teng, Pang-Ning; Hood, Brian L; Phippen, Neil T; Vasicek, Lisa A; McGuire, William P; Paz, Keren; Sidransky, David; Hamilton, Chad A; Maxwell, G Larry; Darcy, Kathleen M; Conrads, Thomas P

2015-04-01

7

Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis  

PubMed Central

Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of the colon and rectum. The hallmark clinical symptom of UC is bloody diarrhea. The clinical course is marked by exacerbations and remissions, which may occur spontaneously or in response to treatment changes or intercurrent illnesses. UC is most commonly diagnosed in late adolescence or early adulthood, but it can occur at any age. The incidence of UC has increased worldwide over recent decades, especially in developing nations. In contrast, during this period, therapeutic advances have improved the life expectancy of patients, and there has been a decrease in the mortality rate over time. It is important to emphasize that there is considerable variability in the phenotypic presentation of UC. Within this context, certain clinical and demographic characteristics are useful in identifying patients who tend to have more severe evolution of the disease and a poor prognosis. In this group of patients, better clinical surveillance and more intensive therapy may change the natural course of the disease. The aim of this article was to review the epidemiology and demographic characteristics of UC and the factors that may be associated with its clinical prognosis. PMID:25071340

da Silva, Bruno César; Lyra, Andre Castro; Rocha, Raquel; Santana, Genoile Oliveira

2014-01-01

8

[Ventricular tachycardia under stress : Characteristic symptom or prognostic relevance?].  

PubMed

Exercise-induced ventricular tachycardia (EIVT) is typical and quite common in patients with long QT-Syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT). Although patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) or hypertrophic cardiomyopathy (HCM) experience EIVT infrequently, the occurrence of EIVT is of great prognostic value in these patients. The following overview will introduce these cardiomyopathies and highlight the importance of their EIVT. PMID:24100620

Biermann, Jürgen; Faber, Thomas S

2013-12-01

9

Aberrant phenotypic expression of CD15 and CD56 identifies poor prognostic acute promyelocytic leukemia patients.  

PubMed

Limited information is available on the relationship between expression of some additional aberrant phenotypic features and outcome of acute promyelocytic leukemia (APL) patients. Here, we set out to assess the frequency of CD15 and CD56 expression, and their prognostic value in a large series of APL patients. One hundred and fourteen adult patients consecutively diagnosed with PML/RAR?-positive APL and homogeneously treated with the AIDA induction schedule at a single institution were included in the study. Twelve (10.5%) and 9 (8%) of the 114 patients expressed CD15 and CD56, respectively. CD15 expression identified a subset of patients with a classic morphologic subtype (92%), a prevalent association with a bcr1 expression (67%) with an unexpectedly higher frequency of relapses (42% vs 20% for the CD15- patients, p=0.03) and a low overall survival (OS) (median OS at 5 years 58% vs 85% for the CD15- patients, p=0.01). CD56 expression was detected only in patients with a classic morphologic subtype, a prevalent bcr3 expression (67%), high incidence of differentiation syndrome (55%), higher frequency of relapse (34% vs 20% for the CD56- population, p=0.04) and a low OS (60% vs 85% for the CD56- population p=0.02). We hereby confirm the negative prognostic value of CD56 and we show that the same applies also to cases expressing CD15. These aberrant markers may be considered for the refinement of risk-adapted therapeutic strategies in APL patients. PMID:24296270

Breccia, Massimo; De Propris, Maria Stefania; Minotti, Clara; Stefanizzi, Caterina; Raponi, Sara; Colafigli, Gioia; Latagliata, Roberto; Guarini, Anna; Foà, Robin

2014-02-01

10

A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival.  

PubMed

Sox2 overlapping transcript (Sox2ot) is a long noncoding RNA (lncRNA), localized on human chromosome 3q26.33, which is frequently amplified in lung squamous cell carcinomas (SCCs). However, its roles in lung cancer remain under investigation. In this study, we found that Sox2ot was up-regulated over two folds in 53.01% of human primary lung cancers (44/83). The expression level of Sox2ot is significantly higher in SCCs than that in adenocarcinomas (ADCs) of the lung. Further study found high Sox2ot expression predicted poor survival in lung cancer patients (P=0.0053), implying Sox2ot is a novel prognostic factor. In two human lung cancer cell lines, HCC827 and SK-MES-1, knocking down Sox2ot inhibited cell proliferation by inducing G2/M arrest, with a concomitant decrease of cells in S phase. Reduced protein levels of Cyclin B1 and Cdc2 were also observed. Importantly, knocking down Sox2ot decreased EZH2 expression and reintroduction of EZH2 allowed Sox2ot knockdown cells progressed through G2/M phase, which correlates with the restoration of Cyclin B1 and Cdc2 expressions. Altogether, our data suggested that Sox2ot plays an important role in regulating lung cancer cell proliferation, and may represent a novel prognostic indicator for the disease. PMID:24927902

Hou, Zhibo; Zhao, Wei; Zhou, Ji; Shen, Lan; Zhan, Ping; Xu, Chunhua; Chang, Cunjie; Bi, Hui; Zou, Jue; Yao, Xin; Huang, Ruimin; Yu, Like; Yan, Jun

2014-08-01

11

Silenced B-cell receptor response to autoantigen in a poor-prognostic subset of chronic lymphocytic leukemia.  

PubMed

Chronic lymphocytic leukemia B cells express auto/xeno antigen-reactive antibodies that bind to self-epitopes and resemble natural IgM antibodies in their repertoire. One of the antigenic structures recognized is oxidation-induced malonedialdehyde that is present on low-density lipoprotein, apoptotic blebs, and on certain microbes. The poor-prognostic stereotyped subset #1 (Clan I IGHV genes-IGKV1(D)-39) express IgM B-cell receptors that bind oxidized low-density lipoprotein. In this study, we have used for the first time this authentic cognate antigen for analysis of downstream B-cell receptor-signal transduction events, since it is more faithful to B-cell physiology than anti-IgM. Multivalent oxidized low-density lipoprotein showed specific binding to subset #1 IgM/IgD B-cell receptors, whereas native low-density lipoprotein did not. The antigen binding induced prompt receptor clustering followed by internalization. However, the receptor-signal transduction was silenced, revealing no Ca(2+) mobilization or cell-cycle entry, while phosphorylated extracellular-regulated kinase 1/2 basal levels were high and could not be elevated further by oxidized low-density lipoprotein. Interestingly, B-cell receptor responsiveness was recovered after 48-h culture in the absence of antigen in half of the cases. Toll-like receptor 9-ligand was found to breach the B-cell receptor-signaling incompetence in 5 of 12 cases pointing to intra-subset heterogeneity. Altogether, this study supports B-cell receptor unresponsiveness to cognate self-antigen on its own in poor-prognostic subset #1 chronic lymphocytic leukemia, indicating that these cells proliferate by other mechanisms that may override B-cell receptor silencing brought about in a context of self-tolerance/anergy. These novel findings have implications for the understanding of chronic lymphocytic leukemia pathobiology and therapy. PMID:25085355

Bergh, Ann-Charlotte; Evaldsson, Chamilly; Pedersen, Lone Bredo; Geisler, Christian; Stamatopoulos, Kostas; Rosenquist, Richard; Rosén, Anders

2014-11-01

12

Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors  

PubMed Central

Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (?10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p?=?0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile. PMID:19124524

Westhovens, R; Robles, M; Ximenes, A C; Nayiager, S; Wollenhaupt, J; Durez, P; Gomez-Reino, J; Grassi, W; Haraoui, B; Shergy, W; Park, S-H; Genant, H; Peterfy, C; Becker, J-C; Covucci, A; Helfrick, R; Bathon, J

2009-01-01

13

Silenced B-cell receptor response to autoantigen in a poor-prognostic subset of chronic lymphocytic leukemia  

PubMed Central

Chronic lymphocytic leukemia B cells express auto/xeno antigen-reactive antibodies that bind to self-epitopes and resemble natural IgM antibodies in their repertoire. One of the antigenic structures recognized is oxidation-induced malonedialdehyde that is present on low-density lipoprotein, apoptotic blebs, and on certain microbes. The poor-prognostic stereotyped subset #1 (Clan I IGHV genes-IGKV1(D)-39) express IgM B-cell receptors that bind oxidized low-density lipoprotein. In this study, we have used for the first time this authentic cognate antigen for analysis of downstream B-cell receptor-signal transduction events, since it is more faithful to B-cell physiology than anti-IgM. Multivalent oxidized low-density lipoprotein showed specific binding to subset #1 IgM/IgD B-cell receptors, whereas native low-density lipoprotein did not. The antigen binding induced prompt receptor clustering followed by internalization. However, the receptor-signal transduction was silenced, revealing no Ca2+ mobilization or cell-cycle entry, while phosphorylated extracellular-regulated kinase 1/2 basal levels were high and could not be elevated further by oxidized low-density lipoprotein. Interestingly, B-cell receptor responsiveness was recovered after 48-h culture in the absence of antigen in half of the cases. Toll-like receptor 9-ligand was found to breach the B-cell receptor-signaling incompetence in 5 of 12 cases pointing to intra-subset heterogeneity. Altogether, this study supports B-cell receptor unresponsiveness to cognate self-antigen on its own in poor-prognostic subset #1 chronic lymphocytic leukemia, indicating that these cells proliferate by other mechanisms that may override B-cell receptor silencing brought about in a context of self-tolerance/anergy. These novel findings have implications for the understanding of chronic lymphocytic leukemia pathobiology and therapy. PMID:25085355

Bergh, Ann-Charlotte; Evaldsson, Chamilly; Pedersen, Lone Bredo; Geisler, Christian; Stamatopoulos, Kostas; Rosenquist, Richard; Rosén, Anders

2014-01-01

14

Prognostic Indices of Poor Nutritional Status and Their Impact on Prolonged Hospital Stay in a Greek University Hospital  

PubMed Central

Background. To ascertain the potential contributors to nutritional risk manifestation and to disclose the factors exerting a negative impact on hospital length of stay (LOS), by means of poor nutritional status, in a nonselected hospitalized population. Materials and Methods. NutritionDay project questionnaires were applied to 295 adult patients. Study parameters included anthropometric data, demographics, medical history, dietary-related factors, and self-perception of health status. Body Mass Index (BMI) and Malnutrition Universal Screening Tool (MUST) were calculated for each participant. MUST score was applied for malnutrition assessment, while hospital LOS constituted the outcome of interest. Results. Of the total cohort, 42.3% were at nutritional risk and 21.4% malnourished. Age, gender, BMI, MUST score, autonomy, health quality, appetite, quantity of food intake, weight loss, arm or calf perimeter (P < 0.001, for all), and dietary type (P < 0.01) affected nutritional status. Poor nutrition status (P = 0.000), deteriorated appetite (P = 0.000) or food intake (P = 0.025), limited autonomy (P = 0.013), artificial nutrition (P = 0.012), weight loss (P = 0.010), and arm circumference <21?cm (P = 0.007) were the most powerful predictors of hospital LOS >7 days. Conclusion. Nutritional status and nutrition-related parameters such as weight loss, quantity of food intake, appetite, arm circumference, dietary type, and extent of dependence confer considerable prognostic value regarding hospital LOS in acute care setting. PMID:24779021

Tsaousi, Georgia; Stavrou, George; Tsouskas, John; Panagiotou, Dimitrios; Kotzampassi, Katerina

2014-01-01

15

Neuroendocrine Differentiation Is a Prognostic Factor for Stage II Poorly Differentiated Colorectal Cancer  

PubMed Central

Neuroendocrine differentiation (NED) in colorectal cancer is an indistinct phenomenon and may define a new cancer subtype, especially in the poorly differentiated colorectal cancer (PDCRC). The clinical features of PDCRC with NED remain controversial, thus confusing the implementation of individualized treatment. This study included 171 patients who underwent surgery from 2000 to 2011 and had pathology-confirmed PDCRC. Each sample was examined by immunohistochemistry for the biological markers of NED, synaptophysin (Syn), and chromogranin (CgA). Patients with Syn(+) and/or CgA(+) cells were classified as NED(+); otherwise, they were NED(?). Data were collected for patients who were followed up for at least two years. NED(+) staining was present in 71 (41.5%) patients. The median survival time was 36.9 months. No survival differences existed between the NED(?) and NED(+) groups (P > 0.05). However, stage II NED(+) patients had a significantly worse prognosis than NED(?) patients (P = 0.018). For the NED(+) group, the median survival was 38.56 months, and the 5-year survival was 65%. For the NED(?) group, the median survival was 53.18 months, and the 5-year survival was 90%. NED is a common event in primary PDCRC. For stage II PDCRC, NED(+) indicates a poor prognosis. PMID:25093184

Liu, Yue; Xu, Jinghong; Jiao, Yurong; Hu, Yeting; Yi, Chenghao; Li, Qiong; Tong, Zhou; Wang, Xiaowei; Hu, Lifeng; Li, Jun; Ding, Kefeng

2014-01-01

16

Human papillomavirus 18 as a poor prognostic factor in stage I-IIA cervical cancer following primary surgical treatment  

PubMed Central

Objective This study evaluates the effect of the specific human papillomavirus (HPV) genotype as a prognostic factor in stage I-IIA cervical cancer patients following primary surgical treatment. Methods The medical records of 116 cervical cancer patients treated with primary surgical treatment were reviewed. The HPV genotypes were categorized into following groups: negative and unclassified, HPV 16, HPV 18, and other high risk (HPV 31, 33, 35, 45, 51, 52, 56, and 58). Results Among the HPV genotypes, HPV 16 predominated (40.52%), followed by intermediate risk and unclassified (25%), HPV 18, 45, and 56 (17.24%) and negative (17.24%). In univariate analysis, HPV genotypes (P=0.03), parametrial spread (P=0.02), depth of invasion (DOI) (P<0.01) and lymph-vascular space invasion (P=0.02) were significantly associated with progression free survival (PFS). In multivariate analysis, HPV 18 (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.29 to 20.90; P=0.02) and ?one half of DOI (HR, 5.4; 95% CI, 1.08 to 27.31; P=0.04) were significantly associated with PFS. HPV genotypes are not significantly associated with overall survival. Conclusion HPV 18 was a poor prognostic factor for the PFS in stage I-IIA cervical cancer patients following primary surgical treatment. Careful long-term observation and regular exams are recommended for cervical cancer patients with HPV 18 compared to those with other HPV genotypes. PMID:25469338

Yang, Sun-Hye; Kong, Su-Kyoung; Lim, So-Yi; Park, Chan-Yong

2014-01-01

17

Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth  

SciTech Connect

Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median ({>=}60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

Hwang, Chung-Feng [Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Huang, Hsuan-Ying [Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Chen, Chang-Han [Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Center for Translational Research in Biomedical Sciences, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Chien, Chih-Yen; Hsu, Yao-Chung [Department of Otolaryngology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Kaohsiung Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Li, Chien-Feng [Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan (China); Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); and others

2012-02-01

18

Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas  

PubMed Central

Background: C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. Methods: CRP immunoreactivity was examined in treatment-naïve HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). Results: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. Conclusions: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC.

Shin, Jin Ho; Kim, Chong Jai; Jeon, Eun Jeong; Sung, Chang Ohk; Shin, Hwa Jeong; Choi, Jene; Yu, Eunsil

2015-01-01

19

Association of Fascin and matrix metalloproteinase-9 expression with poor prognostic parameters in breast carcinoma of Egyptian women  

PubMed Central

Abstract Background The effects of fascin on cell invasiveness involve changes in cell motility and matrix metalloproteinase-9 (MMP-9) activity. Previous studies on the prognostic value of fascin and MMP-9 in breast carcinoma revealed conflicting results. To date, no immunohistochemical studies have been performed to assess the possible association between them in breast carcinoma. This study is designed to correlate their expression with prognostic parameters in breast carcinoma and assess the relationship between them. Methods Immunohistochemical expression of fascin and MMP-9 was evaluated semi quantitatively in 67 cases of breast carcinoma regarding the percentage of positive cells. Chi square test and Fisher’s exact test were used to examine the relationship between categorical variables. Kappa statistics was used to compute the measure of agreement between two investigational methods. Results Fascin and MMP-9 expressions were detected in 43.28% and 50.75% of breast carcinomas (respectively). Regarding the normal breast tissue, fascin expression was observed in myoepithelial cells and luminal cells of few ducts and acini. However, normal tissue showed negative MMP-9 expression. A significant relationship was observed between fascin and MMP-9 expression and lymph node metastases (p = 0.001 and 0.002 respectively), advanced tumor stage (p = 0.004 and 0.005 respectively), estrogen receptor negative (p = 0.002 and 0.005 respectively), progesterone receptor negative (p = 0.001 and 0.003 respectively) hormonal status and molecular subtypes (p = 0.0007 and 0.014 respectively). A significant strong agreement was detected between fascin and MMP-9 expression (p = 0.0001). More intense immunostaining of fascin and MMP-9 was observed at the invasive fronts compared with other areas of the tumor. Moreover, a significant moderate agreement between fascin and MMP-9 was found regarding the site of predominant intensity. Conclusion Fascin and MMP-9 proteins are associated with parameters of poor prognosis in breast cancer. The significant strong agreement between the two markers supports the role of fascin in cell invasiveness by activating matrix proteases besides increasing cell motility. Both proteins may represent potential therapeutic targets for patients with breast cancer especially those with hormone receptor–negative status. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1421167695121127. PMID:24993803

2014-01-01

20

Clinical, pathological and prognostic characteristics of gastroenteropancreatic neuroendocrine neoplasms in China: a retrospective study  

PubMed Central

Background Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare neuroendocrine tumors, and lack of data in Asian populations especially in China. The aim of this retrospective study was to assess the clinical, pathological and prognostic characteristics of GEP-NENs in China. Methods We collected clinical and pathological data of 168 patients diagnosed with GEP-NENs and treated at the First and Second Affiliated Hospitals of Dalian Medical University between January 2003 and December 2012. Kaplan-Meier method and log rank analysis was used to analyze the prognostic significance of clinical and pathological characteristics. Results Mean age was 51.83?±?14.03 and the male-to-female ratio was 1.5:1. Primary sites were the rectum (58.93%), pancreas (13.69%), stomach (9.52%), duodenum (5.36%), colon (4.76%), appendix (4.76%), ileum (2.38%) and jejunum (0.60%). Most patients (95.83%) presented non-functional tumors with non-specific symptoms such as abdominal or back pain (29.17%) and gastrointestinal bleeding (25.60%). Based on the 2010 World Health Organization (WHO) classification, patients were diagnosed with neuroendocrine tumor (NET) (24.40%) or neuroendocrine carcinoma (NEC) (7.14%). The estimated mean survival was 8.94?±?0.28 years (95% CI: 8.40-9.48). Male gender, young age, small tumor size and NET tumor type were favorable prognostic factors. Conclusion Chinese GEP-NENs patients present characteristics that are similar to American and European patients. However, there is an urgent need to establish a national database for understanding the clinical and epidemiological features of GEP-NENs in China. PMID:25001493

2014-01-01

21

Prolonged radiation time and low nadir hemoglobin during postoperative concurrent chemoradiotherapy are both poor prognostic factors with synergistic effect on locally advanced head and neck cancer patients  

PubMed Central

Background Anemia, a common complication of head and neck cancer treatment, is regarded as a poor prognostic factor. We evaluated the impact of low hemoglobin (Hb) levels, measured at different time points, on a consecutive cohort of patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) who underwent postoperative concurrent chemoradiotherapy (CCRT). Materials and methods From 2002 to 2009, 140 patients were enrolled and reviewed retrospectively. Preoperative (pre-op Hb), pre-CCRT Hb, and nadir Hb during CCRT were measured and recorded. The three Hb parameters were analyzed against several well-established pathologic risk factors and radiation-associated variables. Prognostic impacts were investigated with multivariate analysis by Cox proportional hazards model. Results On Cox regression analysis, significantly higher risk of death was associated with pre-op Hb ?13 g/dL (hazard ratio [HR] =1.8; 95% confidence interval [CI], 1.1–3.1; P=0.023), nadir Hb ?11 g/dL (HR =1.9; 95% CI, 1.1–3.3; P=0.020), radiation treatment time (RTT) >7 weeks (HR =1.9; 95% CI, 1.1–3.3; P=0.022), and multiple positive lymph nodes (HR =2.1; 95% CI, 1.2–3.7; P=0.010), after adjusting for primary tumor site and pathologic lymphovascular invasion. Patients with poor prognosticators including low nadir Hb ?11 g/dL and RTT >7 weeks had a higher risk of death (HR =4.0; 95% CI =1.6–10.2; P=0.004). Conclusion In the treatment setting of LA-SCCHN patients who underwent postoperative CCRT, coexistance of lower nadir Hb during CCRT and prolonged RTT resulted in reduced survival. PMID:25670907

Su, Nai-Wen; Liu, Chung-Ji; Leu, Yi-Shing; Lee, Jehn-Chuan; Chen, Yu-Jen; Chang, Yi-Fang

2015-01-01

22

Human BDH2, an anti-apoptosis factor, is a novel poor prognostic factor for de novo cytogenetically normal acute myeloid leukemia  

PubMed Central

Background The relevance of recurrent molecular abnormalities in cytogenetically normal (CN) acute myeloid leukemia (AML) was recently acknowledged by the inclusion of molecular markers such as NPM1, FLT3, and CEBPA as a complement to cytogenetic information within both the World Health Organization and the European Leukemia Net classifications. Mitochondrial metabolism is different in cancer and normal cells. A novel cytosolic type 2-hydroxybutyrate dehydrogenase, BDH2, originally named DHRS6, plays a physiological role in the cytosolic utilization of ketone bodies, which can subsequently enter mitochondria and the tricarboxylic acid cycle. Moreover, BDH2 catalyzes the production of 2, 3-DHBA during enterobactin biosynthesis and participates in 24p3 (LCN2)-mediated iron transport and apoptosis. Results We observed that BDH2 expression is an independent poor prognostic factor for CN-AML, with an anti-apoptotic role. Patients with high BDH2 expression have relatively shorter overall survival (P = 0.007) and a low complete response rate (P = 0.032). BDH2-knockdown (BDH2-KD) in THP1 and HL60 cells increased the apoptosis rate under reactive oxygen species stimulation. Decrease inducible survivin, a member of the inhibitors of apoptosis family, but not members of the Bcl-2 family, induced apoptosis via a caspase-3-independent pathway upon BDH2-KD. Conclusions BDH2 is a novel independent poor prognostic marker for CN-AML, with the role of anti-apoptosis, through surviving. PMID:23941109

2013-01-01

23

miR-224 overexpression is a strong and independent prognosticator of short-term relapse and poor overall survival in colorectal adenocarcinoma.  

PubMed

Colorectal adenocarcinoma constitutes the most frequent form of colorectal cancer and a serious cause of cancer-related deaths. The expression of multiple miRNAs, including miR-224, is deregulated in colorectal adenocarcinoma. The aim of this study was the investigation of the prognostic value of miR-224 in colorectal adenocarcinoma. For this purpose, total RNA was isolated from 115 colorectal adenocarcinomas and 66 adjacent non-cancer mucosae. Total RNA (2 µg) was polyadenylated and reverse transcribed. A quantitative PCR method based on SYBR-Green chemistry was developed and applied for the quantification of miR-224 levels, followed by extensive biostatistical analysis. miR-224 levels in malignant colorectal adenocarcinomas ranged between 1.81 and 187.75 RQU (miR-224 copies/1,000 SNORD48 copies) with a median of 34.27, and were significantly elevated, compared to miR-224 levels in adjacent non-cancer mucosae (p<0.001). Enhanced miR-224 expression constitutes a rather strong prognosticator in colorectal adenocarcinoma, predicting short-term relapse and poor overall survival in these patients (p=0.012 and p=0.005, respectively), independent of established clinicopathological parameters. In conclusion, miR-224 is significantly upregulated in malignant colorectal tumors compared to adjacent non-cancer mucosae, and its enhanced expression constitutes an independent predictor of short-term relapse and poor overall survival in colorectal adenocarcinoma patients. PMID:25420464

Adamopoulos, Panagiotis G; Kontos, Christos K; Rapti, Stamatia-Maria; Papadopoulos, Iordanis N; Scorilas, Andreas

2015-02-01

24

CLINICOEPIDEMIOLOGIC CHARACTERISTICS, PROGNOSTIC FACTORS, AND SURVIVAL ANALYSIS OF PATIENTS COINFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS ANDLEISHMANIAIN AN AREA OF MADRID, SPAIN  

Microsoft Academic Search

From 1987 to 1995, a retrospective case study was conducted at the Ramon y Cajal Hospital in Madrid, Spain, a public teaching hospital with 1,100 beds, to determine the clinicoepidemiologic characteristics, survival, and prognostic factors of patients with visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) infection. The prevalence of VL in HIV1 patients compared with HIV2 patients was studied.

ROGELIO LOPEZ-VELEZ; JOSE A. PEREZ-MOLINA; ANTONIO GUERRERO; FERNANDO BAQUERO

25

High-throughput time-resolved FRET reveals Akt/PKB activation as a poor prognostic marker in breast cancer.  

PubMed

Dysregulation of the Akt/PKB pathway has been associated with poor prognosis in several human carcinomas. Current approaches to assess Akt activation rely on intensity-based methods, which are limited by the subjectivity of manual scoring and poor specificity. Here, we report the development of a novel assay using amplified, time-resolved Förster resonance energy transfer (FRET), which is highly specific and sensitive and can be adapted to any protein. Using this approach to analyze primary breast tissue microarrays, we quantified levels of activated pAkt at a spatial resolution that revealed molecular heterogeneity within tumors. High pAkt status assessed by amplified FRET correlated with worse disease-free survival. Our findings support the use of amplified FRET to determine pAkt status in cancer tissues as candidate biomarker for the identification of high-risk patients. PMID:24970478

Veeriah, Selvaraju; Leboucher, Pierre; de Naurois, Julien; Jethwa, Nirmal; Nye, Emma; Bunting, Tamara; Stone, Richard; Stamp, Gordon; Calleja, Véronique; Jeffrey, Stefanie S; Parker, Peter J; Larijani, Banafshé

2014-09-15

26

Clinical Characteristics and Prognostic Factors in Dogs with Histiocytic Sarcomas in Japan  

PubMed Central

ABSTRACT Canine histiocytic sarcoma (HS) is a rare neoplasm that originates from dendritic cells or macrophages, and there have been a number of cases experienced in Japan. To identify the characteristics and prognostic variables that determine outcome in dogs with HS in Japan, medical records of 73 dogs with HS were retrospectively analyzed. Signalment, clinical signs, complete blood count (CBC), blood chemistry profiles, treatment, response to treatment and overall survival (OS) were analyzed. Diagnosis of HS was determined histologically in 44 cases and cytologically in 29 cases. The most frequently diagnosed breeds were Flat-Coated Retrievers (n=16, odds ratio [OR] 62.0), Pembroke Welsh corgis (n=15, OR 9.7) and Bernese Mountain dogs (n=14, OR 45.0). Median survival time for all dogs in this study was 43 days. In the dogs that received no treatment or only symptomatic treatment, the median OS was 12 days (range 2–254 days) compared with that of dogs that received surgical treatment and/or chemotherapy (85 days, range 4–360 days). Univariate analysis identified anemia, thrombocytopenia, hypoalbuminemia, hypoproteinemia and not receiving antitumor treatment (chemotherapy and/or surgery) as factors significantly associated with shorter OS. Multivariate analysis confirmed that platelet counts, localized/disseminated lesional pattern and whether the dog received antitumor treatment were significantly predictive of survival. PMID:24441652

TAKAHASHI, Masashi; TOMIYASU, Hirotaka; HOTTA, Eri; ASADA, Hajime; FUKUSHIMA, Kenjiro; KANEMOTO, Hideyuki; FUJINO, Yasuhito; OHNO, Koichi; UCHIDA, Kazuyuki; NAKAYAMA, Hiroyuki; TSUJIMOTO, Hajime

2014-01-01

27

Clinical characteristics and prognostic factors in dogs with histiocytic sarcomas in Japan.  

PubMed

Canine histiocytic sarcoma (HS) is a rare neoplasm that originates from dendritic cells or macrophages, and there have been a number of cases experienced in Japan. To identify the characteristics and prognostic variables that determine outcome in dogs with HS in Japan, medical records of 73 dogs with HS were retrospectively analyzed. Signalment, clinical signs, complete blood count (CBC), blood chemistry profiles, treatment, response to treatment and overall survival (OS) were analyzed. Diagnosis of HS was determined histologically in 44 cases and cytologically in 29 cases. The most frequently diagnosed breeds were Flat-Coated Retrievers (n=16, odds ratio [OR] 62.0), Pembroke Welsh corgis (n=15, OR 9.7) and Bernese Mountain dogs (n=14, OR 45.0). Median survival time for all dogs in this study was 43 days. In the dogs that received no treatment or only symptomatic treatment, the median OS was 12 days (range 2-254 days) compared with that of dogs that received surgical treatment and/or chemotherapy (85 days, range 4-360 days). Univariate analysis identified anemia, thrombocytopenia, hypoalbuminemia, hypoproteinemia and not receiving antitumor treatment (chemotherapy and/or surgery) as factors significantly associated with shorter OS. Multivariate analysis confirmed that platelet counts, localized/disseminated lesional pattern and whether the dog received antitumor treatment were significantly predictive of survival. PMID:24441652

Takahashi, Masashi; Tomiyasu, Hirotaka; Hotta, Eri; Asada, Hajime; Fukushima, Kenjiro; Kanemoto, Hideyuki; Fujino, Yasuhito; Ohno, Koichi; Uchida, Kazuyuki; Nakayama, Hiroyuki; Tsujimoto, Hajime

2014-05-01

28

Demographic characteristics and prognostic indicators of childhood burn in a developing country.  

PubMed

Children constitute a significant proportion of burn victims in most studies from the developing countries. While there has been a progressive improvement in the outcome from childhood burn in many developed nations, the morbidity and mortality remains high in many low and middle income countries. The aim of our study is to evaluate the demographic characteristics and prognostic indicators of childhood burn in a major referral teaching hospital in a developing country. A review of the records of 638 patients with acute burns managed over a 10-year period from January 2001 to December 2010 at the University College Hospital, Ibadan Nigeria was done. The clinical and epidemiological data were retrieved from computerized data base using the ISBI proforma. Information obtained includes Biodata, Etiology, location, TBSA, presence of Inhalation injury and the treatment outcome. Data of patients aged 16 years and below were analyzed using the SPSS version 16. The main outcome measure was the patient's survival. 289 children representing 45.3% of the total number of burn patients were managed over the period. The M:F ratio was 1.1:1. The median age of the cohort was 4.0 years while the median TBSA was 21.0%. Non-intentional causes were responsible for 89.6% cases. Most of the injuries (88.6%) occurred at home. Eighty-three patients had inhalation injury out of which 57 (68.7%) deaths were recorded. The overall mortality rate in the cohort was 39.5% with an LA50 of burn size of 45%. The TBSA was also found to be a determinant of outcome. Majority of childhood burns are from preventable causes with attendant dismal mortality figures. Effective burn prevention strategies and improved quality of care remain pivotal in reducing childhood burn morbidity and mortality in the developing countries. PMID:24933574

Olawoye, O A; Iyun, A O; Ademola, S A; Michael, A I; Oluwatosin, O M

2014-12-01

29

Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC? subversion induces up-regulation of PKC?II expression in B lymphocytes.  

PubMed

Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKC? leads to an up-regulation of PKC?II expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKC? inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKC?II in chronic lymphocytic leukemia-like disease progression and suggest a role for PKC? subversion in creating permissive conditions for leukemogenesis. PMID:25616575

Nakagawa, Rinako; Vukovic, Milica; Tarafdar, Anuradha; Cosimo, Emilio; Dunn, Karen; McCaig, Alison M; Holroyd, Ailsa; McClanahan, Fabienne; Ramsay, Alan G; Gribben, John G; Michie, Alison M

2015-04-01

30

Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKC? subversion induces up-regulation of PKC?II expression in B lymphocytes  

PubMed Central

Overwhelming evidence identifies the microenvironment as a critical factor in the development and progression of chronic lymphocytic leukemia, underlining the importance of developing suitable translational models to study the pathogenesis of the disease. We previously established that stable expression of kinase dead protein kinase C alpha in hematopoietic progenitor cells resulted in the development of a chronic lymphocytic leukemia-like disease in mice. Here we demonstrate that this chronic lymphocytic leukemia model resembles the more aggressive subset of chronic lymphocytic leukemia, expressing predominantly unmutated immunoglobulin heavy chain genes, with upregulated tyrosine kinase ZAP-70 expression and elevated ERK-MAPK-mTor signaling, resulting in enhanced proliferation and increased tumor load in lymphoid organs. Reduced function of PKC? leads to an up-regulation of PKC?II expression, which is also associated with a poor prognostic subset of human chronic lymphocytic leukemia samples. Treatment of chronic lymphocytic leukemia-like cells with the selective PKC? inhibitor enzastaurin caused cell cycle arrest and apoptosis both in vitro and in vivo, and a reduction in the leukemic burden in vivo. These results demonstrate the importance of PKC?II in chronic lymphocytic leukemia-like disease progression and suggest a role for PKC? subversion in creating permissive conditions for leukemogenesis. PMID:25616575

Nakagawa, Rinako; Vukovic, Milica; Tarafdar, Anuradha; Cosimo, Emilio; Dunn, Karen; McCaig, Alison M.; Holroyd, Ailsa; McClanahan, Fabienne; Ramsay, Alan G.; Gribben, John G.; Michie, Alison M.

2015-01-01

31

Well-differentiated Thyroid Cancer With a Minor Poorly Differentiated Component: Clonal Heterogeneity Through the Prognostic Role of CXCR4 and BRAF Analysis.  

PubMed

Well-differentiated carcinoma (WDC) accounts for up to 90% of all thyroid cancers. The presence of a minor poorly differentiated (PD) component (mainly insular pattern) might represent an additional critical parameter for patients' prognosis and outcome. The role of both CXCR4 (a chemokine inducing cytoskeletal rearrangement and cell adhesion) and BRAF mutation have been studied in WDC (mainly papillary thyroid cancer and its variants), highlighting their critical role in tumor progression, local infiltration, and metastases. We discussed the clonal heterogeneity through the prognostic role of CXCR4 and BRAF mutation in WDC with a minor PD/insular component. Of our 16 WDC cases with a PD/insular component, up to 40% underwent surgery. The cases were subclassified according to the PD percentage as (1) <20% PD and (2) 20% to 40% PD, and were studied for CXCR4 expression and BRAF mutation. CXCR4 and molecular testing were distinctly performed on both components of each lesion. The majority of the cases (69%) showed an extrathyroid and metastatic dissemination. Regardless of the 2 categories, we had 8/16 (50%) patients with disease-free status. CXCR4 was negative in all 16 cases, whereas 3 of them (19%) had a mutated BRAF only in the WDC component of the lesion. WDCs with a minor PD pattern, even when <20%, showed more aggressive features than pure WDCs and should be entirely considered as PD carcinoma. The absence of CXCR4 expression and BRAF mutation in cancers with a minor PD component underlined different pathogenic and metastatic processes in comparison with WDCs. PMID:24992171

Rossi, Esther D; Martini, Maurizio; Capodimonti, Sara; Straccia, Patrizia; Revelli, Luca; Lombardi, Celestino P; Pontecorvi, Alfredo; Santeusanio, Giuseppe; Larocca, Luigi M; Fadda, Guido

2015-03-01

32

Secondary Intention Healing after Excision of Nonmelanoma Skin Cancer of the Head and Neck: Statistical Evaluation of Prognostic Values of Wound Characteristics and Final Cosmetic Results  

Microsoft Academic Search

Background: Most data on secondary intention healing of skin cancer defects in the head and neck are empirical and descriptive. This study statistically evaluates the prognostic value of several wound characteristics and location on the final cosmetic result of skin defects left to heal by secondary intention after tumor removal. Methods: A chart review of all facial reconstructions using secondary

Paul A. van der Eerden; Peter J. F. M. Lohuis; A. A. M. Hart; W. C. Mulder; Hade Vuyk

2008-01-01

33

Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies  

PubMed Central

Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer that tends to have an aggressive clinical presentation as well as a variety of distinct histologic designations. Few systemic treatment options are available for MBC, as it has consistently shown a suboptimal response to standard chemotherapy regimens. These characteristics result in a worse overall prognosis for patients with MBC compared to those with standard invasive breast cancer. Due to its rarity, data focusing on MBC is limited. This review will discuss the clinical presentation, breast imaging findings, histologic and molecular characteristics of MBC as well as potential future research directions. PMID:24499560

2013-01-01

34

Gut transport characteristics in herbivorous and carnivorous serrasalmid fish from ion-poor Rio Negro water.  

PubMed

Three closely related characids, Tambaqui (omnivore), black Piranha (carnivore), and Pacu (herbivore), all Serrasalmidae, inhabit the ion-poor, acidic Rio Negro. We compared O2-consumption and N excretion rates in vivo, and sodium, chloride, glucose, and ammonia transport characteristics of gut sac preparations in vitro. The Pacu had a significantly higher weight-specific oxygen consumption, and a lower N/Q ratio than the omnivorous Tambaqui, and a significantly lower urea-N excretion rate than the carnivorous black Piranha, suggesting N-limitation in the herbivorous Pacu. With a value of 2.62 ± 0.15, gut to fork length ratio in the Pacu was about 2.5 times higher than in the black Piranha, and 2.0 times higher than in the Tambaqui. Anterior intestinal activities of three enzymes involved in N-fixation for amino acid synthesis (glutamate dehydrogenase, glutamate-oxaloacetate transferase, and glutamate-pyruvate transferase) were generally greatest in the carnivore and lowest in the herbivore species. In all three species, sodium, chloride, glucose, and ammonia were taken up at high rates from the intestine, resulting in an isosmotic fluid flux. Comparing the area-specific fluid flux of the anterior, mid, and posterior gut sections, no difference was detected between the three sections of the Pacu, while in the Tambaqui, it was highest in the anterior section, and in the black Piranha highest in the middle section. Overall, the area-specific uptake rates for sodium, chloride, glucose, and ammonia of anterior, mid, and posterior sections were similar in all three species, indicating that there is no difference in the area-specific transport rates associated with trophic position. The net ammonia uptake flux from gut interior was not significantly different from the net ammonia efflux to the serosal fluid, so that the ammonia removed from the intestine by the mucosal epithelium was quantitatively transferred through the tissue to the serosal side in all three species. Thus, metabolic activity of gut tissue did not significantly influence the net ammonia transfer. Due to the much higher gut to fork length ratio, the overall transport capacity of the gut of the herbivorous Pacu by far exceeded the transport capacity of their carnivorous and omnivorous relatives, thus compensating for the lower digestibility and the low Na(+), Cl(-), and N-content of the plant diet. Accordingly, in order to cope with the more difficult digestible plant material and the very low nitrogen content of plants, herbivorous fish have not evolved more effective area-specific transport capacities, but rather have increased the length of the gut. PMID:25528145

Pelster, Bernd; Wood, Chris M; Speers-Roesch, Ben; Driedzic, William R; Almeida-Val, Vera; Val, Adalberto

2015-02-01

35

Non-aneurysmal non-traumatic subarachnoid hemorrhage: patient characteristics, clinical outcome and prognostic factors based on a single-center experience in 125 patients  

PubMed Central

Background Subarachnoid hemorrhage (SAH) is mainly caused by ruptured cerebral aneurysms but in up to 15% of patients with SAH no bleeding source could be identified. Our objective was to analyze patient characteristics, clinical outcome and prognostic factors in patients suffering from non-aneurysmal SAH. Methods From 1999 to 2009, data of 125 patients with non-aneurysmal SAH were prospectively entered into a database. All patients underwent repetitive cerebral angiography. Outcome was assessed according to the modified Rankin Scale (mRS) (mRS 0–2 favorable vs. 3–6 unfavorable). Also, patients were divided in two groups according to the distribution of blood in the CT scan (perimesencephalic and non-perimesencephalic SAH). Results 106 of the 125 patients were in good WFNS grade (I-III) at admission (85%). Overall, favorable outcome was achieved in 104 of 125 patients (83%). Favorable outcome was associated with younger age (P?poor admission status was the only independent predictor of unfavorable outcome in the multivariate analysis. Patients with a non-perimesencephalic SAH have an increased risk of a worse neurological outcome. These patients should be monitored attentively. PMID:24986457

2014-01-01

36

Forkhead box transcription factor 1 expression in gastric cancer: FOXM1 is a poor prognostic factor and mediates resistance to docetaxel  

PubMed Central

Background Forkhead box transcription factor 1 (FOXM1) has been reported to overexpress and correlate with pathogenesis in a variety of human malignancies. However, little research has been done to investigate its clinical significance in gastric cancer. Methods We examined the expression of FOXM1 in 103 postoperational gastric cancer tissues and 5 gastric cell lines by immunohistochemistry and western blot analysis respectively. Data on clinic-pathological features and relevant prognostic factors in these patients were then analyzed. Moreover, the association of FOXM1 expression and chemosensitivity to docetaxel in gastric cancer cells was further explored. Results Our study demonstrated that the level of FOXM1 expression was significantly higher in gastric cancer than in para-cancer tissues (P??0.1). FOXM1 amplification was identified as an independent prognostic factor in gastric cancer (P?=?0.001), and its affection is more significant in patients with tumor size larger than 5 cm (P?=?0.004), pT3-4 (P?=?0.003) or pIII-IV (P?=?0.001). Additionally, shown to mediate docetaxel resistance in gastric cancers by our research, FOXM1 was revealed to alter microtubule dynamics in response to the treatment of docetaxel, and the drug resistance could be reversed with FOXM1 inhibitor thiostrepton treatment. Conclusions FOXM1 can be a useful marker for predicting patients’ prognosis and monitoring docetaxel response, and might be a new therapeutic target in docetaxel resistant gastric cancer. PMID:24004449

2013-01-01

37

Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study  

Microsoft Academic Search

BackgroundResults from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.Methods and FindingsIn case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade,

Song Yao; Lara E. Sucheston; Amy E. Millen; Candace S. Johnson; Donald L. Trump; Mary K. Nesline; Warren Davis; Chi-Chen Hong; Susan E. McCann; Helena Hwang; Swati Kulkarni; Stephen B. Edge; Tracey L. O'Connor; Christine B. Ambrosone; Yiqing Song

2011-01-01

38

Poor sleepers who do not complain of insomnia: Myths and realities about psychological and lifestyle characteristics of older good and poor sleepers  

Microsoft Academic Search

Psychological adjustment, lifestyle, and sleep parameters were investigated in 634 older community residents. Participants were divided into three categories: good sleepers, poor sleepers experiencing high distress, and poor sleepers experiencing minimal distress. Results indicate that (1) highly distressed poor sleepers manifested an anxious, depressed, negative cognitive-affective set; (2) many coped well with age related changes in sleep quality—they resembled good

Catherine S. Fichten; Laura Creti; Rhonda Amsel; William Brender; Nettie Weinstein; Eva Libman

1995-01-01

39

Clinical characteristics of Pneumocystis pneumonia in non-HIV patients and prognostic factors including microbiological genotypes  

PubMed Central

Background The number of patients with non-HIV Pneumocystis pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We investigated the clinical characteristics of non-HIV PCP and its association with microbiological genotypes. Methods Between January 2005 and March 2010, all patients in 2 university hospitals who had been diagnosed with PCP by PCR were enrolled in this study. Retrospective chart review of patients, microbiological genotypes, and association with 30-day mortality were examined. Results Of the 82 adult patients investigated, 50 patients (61%) had inflammatory diseases, 17 (21%) had solid malignancies, 12 (15%) had hematological malignancies, and 6 (7%) had received transplantations. All patients received immunosuppressive agents or antitumor chemotherapeutic drugs. Plasma (1?3) ?-D-glucan levels were elevated in 80% of patients, and were significantly reduced after treatment in both survivors and non-survivors. However, ?-D-glucan increased in 18% of survivors and was normal in only 33% after treatment. Concomitant invasive pulmonary aspergillosis was detected in 5 patients. Fifty-six respiratory samples were stored for genotyping. A dihydropteroate synthase mutation associated with trimethoprim-sulfamethoxazole resistance was found in only 1 of the 53 patients. The most prevalent genotype of mitochondrial large-subunit rRNA was genotype 1, followed by genotype 4. The most prevalent genotype of internal transcribed spacers of the nuclear rRNA operon was Eb, followed by Eg and Bi. Thirty-day mortality was 24%, in which logistic regression analysis revealed association with serum albumin and mechanical ventilation, but no association with genotypes. Conclusions In non-HIV PCP, poorer general and respiratory conditions at diagnosis were independent predictors of mortality. ?-D-glucan may not be useful for monitoring the response to treatment, and genotypes were not associated with mortality. PMID:21439061

2011-01-01

40

High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma  

Microsoft Academic Search

Survivin (SVV) is a family member of inhibitor of apoptosis proteins (IAPs) and its expression is cell cycle regulated. The gene is mapped to chromosome 17q25, the region of which is frequently gained in advanced stages of neuroblastoma (NBL). However, the role of SVV in NBL is poorly understood. Here we studied the clinical and biological role of SVV in

Ashraful Islam; Hajime Kageyama; Naoyuki Takada; Takemasa Kawamato; Hajime Takayasu; Eriko Isogai; Miki Ohira; Kohei Hashizume; Hirofumi Kobayashi; Yasuhiko Kaneko; Akira Nakagawara

2000-01-01

41

Characteristic and Prognostic Implication of Venous Thromboembolism in Ovarian Clear Cell Carcinoma: A 12-Year Retrospective Study  

PubMed Central

Purpose To profile the characteristic and prognostic implications of venous thromboembolism (VTE) in Chinese ovarian clear cell carcinoma (CCC) patients. Methods We identified all of the cases between 2000 and 2012 by searching our institutional Ovarian CCC Database. A comprehensive review of the medical documentation was performed to collect relevant data. Kaplan-Meier models and Cox regression were employed for survival analysis. Results Of the 227 patients, 33 (14.5%) experienced VTE events. There was no significant difference between VTE and non-VTE group patients regarding age, serum cancer antigen 125 or tumor size. The optimal cytoreduction rate was higher in patients without VTE (70.1%) than in those with VTE (51.5%). VTE events were more likely to occur at presentation (36.4%) and recurrence (33.3%), followed by an adjuvant chemotherapy period (18.2%). VTE was more common in patients with advanced-stage disease than those with early-stage disease (P=0.003), whereas pulmonary embolism (PE) was 10-fold as common in advanced-stage disease as in early-stage disease (8.6% vs. 0.8%, P = 0.012). Patients with advanced disease tended to have thrombi in the proximal veins. Two patients died of PE, as confirmed by autopsy. Patients with VTE had reduced survival compared to those without VTE (median overall survival 54 vs. 140 months, P<0.001; median progression-free survival 17 vs. 43 months, P<0.001). Conclusions Overall, 14.5% of the patients with ovarian CCC experienced VTE, mainly before their cancer diagnosis or at a time of recurrence. VTE adversely impacted patient survival. PMID:25793293

Ye, Shuang; Yang, Jiaxin; Cao, Dongyan; Bai, Huimin; Huang, Huifang; Wu, Ming; Chen, Jie; You, Yan; Lang, Jinghe; Shen, Keng

2015-01-01

42

Pathway-Centric Integrative Analysis Identifies RRM2 as a Prognostic Marker in Breast Cancer Associated with Poor Survival and Tamoxifen Resistance123  

PubMed Central

Breast cancer (BCa) molecular subtypes include luminal A, luminal B, normal-like, HER-2–enriched, and basal-like tumors, among which luminal B and basal-like cancers are highly aggressive. Biochemical pathways associated with patient survival or treatment response in these more aggressive subtypes are not well understood. With the limited availability of pathologically verified clinical specimens, cell line models are routinely used for pathway-centric studies. We measured the metabolome of luminal and basal-like BCa cell lines using mass spectrometry, linked metabolites to biochemical pathways using Gene Set Analysis, and developed a novel rank-based method to select pathways on the basis of their enrichment in patient-derived omics data sets and prognostic relevance. Key mediators of the pathway were then characterized for their role in disease progression. Pyrimidine metabolism was altered in luminal versus basal BCa, whereas the combined expression of its associated genes or expression of one key gene, ribonucleotide reductase subunit M2 (RRM2) alone, associated significantly with decreased survival across all BCa subtypes, as well as in luminal patients resistant to tamoxifen. Increased RRM2 expression in tamoxifen-resistant patients was verified using tissue microarrays, whereas the metabolic products of RRM2 were higher in tamoxifen-resistant cells and in xenograft tumors. Both genetic and pharmacological inhibition of this key enzyme in tamoxifen-resistant cells significantly decreased proliferation, reduced expression of cell cycle genes, and sensitized the cells to tamoxifen treatment. Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance and its pharmacological inhibition as a novel approach to overcome tamoxifen resistance in BCa. PMID:25016594

Putluri, Nagireddy; Maity, Suman; Kommangani, Ramakrishna; Creighton, Chad J.; Putluri, Vasanta; Chen, Fengju; Nanda, Sarmishta; Bhowmik, Salil Kumar; Terunuma, Atsushi; Dorsey, Tiffany; Nardone, Agostina; Fu, Xiaoyong; Shaw, Chad; Sarkar, Tapasree Roy; Schiff, Rachel; Lydon, John P.; O’Malley, Bert W.; Ambs, Stefan; Das, Gokul M.; Michailidis, George; Sreekumar, Arun

2014-01-01

43

Are multiple physical symptoms a poor prognostic factor or just a marker of depression severity? Secondary analysis of the GenPod trial  

PubMed Central

Background Using data from the GenPod trial this study investigates: (i) if depressed individuals with multiple physical symptoms have a poorer response to antidepressants before and after adjustment for baseline Beck Depression Inventory II (BDI-II); and (ii) if reboxetine is more effective than citalopram in depression with multiple physical symptoms. Methods Linear regression models were used to estimate differences in mean BDI-II score at 6 and 12 weeks. Results Before adjusting for baseline BDI-II, the difference in mean BDI-II score between no and multiple physical symptoms was 4.5 (95% CI 1.87, 7.14) at 6 weeks, 4.51 (95% CI 1.60, 7.42) at 12 weeks. After adjustment for baseline BDI-II, there was no evidence of a difference in outcome according to physical symptoms with a difference in mean BDI-II of 2.17 (95% CI ?0.39, 4.73) at 6 weeks and 2.43 (95% CI ?0.46, 5.32) at 12 weeks. There was no evidence that reboxetine was more effective than citalopram in those with multiple physical symptoms at 6 (P=0.18) or 12 weeks (P=0.24). Limitations Differential non-adherence between treatment arms has the potential to bias estimates of treatment efficacy. Conclusion Multiple physical symptoms predict response to antidepressants, but not after adjustment for baseline depression severity. Physical symptoms could be a marker of severe depression rather than an independent prognostic factor and depression should be considered in patients with multiple physical symptoms. Treatment with reboxetine conferred no advantage over citalopram in those with physical symptoms, and it is less well tolerated. PMID:24836086

Green, Amy; Crawford, Andrew; Button, Katherine S.; Wiles, Nicola; Peters, Tim J.; Nutt, David; Lewis, Glyn

2014-01-01

44

Analysis of prognostic factors and comparison of prognostic scores in peripheral T cell lymphoma, not otherwise specified: a single-institution study of 105 Chinese patients.  

PubMed

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous subtype of non-Hodgkin's lymphoma. This study aims to better define the prognostic factors and compare the predictive value of the prognostic scores in Chinese patients with PTCL-NOS. One hundred and five patients diagnosed as PTCL-NOS from our institution were retrospectively studied and grouped according to four previously described prognostic scores [International Prognostic Index (IPI), Prognostic Index for PTCL-NOS (PIT), modified PIT (m-PIT), and International PTCL Project (IPTCLP)]. In addition to clinical parameters, peripheral lymphopenia and thrombocytopenia, serum Epstein-Barr virus positivity, and tumor Ki-67 were significantly associated with poor disease outcome. Multivariate analysis revealed that age >60 years, poor performance status, elevated lactic dehydrogenase, and bone marrow involvement were independent adverse variables for survival. All prognostic scores were successful for survival estimation. Risk subgroups in IPI and PIT could be further discriminated by platelet count (IPTCLP factor) and Ki-67 (m-PIT factor), respectively. Together, patient- and tumor-specific characteristics may be incorporated in risk stratification of PTCL-NOS patients. The prognostic scores could be mutually active to improve their predictive value of disease outcome. PMID:25193354

Xu, Pengpeng; Yu, Dong; Wang, Li; Shen, Yang; Shen, Zhixiang; Zhao, Weili

2015-02-01

45

Class III ?-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel  

PubMed Central

Critics have suggested that neoadjuvant chemotherapy (NACT) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. ?-tubulins are chemotherapeutic targets of taxanes and epothilones. Class III ?-tubulin overexpression has been linked to chemoresistance and hypoxia. Herein, we describe changes in class III ?-tubulin in patients with advanced ovarian carcinoma in response to NACT, in relationship to clinical outcome, and between patients who underwent NACT versus primary debulking; we characterize in vitro chemosensitivity to paclitaxel/patupilone of cell lines established from this patient population, and class III ?-tubulin expression following repeated exposure to paclitaxel. Using immunohistochemistry, we observed among 22 paired specimens obtained before/after NACT decreased expression of class III ?-tubulin following therapy within stroma (p=0.07), but not tumor (p=0.63). Poor median overall survival was predicted by high levels of class III ?-tubulin in both tumor (HR 3.66 [1.11,12.05], p=0.03) and stroma (HR 4.53 [1.28,16.1], p=0.02). Class III ?-tubulin expression by quantitative-real-time-polymerase-chain-reaction was higher among patients who received NACT (n=12) compared to primary cytoreduction (n=14) (mean±SD fold-change: 491.2±115.9 vs 224.1±55.66, p=0.037). In vitro subculture with paclitaxel resulted in class III ?-tubulin upregulation, however, cell lines that overexpressed class III ?-tubulin remained sensitive to patupilone. Overexpression of class III ?-tubulin in patients dispositioned to NACT may thus identify an intrinsically aggressive phenotype, and predict poor overall survival and paclitaxel resistance. Decreases in stromal expression may represent normalization of the tumor microenvironment following therapy. Epothilones warrant study for patients who have received neoadjuvant carboplatin and paclitaxel. PMID:24005572

Roque, Dana M.; Buza, Natalia; Glasgow, Michelle; Bellone, Stefania; Bortolomai, Ileana; Gasparrini, Sara; Cocco, Emiliano; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Rutherford, Thomas J.; Schwartz, Peter E.; Santin, Alessandro D.

2013-01-01

46

Primary Tumor Vascularity, HIF-1? and VEGF expression in vulvar squamous cell carcinomas: their relationships with clinicopathological characteristics and prognostic impact  

PubMed Central

Background Increased vascularity is a crucial event in the tumor progression and has prognostic significance in various cancers. However, the ultimate role of angiogenesis in the pathogenesis and clinical outcome of vulvar carcinoma patients is still not settled. Methods Tumor vascularity using CD34 stained slides measured by Chalkley counting method as well as hypoxia-inducible factor (HIF)-1? and vascular endothelial growth factor (VEGF) immunoexpression was examined in 158 vulvar squamous cell carcinomas. Associations between vascular Chalkley count, HIF-1? and VEGF expression and clinicopathological factors and clinical outcome were evaluated. Results High CD34 Chalkley count was found to correlate with larger tumor diameter (P = 0.002), deep invasion (P < 0.001) and HIF-1? (P = 0.04), whereas high VEGF expression correlate significantly with poor tumor differentiation (P = 0.007). No significant association between CD34 Chalkley counts and VEGF expression and disease-specific survival was observed. High HIF-1? expression showed better disease specific survival in both univariate and multivariate analyses (P = 0.001). Conclusions A significant association between high tumor vascularity and larger tumor size as well as deeper tumor invasion suggests an important role of angiogenesis in the growth and progression of vulvar carcinomas. HIF-1? expression in vulvar carcinomas was a statistically independent prognostic factor. PMID:24165149

2013-01-01

47

A retrospective analysis of clinicopathological and prognostic characteristics of ovarian tumors in the State of Espírito Santo, Brazil  

PubMed Central

Background Ovarian cancer is sixth most common cancer among women and the leading cause of death in women with gynecological malignancies. Despite the great impact ovarian cancer has on women's health and its great impact in public economy, Brazil still lacks valuable information concerning epidemiological aspects of this disease Methods We've compiled clinical data of all ovarian tumors registered at the two public hospitals of reference (1997 - 2007), such as: patients' age at diagnosis, tumor histological type, tumor stage, chemotherapy regimens, chemotherapy responsiveness, disease-free survival, and overall survival. Results Women's mean age at diagnosis was 54.67 ± 13.84 for ovarian cancer, 46.15 ± 11.15 for borderline tumors, and 42.01 ± 15.06 for adenomas. Among epithelial ovarian cancer cases, 30.1% were of serous, 13.7% were of mucinous, and 13.7% were of endometrioid type; exceptionally serous carcinoma was diagnosed in women younger than 30 years old. Endometrioid cancer had lower disease-free survival than others (p < 0.05). Cases were predominantly diagnosed as poor prognosis disease (FIGO III and IV, 56.2%). Regarding responsiveness to platinum-based therapy, 17.1% of patients were resistant, whereas 24.6%, susceptible. From these, we found equally responsiveness to platinum alone or its association with paclitaxel or cyclophosphamide. Discussion Our data agreed with other studies regarding mean patients' age at diagnosis, histological type frequency, FIGO stages distribution, and chemotherapy regimens. However, the histological type distribution, with equal contribution of mucinous and endometrioid types seems to be a unique characteristic of the studied highly miscegenated population. Conclusion We have enlighten the profile of the studied ovarian cancer population, which might enable the development of more efficient political strategies to control this malignancy that is the fifth leading cause of cancer-related deaths among women. PMID:21827671

2011-01-01

48

The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma  

Microsoft Academic Search

The prognostic outcome for hepatocellular carcinoma (HCC) remains poor. Disease progression is accompanied by dedifferentiation\\u000a of the carcinoma, a process that is not well understood. The aim of this study was to get more insight into the molecular\\u000a characteristics of dedifferentiated carcinomas using high throughput techniques. Microarray-based global gene expression analysis\\u000a was performed on five poorly differentiated HCC cell lines

Ludwig Wilkens; Rolf Jaggi; Caroline Hammer; Daniel Inderbitzin; Olivier Giger; Nils von Neuhoff

2011-01-01

49

A Study on Solubilization of Poorly Soluble Drugs by Cyclodextrins and Micelles: Complexation and Binding Characteristics of Sulfamethoxazole and Trimethoprim  

PubMed Central

The present study is focused on the characterization of solubilization of poorly soluble drugs, that is, sulfamethoxazole (SMX) and trimethoprim (TMP) by cyclodextrins (?-, ?-, and ?-CDs) and anionic surfactant sodium dodecyl sulfate (SDS). The phase solubility diagrams drawn from UV spectral measurements are of the AL type and indicate an enhancement of SMX and TMP solubility in the presence of CDs. Complex formation tendency of TMP with CDs followed the order: ?-CD > ?-CD > ?-C. However, the complex formation constant values, for SMX-CD system yielded the different affinity and follow the order: ?-CD > ?-CD > ?-CD. With taking into consideration of solubilization capacity of SDS micelles, it has been found that the solubility enhancement of TMP is much higher than that of SMX in the presence of SDS micelles. The binding constants of SMX and TMP obtained from the Benesi-Hildebrand equation are also confirmed by the estimated surface properties of SDS, employing the surface tension measurements. In order to elucidate the solubilization characteristics the surface tension measurements were also performed for nonionic surfactant Triton X-100. Polarity of the microenvironment and probable location of SMX and TMP were also discussed in the presence of various organic solvents. PMID:22649316

Göktürk, Sinem; Çal??kan, Elif; Talman, R. Ye?im; Var, Umran

2012-01-01

50

A Systematic Review and Meta-Analysis of Diagnostic and Prognostic Serum Biomarkers of Colorectal Cancer  

PubMed Central

Background Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. Results In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with >?=?3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347–3.744) and MMP-7 with lowest (1.099, CI: 1.018–1.187)) pooled HRs are presented. Conclusions The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice. PMID:25105762

Liu, Zhongyu; Zhang, Yingchong; Niu, Yulong; Li, Ke; Liu, Xin; Chen, Huijuan; Gao, Chunfang

2014-01-01

51

The characteristics and prognostic analysis in 213 myeloid malignancy patients with del(20q): a report of a single-center case series.  

PubMed

The clinical and hematological characteristics and the prognostic significance of del(20q) were investigated in a consecutive series of 213 myeloid malignancies. In the analyses, the cases were divided into three subgroups according to diagnosis or four subgroups according to cytogenetic data. Patients in the myeloproliferative neoplasms subgroup had high WBCs and platelet counts at initial diagnosis. The del(20q) occurred predominantly in older men. Sole del(20q) was observed most often in myelodysplastic syndromes, while del(20q) as a part of complex karyotypes was observed predominantly in acute myeloid leukemia. The most frequent additional abnormalities accompanying del(20q) were -5/del(5q), -7/del(7q) and +8; t(20;21)(q11;q11) and double del(20q) were two rare but recurrent abnormalities secondary to del(20q). In all types of diseases, patients with a sole del(20q) had a favorable prognosis. The presence of any additional abnormality with del(20q) had an unfavorable outcome. Patients with i(20q) had an unfavorable prognosis. Patients with the minor del(20q) clone had a better median survival than those with the major del(20q) clone. PMID:24699042

Pan, Jinlan; Wu, Chunxiao; Xue, Yongquan; Qiu, Huiying; Chen, Suning; Zhang, Jun; Bai, Shuxiao; Wu, Yafang; Wang, Yong; Shen, Juan; Gong, Yanlei

2014-03-01

52

Poor performance validity predicts clinical characteristics and cognitive test performance of OEF/OIF/OND Veterans in a research setting.  

PubMed

This study examined the performance of 198 Veteran research participants deployed during Operation Enduring Freedom, Operation Iraqi Freedom, and/or Operation New Dawn (OEF/OIF/OND) on four measures of performance validity: the Medical Symptom Validity Test (MSVT), California Verbal Learning Test: Forced Choice Recognition (FCR), Reliable Digit Span (RDS), and TOVA Symptom Exaggeration Index (SEI). Failure on these performance validity tests (PVTs) ranged from 4% to 9%. The overall base rate of poor performance validity, as measured by failure of the MSVT in conjunction with an embedded PVT (FCR, RDS, SEI), was 5.6%. Regression analyses revealed that poor performance validity predicted cognitive test performance and self-reported psychological symptom severity. Furthermore, a greater prevalence of traumatic brain injury (TBI), Post-Traumatic Stress Disorder (PTSD), co-morbid TBI/PTSD, and other Axis I diagnoses, was observed among participants with poor effort. Although poor performance validity is relatively uncommon in a research setting, these findings demonstrate that clinicians should be cautious when interpreting psychological symptoms and neuropsychological test performance of Veteran participants who fail effort measures. PMID:24766521

Clark, Alexandra L; Amick, Melissa M; Fortier, Catherine; Milberg, William P; McGlinchey, Regina E

2014-01-01

53

High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study  

PubMed Central

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile. PMID:18378853

Langer, Christian; Radmacher, Michael D.; Ruppert, Amy S.; Whitman, Susan P.; Paschka, Peter; Mrózek, Krzysztof; Baldus, Claudia D.; Vukosavljevic, Tamara; Liu, Chang-Gong; Ross, Mary E.; Powell, Bayard L.; de la Chapelle, Albert; Kolitz, Jonathan E.; Larson, Richard A.; Marcucci, Guido

2008-01-01

54

Follicular Lymphoma International Prognostic Index  

Microsoft Academic Search

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evalu- ating and choosing these treatments. Characteristics at diagnosis were col- lected from 4167 patients with FL diag- nosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested

Philippe Solal-Celigny; Pascal Roy; Philippe Colombat; Josephine White; Jim O. Armitage; Reyes Arranz-Saez; Wing Y. Au; Monica Bellei; Pauline Brice; Dolores Caballero; Bertrand Coiffier; Eulogio Conde-Garcia; Chantal Doyen; Massimo Federico; Richard I. Fisher; Javier F. Garcia-Conde; Cesare Guglielmi; Michael LeBlanc; Andrew T. Lister; Armando Lopez-Guillermo; Peter McLaughlin; Noel Milpied; Nicolas Mounier; Stephen J. Proctor; Ama Rohatiner; Paul Smith; Umberto Vitolo; Pier-Luigi Zinzani; Emanuele Zucca; Emili Montserrat; J. Bernard; Hopital H. Mondor; M. D. Anderson; CHU L. Huriez

2004-01-01

55

General Characteristics and Prognostic Factors of Pneumonia Cases Developed During Pandemic (H1N1) Influenza-A Virus Infection in Turkey  

PubMed Central

Objective: Unlike seasonal influenza, seen in previous years, the strain identified in the 2009 influenza-A pandemic involved high mortality. In this study, prognostic factors and general characteristics of pneumonia cases developed in Turkey during the H1N1 pandemic between October 2009 and January 2010 were analyzed. Study Design: Multicenter retrospective study. Material and Methods: This multicentric retrospective study was conducted between August and October 2010 and patients’ data were collected by means of standard forms. Results: The study included 264 pneumonia cases, collected from 14 different centers. Mean age was 47.5±18.6 years. Nineteen patients (7.2%) were pregnant or had a new birth and comorbid diseases were detected in 52.3% of all patients. On admission, 35 (13.8%) cases had altered mental status. Overall, 32.6% were treated in intensive care units (ICU) and invasive/non-invasive mechanical ventilation was performed in 29.7%. The mean duration of ICU stay was 2.9±6.2 and total hospital stay was 12.0±9.4 days. Mortality rate was 16.8% (43-cases). The length of ICU treatment, total hospital stay, and mortality were significantly higher in H1N1-confirmed patients. Mortality was significantly higher in patients with dyspnea, cyanosis, and those who had altered mental status on admission. Patients who died had significantly higher rate of peripheral blood neutrophils, lower platelet counts, higher BUN, and lower SaO2 levels. Conclusion: This study showed that pneumonia developed during H1N1 pandemic in our country had resulted in a high mortality. Mortality was especially high among patients with cyanosis, altered mental state and those with lower SaO2. PMID:25207072

Özlu, Tevfik; Bülbül, Y?lmaz; Ta?bakan, Sezai; K?l?ç, Hatice; Kuyucu, Tülin; Y?ld?z, Tekin; Özdemir, Tarkan; Duru, Serap; Öztuna, Funda; Ad?güzel, Nalan; Sa?lam, Leyla; Co?kun, Ay?in ?akar; Örnek, Tacettin; Gündüz, Gazi; Filiz, Ayten; Özdemir, Levent; Okumu?, Gülfer

2013-01-01

56

Village characteristics and health of rural Chinese older adults: examining the CHARLS Pilot Study of a rich and poor province.  

PubMed

Community (or village) characteristics have received growing attention as researchers have sought factors affecting health. This study examines the association between a variety of environmental, economic, and social village characteristics and health of Chinese older rural adults with health measured in terms of physical limitations. The Chinese Health and Retirement Longitudinal Survey (CHARLS) Pilot Study data were used. Older villagers from a low-income province (Gansu) and a relatively wealthy province (Zhejiang) were surveyed between July and September, 2008. The sample included 1267 respondents in 73 villages age 45 and older. The relationship between a variety of village characteristics and physical limitations of older adults was examined using negative binomial regression (NBR) with standard errors adjusted to account for non-independence of respondents in a village. A comparison of means/percentages shows that Gansu and Zhejiang were significantly different on the dependent and most independent variables. The NBR models show that at the personal-level, decreased risk of physical limitations was associated with being male, less than 60 years old, married, higher in education, and higher in household expenditures (proxy for income). At the village-level, decreased risk of limitations was associated with a continuous supply of electricity, not using coal in the household, the existence of a sewage system, low cost of electricity, and village wealth. Decreased risk of physical limitations was also associated with various characteristics of China's New Cooperative Medical Scheme (NCMS), an insurance program for rural older adults. Policy implications for improved health of rural older adults include: (1) continued use of China's NCMS, (2) establishment of village sewage systems, (3) ending the use of coal in the home, and (4) increased educational opportunities focused on health. PMID:24331884

Yeatts, Dale E; Pei, Xiaomei; Cready, Cynthia M; Shen, Yuying; Luo, Hao; Tan, Junxin

2013-12-01

57

Friend leukemia virus integration 1 expression has prognostic significance in nasopharyngeal carcinoma.  

PubMed

This study aimed to investigate the expression pattern and prognostic value of friend leukemia virus integration 1 (FLI-1) in nasopharyngeal carcinoma (NPC). Immunohistochemistry (IHC) staining of FLI-1 was performed in specimens from 198 untreated NPC patients. Ninety-nine patients were randomly assigned to the training set to analyze the prognostic value of FLI-1 and other clinicopathological characteristics, while the others were assigned to the testing set for validation. Clinicopathological data were compared using the Pearson chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards model to test independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI). Cytoplasmic FLI-1 expression positively correlated with N stage, distant metastasis and death (P<0.05) and also predicted poorer overall survival (OS) (P=0.014), distant metastasis-free survival (DMFS) (P=0.010), progression-free survival (PFS) (P=0.031). In multivariate analysis, FLI-1 expression and clinical stage were both independent prognostic factors of poor OS and DMFS. Prognoses of patients in the training set, the testing set, and the entire set were clearly divided into four risk subgroups by supplementing FLI-1 with clinical stage. These results indicate that FLI-1 expression is an independent prognostic factor for NPC patients and suggest that supplementing FLI-1 with clinical stage could be helpful for more accurate risk definition. PMID:25171891

Liang, Xuexia; Shi, Dingbo; Yun, Jingping; Mao, Yanping; Ouyang, Puyun; Su, Zhen; Fu, Jia; Hou, Jinghui; Deng, Wuguo; Xie, Fangyun

2014-08-01

58

Friend Leukemia Virus Integration 1 Expression Has Prognostic Significance in Nasopharyngeal Carcinoma1  

PubMed Central

This study aimed to investigate the expression pattern and prognostic value of friend leukemia virus integration 1 (FLI-1) in nasopharyngeal carcinoma (NPC). Immunohistochemistry (IHC) staining of FLI-1 was performed in specimens from 198 untreated NPC patients. Ninety-nine patients were randomly assigned to the training set to analyze the prognostic value of FLI-1 and other clinicopathological characteristics, while the others were assigned to the testing set for validation. Clinicopathological data were compared using the Pearson chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards model to test independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI). Cytoplasmic FLI-1 expression positively correlated with N stage, distant metastasis and death (P< 0.05) and also predicted poorer overall survival (OS) (P= 0.014), distant metastasis-free survival (DMFS) (P= 0.010), progression-free survival (PFS) (P= 0.031). In multivariate analysis, FLI-1 expression and clinical stage were both independent prognostic factors of poor OS and DMFS. Prognoses of patients in the training set, the testing set, and the entire set were clearly divided into four risk subgroups by supplementing FLI-1 with clinical stage. These results indicate that FLI-1 expression is an independent prognostic factor for NPC patients and suggest that supplementing FLI-1 with clinical stage could be helpful for more accurate risk definition. PMID:25171891

Liang, Xuexia; Shi, Dingbo; Yun, Jingping; Mao, Yanping; Ouyang, Puyun; Su, Zhen; Fu, Jia; Hou, Jinghui; Deng, Wuguo; Xie, Fangyun

2014-01-01

59

Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors  

Microsoft Academic Search

Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- acteristics, prognostic factors, and out- come of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa

P. Montesinos; J. M. Bergua; E. Vellenga; C. Rayón; R. Parody; J. de la Serna; A. León; J. Esteve; G. Milone; G. Debén; C. Rivas; M. González; M. Tormo; D. M. Joaquín; J. D. González; S. Negri; E. Amutio; S. Brunet; B. Löwenberg; M. A. Sanz

2009-01-01

60

Electronics Prognostics Reference Architecture  

Microsoft Academic Search

Electronics prognostics can be defined as the prediction of the Remaining Useful Life (RUL) of electronic components before a failure occurs. This field, while immature, is increasingly important to Raytheonpsilas customers. Raytheon must develop a common and synergistic strategy to address new prognostic requirements. For this reason, Raytheon established a Prognostics and Health Management (PHM) (formerly known as Health Management

N. Almonte; D. Cook; J. Devereaux; M. Henry; T. Higgins; G. Roth

2008-01-01

61

Incorporating prognostic imaging biomarkers into clinical practice  

PubMed Central

Abstract A prognostic imaging biomarker can be defined as an imaging characteristic that is objectively measurable and provides information on the likely outcome of the cancer disease in an untreated individual and should be distinguished from predictive imaging biomarkers and imaging markers of response. A range of tumour characteristics of potential prognostic value can be measured using a variety imaging modalities. However, none has currently been adopted into routine clinical practice. This article considers key examples of emerging prognostic imaging biomarkers and proposes an evaluation framework that aims to demonstrate clinical efficacy and so support their introduction into the clinical arena. With appropriate validation within an established evaluation framework, prognostic imaging biomarkers have the potential to contribute to individualized cancer care, in some cases reducing the financial burden of expensive cancer treatments by facilitating their more rational use. PMID:24060808

Miles, Kenneth A.

2013-01-01

62

Molecular-pathological prognostic factors of gastric cancer: a review.  

PubMed

Invasion and metastasis are critical determinants of cancer morbidity. Genes and molecules participating in these steps must be regarded as potential prognostic factors. Growth factors and their receptors, cell-cycle regulators, cell-adhesion molecules and matrix-degrading enzymes are those to be used as prognostic factors, including epidermal growth factor (EGF), EGF receptor, K-sam, HER-2, interleukin (IL)-8, vascular endothelial growth factor (VEGF), cyclin E, p27, E-cadherin, CD44v6, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Alterations in epigenetics, such as aberrant DNA methylation and histone modification that are, in part, associated with the tumor progression of gastric cancer, can be candidate prognostic factors. The number of methylated genes may serve as a marker of tumor progression. Genetic polymorphism not only affects cancer susceptibility but also influences malignant phenotype; examples include single-nucleotide polymorphism in the HER-2 and MMP-9 genes. Comprehensive gene expression analyses are useful to search for novel genes related to invasion and metastasis and potential prognostic factors. Serial analysis of gene expression (SAGE) has identified several these genes, such as CDH17, APOE, FUS, COL1A1, COL1A2, GW112, and MIA. Overexpression of MIA is found to be associated with poor prognosis. Microarray analysis has great potential for identifying the characteristics of individual cancers, from the view point of gene expression profiles. A combination of these examinations can not only foretell a patient's prognosis but can also give information directly connected with personalized cancer medicine and prevention. PMID:15864715

Yasui, Wataru; Oue, Naohide; Aung, Phyu Phyu; Matsumura, Shunji; Shutoh, Mariko; Nakayama, Hirofumi

2005-01-01

63

Prognostics for Microgrid Components  

NASA Technical Reports Server (NTRS)

Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

Saxena, Abhinav

2012-01-01

64

What do we mean by validating a prognostic model?  

Microsoft Academic Search

SUMMARY Prognostic models are used in medicine for investigating patient outcome in relation to patient and disease characteristics. Such models do not always work well in practice, so it is widely recommended that they need to be validated. The idea of validating a prognostic model is generally taken to mean establishing that it works satisfactorily for patients other than those

Douglas G. Altman; Patrick Royston

2000-01-01

65

Toward IVHM Prognostics  

NASA Technical Reports Server (NTRS)

This viewgraph presentation reviews the prognostics of Integrated Vehicle Health Management. The contents include: 1) Aircraft Operations-Today's way of doing business; 2) Prognostics; 3) NASA's instrumentation data-system rack; 4) Data mining for IVHM; 5) NASA GRC's C-MAPSS generic engine model; and 6) Concluding thoughts.

Walsh, Kevin; Venti, Mike

2007-01-01

66

Metrics for Offline Evaluation of Prognostic Performance  

NASA Technical Reports Server (NTRS)

Prognostic performance evaluation has gained significant attention in the past few years. Currently, prognostics concepts lack standard definitions and suffer from ambiguous and inconsistent interpretations. This lack of standards is in part due to the varied end-user requirements for different applications, time scales, available information, domain dynamics, etc. to name a few. The research community has used a variety of metrics largely based on convenience and their respective requirements. Very little attention has been focused on establishing a standardized approach to compare different efforts. This paper presents several new evaluation metrics tailored for prognostics that were recently introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. These metrics have the capability of incorporating probabilistic uncertainty estimates from prognostic algorithms. In addition to quantitative assessment they also offer a comprehensive visual perspective that can be used in designing the prognostic system. Several methods are suggested to customize these metrics for different applications. Guidelines are provided to help choose one method over another based on distribution characteristics. Various issues faced by prognostics and its performance evaluation are discussed followed by a formal notational framework to help standardize subsequent developments.

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2010-01-01

67

The Prognostic Value of Intermedin in Patients with Breast Cancer  

PubMed Central

This study aimed to evaluate the prognostic value of preoperative plasma intermedin levels in breast cancer patients. Plasma intermedin levels of 252 breast cancer women and 100 healthy women were determined using radioimmunoassay kit. Adverse event was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause during 5-year follow-up. Disease-free survival was defined as the time between surgery and the date of any adverse event whichever appeared first. Overall survival was defined from surgery to death for any cause. The relationships between plasma intermedin levels and clinical outcomes of breast cancer patients were evaluated using multivariate analysis. The results showed that preoperative plasma intermedin levels were substantially higher in patients than in healthy subjects using t-test. Intermedin was identified as an independent predictor for 5-year mortality, adverse event, disease-free survival, and overall survival using multivariate analysis. Based on receiver operating characteristic curve analysis, preoperative plasma intermedin levels had high predictive value for 5-year mortality and adverse event. In conclusion, preoperative plasma intermedin levels are highly associated with poor patient outcomes and intermedin may be a potential prognostic biomarker for patients with breast cancer. PMID:25694747

Lu, Yi-Min; Zhong, Jian-Bo; Wang, Hai-Yong; Yu, Xiong-Fei; Li, Zhong-Qi

2015-01-01

68

Prognostic factors and survival in patients with gastric stump cancer  

PubMed Central

AIM: To elucidate the clinicopathological characteristics and prognostic factors of gastric stump cancer (GSC). METHODS: The clinical data for 92 patients with GSC were collected at Fudan University Shanghai Cancer Center. The prognostic factors were analyzed with Cox proportional hazard models. RESULTS: GSC tended to occur within 25 years following the primary surgery, when the initial disease is benign, whereas it primarily occurred within the first 15 years post-operation for gastric cancer. Patients with regular follow-up after primary surgery had a better survival rate. The multivariate Cox regression analysis revealed that Borrmann type?I/II (HR = 3.165, 95%CI: 1.055-9.500, P = 0.040) and radical resection (HR = 1.780, 95%CI: 1.061-2.987, P = 0.029) were independent prognostic factors for GSC. The overall 1-, 3-, and 5-year survival rates of the 92 patients were 78.3%, 45.6% and 27.6%, respectively. The 1-, 3-, and 5-year survival rates of those undergoing radical resection were 79.3%, 52.2%, and 37.8%, respectively. The 5-year survival rates for stages?I, II, III, and IV were 85.7%, 47.4%, 16.0%, and 13.3%, respectively (P = 0.005). CONCLUSION: The appearance of GSC occurs sooner in patients with primary malignant cancer than in patients with a primary benign disease. Therefore, close follow-up is necessary. The overall survival of patients with GSC is poor, and curative resection can improve their prognosis. PMID:25684953

Huang, Hua; Wang, Wei; Chen, Zhong; Jin, Jie-Jie; Long, Zi-Wen; Cai, Hong; Liu, Xiao-Wen; Zhou, Ye; Wang, Ya-Nong

2015-01-01

69

Loss of CDX2 expression is associated with poor prognosis in colorectal cancer patients  

PubMed Central

AIM: To investigate the clinicopathologic characteristics and prognostic implications associated with loss of CDX2 expression in colorectal cancers (CRCs). METHODS: We immunohistochemically evaluated CDX2 expression in 713 CRCs and paired our findings to clinicopathologic and molecular characteristics of each individual. Endpoints included cytokeratin 7 and CK20 expression, microsatellite instability, CpG island methylator phenotype, and KRAS and BRAF mutation statuses. Univariate and multivariate survival analysis was performed to reveal the prognostic value of CDX2 downregulation. RESULTS: CDX2 expression was lost in 42 (5.9%) patients. Moreover, loss of CDX2 expression was associated with proximal location, infiltrative growth, advanced T, N, M and overall stage. On microscopic examination, loss of CDX2 expression was associated with poor differentiation, increased number of tumor-infiltrating lymphocytes, luminal serration and mucin production. Loss of CDX2 expression was also associated with increased CK7 expression, decreased CK20 expression, CpG island methylator phenotype, microsatellite instability and BRAF mutation. In a univariate survival analysis, patients with loss of CDX2 expression showed worse overall survival (P < 0.001) and progression-free survival (P < 0.001). In a multivariate survival analysis, loss of CDX2 expression was an independent poor prognostic factor of overall survival [hazard ratio (HR) = 1.72, 95%CI: 1.04-2.85, P = 0.034] and progression-free survival (HR = 1.94, 95%CI: 1.22-3.07, P = 0.005). CONCLUSION: Loss of CDX2 expression is associated with aggressive clinical behavior and can be used as a prognostic marker in CRCs. PMID:25663765

Bae, Jeong Mo; Lee, Tae Hun; Cho, Nam-Yun; Kim, Tae-You; Kang, Gyeong Hoon

2015-01-01

70

Prognostics of power MOSFET  

Microsoft Academic Search

This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and Gaussian process regression to perform prognostics. The approach is validated with experiments on 100V power MOSFETs. The failure mechanism for the stress conditions is determined to be die-attachment degradation. Change in ON-state resistance is used as

Jose R. Celaya; Abhinav Saxena; Sankalita Saha; Vladislav Vashchenko; Kai Goebel

2011-01-01

71

Prognostic microRNAs in high-grade glioma reveal a link to oligodendrocyte precursor differentiation  

PubMed Central

MicroRNA expression can be exploited to define tumor prognosis and stratification for precision medicine. It remains unclear whether prognostic microRNA signatures are exclusively tumor grade and/or molecular subtype-specific, or whether common signatures of aggressive clinical behavior can be identified. Here, we defined microRNAs that are associated with good and poor prognosis in grade III and IV gliomas using data from The Cancer Genome Atlas. Pathway analysis of microRNA targets that are differentially expressed in good and poor prognosis glioma identified a link to oligodendrocyte development. Notably, a microRNA expression profile that is characteristic of a specific oligodendrocyte precursor cell type (OP1) correlates with microRNA expression from 597 of these tumors and is consistently associated with poor patient outcome in grade III and IV gliomas. Our study reveals grade-independent and subtype-independent prognostic molecular signatures in high-grade glioma and provides a framework for investigating the mechanisms of brain tumor aggressiveness.

Hayes, Josie; Thygesen, Helene; Droop, Alastair; Hughes, Thomas A.; Westhead, David; Lawler, Sean E.; Wurdak, Heiko; Short, Susan C.

2015-01-01

72

Sinonasal Rhabdomyosarcoma: Prognostic Factors and Treatment Outcomes  

PubMed Central

Background Despite the improvement in survival of pediatric patients with rhabdomyosarcoma, the outcome of patients with sinonasal rhabdomyosarcoma is poor and has not significantly changed. Since few institutions have extensive experience with sinonasal rhabdomyosarcoma in children and adults, our objective was to determine prognostic factors and treatment outcomes for this rare malignancy. Methods A retrospective review was performed of consecutive patients with sinonasal rhabdomyosarcoma treated at our institution from 1992 to 2012. Kaplan-Meier estimates and the log rank test were performed to determine factors associated with disease recurrence and disease specific survival. Results Initial remission was achieved in 12 of the 16 patients. Age younger than 18 years (n=9) was a positive prognostic factor, as there were no recurrences (p<0.01) and no deaths (p<0.01). The alveolar subtype was a poor prognostic factor, as four of the five patients with this histology died of disease (p<0.01), and both patients with initial remission developed recurrence (p<0.01). Presentation with later TNM stage was also significant for poorer survival, as two of the three patients with stage IV died of disease (p=0.05). Patient sex and treatment modality were not significant. Conclusions Although the sinonasal region is an unfavorable site for rhabdomyosarcomas, in our series patients younger than 18 years and those with embryonal or botryoid subtypes responded very well to current multimodality treatment. However, a poor prognostic trend is evident in patients with sinonasal alveolar rhabdomyosarcomas, as they appear to present more often with regional and distant metastases, have increased recurrence, and decreased survival. PMID:23424037

Thompson, Christopher F.; Kim, Brandon J.; Lai, Chi; Grogan, Tristan; Elashoff, David; John, Maie A. St.; Wang, Marilene B.

2015-01-01

73

Prognostic performance of inflammation-based prognostic indices in patients with resectable colorectal liver metastases.  

PubMed

A range of prognostic cellular indices of the systemic inflammatory response, namely the neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognostic nutritional index (PNI), have been developed and found to have prognostic utility across varied malignancies. The current study is the first to examine the prognostic value of these six inflammatory scores in patients with resectable colorectal liver metastases (CRLM). Data from 302 consecutive patients undergoing surgery for resectable CRLM were evaluated. The prognostic influence of clinicopathological variables and the inflammatory scores NLR, dNLR, PLR, LMR, COP-NLR and PNI upon overall survival (OS) and cancer-specific survival (CSS) were determined by log-rank analysis and univariate and multivariate Cox regression analyses. High preoperative NLR was the only inflammatory variable independently associated with shortened OS (HR 1.769, 95 % CI 1.302-2.403, P < 0.001) or CSS (HR 1.927, 95 % CI 1.398-2.655, P < 0.001) following metastasectomy. When NLR was replaced by dNLR in analyses, high dNLR was independently associated with shortened OS (HR 1.932, 95 % CI 1.356-2.754, P < 0.001) and CSS (HR 1.807, 95 % CI 1.209-2.702, P = 0.004). The inflammatory scores PLR, LMR, COP-NLR and PNI demonstrated no independent association with either overall or cancer-specific survival in the study population. Our findings support high preoperative NLR and dNLR as independent prognostic factors for poor outcome in patients undergoing CRLM resection, with prognostic value superior to other cellular-based systemic inflammatory scores. PMID:25807934

Neal, Christopher P; Cairns, Vaux; Jones, Michael J; Masood, Muhammad M; Nana, Gael R; Mann, Christopher D; Garcea, Giuseppe; Dennison, Ashley R

2015-05-01

74

Congenital Aniridia: Long-term Clinical Course, Visual Outcome, and Prognostic Factors  

PubMed Central

Purpose To describe the clinical course of congenital aniridia and to evaluate prognostic factors for visual outcome after long-term follow-up. Methods The medical records of 120 eyes from 60 patients with congenital aniridia were retrospectively reviewed. The prevalence and clinical course of ophthalmic characteristics, systemic disease, refractive errors, and visual acuity were assessed. Prognostic factors for final visual outcomes were analyzed. Results Aniridic keratopathy developed in 82 (69%) of 119 eyes. Macular hypoplasia was observed in 70 eyes of 35 patients (91%). Cataract was observed in 63 of 120 eyes (53%). Nystagmus was present in 41 patients (68% of 60 patients) at the initial visit but decreased in five patients (8% of 60 patients). Ocular hypertension was detected in 19 eyes (20% of 93 eyes), six (32% of 19 eyes) of which developed secondarily after cataract surgery. The mean changes in spherical equivalent and astigmatism during the follow-up period were -1.10 and 1.53 diopter, respectively. The mean final visual acuity was 1.028 logarithm of minimal angle of resolution. Nystagmus and ocular hypertension were identified as prognostic factors for poor visual outcome. Conclusions Identification of nystagmus and ocular hypertension was important to predict final visual outcome. Based on the high rate of secondary ocular hypertension after cataract surgery, careful management is needed. PMID:25435751

Chang, Ji Woong; Kim, Jeong Hun; Kim, Seong-Joon

2014-01-01

75

Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia  

PubMed Central

Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics. This trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374. PMID:23065509

Nguyen-Khac, Florence; Lambert, Jerome; Chapiro, Elise; Grelier, Aurore; Mould, Sarah; Barin, Carole; Daudignon, Agnes; Gachard, Nathalie; Struski, Stéphanie; Henry, Catherine; Penther, Dominique; Mossafa, Hossein; Andrieux, Joris; Eclache, Virginie; Bilhou-Nabera, Chrystèle; Luquet, Isabelle; Terre, Christine; Baranger, Laurence; Mugneret, Francine; Chiesa, Jean; Mozziconacci, Marie-Joelle; Callet-Bauchu, Evelyne; Veronese, Lauren; Blons, Hélène; Owen, Roger; Lejeune, Julie; Chevret, Sylvie; Merle-Beral, Hélène; Leblondon, Véronique

2013-01-01

76

Absolute monocyte and lymphocyte count prognostic score for patients with gastric cancer  

PubMed Central

AIM: To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score (AMLPS) in patients with gastric cancer. METHODS: We retrospectively examined the combination of absolute monocyte count (AMC) and absolute lymphocyte count (ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution. Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis. An AMLPS was generated, which stratified patients into three risk groups: low risk (both low AMC and high ALC), intermediate risk (either high AMC or low ALC), and high risk (both high AMC and low ALC). The primary objective of the study was to validate the impact of AMLPS on both disease-free survival (DFS) and overall survival (OS), and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors. RESULTS: Using data from the entire cohort, the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/?L and 1734/?L for DFS and OS. AMLPS risk groups included 158 (52.8%) patients in the low-risk, 128 (42.8%) in the intermediate-risk, and 13 (4.3%) in the high-risk group. With a median follow-up of 37.2 mo (range: 1.7-91.4 mo), five-year DFS rates in the low-, intermediate-, and high-risk groups were 83.4%, 78.7%, and 19.8%, respectively. And five-year OS rates in the low-, intermediate-, and high-risk groups were 89.3%, 81.1%, and 14.4%, respectively. On multivariate analysis performed with patient- and tumor-related factors, we identified AMLPS, age, and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS. CONCLUSION: AMLPS identified patients with a poor DFS and OS, and it was independent of age, pathologic stage, and various inflammatory markers. PMID:25759535

Eo, Wan Kyu; Jeong, Da Wun; Chang, Hye Jung; Won, Kyu Yeoun; Choi, Sung Il; Kim, Se Hyun; Chun, Sung Wook; Oh, Young Lim; Lee, Tae Hwa; Kim, Young Ok; Kim, Ki Hyung; Ji, Yong Il; Kim, Ari; Kim, Heung Yeol

2015-01-01

77

The prognostic value of the fracture level in the treatment of Gartland type III supracondylar humeral fracture in children.  

PubMed

A small proportion of children with Gartland type III supracondylar humeral fracture (SCHF) experience troubling limited or delayed recovery after operative treatment. We hypothesised that the fracture level relative to the isthmus of the humerus would affect the outcome. We retrospectively reviewed 230 children who underwent closed reduction and percutaneous pinning (CRPP) for their Gartland type III SCHFs between March 2003 and December 2012. There were 144 boys and 86 girls, with the mean age of six years (1.1 to 15.2). The clinico-radiological characteristics and surgical outcomes (recovery of the elbow range of movement, post-operative angulation, and the final Flynn grade) were recorded. Multivariate analysis was employed to identify prognostic factors that influenced outcome, including fracture level. Multivariate analysis revealed that a fracture below the humeral isthmus was significantly associated with poor prognosis in terms of the range of elbow movement (p < 0.001), angulation (p = 0.001) and Flynn grade (p = 0.003). Age over ten years was also a poor prognostic factor for recovery of the range of elbow movement (p = 0.027). This is the first study demonstrating a subclassification system of Gartland III fractures with prognostic significance. This will guide surgeons in peri-operative planning and counselling as well as directing future research aimed at improving outcomes. PMID:25568427

Kang, S; Kam, M; Miraj, F; Park, S-S

2015-01-01

78

Prognostics of Power MOSFET  

NASA Technical Reports Server (NTRS)

This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and Gaussian process regression to perform prognostics. The approach is validated with experiments on 100V power MOSFETs. The failure mechanism for the stress conditions is determined to be die-attachment degradation. Change in ON-state resistance is used as a precursor of failure due to its dependence on junction temperature. The experimental data is augmented with a finite element analysis simulation that is based on a two-transistor model. The simulation assists in the interpretation of the degradation phenomena and SOA (safe operation area) change.

Celaya, Jose Ramon; Saxena, Abhinav; Vashchenko, Vladislay; Saha, Sankalita; Goebel, Kai Frank

2011-01-01

79

Standardizing Research Methods for Prognostics  

E-print Network

Standardizing Research Methods for Prognostics Serdar Uckun, Member, IEEE, Kai Goebel, and Peter J statistical rigor. In this paper, we provide a critical review of current research methods in PHM and contrast business impact. Index Terms--Prognostics, Prognostics and Health Management, Research Methods, Performance

Lucas, Peter

80

Prognostic features of renal sarcomas (Review)  

PubMed Central

The aim of the present review was to evaluate the prognostic features of primary sarcomas of the kidney. A literature review was conducted using a number of databases, including Medline (PubMed) and Scopus, for studies published between January 1992 and December 2013. Of the studies published in English, those describing the prognostic features of primary sarcomas of the kidney were recorded. The electronic search was limited to the following keywords: Sarcoma, renal sarcoma, prognosis, diagnosis, immunohistochemistry, genetic and survey. Subsequent to the search, no review articles and/or meta-analyses associated with the prognosis of primary sarcomas of the kidney were identified. In total, 31 studies, which consisted of case studies, case series and studies concerned with the overall prognosis of urological soft-tissue sarcomas, were reviewed. Primary sarcoma of the kidney has a poor prognosis compared with other sarcomas of the urogenital system. In addition to the surgical excision of renal sarcomas, pathological, molecular and genetic prognostic factors are also considered. Due to the small number of cases, previous studies have not randomized the prognostic features of primary sarcomas of the kidney. The elucidation of the so-called ‘chaotic’ genetic and molecular basis of renal sarcomas will help to predict patient prognoses. Surgical excision is the most significant parameter for determining the prognosis of sarcomas of the kidney. However, sarcomas also exhibit prognostic features that are based upon pathological, genetic and molecular factors. The present review suggests that additional factors may be important in predicting the prognosis of patients with renal sarcomas, and that clinicians should plan treatment and follow-up regimens according to these factors. PMID:25663853

ÖZTÜRK, HAKAN

2015-01-01

81

Validation of a Dutch Risk Score Predicting Poor Outcome in Adults with Bacterial Meningitis in Vietnam and Malawi  

PubMed Central

We have previously developed and validated a prognostic model to predict the risk for unfavorable outcome in Dutch adults with bacterial meningitis. The aim of the current study was to validate this model in adults with bacterial meningitis from two developing countries, Vietnam and Malawi. Demographic and clinical characteristics of Vietnamese (n?=?426), Malawian patients (n?=?465) differed substantially from those of Dutch patients (n?=?696). The Dutch model underestimated the risk of poor outcome in both Malawi and Vietnam. The discrimination of the original model (c-statistic [c] 0.84; 95% confidence interval 0.81 to 0.86) fell considerably when re-estimated in the Vietnam cohort (c?=?0.70) or in the Malawian cohort (c?=?0.68). Our validation study shows that new prognostic models have to be developed for these countries in a sufficiently large series of unselected patients. PMID:22470555

Schut, Ewout S.; Brouwer, Matthijs C.; Scarborough, Matthew; Mai, Nguyen Thi Hoang; Thwaites, Guy E.; Farrar, Jeremy J.; Reitsma, Johannes B.; van de Beek, Diederik

2012-01-01

82

Prognostic factors related with survival in patients with pancreatic adenocarcinoma  

PubMed Central

The prognosis in patients with pancreatic cancer is poor and this cancer is the fourth leading cause of cancer-related death worldwide. Although surgical resection is the only curative treatment of choice for pancreatic cancer, the majority of patients are diagnosed at an advanced stage, thus only 10%-15% of them are suitable for curative resection and the overall survival is less than 5%. Chemotherapy for metastatic disease is to palliate symptoms of patients and to improve survival. Therefore, prognostic factors are important and a correct definition of poor prognostic factors may help to guide more aggressive adjuvant or aggressive treatment protocols in patients with pancreatic cancer. This article reviews the prognostic factors affecting survival of patients with pancreatic cancer in the light of recent advances in the literature. PMID:25152583

Bilici, Ahmet

2014-01-01

83

Prognostic Impacts of Hypoxic Markers in Soft Tissue Sarcoma  

PubMed Central

Background. We aimed to explore the prognostic impact of the hypoxia-induced factors (HIF?s) 1 and 2, the metabolic HIF-regulated glucose transporter GLUT-1, and carbonic anhydrase IX (CAIX) in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STS). Methods. Duplicate cores with viable tumor tissue from 206 patients with non-GIST STS were obtained and tissue microarrays were constructed. Immunohistochemistry (IHC) was used to evaluate expression of hypoxic markers. Results. In univariate analyses, GLUT-1 (P < 0.001) and HIF-2? (P = 0.032) expression correlated significantly with a poor disease-specific survival (DSS). In the multivariate analysis, however, only high expression of GLUT-1 (HR 1.7, CI 95% 1.1–2.7, P = 0.021) was a significant independent prognostic indicator of poor DSS. Conclusion. GLUT-1 is a significant independent negative prognostic factor in non-GIST STS. PMID:22454562

Smeland, Eivind; Kilvaer, Thomas K.; Sorbye, Sveinung; Valkov, Andrej; Andersen, Sigve; Bremnes, Roy M.; Busund, Lill-Tove; Donnem, Tom

2012-01-01

84

Detection of dicentric chromosome (9;20) in paediatric B-cell acute lymphoblastic leukaemia: prognostic significance.  

PubMed

The dicentric chromosome (9;20) (dic(9;20)) is described in 2 % of childhood B-acute lymphoblastic leukaemia. Fluorescence in situ hybridization (FISH) is the most reliable method to identify dic(9;20) when compared with conventional cytogenetics. To define the prognostic importance of dic(9;20), we evaluated treatment response and patient survival. This was a retrospective study in three French university centres. Patients' clinical and laboratory characteristics and treatment response are described. Nine children with dic(9;20) have been identified since 1995. All patients had at least one poor prognostic feature either among the clinical features, the initial laboratory results or in the initial treatment response: central nervous system involvement (2/9), high median leucocyte count (?50 G/L) (8/9) and poor response to prednisone (2/9). All patients were in complete cytological remission after induction therapy but only three had a good molecular response with minimal residual disease (MRD) <10(-3). Five out of nine patients relapsed and two died, 4 and 12 months after diagnosis, respectively. The event-free survival rate in this population was 44 % (95 % confidence interval (CI)?=?0.09-0.79) and overall survival 78 % (95 % CI?=?0.51-1.05). In this population, dic(9;20) is associated with a relatively poor prognosis. Patients showing dic(9;20), whether this cytogenetic abnormality is associated with other poor prognostic factors or not, should be identified at the outset in order to be offered a more intensive treatment protocol. PMID:25193356

Letouzey, Mathilde; Penther, Dominique; Roche-Lestienne, Catherine; Nelken, Brigitte; Devoldère, Catherine; Vannier, Jean-Pierre; Schneider, Pascale

2015-02-01

85

ULK1: A Promising Biomarker in Predicting Poor Prognosis and Therapeutic Response in Human Nasopharygeal Carcinoma  

PubMed Central

Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients’ prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC) method in two independent cohorts of nasopharygeal carcinoma (NPC) cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients’ clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS) (P<0.05). Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response) could significantly stratify risk (low, intermediate and high) for DSS in NPC patients (P<0.001). These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients’ survival outcome in NPC patients. PMID:25714809

Yun, Miao; Bai, Hai-Yan; Zhang, Jia-Xing; Rong, Jian; Weng, Hui-Wen; Zheng, Zhou-San; Xu, Yi; Tong, Zhu-Ting; Huang, Xiao-Xia; Liao, Yi-Ji; Mai, Shi-Juan; Ye, Sheng; Xie, Dan

2015-01-01

86

Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements  

PubMed Central

Purpose Cardiac involvement predicts poor prognosis in light chain (AL) amyloidosis, and the current prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro–B-type natriuretic peptide (NT-ProBNP). However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification. Patients and Methods We developed a prognostic model based on 810 patients with newly diagnosed AL amyloidosis, which was further examined in two other datasets: 303 patients undergoing stem-cell transplantation, and 103 patients enrolled onto different clinical trials. Results We examined the prognostic value of plasma cell–related characteristics (ie, difference between involved and uninvolved light chain [FLC-diff], marrow plasma cell percentage, circulating plasma cells, plasma cell labeling index, and ?2 microglobulin). In a multivariate model that included these characteristics as well as cTnT and NT-ProBNP, only FLC-diff, cTnT, and NT-ProBNP were independently prognostic for overall survival (OS). Patients were assigned a score of 1 for each of FLC-diff ? 18 mg/dL, cTnT ? 0.025 ng/mL, and NT-ProBNP ? 1,800 pg/mL, creating stages I to IV with scores of 0 to 3 points, respectively. The proportions of patients with stages I, II, III and IV disease were 189 (25%), 206 (27%), 186 (25%) and 177 (23%), and their median OS from diagnosis was 94.1, 40.3, 14, and 5.8 months, respectively (P < .001). This classification system was validated in the other datasets. Conclusion Incorporation of serum FLC-diff into the current staging system improves risk stratification for patients with AL amyloidosis and will help develop risk-adapted therapies for AL amyloidosis. PMID:22331953

Kumar, Shaji; Dispenzieri, Angela; Lacy, Martha Q.; Hayman, Suzanne R.; Buadi, Francis K.; Colby, Colin; Laumann, Kristina; Zeldenrust, Steve R.; Leung, Nelson; Dingli, David; Greipp, Philip R.; Lust, John A.; Russell, Stephen J.; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

2012-01-01

87

Significance Analysis of Prognostic Signatures  

PubMed Central

A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that “random” gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated genomic datasets. PMID:23365551

Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.; Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John; Haibe-Kains, Benjamin

2013-01-01

88

Contemporary approach to neurologic prognostication of coma after cardiac arrest.  

PubMed

Coma after cardiac arrest (CA) is an important cause of admission to the ICU. Prognosis of post-CA coma has significantly improved over the past decade, particularly because of aggressive postresuscitation care and the use of therapeutic targeted temperature management (TTM). TTM and sedatives used to maintain controlled cooling might delay neurologic reflexes and reduce the accuracy of clinical examination. In the early ICU phase, patients' good recovery may often be indistinguishable (based on neurologic examination alone) from patients who eventually will have a poor prognosis. Prognostication of post-CA coma, therefore, has evolved toward a multimodal approach that combines neurologic examination with EEG and evoked potentials. Blood biomarkers (eg, neuron-specific enolase [NSE] and soluble 100-? protein) are useful complements for coma prognostication; however, results vary among commercial laboratory assays, and applying one single cutoff level (eg, >?33 ?g/L for NSE) for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI, is emerging as a promising tool for prognostication, but its precise role needs further study before it can be widely used. This multimodal approach might reduce false-positive rates of poor prognosis, thereby providing optimal prognostication of comatose CA survivors. The aim of this review is to summarize studies and the principal tools presently available for outcome prediction and to describe a practical approach to the multimodal prognostication of coma after CA, with a particular focus on neuromonitoring tools. We also propose an algorithm for the optimal use of such multimodal tools during the early ICU phase of post-CA coma. PMID:25367474

Ben-Hamouda, Nawfel; Taccone, Fabio S; Rossetti, Andrea O; Oddo, Mauro

2014-11-01

89

Special considerations in prognostic research in cancer involving genetic polymorphisms.  

PubMed

Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794

Savas, Sevtap; Liu, Geoffrey; Xu, Wei

2013-01-01

90

Current management and prognostic factors in physiotherapy practice for patients with shoulder pain: design of a prospective cohort study  

PubMed Central

Background Shoulder pain is disabling and has a considerable socio-economic impact. Over 50% of patients presenting in primary care still have symptoms after 6 months; moreover, prognostic factors such as pain intensity, age, disability level and duration of complaints are associated with poor outcome. Most shoulder complaints in this group are categorized as non-specific. Musculoskeletal ultrasound might be a useful imaging method to detect subgroups of patients with subacromial disorders. This article describes the design of a prospective cohort study evaluating the influence of known prognostic and possible prognostic factors, such as findings from musculoskeletal ultrasound outcome and working alliance, on the recovery of shoulder pain. Also, to assess the usual physiotherapy care for shoulder pain and examine the inter-rater reliability of musculoskeletal ultrasound between radiologists and physiotherapists for patients with shoulder pain. Methods A prospective cohort study including an inter-rater reliability study. Patients presenting in primary care physiotherapy practice with shoulder pain are enrolled. At baseline validated questionnaires are used to measure patient characteristics, disease-specific characteristics and social factors. Physical examination is performed according to the expertise of the physiotherapists. Follow-up measurements will be performed 6, 12 and 26 weeks after inclusion. Primary outcome measure is perceived recovery, measured on a 7-point Likert scale. Logistic regression analysis will be used to evaluate the association between prognostic factors and recovery. Discussion The ShoCoDiP (Shoulder Complaints and using Diagnostic ultrasound in Physiotherapy practice) cohort study will provide information on current management of patients with shoulder pain in primary care, provide data to develop a prediction model for shoulder pain in primary care and to evaluate whether musculoskeletal ultrasound can improve prognosis. PMID:23399098

2013-01-01

91

Poor Americans: How the Poor White Live.  

ERIC Educational Resources Information Center

Contents of this book include the following essays which originally appeared in "Transaction" magazine: (1) "Poor Americans: an introduction," Marc Pilisuk and Phyllis Pilisuk; (2) "How the white poor live," Marc Pilisuk and Phyllis Pilisuk; (3) "The culture of poverty," Oscar Lewis; (4) "Life in Appalachia--the case of Hugh McCaslin," Robert…

Pilisuk, Marc; Pilisuk, Phyllis

92

Contribution of vascular endothelial growth factor to the Nottingham prognostic index in node-negative breast cancer.  

PubMed

The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for. VEGF provided an additional prognostic contribution to NPI mainly within ER-poor tumours. PMID:11556826

Coradini, D; Boracchi, P; Daidone, M G; Pellizzaro, C; Miodini, P; Ammatuna, M; Tomasic, G; Biganzoli, E

2001-09-14

93

Performance of nutritional screening tools in predicting poor six-month outcome in hospitalised older patients.  

PubMed

Malnutrition is a major problem in hospitalised older people. Many nutrition screening tools are available for malnutrition identification, however little is known about their prognostic ability. This prospective, observational study investigated the prognostic value of three nutritional screening tools in a Geriatric Evaluation and Management Unit: the Geriatric Nutritional Risk Index (GNRI), the Mini Nutritional Assessment (MNA) and the Mini Nutritional Assessment short form (MNA-SF), incorporating either body mass index or calf circumference. Poor six- month outcome was defined as new admission to higher level residential care or mortality at six months post-discharge. Predictive ability of poor outcome was assessed by logistic regression models, adjusting for age, gender, cognition and co-morbidity. Predictive accuracy was determined by area under Receiver Operator Characteristic curves, sensitivity, specificity, predictive values and Youden Index. One hundred and seventy-two consecutive patients with a mean (SD) age=85.2 (6.4) years were included in the study. Malnutrition was identified in 31% of patients using the MNA and was associated with a higher risk of poor six-month outcome when identified by the MNA (OR, 95% CI=3.29, 1.17-9.23) and the GNRI (OR, 95% CI=2.84, 1.31-6.19), but not by the MNA-SF. All screening tools lacked discriminative power for outcome prediction. The MNA and GNRI were useful clinical predictors of poor six-month outcome, although their accuracy of prediction was low. Nutritional screening remains a priority in the routine assessment of hospitalised older people. PMID:25164449

Dent, Elsa; Chapman, Ian M; Piantadosi, Cynthia; Visvanathan, Renuka

2014-01-01

94

and the Epistemology of Prognostic  

E-print Network

Divination and the Epistemology of Prognostic Sciences in the Middle Ages Divination Fate, Freedom of Prognostic Sciences in the Middle Ages Conference Location: Altbau der Universitätsbibliothek in the Middle Ages. Examples are astronomy, meteorology, and medicine. These disciplines claimed to predict

Fiebig, Peter

95

Protein Expression of ZEB2 in Renal Cell Carcinoma and Its Prognostic Significance in Patient Survival  

PubMed Central

Background ZEB2 has been reportedly shown to mediate the epithelial-to-mesenchymal transition (EMT) and disease aggressiveness in human tumors. However, the expression status of ZEB2 in renal cell carcinoma (RCC) and ZEB2’s clinicopathologic/prognostic significance are poorly understood. Methodology/Principal Findings In this study, tissue microarray, immunohistochemistry (IHC) and western blot analyses were utilized to investigate the ZEB2 expression status in RCC and adjacent renal tissue samples. In our study, samples from 116 RCC patients treated with radical nephrectomy were used as a training set to generate a ZEB2 optimal cut-point for patient outcome by receiver operating characteristic (ROC) analysis. For validation, the correlation of ZEB2 expression with the clinical characteristics and patient outcomes in another set (including 113 patients) was analyzed to validate the obtained cut-point. In the training and validation sets, high expression of ZEB2, defined by ROC analysis, predicted a poorer overall survival and progression-free survival, as evidenced by the univariate and multivariate analyses. In different subsets of overall patients, ZEB2 expression was also a prognostic indicator in patients with stage I/II, stage III/IV, grade 1/2 and grade 3/4 disease (P<0.05). Downregulation of ZEB2 by shRNA decreased the migration and invasion ability of 769-P cells in vitro. Furthermore, high ZEB2 expression was positively correlated with vimentin expression and inversely linked to E-cadherin expression in RCC. Conclusions/Significance Our findings provide a basis for the concept that high ZEB2 expression in RCC may be important in the acquisition of an aggressive phenotype. This evidence suggests that ZEB2 overexpression (examined by IHC) is an independent biomarker for the poor prognosis of patients with RCC. PMID:23658743

Cao, Jiazheng; Zhao, Hongwei; Liao, Bing; Qiu, Shaopeng; Wang, Daohu; Luo, Junhang; Chen, Wei

2013-01-01

96

Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma  

PubMed Central

Tumor hypoxia is significant in promoting tumor progression and resistance to therapy, and hypoxia-inducible factor 1? (HIF-1?) is essential in the adaptive response of cells to hypoxia. The aim of the present study was to investigate the expression of hypoxic markers and evaluate their prognostic significance in soft tissue sarcoma (STS). A retrospective analysis of 55 patients with STS from Pusan National University Hospital (Busan, Korea) between 1998 and 2007 was conducted, using immunohistochemistry to analyze the expression of HIF-1?, carbonic anhydrase 9 (CA9), glucose transporter-1 (GLUT1) and vascular endothelial growth factor (VEGF). The association between the overexpression of these markers and clinicopathological characteristics, including the overall survival (OS) and progression-free survival (PFS) in cases of STS, were investigated. Overexpression of HIF-1?, CA9, GLUT1 and VEGF was shown in 54.5, 32.7, 52.7 and 25.5% of tumors, respectively, and all exhibited a significant association with high French Federation of Cancer Centers (FNCLCC) grade and high American Joint Committee on Cancer (AJCC) stage. Overexpression of HIF-1? and CA9 was associated with a shorter OS and a shorter PFS. On multivariate analysis, AJCC stage and HIF-1? overexpression had independent prognostic significance. In the group receiving chemotherapy (n=27), HIF-1? overexpression was independently associated with a decreased OS. These results indicate that overexpression of HIF-1? and CA9 is associated with poor prognosis, and that HIF-1? overexpression is an independent unfavorable prognostic factor in STS. PMID:25789026

KIM, JEUNG IL; CHOI, KYUNG UN; LEE, IN SOOK; CHOI, YOUNG JIN; KIM, WON TACK; SHIN, DONG HOON; KIM, KYUNGBIN; LEE, JEONG HEE; KIM, JEE YEON; SOL, MEE YOUNG

2015-01-01

97

Prognostic value of nuclear DNA content in papillary thyroid carcinoma  

Microsoft Academic Search

The prognostic value of nuclear DNA content in papillary thyroid carcinoma was studied retrospectively in 90 patients. Eighty survived for at least 10 years, and 10 died, of papillary thyroid carcinoma, between 6 months and 12 years after diagnosis. Clinical data as well as morphological tumor characteristics were examined. DNA measurements in morphologically identified single tumor cells were performed either

Kenneth Cohn; Martin Bfickdahl; Gun Forsslund; Gert Auer; Göran Lundell; Torsten Löwhagen; Eva Tallroth; Jan-Silvester Willems; Anders Zetterberg; Per-Ola Granberg

1984-01-01

98

The challenge of prognostic markers in pleural mesothelioma  

PubMed Central

Malignant pleural mesothelioma (MPM) is a very aggressive tumor, highly resistant to chemo- and radio-therapy. Treatment of MPM patients is often disappointing, regardless of the modality used. Inter-individual variability of response to multimodal treatment remains a challenge and generally the MPM prognosis continues to be poor. Knowledge of predicting factors of outcome is currently insufficient; therefore, it would be highly desirable to find specific prognostic markers for MPM. Translational research projects are to be implemented. PMID:23825744

Castiglioni, Massimo; Mortara, Lorenzo; Nardecchia, Elisa; Rotolo, Nicola

2013-01-01

99

Prognostic Biomarkers in Ovarian Cancer  

PubMed Central

Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice. PMID:22045356

Huang, Jie; Hu, Wei; Sood, Anil K

2014-01-01

100

Prognostic biomarkers in osteoarthritis  

PubMed Central

Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

2013-01-01

101

Peripheral blood involvement in patients with follicular lymphoma: a rare disease manifestation associated with poor prognosis.  

PubMed

Follicular Lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL) subtype and its course is heterogeneous. At diagnosis, some patients with FL manifest a detectable leukaemic phase (FL-LP), but this feature has been seldom described and is poorly characterized. Among 499 patients diagnosed with FL in Lyon-Sud hospital, 37 (7·4%) had characteristic FL-LP (by cytological blood smears and flow cytometric analysis). In addition, 91/1135 FL patients from the PRIMA study presented FL-LP at study entry. In order to evaluate the outcome of this Lyon-Sud cohort, FL-LP patients were matched with 111 newly diagnosed FL without LP according to the Follicular Lymphoma International Prognostic Index (FLIPI) score, age and treatment. Presence of FL-LP was associated with shorter progression-free survival (PFS) and overall survival (OS) (P = 0·004 and P = 0·031, respectively). Presence of FL-LP and high FLIPI score remained independent prognostic factors in a Cox model for time to progression (TTP). A number of circulating lymphoma cells (CLC) >4 × 10(9) /l was the most significant predictor for a shorter TTP in this Cox model. The prognostic impact of FL-LP on TTP was validated in the PRIMA cohort (P = 0·0004). In conclusion, FL-LP is a rare event associated with shorter PFS and patients with CLC >4 × 10(9) /l have a poorer outcome. These patients should be monitored carefully to consider alternative therapeutic options. PMID:24274024

Sarkozy, Clémentine; Baseggio, Lucile; Feugier, Pierre; Callet-Bauchu, Evelyne; Karlin, Lionel; Seymour, John F; Lebras, Laure; Michallet, Anne-Sophie; Offner, Fritz; Dumas, Olivier; Traverse-Glehen, Alexandra; Ffrench, Martine; Lopez-Guillermo, Armando; Berger, Françoise; Coiffier, Bertrand; Felman, Pascale; Salles, Gilles

2014-03-01

102

Low expression of RSK4 predicts poor prognosis in patients with colorectal cancer  

PubMed Central

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death all over the world. Ribosomal s6 kinase4 (RSK4), an X-linked gene, firstly was found as to be a potential tumor suppressive gene in a variety of cancers and is widely participated in signaling pathway. However its role in CRC is unclear. This study is to explore the correlation between the protein expression of RSK4 and clinical pathologic characteristics in colorectal tumors, which might serve as a prognostic determinant of colorectal cancers. Methods: Biopsies of 103 colorectal cancer and 46 matched adjacent noncancerous tissues were collected for analysis of RSK4 protein by immunohistochemistry. The correlation between RSK4 protein expression and the clinical pathological features of colorectal cancers were evaluated by Chi-square test and Fisher’s exact test. The survival rates were analyzed by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was analyzed by the Cox proportional hazard models. Results: RSK4 was conversely correlated with some pathological classifications (P<0.05 for N, G and clinical staging), and there were no statistically significant differences in age, CEA expression in blood, CA199 and tumors t-staging (x2 test, P>0.05 for all categories) respectively. Furthermore, patients with high protein level of RSK4 showed prolonged overall survivals (P<0.05). Moreover, multivariate analysis showed that low expression level of RSK is an independent risk factor for high mortality in colorectal cancer. Conclusions: Low RSK4 expression is correlated with advanced clinical pathologic classifications and is a poor overall survival in colorectal cancer patients. These findings suggest that RSK4 may serve as a useful marker in prognostic evaluation for patients with colorectal cancer. PMID:25197367

Cai, Jun; Ma, Hong; Huang, Fang; zhu, Dichao; Zhao, Lei; Yang, Yudan; Bi, Jianping; Zhang, Tao

2014-01-01

103

Inference in `poor` languages  

SciTech Connect

Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

Petrov, S.

1996-10-01

104

Rich Donors, Poor Countries  

ERIC Educational Resources Information Center

The shifting ideological winds of foreign aid donors have driven their policy towards governments in poor countries. Donors supported state-led development policies in poor countries from the 1940s to the 1970s; market and private-sector driven reforms during the 1980s and 1990s; and returned their attention to the state with an emphasis on…

Thomas, M. A.

2012-01-01

105

Prognostic Factors in Hodgkin Lymphoma  

PubMed Central

Hodgkin lymphoma (HL) is among the neoplastic diseases that has the best long-term outcome after cytotoxic treatment. Cure rates approach 80–90%; however, 15–20% of patients will be resistant to therapy (primary refractory) or relapse after treatment. Prognostic factors should help to stratify treatment according to the risk profile and identify patients at risk for failure. Significance of prognostic factors partly depends on the efficacy of the treatments administered, since new effective therapies can variably counterbalance the adverse effects of some unfavorable clinical determinants. As a consequence, some prognostic factors thought to be important in the past may become meaningless when modern successful therapies are used. Therefore, the value of prognostic factors has to be updated periodically, and then adapted to new emerging biomarkers. Besides the prognostic role of PET imaging, tissue and circulating biomarkers, as the number of tumor-infiltrating macrophages, cytokine and chemokine levels and profiling of circulating nucleic acids (DNA and microRNAs) have shown promise. PMID:25045461

Cuccaro, Annarosa; Bartolomei, Francesca; Cupelli, Elisa; Galli, Eugenio; Giachelia, Manuela; Hohaus, Stefan

2014-01-01

106

Prognostic Factors After Extraneural Metastasis of Medulloblastoma  

SciTech Connect

Purpose: To review the existing literature regarding the characteristics, prognostic factors, treatment, and survival of patients with medulloblastoma, who develop extraneural metastasis (ENM). Methods and Materials: A PubMed search of English language articles from 1961 to 2007 was performed, yielding 47 articles reporting on 119 patients. Factors analyzed included age, time interval to development of ENM, ENM location, central nervous system (CNS) involvement, treatment, and outcome. Results: Sites of ENM included bone in 84% of patients, bone marrow in 27% of patients, lymph nodes in 15% of patients, lung in 6% of patients, and liver in 6% of patients. Median survival was 8 months after diagnosis of ENM. The 1-, 2-, and 5-year overall survival (OS) rates after diagnosis of ENM were 41.9%, 31.0%, and 26.0%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates after diagnosis of ENM were 34.5%, 23.2%, and 13.4%, respectively. For patients without CNS involvement at the time of ENM diagnosis, the 1-, 2-, and 5-year OS rates for those treated with and without radiotherapy (RT) were 82.4%, 64.8%, and 64.8% vs. 51.0%, 36.6%, and 30.5%, respectively (p = 0.03, log-rank test). RT did not significantly improve OS or PFS rates for those with CNS involvement. Concurrent CNS involvement, ENM in the lung or liver, a time interval of <18 months to development of ENM, and a patient age of <16 years at ENM diagnosis were found to be negative prognostic factors for both OS and PFS. Conclusions: Several prognostic factors were identified for patients with ENM from medulloblastoma. Patients without concurrent CNS involvement, who received RT after ENM diagnosis had an OS and PFS benefit compared to those who did not receive RT.

Mazloom, Ali [Department of Radiology, Section of Radiation Oncology, Methodist Hospital, Houston, Texas (United States); Zangeneh, Azy H. [Division of Health Promotion and Behavioral Sciences, University of Texas School of Public Health, Houston, Texas (United States); Paulino, Arnold C., E-mail: apaulino@tmhs.or [Department of Radiology, Section of Radiation Oncology, Methodist Hospital, Houston, Texas (United States); Department of Radiation Oncology, Methodist Hospital, Houston, Texas (United States)

2010-09-01

107

A prognostic index for multiple myeloma.  

PubMed Central

The current prognostic systems have failed to identify multiple myeloma (MM) patients who require aggressive therapy. These staging systems do not reliably distinguish patients with different prognoses. This paper explores the possibility of improving the prognostic forecast in MM by considering some clinical characteristics at diagnosis together with response to first-line chemotherapy. A total of 231 patients were prospectively randomised in a multicentre trial to no therapy vs melphalan + prednisone (MP) for stage I, MP in stage II, and MP vs peptichemio, vincristine and prednisone for stage III. The clinical features of these groups were evaluated for prognostic variables predictive of overall survival by means of univariate and multivariate analysis. The independently significant variables were incorporated into a model that identified three groups of patients with different risks of death and different overall survival. Three variables retained statistical significance: the staging system proposed by the British Medical Research Council, a composite parameter integrating the percentage of bone marrow plasma cells with cytological features of the infiltrating elements (plasma cell vs plasmablast), and response to 6 months of first-line chemotherapy. These three variables led the proposal of a scoring system able to identify three different risk classes (with median overall survival of 52, 28 and 13 months respectively) and to estimate individual patient prognosis more flexibly. The proposed risk classes, drawn from both diagnostic and therapeutic parameters, are thought to be a clinical and investigational instrument for separating MM patients into comparable groups, for selecting the best available therapy and for evaluating response with respect to the disease of each new patient. PMID:8624271

Grignani, G.; Gobbi, P. G.; Formisano, R.; Pieresca, C.; Ucci, G.; Brugnatelli, S.; Riccardi, A.; Ascari, E.

1996-01-01

108

Factors prognosticating the outcome of decompressive craniectomy in severe traumatic brain injury: A Malaysian experience  

PubMed Central

Objective: The objective of this prospective cohort study was to analyse the characteristics of severe Traumatic Brain Injury (TBI) in a regional trauma centre Hospital Kuala Lumpur (HKL) along with its impact of various prognostic factors post Decompressive Craniectomy (DC). Materials and Methods: Duration of the study was of 13 months in HKL. 110 consecutive patients undergoing DC and remained in our centre were recruited. They were then analysed categorically with standard analytical software. Results: Age group have highest range between 12-30 category with male preponderance. Common mechanism of injury was motor vehicle accident involving motorcyclist. Univariate analysis showed statistically significant in referral area (P = 0.006). In clinical evaluation statistically significant was the motor score (P = 0.040), pupillary state (P = 0.010), blood pressure stability (P = 0.013) and evidence of Diabetes Insipidus (P < 0.001). In biochemical status the significant statistics included evidence of coagulopathy (P < 0.001), evidence of acidosis (P = 0.003) and evidence of hypoxia (P = 0.030). In Radiological sector, significant univariate analysis proved in location of the subdural clot (P < 0.010), location of the contusion (P = 0.045), site of existence of both type of clots (P = 0.031) and the evidence of edema (P = 0.041). The timing of injury was noted to be significant as well (P = 0.061). In the post operative care was, there were significance in the overall stability in intensive care (P < 0.001), the stability of blood pressure, cerebral perfusion pressure, pulse rates and oxygen saturation (all P < 0.001)seen individually, post operative ICP monitoring in the immediate (P = 0.002), within 24 hours (P < 0.001) and within 24-48 hours (P < 0.001) period, along with post operative pupillary size (P < 0.001) and motor score (P < 0.001). Post operatively, radiologically significant statistics included evidence of midline shift post operatively in the CT scan (P < 0.001). Multivariate logistic regression with stepwise likelihood ratio (LR) method concluded that hypoxia post operatively (P = 0.152), the unmaintained Cerebral Perfusion Pressure (CPP) (P = 0.007) and unstable blood pressure (BP) (P = <0.001). Poor outcome noted 10.2 times higher in post operative hypoxia [OR10.184; 95% CI: 0.424, 244.495]. Odds of having poor outcome if CPP unmaintained was 13.8 times higher [OR: 13.754; CI: 2.050, 92.301]. Highest predictor of poor outcome was the unstable BP, 32 times higher [OR 31.600; CI: 4.530, 220440]. Conclusion: Our series represent both urban and rural population, noted to be the largest series in severe TBI in this region. Severe head injury accounts for significant proportion of neurosurgical admissions, resources with its impact on socio-economic concerns to a growing population like Malaysia. This study concludes that the predictors of outcome in severe TBI post DC were postoperative hypoxia, unmaintained cerebral perfusion pressure and unstable blood pressure as independent predictors of poor outcome. Key words: Decompressive craniectomy, prognostication of decompressive craniectomy, prognostication of severe head injury, prognostication of traumatic brain injury, severe head injury, severe traumatic brain injury, traumatic brain injury. PMID:25685217

Sharda, Priya; Haspani, Saffari; Idris, Zamzuri

2014-01-01

109

Accounting for the Poor  

E-print Network

Economists and other social scientists have long tried to understand the nature of poverty and how poor people make decisions. For example, T.W. Schultz, a Nobel Laureate, former professor of economics at the University ...

Townsend, Robert

110

Inflation and the Poor  

Microsoft Academic Search

Using polling data for 31,869 households in 38 countries and allowing for country effects, we show that the poor are more likely than the rich to mention inflation as a top national concern. This result survives several robustness checks. We also find direct measures of improvements in well-being of the poor--the change in their share in national income, the percent

William Easterly; Stanley Fischer

2001-01-01

111

Pro-Poor Tourism  

NSDL National Science Digital Library

Provided by the Overseas Development Institute (ODI), an independent, UK-based, think tank, this site contains a selection of resources related to pro-poor tourism (PPT). Different than "sustainable tourism" and related initiatives, PPT is defined simply as "tourism that generates net benefits for the poor." At this site, visitors can learn more about PPT and read case studies, a report, a policy briefing, working papers, and other publications.

112

Model-based Prognostic Techniques  

Microsoft Academic Search

Conventional maintenance strategies, such as cor- rective and preventive maintenance, are not adequate to fulfill the needs of expensive and high availability industrial systems. A new strategy based on forecasting of system degradation through a prognostic process is required. The recent advances in model- based design technology have realized significant time savings in product development cycle. These advances facilitate the

Jianhui Luo; Madhavi Namburu; Krishna Pattipati; Liu Qiao; Masayuki Kawamoto; Shunsuke Chigusa

113

Systematic review of multivariable prognostic models for mild traumatic brain injury.  

PubMed

Prognostic models can guide clinical management and increase statistical power in clinical trials. The availability and adequacy of prognostic models for mild traumatic brain injury (MTBI) is uncertain. The present study aimed to (1) identify and evaluate multivariable prognostic models for MTBI, and (2) determine which pre-, peri-, and early post-injury variables have independent prognostic value in the context of multivariable models. An electronic search of MEDLINE, PsycINFO, PubMed, EMBASE, and CINAHL databases for English-language MTBI cohort studies from 1970-2013 was supplemented by Web of Science citation and hand searching. This search strategy identified 7789 articles after removing duplicates. Of 182 full-text articles reviewed, 26 met eligibility criteria including (1) prospective inception cohort design, (2) prognostic information collected within 1 month post-injury, and (3) 2+variables combined to predict clinical outcome (e.g., post-concussion syndrome) at least 1 month later. Independent reviewers extracted sample characteristics, study design features, clinical outcome variables, predictor selection methods, and prognostic model discrimination, calibration, and cross-validation. These data elements were synthesized qualitatively. The present review found no multivariable prognostic model that adequately predicts individual patient outcomes from MTBI. Suboptimal methodology limits their reproducibility and clinical usefulness. The most robust prognostic factors in the context of multivariable models were pre-injury mental health and early post-injury neuropsychological functioning. Women and adults with early post-injury anxiety also have worse prognoses. Relative to these factors, the severity of MTBI had little long-term prognostic value. Future prognostic studies should consider a broad range of biopsychosocial predictors in large inception cohorts. PMID:25222514

Silverberg, Noah D; Gardner, Andrew J; Brubacher, Jeffrey R; Panenka, William J; Li, Jun Jian; Iverson, Grant L

2015-04-15

114

Fibroblast activation protein and its prognostic significance in correlation with vascular endothelial growth factor in pancreatic adenocarcinoma.  

PubMed

Fibroblast activation protein (FAP), a selective protein for tumor stromal fibroblasts, is expressed in >90% of human epithelial carcinomas. A characteristic feature of pancreatic cancer is an extensive fibrotic or desmoplastic reaction surrounding the primary tumor. The present study aimed to evaluate the expression levels of FAP and vascular endothelial growth factor (VEGF) and determine their correlation in pancreatic adenocarcinoma. Confocal laser scanning microscopy and conventional immunohistochemical analysis were used to quantify FAP and VEGF expression levels in formalin?fixed and paraffin?embedded tissue biopsies from 46 patients (male, 26; female, 20; mean age, 66 years; age range, 53?80 years) with pancreatic adenocarcinoma stage IIA or IIB. The expression levels of FAP in the neoplastic and adjacent normal tissue were significantly higher in stage IIB patients, compared with stage IIA patients. FAP expression was correlated with positive lymph nodes, resulting in poor prognosis for stage IIB patients. The partial correlation coefficient between FAP and VEGF expression levels was 0.39 (P=0.007), and the two factors had an effect on patient survival. Multivariate analysis demonstrated the prognostic superiority of FAP over VEGF, which is considered to be the most consistently reproducible molecular marker with prognostic value in resected pancreatic adenocarcinoma. Due to the limited beneficial effect of current systemic therapies for pancreatic adenocarcinoma, targeting FAP may be a potential therapeutic strategy and requires further investigation. PMID:25625587

Patsouras, Dimitrios; Papaxoinis, Kostis; Kostakis, Alkiviadis; Safioleas, Michael C; Lazaris, Andreas C; Nicolopoulou-Stamati, Polyxeni

2015-06-01

115

Sensor Systems for Prognostics and Health Management  

PubMed Central

Prognostics and health management (PHM) is an enabling discipline consisting of technologies and methods to assess the reliability of a product in its actual life cycle conditions to determine the advent of failure and mitigate system risk. Sensor systems are needed for PHM to monitor environmental, operational, and performance-related characteristics. The gathered data can be analyzed to assess product health and predict remaining life. In this paper, the considerations for sensor system selection for PHM applications, including the parameters to be measured, the performance needs, the electrical and physical attributes, reliability, and cost of the sensor system, are discussed. The state-of-the-art sensor systems for PHM and the emerging trends in technologies of sensor systems for PHM are presented. PMID:22219686

Cheng, Shunfeng; Azarian, Michael H.; Pecht, Michael G.

2010-01-01

116

Prognostic factors in prostate cancer.  

PubMed

In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before assessing screening. PMID:17432552

Braeckman, Johan; Michielsen, Dirk

2007-01-01

117

Prognostic significance of the co-overexpression of fibroblast growth factor receptors 1, 2 and 4 in gastric cancer  

PubMed Central

The overexpression of fibroblast growth factor receptor (FGFR) 2 is an established prognostic factor and treatment target in gastric cancer. However, the roles of other FGFRs have not been fully elucidated. In this study, we investigated the correlations of the expression of FGFR1-4 with clinicopathological characteristics and outcomes in gastric cancer. Tumor samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy between 2003 and 2007. The expression of each FGFR was measured in the tumors by immunohistochemical analysis. The overexpression of FGFR1, FGFR2 or FGFR4 was found to be significantly associated with tumor progression, including depth of invasion, lymph node metastasis, pathological stage and distant metastasis or recurrent disease. Patients exhibiting overexpression of FGFR1, FGFR2 or FGFR4 had a significantly poorer disease-specific survival (DSS; P<0.001, P=0.008 and P<0.001, respectively). Moreover, the co-overexpression of all three FGFRs was significantly associated with a poorer DSS compared to the expression of none or only one of the FGFRs (P<0.001 and P=0.001, respectively) and it was found to be an independent prognostic factor (HR=1.71, 95% CI: 1.02–2.85, P=0.041). In conclusion, high expression of FGFR1, FGFR2 or FGFR4 was associated with tumor progression and poor survival in patients with gastric cancer. Similar to FGFR2, FGFR1 and FGFR4 may be considered as prognostic factors and treatment targets in gastric cancer. PMID:24940486

MURASE, HIDEAKI; INOKUCHI, MIKITO; TAKAGI, YOKO; KATO, KEIJI; KOJIMA, KAZUYUKI; SUGIHARA, KENICHI

2014-01-01

118

The prognostic importance of different definitions of worsening renal function in congestive heart failure  

Microsoft Academic Search

Background: Worsening renal function in patients hospitalized for heart failure portends a poor prognosis. However, criteria used to define worsening renal function are arbitrary, and the implications of different definitions remain unclear. We therefore compared the prognostic importance of various definitions of worsening renal function in 1,002 patients hospitalized for congestive heart failure (CHF). Methods and Results: The patient population

Stephen S. Gottlieb; William Abraham; Javed Butler; Daniel E. Forman; Evan Loh; Barry M. Massie; Christopher M. O'Connor; Michael W. Rich; Lynne Warner Stevenson; James Young; Harlan M. Krumholz

2002-01-01

119

The prognostic value of concurrent phrenic nerve palsy in newborn children with Erb's palsy  

Microsoft Academic Search

The prognostic value of concurrent phrenic nerve palsy in newborn babies with Erb’s palsy was investigated. The records of 191 babies with Erb’s palsy were reviewed retrospectively at two institutions. Poor spontaneous return of the motor function of the limb was found for infants both with and without concurrent phrenic nerve palsy. Concurrent phrenic nerve palsy in newborn babies with

M. M. Al-Qattan; H. M. Clarke; C. G. Curtis

1998-01-01

120

Contribution of vascular endothelial growth factor to the Nottingham prognostic index in node-negative breast cancer  

Microsoft Academic Search

The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for. VEGF provided an additional prognostic contribution to NPI mainly within ER-poor tumours. © 2001 Cancer Research Campaign http:\\/\\/www.bjcancer.com

D Coradini; P Boracchi; M Grazia Daidone; C Pellizzaro; P Miodini; M Ammatuna; G Tomasic; E Biganzoli

2001-01-01

121

Contribution of vascular endothelial growth factor to the Nottingham prognostic index in node-negative breast cancer  

PubMed Central

The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for. VEGF provided an additional prognostic contribution to NPI mainly within ER-poor tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556826

Coradini, D; Boracchi, P; Daidone, M Grazia; Pellizzaro, C; Miodini, P; Ammatuna, M; Tomasic, G; Biganzoli, E

2001-01-01

122

Twist2 is a valuable prognostic biomarker for colorectal cancer  

PubMed Central

AIM: To investigate the significance of Twist2 for colorectal cancer (CRC). METHODS: In this study, 93 CRC patients were included who received curative surgery in Eastern Hepatobiliary Surgery Hospital from January 1999 to December 2010. Records of patients’ clinicopathological characteristics and follow up data were reviewed. Formalin-fixed, paraffin-embedded tissue blocks were used to observe the protein expression of Twist2 and E-cadherin by immunohistochemistry. Two independent pathologists who were blinded to the clinical information performed semiquantitative scoring of immunostaining. A total score of 3-6 (sum of extent + intensity) was considered as Twist2-positive expression. The expression of E-cadherin was divided into two levels (preserved and reduced). An exploratory statistical analysis was conducted to determine the association between Twist2 expression and clinicopathological parameters, as well as E-cadherin expression. Furthermore, the variables associated with prognosis were analyzed by Cox’s proportional hazards model. Kaplan-Meier analysis was used to plot survival curves according to different expression levels of Twist2. RESULTS: Twist2-positive expression was observed in 66 (71.0%) samples and mainly located in the cytoplasm. Forty-three (46.2%) samples showed reduced expression of E-cadherin. There were no significant correlations between Twist2 expression and any of the clinicopathological parameters. However, Twist2-positive expression was significantly associated with reduced expression of E-cadherin (P = 0.040). Multivariate analysis revealed that bad M-stage [hazard ratio (HR) = 7.694, 95%CI: 2.927-20.224, P < 0.001] and Twist2-positive (HR = 5.744, 95%CI: 1.347-24.298, P = 0.018) were the independent risk factors for poor overall survival (OS), while Twist2-positive (HR = 3.264, 95%CI: 1.455-7.375, P = 0.004), bad N-stage (HR = 2.149, 95%CI: 1.226-3.767, P = 0.008) and bad M-stage (HR = 10.907, 95%CI: 4.937-24.096, P < 0.001) were independently associated with poor disease-free survival (DFS). Survival curves showed a definite trend for Twist2-negative patients to have longer OS and DFS than Twist2-negative patients, not only overall, but also for patients in different stages, especially for DFS of patients in stage III (P = 0.033) and IV (P = 0.026). CONCLUSION: Our data suggests, for the first time, that Twist2 is a valuable prognostic biomarker for CRC, particularly for patients in stage III and IV. PMID:23613636

Yu, Hao; Jin, Guang-Zhi; Liu, Kai; Dong, Hui; Yu, Hua; Duan, Ji-Cheng; Li, Zhe; Dong, Wei; Cong, Wen-Ming; Yang, Jia-He

2013-01-01

123

Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer.  

PubMed

Cadherin-17 (CDH17), also called liver-intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis. PMID:16044349

Ito, Reiko; Oue, Naohide; Yoshida, Kazuhiro; Kunimitsu, Kyoko; Nakayama, Hirofumi; Nakachi, Kei; Yasui, Wataru

2005-10-01

124

The homeobox gene HLXB9 is upregulated in a morphological subset of poorly differentiated hepatocellular carcinoma.  

PubMed

The prognostic outcome for hepatocellular carcinoma (HCC) remains poor. Disease progression is accompanied by dedifferentiation of the carcinoma, a process that is not well understood. The aim of this study was to get more insight into the molecular characteristics of dedifferentiated carcinomas using high throughput techniques. Microarray-based global gene expression analysis was performed on five poorly differentiated HCC cell lines compared with non-neoplastic hepatic controls and a set of three cholangiolar carcinoma (CC) cell lines. The gene with the highest upregulation was HLXB9. HLXB9 is a gene of the homeobox genfamily important for the development of the pancreas. RT-PCR confirmed the upregulation of HLXB9 in surgical specimens of carcinoma tissue, suggesting its biological significance. Interestingly, HLXB9 upregulation was primary observed in poorly differentiated HCC with a pseudoglandular pattern compared with a solid pattern HCC or in moderate or well-differentiated HCC. Additional the expression of translated HLXB9, the protein HB9 (NCBI: NP_001158727), was analyzed by western blotting. Expression of HB9 was only detected in the cytoplasm but not in the nuclei of the HCC cells. For validation CC were also investigated. Again, we found an upregulation of HLXB9 in CC cells accompanied by an expression of HB9 in the cytoplasms of these tumor cells, respectively. In conclusion, homeobox HLXB9 is upregulated in poorly differentiated HCC with a pseudoglandular pattern. The translated HB9 protein is found in the cytoplasm of these HCC and CC. We therefore assume HLXB9 as a possible link in the understanding of the development of HCC and CC, respectively. PMID:21484430

Wilkens, Ludwig; Jaggi, Rolf; Hammer, Caroline; Inderbitzin, Daniel; Giger, Olivier; von Neuhoff, Nils

2011-06-01

125

Analytic prognostic for petrochemical pipelines  

E-print Network

Pipelines tubes are part of vital mechanical systems largely used in petrochemical industries. They serve to transport natural gases or liquids. They are cylindrical tubes and are submitted to the risks of corrosion due to high PH concentrations of the transported liquids in addition to fatigue cracks due to the alternation of pressure-depression of gas along the time, initiating therefore in the tubes body micro-cracks that can propagate abruptly to lead to failure. The development of the prognostic process for such systems increases largely their performance and their availability, as well decreases the global cost of their missions. Therefore, this paper deals with a new prognostic approach to improve the performance of these pipelines. Only the first mode of crack, that is, the opening mode, is considered.

Jaoude, Abdo Abou; El-Tawil, Khaled; Noura, Hassan; Ouladsine, Mustapha

2012-01-01

126

Analytic prognostic for petrochemical pipelines  

E-print Network

Pipelines tubes are part of vital mechanical systems largely used in petrochemical industries. They serve to transport natural gases or liquids. They are cylindrical tubes and are submitted to the risks of corrosion due to high PH concentrations of the transported liquids in addition to fatigue cracks due to the alternation of pressure-depression of gas along the time, initiating therefore in the tubes body micro-cracks that can propagate abruptly to lead to failure. The development of the prognostic process for such systems increases largely their performance and their availability, as well decreases the global cost of their missions. Therefore, this paper deals with a new prognostic approach to improve the performance of these pipelines. Only the first mode of crack, that is, the opening mode, is considered.

Abdo Abou Jaoude; Seifedine Kadry; Khaled El-Tawil; Hassan Noura; Mustapha Ouladsine

2012-12-25

127

Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome.  

PubMed

Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. In this study, we investigated the relationship of a subset of macrophages-proliferating macrophages (promacs)-with clinico-pathologic characteristics of breast cancer, including tumor size, grade, stage, lymph node metastases, hormone receptor status, subtype, as well as early recurrence, and survival. This study included a discovery and validation set that was conducted at two institutions and laboratories (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The presence of intratumoral promacs was significantly correlated with high grade, hormone receptor negative tumors, and a basal-like subtype. In contrast, there was no correlation between promacs and tumor size, stage, or the number of the involved lymph nodes. These findings were consistent between the two study cohorts. Finally, promac numbers were a significant predictor of recurrence and survival. In the pooled analysis, elevated promac levels were associated with a 77% increased risk of dying (P = 0.015). The presence of promacs in human breast cancer may serve as a prognostic indicator for poor outcomes and early recurrence and serve as a potential cellular target for novel therapeutic interventions. PMID:20842526

Campbell, Michael J; Tonlaar, Nathan Y; Garwood, Elisabeth R; Huo, Dezheng; Moore, Dan H; Khramtsov, Andrey I; Au, Afred; Baehner, Frederick; Chen, Yinghua; Malaka, David O; Lin, Amy; Adeyanju, Oyinlolu O; Li, Shihong; Gong, Can; McGrath, Michael; Olopade, Olufunmilayo I; Esserman, Laura J

2011-08-01

128

Prognostic Indexes for Brain Metastases: Which Is the Most Powerful?  

SciTech Connect

Purpose: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. Methods and Materials: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural data consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. Results: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. Conclusion: A variety of prognostic models describe the survival of patients with BMs to a more or less satisfactory degree. Among the 5 PIs evaluated in the present study, GPA was the most powerful in predicting survival. Additional studies should include emerging biologic prognostic factors to improve the sensibility of these PIs.

Arruda Viani, Gustavo, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo, SP (Brazil); Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medical School, Marilia, Sao Paulo, SP (Brazil)

2012-07-01

129

Empowering Poor Communities  

Microsoft Academic Search

\\u000a One of the most promising usages of ICT for development is to reduce poverty and promote broad participation, grassroots innovation,\\u000a social learning, and social inclusion. This chapter calls ICT applications that are targeted for poor communities and poverty\\u000a reduction, e-society or grassroots innovation. Much of these empowered local initiatives and innovations are about building\\u000a the local capabilities to appropriate the

Nagy K. Hanna

130

Increased expression of forkhead box m1 is associated with aggressive phenotype and poor prognosis in estrogen receptor-positive breast cancer.  

PubMed

Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy. PMID:25829806

Ahn, Hyein; Sim, Jongmin; Abdul, Rehman; Chung, Min Sung; Paik, Seung Sam; Oh, Young-Ha; Park, Chan Kum; Jang, Kiseok

2015-04-01

131

Prognostic factors in patients with intracerebral haematoma.  

PubMed Central

In a prospective study, the prognostic value of clinical characteristics in 157 consecutive patients with spontaneous supratentorial intracerebral haemorrhage were examined by means of multivariate analysis. Two days after the event 37 (24%) patients had died. Factors independently contributing to the prediction of two day mortality were pineal gland displacement on CT of 3 mm or more (p less than 0.001), blood glucose level on admission of 8.0 mmol/l or more (p = 0.01), eye and motor score on the Glasgow Coma Scale of eight out of 10 or less (p = 0.022) and haematoma volume of 40 cm3 or more (p = 0.037). Between the third day and one year after the event another 46 of the 120 two day survivors had died; the independent prognostic indicators for death during that period were: age 70 years or more (p less than 0.001) and severe handicap (Rankin grade five) on the third day (p less than 0.001). Functional independence (Rankin grade two or less) at one year was most common not only with the converse features of age less than 70 years (p less than 0.01) and Rankin grade four or less on the third day (p = 0.002), but also with an eye and motor score on the Glasgow Coma Scale of nine or 10 on the third day (p less than 0.001). The 120 patients with intracerebral haemorrhage who were still alive two days after the event were matched with 120 patients with cerebral infarction, according to age, level of consciousness on the third day after stroke (Glasgow Coma Scale) and handicap (Rankin grade). Survival and handicap after one year did not differ between these two groups. The conclusion drawn is that it is not the cause (intracerebral haemorrhage or cerebral infarction) but the extent of the brain lesion that determines the outcome in patients who survive the first two days. PMID:1527534

Franke, C L; van Swieten, J C; Algra, A; van Gijn, J

1992-01-01

132

Natural History and Prognostic Value of Corticospinal Tract Wallerian Degeneration in Intracerebral Hemorrhage  

PubMed Central

Background The purpose of this study was to define the incidence, imaging characteristics, natural history, and prognostic implication of corticospinal tract Wallerian degeneration (CST?WD) in spontaneous intracerebral hemorrhage (ICH) using serial MR imaging. Methods and Results Consecutive ICH patients with supratentorial ICH prospectively underwent serial MRIs at 2, 7, 14, and 21 days. MRIs were analyzed by independent raters for the presence and topographical distribution of CST?WD on diffusion?weighted imaging (DWI). Baseline demographics, hematoma characteristics, ICH score, and admission National Institute of Health Stroke Score (NIHSS) were systematically recorded. Functional outcome at 3 months was assessed by the modified Rankin Scale (mRS) and the motor?NIHSS. Twenty?seven patients underwent 93 MRIs; 88 of these were serially obtained in the first month. In 13 patients (48%), all with deep ICH, CST?WD changes were observed after a median of 7 days (interquartile range, 7 to 8) as reduced diffusion on DWI and progressed rostrocaudally along the CST. CST?WD changes evolved into T2?hyperintense areas after a median of 11 days (interquartile range, 6 to 14) and became atrophic on MRIs obtained after 3 months. In univariate analyses, the presence of CST?WD was associated with poor functional outcome (ie, mRS 4 to 6; P=0.046) and worse motor?NIHSS (5 versus 1, P=0.001) at 3 months. Conclusions Wallerian degeneration along the CST is common in spontaneous supratentorial ICH, particularly in deep ICH. It can be detected 1 week after ICH on DWI and progresses rostrocaudally along the CST over time. The presence of CST?WD is associated with poor motor and functional recovery after ICH. PMID:23913508

Venkatasubramanian, Chitra; Kleinman, Jonathan T.; Fischbein, Nancy J.; Olivot, Jean?Marc; Gean, Alisa D.; Eyngorn, Irina; Snider, Ryan W.; Mlynash, Michael; Wijman, Christine A. C.

2013-01-01

133

Bell's palsy; prognostic accuracy of case history, sialometry and taste impairment.  

PubMed

A prognostic test in cases of Bell's palsy must be accurate and applicable early in the course of the disease. The case history is examined in 239 patients with Bell's palsy. The prognostic value of the case history, taste impairment and sialometry is investigated in a series of untreated patients who were followed up for 12 months. Sialometry is advocated as a reliable progostic indicator in the individual patient if a strong stimulant is used. None of the other examined parameters discrimates between good and poor outcome with reasonable accuracy. A follow-up time of 12 months is advocated in determining the ultimate outcome of a Bell's palsy. PMID:466842

Ekstrand, T

1979-06-01

134

Treatment outcome and prognostic factors of head and neck hemangiopericytoma: A meta-analysis.  

PubMed

Background. Head and Neck hemangiopericytoma (HNHPC) is rare. Treatment outcome and specific prognostic factors were unexplored. Method. A case-meta-analysis, in which treatment and outcome data were available, was performed. Results. A total of 116 primary HNHPC cases were analyzed. Poor pathologic differentiation was associated with increased risk of tumor recurrence (OR=2.378, P=0.005), metastasis (OR=3.634, P=0.011) and mortality (OR=4.563, P=0.002), while surgery with decreased risk of tumor recurrence (OR=0.109, P=0.004). The tumor size >5.0cm in diameter (HR=6.391, P=0.002), non-surgical treatment (HR=7.648, P=0.000), and poor pathologic differentiation (HR=1.705, P=0.012) were the independent unfavorable prognostic factors for disease free survival. Moreover, non-surgical treatment (HR=8.097, P=0.002) and deep tumor location (HR=4.074, P=0.013) were independent adverse prognostic factors for overall survival. Conclusions. These results suggest a management emphasizing the surgical removal of the tumor as ?rst-line treatment. Tumor size >5.0cm, poor pathologic differentiation, deep tumor location and non-surgical treatment were independent adverse prognostic factors. Head Neck, 2014. PMID:24954602

Wushou, Alimujiang; Miao, Xin-Chao; Shao, Zhi-Min

2014-06-21

135

Distilling the Verification Process for Prognostics Algorithms  

NASA Technical Reports Server (NTRS)

The goal of prognostics and health management (PHM) systems is to ensure system safety, and reduce downtime and maintenance costs. It is important that a PHM system is verified and validated before it can be successfully deployed. Prognostics algorithms are integral parts of PHM systems. This paper investigates a systematic process of verification of such prognostics algorithms. To this end, first, this paper distinguishes between technology maturation and product development. Then, the paper describes the verification process for a prognostics algorithm as it moves up to higher maturity levels. This process is shown to be an iterative process where verification activities are interleaved with validation activities at each maturation level. In this work, we adopt the concept of technology readiness levels (TRLs) to represent the different maturity levels of a prognostics algorithm. It is shown that at each TRL, the verification of a prognostics algorithm depends on verifying the different components of the algorithm according to the requirements laid out by the PHM system that adopts this prognostics algorithm. Finally, using simplified examples, the systematic process for verifying a prognostics algorithm is demonstrated as the prognostics algorithm moves up TRLs.

Roychoudhury, Indranil; Saxena, Abhinav; Celaya, Jose R.; Goebel, Kai

2013-01-01

136

Cognitive Functions and Depression as Predictors of Poor Outcome 15 Months after Stroke  

Microsoft Academic Search

The prognostic predictors of poor outcome, as defined by death between 3 and 15 months and dependent living at 15 months, were examined in the Helsinki Stroke Aging Memory (SAM) study cohort. Death between 3 and 15 months was registered from the whole study group of 486 consecutive patients aged 55–85 years. Altogether 286 of the 486 patients went through

T. Pohjasvaara; R. Vataja; A. Leppävuori; M. Kaste; T. Erkinjuntti

2002-01-01

137

[Angiogenesis in laryngeal squamous carcinoma and its prognostic significance].  

PubMed

Prognosis for laryngeal squamous carcinoma patients depends on numerous factors, and tumor-related angiogenesis is one of them. Our study was concerned with prognostic significance of intra-tumor vascular bed in such patients. Bioptic material was sampled from 61 patients, aged 34-77, after combined treatment at the Center's Clinic. Microvascular density, overall perimeter of vascular wall and overall vascular area were compared with such clinical characteristics as T stage, tumor cell differentiation and presence of regional metastases using t-test (Student) and contingency tables (2x2) (chi2, Fisher's accuracy criterion). The Caplan-Meyer method was used to evaluate survival and Cox F-test--to assess survival curve difference significance (p < or = 0.05). The angiogenesis pattern proved a significant prognosticator for relapse, relapse-free and specific survival. PMID:19435199

Gorban', N A; Ten, V P; Pankratov, V A

2009-01-01

138

Aneurysmal acute subdural hemorrhage: prognostic factors associated with treatment.  

PubMed

Acute subdural hematoma is an uncommon presentation of aneurysmal hemorrhage that has been identified as a poor prognostic sign. Current series are small, have short follow-up, or were collected over a long period during which treatment evolved. To evaluate prognostic factors, we analyzed a large modern series of aneurysmal subdural hematoma (aSDH) with long-term follow-up. A prospectively maintained database was queried for patients presenting with aSDH from 2001-2013. Thirty patients met the study criteria. Statistical analysis was performed with unpaired t-test or Fisher's exact test. Aneurysm treatment involved open clipping (n=18), endosaccular coiling (n=8), both (n=1), or no treatment (n=3). Good Glasgow Outcome Scale score at discharge was present in 20% and increased to 40% at 6-12 months postoperatively. Good clinical presentation was associated with good final outcome in 75%, whereas poor clinical presentation correlated with good outcome in 30%. Good outcome correlated with younger age (p=0.04), smaller aneurysm (p=0.04), and lower Hunt-Hess score (HH) at intervention (p=0.04). Favorable outcome did not correlate with sex, race, presence of subarachnoid or intraparenchymal hemorrhage, size or laterality of hemorrhage, midline shift, aneurysm treatment modality, or HH at admission (p>0.15). There was no difference between good and poor outcomes in terms of time to treatment or hematoma evacuation. Poor clinical presentation may be exaggerated by mass effect of hematoma; aggressive treatment is not futile. Presenting neurological status, age, and aneurysm size are predictors of outcome, while laterality and size of hematoma and extent of midline shift are not, suggesting that clinical status is more important than radiographic findings. PMID:24679648

Kulwin, Charles; Bohnstedt, Bradley N; Payner, Troy D; Leipzig, Thomas J; Scott, John A; DeNardo, Andrew J; Cohen-Gadol, Aaron A

2014-08-01

139

Angiocentric nasal T/natural killer cell lymphoma: a single centre study of prognostic factors in 108 patients.  

PubMed

Angiocentric T cell/natural killer (NK) nasal lymphoma remains a rare clinical presentation in North America and Europe but is more common in Asia and Latin America. We have reviewed 108 cases of angiocentric T/NK cell lymphoma of the nasal cavity with a view to establishing prognostic factors. Most patients were high or high intermediate clinical risk and had additional poor prognostic factors such as bulky disease, high levels of beta 2 microglobulin, advanced stage and multiple extranodal involvement. At 8 years, overall survival was 82%, 90% and 84% for low-intermediate, high-intermediate and high clinical, respectively. Disease free survival was very similar: 79%, 83% and 80%, respectively. Multivariate analysis did not identify any factor influencing overall survival and disease-free survival. There was no evidence that the international prognostic index (IPI) was applicable in these patients and it appears that angiocentric T/NK cell lymphoma is an independent prognostic factor itself. PMID:11012633

Avilés, A; Díaz, N R; Neri, N; Cleto, S; Talavera, A

2000-08-01

140

Prognostic Analysis System and Methods of Operation  

NASA Technical Reports Server (NTRS)

A prognostic analysis system and methods of operating the system are provided. In particular, a prognostic analysis system for the analysis of physical system health applicable to mechanical, electrical, chemical and optical systems and methods of operating the system are described herein.

MacKey, Ryan M. E. (Inventor); Sneddon, Robert (Inventor)

2014-01-01

141

Distributed Prognostics based on Structural Model Decomposition  

NASA Technical Reports Server (NTRS)

Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based models are constructed that describe the operation of a system and how it fails. Such approaches consist of an estimation phase, in which the health state of the system is first identified, and a prediction phase, in which the health state is projected forward in time to determine the end of life. Centralized solutions to these problems are often computationally expensive, do not scale well as the size of the system grows, and introduce a single point of failure. In this paper, we propose a novel distributed model-based prognostics scheme that formally describes how to decompose both the estimation and prediction problems into independent local subproblems whose solutions may be easily composed into a global solution. The decomposition of the prognostics problem is achieved through structural decomposition of the underlying models. The decomposition algorithm creates from the global system model a set of local submodels suitable for prognostics. Independent local estimation and prediction problems are formed based on these local submodels, resulting in a scalable distributed prognostics approach that allows the local subproblems to be solved in parallel, thus offering increases in computational efficiency. Using a centrifugal pump as a case study, we perform a number of simulation-based experiments to demonstrate the distributed approach, compare the performance with a centralized approach, and establish its scalability. Index Terms-model-based prognostics, distributed prognostics, structural model decomposition ABBREVIATIONS

Daigle, Matthew J.; Bregon, Anibal; Roychoudhury, I.

2014-01-01

142

A regression analysis of prognostic factors after resection of Dukes' B and C carcinoma of the rectum and rectosigmoid. Does post-operative radiotherapy change the prognosis?  

PubMed Central

The prognostic value of several clinical and histopathological characteristics has been evaluated in patients with Dukes' B and C carcinoma of the rectum and the rectosigmoid. Data on 260 Dukes' B and 208 Dukes' C tumours entered into a prospective, randomized clinical trial of post-operative radiotherapy (50 Gy given with 2 Gy/fraction in an overall time of 7 weeks) were analyzed by means of the Cox proportional hazards model. The Dukes' stages B and C were analyzed in two separate multivariate analyses. In patients with Dukes' B tumours, a poor prognosis was associated with age above 60, perineural and venous invasion, tumour located less than 10 cm from the anal verge and elevated pre-operative carcinoembryonic antigen (CEA) (greater than 3.2 ng ml-1). In patients with Dukes' C tumours, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and elevated pre-operative CEA were associated with a poor prognosis. In addition, a large tumour diameter had a strong, negative influence on the prognosis. Males seemed to have a poorer prognosis than females among the Dukes' C patients. Resection of neighbouring organs was also associated with a poor prognosis in this stage. Post-operative radiotherapy as administered in the present series had no significant influence on prognosis. Based on the derived prognostic models patients with a hazard of death above the median in each stage were selected. A separate analysis of the survival in these high risk patients showed no survival benefit from radiotherapy. The proportional hazards model may be a useful tool in selecting patients for more aggressive adjuvant treatment. PMID:3166910

Bentzen, S. M.; Balslev, I.; Pedersen, M.; Teglbjaerg, P. S.; Hanberg-Soerensen, F.; Bone, J.; Jacobsen, N. O.; Overgaard, J.; Sell, A.; Bertelsen, K.

1988-01-01

143

Prognostic role of transthoracic echocardiography in patients affected by heart failure and reduced ejection fraction.  

PubMed

Heart failure with reduced ejection fraction is a common and malignant condition, which recognizes a lot of causes and that carries a poor long-term prognosis. All patients with reduced left ventricular ejection fraction, both asymptomatic and symptomatic, should be evaluated with transthoracic echocardiography as a depth analysis of first level, due to its characteristics of accuracy, availability, safety and low costs. In fact, echocardiography is an essential tool to establish not only the diagnosis, but also the aetiology and the understanding pathophysiology of heart failure. Moreover, by the new more sensitive and more specific echocardiographic technologies, such as tissue Doppler imaging or strain rate or speckle tracking or three-dimensional echocardiography, it is possible to identify other recognized high-risk parameters associated with adverse outcome, which are useful to guide therapy and follow-up management of heart failure patients. Therefore, this review would underline the prognostic role of some echocardiographic parameters in the evaluation and management of patients with heart failure and reduced ejection fraction. PMID:25355298

Prastaro, Maria; D'Amore, Carmen; Paolillo, Stefania; Losi, Mariangela; Marciano, Caterina; Perrino, Cinzia; Ruggiero, Donatella; Gargiulo, Paola; Savarese, Gianluigi; Trimarco, Bruno; Perrone Filardi, Pasquale

2015-05-01

144

A population based analysis of prognostic factors in advanced biliary tract cancer  

PubMed Central

Background Data regarding prognostic factors in advanced biliary tract cancer (BTC) remains scarce. The aim of this study was to review our institutional experience with cisplatin and gemcitabine in advanced BTC as well as to evaluate potential prognostic factors for overall survival (OS). Material and methods Consecutive patients with advanced BTC who initiated palliative chemotherapy with cisplatin and gemcitabine from 2009 to 2012 at the BC Cancer Agency were identified using the pharmacy database. Clinicopathologic variables and treatment outcome were retrospectively collected. Potential prognostic factors were assessed by univariate and multivariate analyses. Results A total of 106 patients were included in the analysis. Median OS was 8.5 months (95% CI: 6.5-10.5). On univariate analysis, poor ECOG performance status (ECOG PS) at diagnosis, primary tumor location (extra-hepatic cholangiocarcinoma, and unknown biliary cancer), and sites of advanced disease (extra-hepatic metastasis) were significantly associated with worse OS (P<0.001, 0.036 and 0.034, respectively). Age, gender, CA19-9, CEA, hemoglobin, neutrophil count, and prior stent were not significantly associated with OS. On multivariate analysis, ECOG PS 2/3 was the only predictor of poor OS (P<0.001), while primary location (P=0.089) and sites of advanced disease (P=0.079) had a non-significant trend towards prognostic significance. Conclusions In this population based analysis, a poorer performance status was significantly prognostic of worse OS. Although not significant in our analysis, primary tumor location and sites of advanced disease may also have prognostic relevance. PMID:25436121

Renouf, Daniel; Lim, Howard

2014-01-01

145

Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer  

PubMed Central

Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ? 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients. PMID:23569316

Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D. Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E.; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M. John; Side, Lucy E.; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C.; Easton, Douglas F.; Kote-Jarai, Zsofia; Eeles, Rosalind

2013-01-01

146

HMGA2 is associated with epithelial–mesenchymal transition and can predict poor prognosis in nasopharyngeal carcinoma  

PubMed Central

Objective High-mobility group protein 2 (HMGA2) and epithelial–mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis. However, the clinical significance of HMGA2 and its relationship with EMT markers in nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the clinicopathological significance and prognostic value of HMGA2, E-cadherin, and vimentin in NPC. Methods Using immunohistochemistry, HMGA2, E-cadherin, and vimentin expression levels were evaluated in NPC (n=124) and non-tumoral inflammatory nasopharynx (n=20) tissues. The association of HMGA2 and EMT markers with clinicopathological characteristics and relationships between the protein levels and overall survival were analyzed. Results Compared with non-tumorous tissues, HMGA2 and vimentin levels were markedly increased in NPC tissues, whereas decreased E-cadherin levels were observed (P<0.001). Moreover, HMGA2 expression was positively correlated with vimentin levels (r=0.431, P<0.001) and negatively correlated with E-cadherin amounts (r=?0.413, P<0.001) in NPC tissues. The expression of all three proteins correlated significantly with tumor N stage, TNM stage, and 2-year metastasis. Furthermore, significant correlations were found for T stage, N stage, TNM stage, HMGA2, E-cadherin, and vimentin (all P<0.013) with poor prognosis (univariate analysis). However, multivariate analyses showed that only HMGA2 (hazard ratio [HR]: 2.683, 95% confidence interval [CI]: 1.185–6.077, P=0.018) and N stage (HR: 7.892, 95% CI: 2.731–22.807, P<0.001) were independent predictors of poor prognosis. Conclusion These results demonstrated that HMGA2, an independent prognostic factor, may promote NPC progression and metastasis, and is significantly associated with EMT proteins. Therefore, HMGA2 may be considered a potential therapeutic target in NPC. PMID:25653540

Xia, You-You; Yin, Li; Tian, Hao; Guo, Wen-Jie; Jiang, Ning; Jiang, Xue-Song; Wu, Jing; Chen, Meng; Wu, Jian-Zhong; He, Xia

2015-01-01

147

Utility of Hippocrates’ prognostic aphorism to predict death in the modern era: prospective cohort study  

PubMed Central

Objective To determine if one of Hippocrates’ aphorisms, identifying good cognition and good appetite as two prognostic factors, predicts death in community living older adults in the modern era. Design Secondary analysis of an existing population based cohort study. Setting Manitoba Study of Health and Aging. Participants 1751 community living adults aged more than 65 enrolled in the Manitoba Study of Health and Aging in 1991 and followed over five years. Main outcome measure Time to death. Methods We recreated the hippocratic prognosticator using an item that measures appetite drawn from the Center for Epidemiologic Studies-depression subscale, and the mini-mental state examination, with a score of >25 being considered as normal. People with normal cognition and appetite were compared with those with either poor cognition or poor appetite. We constructed Cox regression models, adjusted for age, sex, education, and functional status. Results The prognostic aphorism predicted death, with an unadjusted hazard ratio of 2.37 (95% confidence interval 1.93 to 2.88) and a hazard ratio of 1.71 (1.37 to 2.12) adjusted for age, sex, and education. Both poor appetite and poor cognition predicted death. The sensitivity and specificity were not, however, sufficient for the measure to be used alone. Conclusion An aphorism devised by Hippocrates millennia ago can predict death in the modern era. PMID:25512328

Montgomery, Patrick R

2014-01-01

148

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma.  

PubMed

In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (Delta13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n=794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if Delta13, p53 deletion or t(4;14) was present, but only Delta13 remained significant on multivariate analysis. Patients with Delta13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with Delta13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable Delta13 disappeared; their outcome matched that of patients with no detectable Delta13 (P=0.115). Addition of ploidy status to iFISH-Delta13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH Delta13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with Delta13. We conclude that Delta13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of Delta13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis. PMID:16826223

Chiecchio, L; Protheroe, R K M; Ibrahim, A H; Cheung, K L; Rudduck, C; Dagrada, G P; Cabanas, E D; Parker, T; Nightingale, M; Wechalekar, A; Orchard, K H; Harrison, C J; Cross, N C P; Morgan, G J; Ross, F M

2006-09-01

149

Survival rates, prognostic factors and treatment of anaplastic meningiomas.  

PubMed

Intracranial anaplastic meningioma is a malignant type of meningioma with a high rate of recurrence and death. Given its rarity, minimal information regarding this tumour is available. Thus, we studied a series of patients with anaplastic meningiomas and analysed the survival rates, prognostic factors and treatment methods associated with these patients. Forty-three anaplastic meningioma cases treated at our hospital between July 2002 and June 2012 were compiled into a single database used to summarise the clinical characteristics from a retrospective review of patient records. Progression free survival (PFS) and overall survival (OS) were analysed as a function of each possible prognostic factor. The 1, 3 and 5year PFS rates were 90.7%, 51.3%, and 37.0%, respectively, whereas the corresponding values of OS rates were 95.3%, 68.0% and 49.2%, respectively. A number of factors were selected to analyse association with prognosis. Simpson Grade I and II resections exhibited increased PFS rates and radiotherapy improved the OS rate in anaplastic meningiomas. Tumours with homogeneous contrast enhancement on MRI were associated with increased PFS and OS. Sex, age, tumour location, first or transformed anaplastic tumour, pre-operative Karnofsky Performance Scores, tumour volumes and bone involvement had no significant effect on either PFS or OS. MRI homogeneous contrast may be a useful prognostic factor and surgery followed by radiotherapy is recommended for the treatment of anaplastic meningiomas. PMID:25827863

Cao, Xiaoyu; Hao, Shuyu; Wu, Zhen; Wang, Liang; Jia, Guijun; Zhang, Liwei; Zhang, Junting

2015-05-01

150

Reduced NKX2.1 Expression Predicts Poor Prognosis of Gastric Carcinoma  

PubMed Central

Thyroid transcription factor-1 (NKX2.1/TITF-1) is a member of the thyroid tissue-specific transcription factor family that has been proven to be closely associated with many human diseases. Recently, it was reported that NKX2.1 expression is lost or reduced in some human cancers such as lung cancer and thyroid cancer. However, there was insufficient data to suggest that NKX2.1 functionality could be used as a prognostic factor. Therefore, this study aims to investigate NKX2.1 expression and its prognostic significance in primary gastric carcinoma. Then, we attempted to investigate if NKX2.1 expression was related to the clinicopathological characteristics and prognosis of gastric carcinoma (GC)patients. The expression levels of NKX2.1 were analyzed in tissue samples from 205 gastric carcinoma patients by real-time quantitative PCR (qRT-PCR), Western blotting, and immunohistochemical staining(IHC). Our qRT-PCR results showed that the expression of NKX2.1 mRNA was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples (P<0.001); this finding was confirmed by Western blot analysis (P<0.001). Our immunohistochemical staining data indicated that NKX2.1 expression was significantly decreased in 87 of 205 (42.4%) gastric carcinoma cases. Kaplan-Meier survival curves revealed that the decreased expression of NKX2.1 was significantly associated with poor prognosis in gastric carcinoma patients (P<0.001). Multivariate Cox analysis identified NKX2.1 expression as an independent prognostic factor for overall survival (P?=?0.005). Furthermore, the functions of Nkx2.1 were analyzed with respect to the proliferation, migration, and invasion of GC cell lines. Our data suggest that NKX2.1 may function as a tumor suppressor in primary gastric carcinoma and that its reduced expression independently predicts an unsatisfactory prognosis in gastric carcinoma patients. PMID:25478793

Chen, Yong-Ming; Huang, Chun-Yu; Li, Yuan-Fang

2014-01-01

151

Monocarboxylate Transporters 1–4 in NSCLC: MCT1 Is an Independent Prognostic Marker for Survival  

PubMed Central

Introduction Monocarboxylate transporters (MCTs) 1–4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC. Methods Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I–IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. Results In univariate analyses; ?MCT1 (P?=?0.021) and ?MCT4 (P?=?0.027) expression in cancer cells, and ?MCT1 (P?=?0.003), ?MCT2 (P?=?0.006), ?MCT3 (P?=?0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ?MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3–2.8, P?=?0.001), ?MCT2 (HR: 2.4, CI 95%: 1.5–3.9, P<0.001), ?MCT3 (HR: 1.9, CI 95%: 1.1–3.5, P?=?0.031) and ?MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1–2.7, P?=?0.016) were significant independent poor prognostic markers for DSS. Conclusions We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments. PMID:25225794

Eilertsen, Marte; Andersen, Sigve; Al-Saad, Samer; Kiselev, Yury; Donnem, Tom; Stenvold, Helge; Pettersen, Ingvild; Al-Shibli, Khalid; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M.

2014-01-01

152

Urban poor program launched.  

PubMed

The government of the Philippines has launched a program to deal with the rapidly growing urban poor population. 60 cities (including Metro Manila) are expected to increase their bloated population by 3.8% over 1990 which would be 27.7 million for 1991. Currently there is an exodus of people from the rural areas and by 2000 half the urban population will be squatters and slum dwellers. Basic services like health and nutrition are not expected to be able to handle this type of volume without a loss in the quality of service. The basic strategy of the new program is to recruit private medical practitioners to fortify the health care delivery and nutrition services. Currently the doctor/urban dweller ration is 1:9000. The program will develop a system to pool the efforts of government and private physicians in servicing the target population. Barangay Escopa has been chosen as the pilot city because it typifies the conditions of a highly populated urban area. The projects has 2 objectives: 1) demonstrate the systematic delivery of health and nutrition services by the private sector through the coordination of the government, 2) reduce mortality and morbidity in the community, especially in the 0-6 age group as well as pregnant women and lactating mothers. PMID:12284664

1991-01-01

153

Prognostic significance of antenatally detected fetal pyelectasis.  

PubMed

In order to evaluate the prognostic significance of ultrasonographically detected fetal pyelectasis, a retrospective review was performed of patients evaluated for fetal pyelectasis over a 24-month period. From 84 patients a total of 98 fetal kidneys with pyelectasis were identified. Fetal pyelectasis was more common in the left kidney and in males. Postpartum evaluation revealed 48 (57.1%) neonates with hydronephrosis. Among these, mean (SD; range) values of antenatal fetal pyelectasis were 17.0 mm (8.4; 5-26) before 33 weeks and 16.9 mm (8.5; 5-34) after 33 weeks in the left kidney and 15.4 mm (3.3; 10-24) and 17.1 mm (5.1; 5-36), respectively, in the right kidney. Thirteen infants (15.4%) with hydronephrosis required surgical pyeloplasties (mean age 6 months; range 3-18 months). It was found, from a receiver-operating characteristic curve, that fetal pyelectasis of 8 mm was 91% sensitive and 72% specific in predicting subsequent hydronephrosis. Use of a threshold of 5 mm yielded a sensitivity of 100% and a specificity of 24%. On the basis of these findings, we recommend that women with ultrasonographically detected antenatal fetal pyelectasis of > or = 5 mm at any gestational age have follow-up ultrasound examinations and detailed postnatal evaluation. PMID:8807759

Ouzounian, J G; Castro, M A; Fresquez, M; al-Sulyman, O M; Kovacs, B W

1996-06-01

154

Histopathology and Prognostic Indices of Carcinoma Breast with Special Reference to p53 Marker  

PubMed Central

Introduction: Cancer of the breast is one of the commonest carcinomas in women, both in western world and in India. The high frequency of breast cancer in women has prompted an intensive study of possible modifiable risk factors (clinical parameters, morphological typing, and biological markers) for assessment of prognosis, prevention strategies, and treatment modalities. p53 is one of the most significant prognostic markers for breast carcinomas. Aims and Objectives: This study was undertaken to ascertain the prevalence of p53 mutated protein in breast carcinomas by immunohistochemistry and correlating the results with clinical and histological parameters and also determine its influence on axillary node metastasis. Materials and Methods: Clinico-pathological evaluation of 50 cases of infiltrating ductal carcinoma of the breast, with reference to p53 mutated protein expression by means of immunohistochemistry was undertaken. Results: The percentage positivity of p53 immunohistochemistry of this study was 22% which is similar to the reported statistics of various other studies. The immunohistochemistry results also showed an equivocal p53 status in both the positive and negative cases of lymph node metastases. The carcinomas with p53 positivity demonstrated aggressive characteristics, including larger size, higher grade, in comparison with p53 negative cases. The probability of getting positive p53 status was higher for those with severe lymphocytic reaction of tumours, for patients less than 35 years of age and for those with tumour on the left side. This study clearly indicates that p53 over expression in breast cancers are mostly aggressive tumours and they confer poor prognosis and likelihood of a poor response to endocrine therapy and chemotherapy. PMID:25177567

P, Viswanathan; B, Krishnaswamy

2014-01-01

155

Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential  

Microsoft Academic Search

BACKGROUND: Soft tissue sarcoma (STS) diagnosis is challenging because of a multitude of histopathological subtypes, different genetic characteristics, and frequent intratumoral pleomorphism. One-third of STS metastasize and current risk-stratification is suboptimal, therefore, novel diagnostic and prognostic markers would be clinically valuable. We assessed the diagnostic and prognostic value of array-based gene expression profiles using 27 k cDNA microarrays in 177,

Princy Francis; Heidi Maria Namløs; Christoph Müller; Patrik Edén; Josefin Fernebro; Jeanne-Marie Berner; Bodil Bjerkehagen; Måns Åkerman; Pär-Ola Bendahl; Anna Isinger; Anders Rydholm; Ola Myklebost; Mef Nilbert

2007-01-01

156

School Readiness and Poor Children.  

ERIC Educational Resources Information Center

More and more frequently, poor families are described in pathological terms. The emphasis is on the deficits that interfere with the education of poor children, rather than the strengths that they can bring to schooling. A focus on the devastating effects of poverty may lead to the belief that poor children are so disadvantaged that nothing can be…

Seabrook, Luther W.

157

Factors associated with poor outcomes in adults with newly diagnosed ulcerative colitis.  

PubMed

It is a challenge to accurately identify patients with early stage ulcerative colitis (UC) who are at highest risk for a poor outcome and therefore might require salvage therapy. Several epidemiologic and clinical studies have analyzed factors associated with poor prognosis and increased risk for colectomy. We review prognostic factors for adults with newly diagnosed UC and discuss which patients might benefit from rapid and progressive therapy. Patients with poor prognoses tend to be young nonsmokers with high levels of inflammatory biomarkers, low levels of hemoglobin, and extensive disease, based on colonoscopy. We examine these risk factors in 2 hypothetical patients who have been newly diagnosed with UC. PMID:24887059

Reinisch, Walter; Reinink, Andrew R; Higgins, Peter D R

2015-04-01

158

An Integrated Approach for Gear Health Prognostics  

NASA Technical Reports Server (NTRS)

In this paper, an integrated approach for gear health prognostics using particle filters is presented. The presented method effectively addresses the issues in applying particle filters to gear health prognostics by integrating several new components into a particle filter: (1) data mining based techniques to effectively define the degradation state transition and measurement functions using a one-dimensional health index obtained by whitening transform; (2) an unbiased l-step ahead RUL estimator updated with measurement errors. The feasibility of the presented prognostics method is validated using data from a spiral bevel gear case study.

He, David; Bechhoefer, Eric; Dempsey, Paula; Ma, Jinghua

2012-01-01

159

Implementation and evaluation of prognostic representations of the optical diameter of snow in the  

E-print Network

Implementation and evaluation of prognostic representations of the optical diameter of snow Grenoble 1, LGGE, Grenoble, France A good representation of snow metamorphism processes within snowpack models is crucial, since the characteristics of snow grains have a significant impact on many

Ribes, Aurélien

160

Correlation of Foxp3 positive regulatory T cells with prognostic factors in canine mammary carcinomas  

Microsoft Academic Search

Regulatory T cells (Treg) cells play a crucial role in tumor progression by suppressing anti-tumor immunity, but are not well-documented in veterinary oncology. To identify the characteristics of Treg cells in tumor microenvironments, the numbers of Treg cells were analyzed and compared with histological prognostic factors and molecular biomarkers in canine mammary carcinoma (MC) tissues (n = 37).Abundant Treg cells

J. H. Kim; J. H. Hur; S. M. Lee; K. S. Im; N. H. Kim; J. H. Sur

161

Remaining useful life prognostic estimation for aircraft subsystems or components: A review  

Microsoft Academic Search

The techniques of remaining useful life (RUL) estimation are playing a more and more important role in aircraft safety and condition based maintenance. This paper gives an overview of RUL prognostic estimation approaches applied to aircraft subsystems or components. Existing RUL estimation approaches are categorized into three types, namely model-based approaches, data-driven approaches and fusion approaches and their characteristics are

Chen Xiongzi; Yu Jinsong; Tang Diyin; Wang Yingxun

2011-01-01

162

A gene expression signature identifies two prognostic subgroups of basal breast cancer  

Microsoft Academic Search

Prognosis of basal breast cancers is poor but heterogeneous. Medullary breast cancers (MBC) display a basal profile, but a\\u000a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve\\u000a to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive\\u000a early breast adenocarcinomas. We developed a

Renaud Sabatier; Pascal Finetti; Nathalie Cervera; Eric Lambaudie; Benjamin Esterni; Emilie Mamessier; Agnès Tallet; Christian Chabannon; Jean-Marc Extra; Jocelyne Jacquemier; Patrice Viens; Daniel Birnbaum; François Bertucci

2011-01-01

163

No Way Out: Working Poor Women in the United States.  

ERIC Educational Resources Information Center

This report examines the situation of the one-half of the nation's nine million working poor who are female. It begins by looking at just who the working poor are. Two areas of study are education levels and types of jobs. The discussion then shifts to minimum wage earners and their characteristics, the current status of the minimum wage, and the…

National Commission on Working Women, Washington, DC.

164

Prognostic Significance of DNA and Histone Methylation  

Cancer.gov

Nutritional Science Research Group Recently Funded Projects Prognostic Significance of DNA and Histone Methylation Principal Investigator: Piyathilake, Chandrika J Institution: University of Alabama at Birmingham   NCI/DCP Program Director: Ross, Sharon

165

Serum peptidomic profiling identifies a minimal residual disease detection and prognostic biomarker for patients with acute leukemia  

PubMed Central

The evaluation of minimal residual disease (MRD) in acute leukemia (AL) is currently recognized as a potential critical tool to assess the response and relapse rate of treatments. The present study investigated serum peptides from patients with AL to identify biomarkers that would be useful in providing clinical evaluations and independent prognostic information. The patterns of serum peptides from 123 patients with AL and 49 healthy controls were analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Furthermore, diagnostic models of differential peptides were established using the support vector machine (SVM) algorithm to discriminate between the AL patients and healthy controls or between the AL patients with various degrees of remission. Finally, the peptides were applied to evaluate the prognosis of the affected patients. The area under the receiver operating characteristic (ROC) curve (AUC), analyzed using the SVM algorithm to distinguish between the AL patients and healthy controls, was 0.921. The AUC of the models for distinguishing between the newly-diagnosed AL patients and those in AL-hematological complete remission (HCR) and between the AL-HCR patients from those in AL-molecular remission (MR), was 0.824 and 0.919, respectively. A short serum peptide of m/z 4625 was identified to decrease in density in parallel with an increase in the degree of remission, which was used to monitor the MRD level. The intensity of the m/z 4625 peptide was significantly correlated with a poor overall survival (OS). The m/z 4625 peptide was identified to be a partial fragment of SERPINA3. The serum peptide pattern is high in sensitivity and specificity and may be used to discriminate between AL patients with various degrees of remission. The m/z 4625 peptide may be used to monitor the MRD levels and provide independent prognostic information in patients with AL. PMID:24179540

SONG, WEI; WANG, NA; LI, WEI; WANG, GUANJUN; HU, JIFAN; HE, KUN; LI, YAN; MENG, YING; CHEN, NAIFEI; WANG, SHAOXIN; HU, LINGYUN; XU, BIN; WANG, JIE; LI, AILING; CUI, JIUWEI

2013-01-01

166

Upregulated TIMP-1 correlates with poor prognosis of laryngeal squamous cell carcinoma  

PubMed Central

The tissue inhibitor of metalloproteinase-1 (TIMP-1) is an endogenous inhibitor of matrix metalloproteinases and potential biomarker of various types of human cancers. However, the association between TIMP-1 expression and the clinical features of laryngeal squamous cell carcinoma (LSCC) is barely investigated. In this study, one-step quantitative reverse transcription-polymerase chain reaction and immunohistochemical staining with tissue microarrays were employed to evaluate the relationship between TIMP-1 expression and the clinicopathological characteristics of LSCC. Results showed that the TIMP-1 mRNA and protein expression levels were significantly higher in LSCC than in the corresponding non-cancerous tissues (p<0.05). TIMP-1 protein expression in LSCC was associated with tumor differentiation (p=0.012) and overall survival (p=0.043). Kaplan-Meier method and Cox multi-factor analysis suggested that high TIMP-1 expression (p=0.008) and positive lymph node metastasis (p=0.029) were significantly associated with the poor survival of patients with LSCC. These data indicated that TIMP-1 may be identified as a prognostic marker of LSCC. PMID:24427345

Ma, Jun; Wang, Jun; Fan, Weifei; Pu, Xiaolin; Zhang, Dawei; Fan, Chou; Xiong, Lin; Zhu, Huijun; Xu, Ning; Chen, Renjie; Liu, Shaofeng

2014-01-01

167

High CD133 Expression in the Nucleus and Cytoplasm Predicts Poor Prognosis in Non-Small Cell Lung Cancer  

PubMed Central

Objective. The aim of this study was to investigate the expression of Prominin-1 (CD133) in cancer cells and its potential value as a prognostic indicator of survival in patients with non-small cell lung cancer (NSCLC). Methods. Cancerous tissues and matched normal tissues adjacent to the carcinoma from 239 NSCLC patients were obtained immediately after surgery. Immunohistochemistry of tissue microarrays was used to characterize the expression of CD133 in NSCLC and adjacent tissues. The correlation of CD133 expression with clinical characteristics and prognosis was determined by statistical analysis. Results. CD133 protein expression levels in both the cytoplasm and nucleus were significantly higher in NSCLC tissues compared with corresponding peritumoral tissue (P < 0.05). CD133 expression in the nucleus of NSCLC cells was related to tumor diameter (P = 0.027), tumor differentiation (P < 0.001), and TNM stage (P = 0.007). Kaplan-Meier survival and Cox regression analyses revealed that high CD133 expression in the nucleus was an independent predictor of poor prognosis of NSCLC, as was high cytoplasmic CD133 expression (P < 0.001). Conclusion. Our findings provide the first evidence that high expression of CD133 in both the nucleus and cytoplasm is associated with poor prognosis in NSCLC. PMID:25691807

Zhu, Huijun; Feng, Jian; Ni, Songshi; Huang, Jianfei

2015-01-01

168

Plasma cathepsin L: A prognostic marker for pancreatic cancer  

PubMed Central

AIM: To assess the prognostic significance of cathepsin L, a cysteine protease that degrades the peri-tumoral tissue, in patients with pancreatic cancer. METHODS: Plasma samples from 127 pancreatic cancer patients were analyzed for cathepsin L levels by ELISA. Out of these patients, 25 underwent surgery and their paraffin-embedded tissue was analyzed for cathepsin L expression by immunohistochemistry. Survival of patients and clinicopathological parameters was correlated with cathepsin L expression in plasma and tissue using appropriate statistical analysis. RESULTS: The mean (± SD) cathepsin L in plasma samples of pancreatic cancer patients was 5.98 ± 2.5 ng/mL that was significantly higher compared to the levels in healthy controls (3.83 ± 0.45) or chronic pancreatitis patients (3.97 ± 1.06). Using ROC curve, a cut-off level of 5.0 ng/mL was decided for survival analysis. Elevated plasma levels of cathepsin L were found to be associated with poor prognosis (P = 0.01) in multivariate analysis. The plasma levels of the protease decreased after surgery. Though no significant correlation was seen between plasma and tissue expression of this protease, a trend did emerge that high cathepsin L expression in tissue correlated with its high levels in plasma. CONCLUSION: Cathepsin L levels in plasma of pancreatic cancer patients may be used as a potential prognostic marker for the disease. PMID:25516668

Singh, Nidhi; Das, Prasenjit; Gupta, Surabhi; Sachdev, Vikas; Srivasatava, Siddhartha; Datta Gupta, Siddhartha; Pandey, Ravindra Mohan; Sahni, Peush; Chauhan, Shyam S; Saraya, Anoop

2014-01-01

169

Prognostic value of oncoprotein expressions in thyroid papillary carcinoma.  

PubMed

The aim of this study was to evaluate the expressions of oncoproteins and to correlate the results with clinicopathologic parameters in papillary thyroid carcinoma (PTC). Papillary thyroid cancer (PTC) is the most common form and accounts for about 80% of all thyroid cancers. Although PTC generally has a good prognosis, some patients suffer from local recurrence and/or distant metastasis. Oncogenes have reported to be related not only in carcinogenesis but also in tumor prognosis, tumor type, differentiation and site of tumor in epithelial malignant tumors such as thyroid, breast, ovarian, and stomach cancer. This study was planned retrospectively and was performed in 87 patients (47 PTC, 40 benign lesions). The data of clinicopathologic parameters and tissue samples were collected from the archives. Sections stained with H&E were evaluated for each case and after confirming the diagnosis of PTC, oncoprotein expressions were determined by immunohistochemical analysis. The differences of oncoprotein expressions in PTC compared with control group were statistically significant. Cyclin D1 and p53 expressions were significantly increased in PTC. The expressions of bcl-2 and c-erbB-2 in PTC were found as increased, but the correlation between these proteins and poor prognostic parameters were not significant. We suggest that increased expressions of cyclin D1 and p53 could be used as prognostic factors in patients with PTC. PMID:21547408

Balta, A Z; Filiz, A I; Kurt, Y; Sucullu, I; Yucel, E; Akin, M L

2012-06-01

170

Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report  

NASA Technical Reports Server (NTRS)

This document outlines a set of metrics for evaluating the diagnostic and prognostic schemes developed for the Vehicle Integrated Prognostic Reasoner (VIPR), a system-level reasoner that encompasses the multiple levels of large, complex systems such as those for aircraft and spacecraft. VIPR health managers are organized hierarchically and operate together to derive diagnostic and prognostic inferences from symptoms and conditions reported by a set of diagnostic and prognostic monitors. For layered reasoners such as VIPR, the overall performance cannot be evaluated by metrics solely directed toward timely detection and accuracy of estimation of the faults in individual components. Among other factors, overall vehicle reasoner performance is governed by the effectiveness of the communication schemes between monitors and reasoners in the architecture, and the ability to propagate and fuse relevant information to make accurate, consistent, and timely predictions at different levels of the reasoner hierarchy. We outline an extended set of diagnostic and prognostics metrics that can be broadly categorized as evaluation measures for diagnostic coverage, prognostic coverage, accuracy of inferences, latency in making inferences, computational cost, and sensitivity to different fault and degradation conditions. We report metrics from Monte Carlo experiments using two variations of an aircraft reference model that supported both flat and hierarchical reasoning.

Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar

2013-01-01

171

Poor readers in secondary school  

Microsoft Academic Search

A follow-up of a representative sample of poor readers through secondary schooling confirmed persisting reading problems for most children. As a group, poor readers fell further behind a normal-reading comparison group during their early teens. Later reading progress was unrelated to gender, SES background, behavior problems or non-school attendance, though these factors did influence wider school attainments. Poor readers were

Barbara Maughan; Ann Hagell; Michael Rutter; William Yule

1994-01-01

172

Bone Scan Index as a prognostic imaging biomarker during androgen deprivation therapy  

PubMed Central

Background Bone Scan Index (BSI) is a quantitative measurement of tumour burden in the skeleton calculated from bone scan images. When analysed at the time of diagnosis, it has been shown to provide prognostic information on survival in men with metastatic prostate cancer (PCa). In this study, we evaluated the prognostic value of BSI during androgen deprivation therapy (ADT). Methods Prostate cancer patients who were at high risk of a poor outcome and who had undergone bone scan at the time of diagnosis and during ADT were recruited from two university hospitals for a retrospective study. BSI at baseline and follow-up were calculated using an automated software package (EXINIbonebsi). Associations between BSI, other prognostic biomarkers and overall survival (OS) were evaluated using a Cox proportional hazards regression model. Results One hundred forty-six PCa patients were included in the study. A total of 102 patient deaths were registered, with a median survival time after the follow-up bone scan of 2.4 years (interquartile range (IQR) =0.8 to 4.4). Both at baseline and during ADT, BSI was significantly associated with OS in univariate and multivariate analyses. When BSI was added to a prognostic base model including age, prostate-specific antigen, clinical tumour stage and Gleason score, the concordance index increased from 0.73 to 0.77 (p =0.0005) at baseline and from 0.77 to 0.82 (p <0.0001) during ADT. Conclusions Automated BSI during ADT is an independent prognostic indicator of OS in PCa patients with bone metastasis. It represents an emerging imaging biomarker that can be used in a prognostic model for risk stratification of PCa patients at the time of diagnosis and at later stages of the disease. BSI could then help physicians identify patients who could benefit from more aggressive therapies. PMID:25386390

2014-01-01

173

Critical illness neuromuscular disease: clinical, electrophysiological, and prognostic aspects  

PubMed Central

Background: Critical illness neuromuscular disease, which has been recognised as a distinct clinical entity in adults, remains poorly described in children. Aims: To assess retrospectively the clinical, electrophysiological, and prognostic features of the disease. Methods: Retrospective study in a children's university hospital. Results: Five critically ill patients presented with generalised paralysis, associated with long lasting failure to breathe in three. The cause of the generalised paralysis was critical illness neuropathy in two, acute myopathy in two, and mixed neuromyopathy in one. Conclusions: Neuromuscular disease should be suspected in critically ill children with muscle weakness. Because corticosteroids and muscle relaxants appear to trigger some types of intensive care unit neuromuscular disease in children, their use should be restricted or administered at the lowest doses possible. PMID:11827903

Tabarki, B; Coffinieres, A; Van den Bergh, P; Huault, G; Landrieu, P; Sebire, G

2002-01-01

174

Prognostic factors of postherpetic neuralgia.  

PubMed Central

The investigation was aimed to determine prognostic factors related to postherpetic neuralgia (PHN), and treatment options for preventing PHN. The data showed 34 (17.0%) out of 188 patients with herpes zoster had severe pain after 4 weeks, and 22 (11.7%) after 8 weeks, compared with 109 (58.0%) at presentation. The age (>/=50 yr), surface area involved (>/=9%), and duration of severe pain (>/=4 weeks) might be the main factors that lead to PHN. On the other hand, gender, dermatomal distribution, accompanied systemic conditions, and interval between initial pain and initiation of treatment might not be implicated in PHN. The subjects were orally received antiviral (valacyclovir), tricyclic antidepressant (amitriptyline), and analgesic (ibuprofen) as the standard treatment in the group 1. In addition to the standard medication, lidocaine solution was sub- and/or perilesionally injected in the group 2, while lidocaine plus prilocaine cream was topically applied to the skin lesions in the group 3. The rates of PHN in the 3 treatment groups were not significantly different, suggesting adjuvant anesthetics may not be helpful to reduce the severity of pain. PMID:12378018

Herr, Hwan

2002-01-01

175

Classical and Novel Prognostic Markers for Breast Cancer and their Clinical Significance  

PubMed Central

The use of biomarkers ensures breast cancer patients receive optimal treatment. Established biomarkers such as estrogen receptor (ER) and progesterone receptor (PR) have been playing significant roles in the selection and management of patients for endocrine therapy. HER2 is a strong predictor of response to trastuzumab. Recently, the roles of ER as a negative and HER2 as a positive indicator for chemotherapy have been established. Ki67 has traditionally been recognized as a poor prognostic factor, but recent studies suggest that measurement of Ki67-positive cells during treatment will more effectively predict treatment efficacy for both anti-hormonal and chemotherapy. p53 mutations are found in 20–35% of human breast cancers and are associated with aggressive disease with poor clinical outcome when the DNA-binding domain is mutated. The utility of cyclin D1 as a predictor of breast cancer prognosis is controversial, but cyclin D1b overexpression is associated with poor prognosis. Likewise, overexpression of the low molecular weight form of cyclin E1 protein predicts poor prognosis. Breast cancers from BRCA1/2 carriers often show high nuclear grades, negativity to ER/PR/HER2, and p53 mutations, and thus, are associated with poor prognosis. The prognostic values of other molecular markers, such as p14ARF, TBX2/3, VEGF in breast cancer are also discussed. Careful evaluation of these biomarkers with current treatment modality is required to determine whether their measurement or monitoring offer significant clinical benefits. PMID:20567632

Taneja, Pankaj; Maglic, Dejan; Kai, Fumitake; Zhu, Sinan; Kendig, Robert D.; Fry, Elizabeth A.; Inoue, Kazushi

2010-01-01

176

Malignant Peritoneal Mesothelioma: Prognostic Factors and Oncologic Outcome Analysis  

PubMed Central

Background Most patients with malignant peritoneal mesothelioma (MPM) present with late-stage, unresectable disease that responds poorly to systemic chemotherapy while, at the same time, effective targeted therapies are lacking. We assessed the efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) in MPM. Methods We prospectively analyzed 65 patients with MPM undergoing CRS/HIPEC between 2001 and 2010. Kaplan–Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. Results Adequate CRS was achieved in 56 patients (CC-0 = 35; CC-1 = 21), and median simplified peritoneal cancer index (SPCI) was 12. Pathologic assessment revealed predominantly epithelioid histology (81 %) and biphasic histology (8 %), while lymph node involvement was uncommon (8 %). Major postoperative morbidity (grade III/IV) occurred in 23 patients (35 %), and 60-day mortality rate was 6 %. With median follow-up of 37 months, median overall survival was 46.2 months, with 1-, 2-, and 5-year overall survival probability of 77, 57, and 39 %, respectively. Median progression-free survival was 13.9 months, with 1-, 2-, and 5-year disease failure probability of 47, 68, and 83 %, respectively. In a multivariate Cox-regression model, age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), aggressive histology (epithelioid, biphasic), and postoperative sepsis were joint significant predictors of poor survival (chi square = 42.8; p = 0.00001), while age at surgery, SPCI >15, incomplete cytoreduction (CC-2/3), and aggressive histology (epithelioid, biphasic) were joint significant predictors of disease progression (Chi square = 30.6; p = 0.00001). Conclusions Tumor histology, disease burden, and the ability to achieve adequate surgical cytoreduction are essential prognostic factors in MPM patients undergoing CRS/HIPEC. PMID:24322529

Magge, Deepa; Zenati, Mazen S.; Austin, Frances; Mavanur, Arun; Sathaiah, Magesh; Ramalingam, Lekshmi; Jones, Heather; Zureikat, Amer H.; Holtzman, Matthew; Ahrendt, Steven; Pingpank, James; Zeh, Herbert J.; Bartlett, David L.; Choudry, Haroon A.

2014-01-01

177

Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems  

Microsoft Academic Search

BACKGROUNDThe incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring

J G Edwards; K R Abrams; J N Leverment; T J Spyt; D A Waller; K J OByrne

2000-01-01

178

Prognostic Value of Human Apurinic/Apyrimidinic Endonuclease 1 (APE1) Expression in Breast Cancer  

PubMed Central

Human apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein for DNA base excision repair (BER) and redox regulation. The ability of cancer cells to recognize DNA damage and initiate DNA repair is an important mechanism for therapeutic resistance. Several recent studies have suggested that APE1 expression levels and/or subcellular dysregulation may be used to indicate the sensitivity of tumors to radiotherapy or chemotherapy. In this study, we assessed the prognostic significance of APE1 and differences in APE1 expression levels according to breast cancer molecular subtypes. We analyzed formalin-fixed, paraffin-embedded tumor tissue sections from 243 cases diagnosed as invasive breast cancer at Ewha Womans University Medical Center between January 2003 and December 2008. Immunohistochemistry was performed and the nuclear level of APE1 was scored by taking into account the percentage of positive cells. Medical records were reviewed to investigate clinicopathologic characteristics. We found that nuclear APE1 high-level expression (proportion ?50%) in breast cancer showed a tendency towards unfavorable prognosis regarding disease-free survival (p?=?0.093). However, there was no significant difference in overall survival between low and high-level expression groups (p?=?0.294). Interestingly, within the Ki-67 low-level expression group, APE1 low-level expression was significantly associated with poor overall survival (p?=?0.007). A significant positive correlation was observed between APE1 nuclear expression and estrogen receptor status (75.7% vs. 59.7%, p?=?0.022). Also, the luminal A subtype was the most commonly observed breast cancer subtype in the APE1 high-level expression group (61.6% vs. 45.2%, p?=?0.000). This study suggests that APE1 expression may be associated with breast cancer prognosis. In particular, its role as a prognostic factor would be significant for breast cancers with a low Ki-67 proliferation index. It is proposed that nuclear APE1 may be a novel target in breast cancer with a low proliferation rate to obtain better outcome. PMID:24914806

Woo, Joohyun; Park, Heejung; Sung, Sun Hee; Moon, Byung-In; Suh, Hyunsuk; Lim, Woosung

2014-01-01

179

Classification of patients with breast cancer according to Nottingham Prognostic Index highlights significant differences in immunohistochemical marker expression  

PubMed Central

Background Prognosis and treatment of patients with breast carcinoma of no special type (NST) is dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor, progesterone receptor, and HER-2/neu, and proliferation index. The original Nottingham Prognostic Index (NPI) employs a three-tiered classification system that stratifies patients with breast cancer into good, moderate, and poor prognostic groups. The aim of our study was to use robust immunohistochemical methodology for determination of ER, PR, HER-2/neu, Ki-67, p53, and Bcl-2, and to observe differences in the expression of these markers when patients are stratified according to the original, three-tiered Nottingham Prognostic Index. Methods Paraffin blocks from 120 patients diagnosed with breast carcinoma, NST, were retrieved from our archive. Cases included in the study were female patients previously treated with modified radical mastectomy and axillary dissection. Results Our study demonstrates that expression of markers of good prognosis, such as ER, PR, and Bcl-2, is seen with higher frequency in good and moderate NPI groups. In contrast, overexpression of HER-2/neu, a marker of adverse prognosis, is more frequent in moderate and poor NPI groups. High proliferation index, as measured by Ki-67, is seen in moderate and poor NPI groups, whereas low proliferation index is seen in good NPI groups. Conclusions These data confirm that the original, three-tiered NPI statistically correlates with the expression of prognostic immunohistochemical markers in breast carcinoma NST. PMID:25082024

2014-01-01

180

GLOBAL HEALTH Paying the poor  

E-print Network

GLOBAL HEALTH Paying the poor Using cash incentives to encourage healthy behaviour among poor communities is being hailed as a new silver bullet in global health. Megan Tan and GavinYamey investigate why this popular idea went so badly wrong in Guatemala Megan Tan masters student, Global Health Sciences, Gavin

Klein, Ophir

181

HER-2 expression in immunohistochemistry has no prognostic significance in gastric cancer patients.  

PubMed

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4-12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P = 0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient's age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC. PMID:22645475

Halon, Agnieszka; Donizy, Piotr; Biecek, Przemyslaw; Rudno-Rudzinska, Julia; Kielan, Wojciech; Matkowski, Rafal

2012-01-01

182

HER-2 Expression in Immunohistochemistry Has No Prognostic Significance in Gastric Cancer Patients  

PubMed Central

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P = 0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient's age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC. PMID:22645475

Halon, Agnieszka; Donizy, Piotr; Biecek, Przemyslaw; Rudno-Rudzinska, Julia; Kielan, Wojciech; Matkowski, Rafal

2012-01-01

183

CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study  

PubMed Central

Background CD69 is expressed in several hemopoietic cells and is an early activation marker in chronic lymphocytic leukemia. Chronic lymphocytic leukemia is a clinically heterogeneous disease which needs novel prognostic parameters which can be easily and efficiently managed. Design and Methods We investigated CD69 by flow cytometry in a series of 417 patients affected by chronic lymphocytic leukemia and compared this to other biological and clinical prognosticators. Results CD69 was associated with Rai stages (P=0.00002), ?2-microglobulin (P=0.0005) and soluble CD23 (P<0.0001). CD69 and ZAP-70 (P=0.018) or CD38 (P=0.00015) or immunoglobulin variable heavy chain gene mutations (P=0.0005) were also significantly correlated. Clinically, CD69 positive chronic lymphocytic leukemias received chemotherapy more frequently (74%; P<0.0001), and presented a shorter duration of response after fludarabine plus rituximab (P=0.010) as well as shorter progression free survival and overall survival (P<0.0001). CD69 demonstrated true additive prognostic properties, since the CD69+ plus ZAP-70+ or CD38+ or immunoglobulin variable heavy chain gene unmutated patients had the worst progression free survival and overall survival (P<0.0001). Interestingly, low CD69 expression was necessary to correctly prognosticate the longer progression free survival of patients with a low tumor burden of ?2-microglobulin (P=0.002), of soluble CD23 (P=0.020), or of Rai stages 0-I (P=0.005). CD69 was confirmed to be an independent prognostic factor in multivariate analysis of progression free survival (P=0.017) and overall survival (P=0.039). Conclusions Our data indicate that CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator. This supports its introduction in a routine laboratory assessment and, possibly, in a prognostic scoring system for chronic lymphocytic leukemia, after an adequate standardization process. PMID:21993667

Del Poeta, Giovanni; Del Principe, Maria Ilaria; Zucchetto, Antonella; Luciano, Fabrizio; Buccisano, Francesco; Maria Rossi, Francesca; Bruno, Antonio; Biagi, Annalisa; Bulian, Pietro; Maurillo, Luca; Neri, Benedetta; Bomben, Riccardo; Simotti, Cristina; Coletta, Angela Maria; Dal Bo, Michele; de Fabritiis, Paolo; Venditti, Adriano; Gattei, Valter; Amadori, Sergio

2012-01-01

184

A Distributed Prognostic Health Management Architecture  

NASA Technical Reports Server (NTRS)

This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current state-of-the-art PHM systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to loss of functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become unsuitable for successful deployment, and efficient distributed architectures are required. A distributed architecture though, is not effective unless there is an algorithmic framework to take advantage of its unique abilities. The health management paradigm envisaged here incorporates a heterogeneous set of system components monitored by a varied suite of sensors and a particle filtering (PF) framework that has the power and the flexibility to adapt to the different diagnostic and prognostic needs. Both the diagnostic and prognostic tasks are formulated as a particle filtering problem in order to explicitly represent and manage uncertainties; however, typically the complexity of the prognostic routine is higher than the computational power of one computational element ( CE). Individual CEs run diagnostic routines until the system variable being monitored crosses beyond a nominal threshold, upon which it coordinates with other networked CEs to run the prognostic routine in a distributed fashion. Implementation results from a network of distributed embedded devices monitoring a prototypical aircraft electrical power system are presented, where the CEs are Sun Microsystems Small Programmable Object Technology (SPOT) devices.

Bhaskar, Saha; Saha, Sankalita; Goebel, Kai

2009-01-01

185

Prognostic DNA Methylation Markers for Prostate Cancer  

PubMed Central

Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

2014-01-01

186

Evaluating Algorithm Performance Metrics Tailored for Prognostics  

NASA Technical Reports Server (NTRS)

Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used in the research community are not standardized and in many cases do not sufficiently assess key performance aspects expected out of a prognostics algorithm. In this paper we introduce several new evaluation metrics tailored for prognostics and show that they can effectively evaluate various algorithms as compared to other conventional metrics. Specifically four algorithms namely; Relevance Vector Machine (RVM), Gaussian Process Regression (GPR), Artificial Neural Network (ANN), and Polynomial Regression (PR) are compared. These algorithms vary in complexity and their ability to manage uncertainty around predicted estimates. Results show that the new metrics rank these algorithms in different manner and depending on the requirements and constraints suitable metrics may be chosen. Beyond these results, these metrics offer ideas about how metrics suitable to prognostics may be designed so that the evaluation procedure can be standardized. 1

Saxena, Abhinav; Celaya, Jose; Saha, Bhaskar; Saha, Sankalita; Goebel, Kai

2009-01-01

187

On the joint use of propensity and prognostic scores in estimation of the average treatment effect on the treated: a simulation study.  

PubMed

Propensity and prognostic score methods seek to improve the quality of causal inference in non-randomized or observational studies by replicating the conditions found in a controlled experiment, at least with respect to observed characteristics. Propensity scores model receipt of the treatment of interest; prognostic scores model the potential outcome under a single treatment condition. While the popularity of propensity score methods continues to grow, prognostic score methods and methods combining propensity and prognostic scores have thus far received little attention. To this end, we performed a simulation study that compared subclassification and full matching on a single estimated propensity or prognostic score with three approaches combining the estimated propensity and prognostic scores: full matching on a Mahalanobis distance combining the estimated propensity and prognostic scores (FULL-MAHAL); full matching on the estimated prognostic propensity score within propensity score calipers (FULL-PGPPTY); and subclassification on an estimated propensity and prognostic score grid with 5?×?5 subclasses (SUBCLASS(5*5)). We considered settings in which one, both, or neither score model was misspecified. The data generating mechanisms varied in the degree of linearity and additivity in the true treatment assignment and outcome models. FULL-MAHAL and FULL-PGPPTY exhibited strong to superior performance in root mean square error terms across all simulation settings and scenarios. Methods combining propensity and prognostic scores were no less robust to model misspecification than single-score methods even when both score models were incorrectly specified. Our findings support the joint use of propensity and prognostic scores in estimation of the average treatment effect on the treated. PMID:24151187

Leacy, Finbarr P; Stuart, Elizabeth A

2014-09-10

188

Prediction of Poor Prognosis in Breast Cancer Patients Based on MicroRNA-21 Expression: A Meta-Analysis  

PubMed Central

Background MicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer. Methods The meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI). Results Our meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37—4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16—1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89—8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99—2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics. Conclusion Our results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians. PMID:25706383

Wang, Yanyan; Zhang, Yujie; Pan, Chi; Ma, Feixia; Zhang, Suzhan

2015-01-01

189

CA9 overexpression is an independent favorable prognostic marker in intrahepatic cholangiocarcinoma  

PubMed Central

The aim of this study is to evaluate the expression of carbonic anhydrase IX (CA9) and to identify its prognostic significance in intrahepatic cholangiocarcinoma (IHCC). We performed immunohistochemistry (IHC) for CA9 in a total of 85 IHCCs. CA9 overexpression was observed in 38 of 85 (44.7%) IHCCs. CA9 overexpression was related to tumors with intraductal growth than mass forming or periductal infiltrative type. CA9 overexpression was more observed in tumors with well/moderate differentiation than poor differentiation and without lymph node metastasis. No significant correlation was observed in CA9 overexpression with tumor size, pT, stage and lymphovascular invasion. Intrahepatic cholangiocarcinomas with CA9 overexpression showed better overall survival than that without expression (P = 0.001). In multivariate analysis, lymph node metastasis (95% CI: 2.103 (1.167-3.791), P = 0.013) was an independent poor prognostic factor. IHCC with CA9 overexpression showed a 0.5-fold (95% confidence interval, 0.328-0.944) lower risk of death compared with those of no or weak expression. CA9 overexpression was related to histologic differentiation and an independent good prognostic factor. PMID:25755787

Gu, Mijin

2015-01-01

190

KL-6, a Human MUC1 Mucin, as a prognostic marker for diffuse alveolar hemorrhage syndrome  

PubMed Central

Background Diffuse alveolar hemorrhage syndrome is a life threatening condition with diverse etiologies. Sensitive prognostic markers for diffuse alveolar hemorrhage have not been well investigated. Serum KL-6 is a biomarker for various interstitial lung disease associated with disease activity and prognosis. The purpose of the present study was to evaluate the clinical utility of serum KL-6 level as a prognostic marker for diffuse alveolar hemorrhage. Methods We retrospectively collected 41 consecutive patients clinically diagnosed as having diffuse alveolar hemorrhage who were admitted to the Intensive Care Unit of Hiroshima University Hospital between 2004 and 2011. Correlation between prognosis and age, sex, laboratory findings including serum KL-6, radiological findings, ventilatory modes or therapeutic regimens were evaluated. Results Baseline and peak serum KL-6 levels were significantly higher in non-survivors compared with survivors. An increase in KL-6 levels during the initial week was associated with a subsequent deterioration of the oxygenation index. Higher baseline KL-6 levels and higher peak KL-6 levels were strongly correlated with death. With a cut-off level of 700 U/mL for peak KL-6, the sensitivity, specificity and accuracy for non-survival were 75%, 85% and 78%, respectively. In the multivariate analysis, only the peak KL-6 level ?700 U/ml was an independent poor prognostic factor for diffuse alveolar hemorrhage. Conclusions Peak serum KL-6 level ?700 U/ml may become a clinically useful marker of poor prognosis for diffuse alveolar hemorrhage. PMID:23244165

2012-01-01

191

Prognostic significance of neutrophil-to- lymphocyte ratio in esophageal cancer: a meta-analysis  

PubMed Central

Background The neutrophil-to-lymphocyte ratio (NLR) is a useful predictive factor in several cancers. However, the prognostic value of NLR in patients with esophageal cancer (EC) is still controversial. Therefore, it was necessary for us to perform a meta-analysis to evaluate the prognostic value of NLR in patients with EC. Methods A systematic literature search was performed by using Web of Science, PubMed Central, and Medline to evaluate the prognostic value of NLR in patients with EC. The deadline of our primary search was July 10, 2014. This meta-analysis was conducted in accordance with PRISMA guidelines. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to assess the association of NLR and overall survival (OS) and disease-free survival (DFS). Results Six studies involving 1,633 patients were included in our meta-analysis. Our pooled results demonstrated that high NLR was associated with poor OS (HR: 1.54, 95% CI: 1.32–1.80, I 2=25.3%, P=0.254) and DFS (HR: 1.74, 95% CI: 1.25–2.43, I 2=63.9%, P=0.096). Subgroup analysis between NLR and OS was performed in a further investigation. When the patients were segregated according to country, sample size, and pathological type, high NLR was also significantly correlated with OS. Conclusion High NLR is associated with poor prognosis in patients with EC. NLR may be a significant predictive biomarker in patients with EC.

Yang, Xun; Huang, Ying; Feng, Ji-Feng; Liu, Jin-Shi

2015-01-01

192

Instructions for use Prognostic Implication of Histological Oligodendroglial  

E-print Network

Instructions for use #12;Prognostic Implication of Histological Oligodendroglial Tumor Component, suggesting that the histological identification of oligodendroglial tumor component, even partially to the prognostic value of histological oligodendroglial tumor component; in addition, our results might offer

Tachizawa, Kazuya

193

Prognostic Factors in Childhood Leukemia (ALL or AML)  

MedlinePLUS

... for childhood leukemias Prognostic factors in childhood leukemia (ALL or AML) Certain differences among patients that affect ... myelogenous leukemia (AML). Prognostic factors for children with ALL Different systems are used to classify childhood ALL ...

194

Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study  

PubMed Central

Acute myeloid leukemia and myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) have a poor prognosis. Indeed, the inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has been recognized as a poor risk karyotype in the revised International Prognostic Scoring System. However, inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is not among the cytogenetic abnormalities pathognomonic for diagnosis of acute myeloid leukemia irrespective of blast percentage in the 2008 WHO classification. This multicenter study evaluated the clinico-pathological features of acute myeloid leukemia/myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and applied the revised International Prognostic Scoring System to myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2). A total of 103 inv(3)(q21q26.2)/t(3;3)(q21;q26.2) patients were reviewed and had a median bone marrow blast count of 4% in myelodysplastic syndrome (n=40) and 52% in acute myeloid leukemia (n=63) (P<0.001). Ninety-one percent of patients showed characteristic dysmegakaryopoiesis. There was no difference in overall survival between acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) (12.9 vs. 7.9 months; P=0.16). Eighty-three percent of patients died (median follow up 7.9 months). Complex karyotype, monosomal karyotype and dysgranulopoiesis (but not blast percentage) were independent poor prognostic factors in the entire cohort on multivariable analysis. The revised International Prognostic Scoring System better reflected overall survival of inv(3)(q21q26.2)/t(3;3)(q21;q26.2) than the International Prognostic Scoring System but did not fully reflect the generally dismal prognosis. Our data support consideration of myelodysplastic syndrome with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) as an acute myeloid leukemia with recurrent genetic abnormalities, irrespective of blast percentage. PMID:24463215

Rogers, Heesun J.; Vardiman, James W.; Anastasi, John; Raca, Gordana; Savage, Natasha M.; Cherry, Athena M.; Arber, Daniel; Moore, Erika; Morrissette, Jennifer JD.; Bagg, Adam; Liu, Yen-Chun; Mathew, Susan; Orazi, Attilio; Lin, Pei; Wang, Sa A.; Bueso-Ramos, Carlos E.; Foucar, Kathryn; Hasserjian, Robert P.; Tiu, Ramon V.; Karafa, Matthew; Hsi, Eric D.

2014-01-01

195

Immunophenotype of acute myeloid leukemia with NPM mutations: prognostic impact of the leukemic compartment size.  

PubMed

NPM mutations are the most common genetic abnormalities found in non-promyelocytic AML. NPM-positive patients usually show a normal karyotype, a peculiar morphologic appearance with frequent monocytic traits and good prognosis in the absence of an associated FLT3 mutation. This report describes the immunophenotypic and genetic characteristics of a consecutive series of NPM-mutated de novo AML patients enroled in the CETLAM trial. Eighty-three patients were included in the study. Complete immunophenotype was obtained using multiparametric flow cytometry. Associated genetic lesions (FLT3, MLL, CEBPA and WT1 mutations) were studied by standardized methods. Real-time PCR was employed to assess the minimal residual status. The most common pattern was CD34-CD15+ and HLA-DR+. Small CD34 populations with immunophenotypic aberrations (CD15 and CD19 coexpression, abnormal SSC) were detected even in CD34 negative samples. Nearly all cases expressed CD33 (strong positivity), CD13 and CD117, and all were CD123+. The stem cell marker CD110 was also positive in most cases. Biologic parameters such as a high percentage of intermediate CD45+ (blast gate) (>75% nucleated cells), CD123+ and FLT3-ITD mutations were associated with a poor outcome. Quantitative PCR positivity had no prognostic impact either after induction or at the end of chemotherapy. Only PCR positivity (greater than 10 copies) detected in patients in haematological remission was associated with an increased relapse rate. Further studies are required to determine whether the degree of leukemic stem cell expansion (CD45+CD123+cells) increases the risk of acquisition of FLT3-ITD and/or provides selective advantages. PMID:20542566

Nomdedeu, J; Bussaglia, E; Villamor, N; Martinez, C; Esteve, J; Tormo, M; Estivill, C; Queipo, M P; Guardia, R; Carricondo, M; Hoyos, M; Llorente, A; Juncà, J; Gallart, M; Domingo, A; Bargay, J; Mascaró, M; Moraleda, J M; Florensa, L; Ribera, J M; Gallardo, D; Brunet, S; Aventin, A; Sierra, J

2011-02-01

196

The Modified Glasgow Prognostic Scores as a Predictor in Diffuse Large B Cell Lymphoma Treated with R-CHOP Regimen  

PubMed Central

Purpose The modified Glasgow Prognostic Score (mGPS) consisting of serum C-reactive protein and albumin levels, shows significant prognostic value in several types of tumors. We evaluated the prognostic significance of mGPS in 285 patients with diffuse large B cell lymphoma (DLBCL), retrospectively. Materials and Methods According to mGPS classification, 204 patients (71.5%) had an mGPS of 0, 57 (20%) had an mGPS of 1, and 24 (8.5%) had an mGPS of 2. Results Our study found that high mGPS were associated with poor prognostic factors including older age, extranodal involvement, advanced disease stage, unfavorable International Prognostic Index scores, and the presence of B symptoms. The complete response (CR) rate after 3 cycles of R-CHOP chemotherapy was higher in patients with mGPS of 0 (53.8%) compared to those with mGPS of 1 (33.3%) or 2 (25.0%) (p=0.001). Patients with mGPS of 0 had significantly better overall survival (OS) than those with mGPS=1 and those with mGPS=2 (p=0.036). Multivariate analyses revealed that the GPS score was a prognostic factor for the CR rate of 3 cycle R-CHOP therapy (p=0.044) as well as OS (p=0.037). Conclusion mGPS can be considered a potential prognostic factor that may predict early responses to R-CHOP therapy in DLBCL patients. PMID:25323893

Kim, Yundeok; Kim, Soo Jeong; Hwang, Dohyu; Jang, Jieun; Hyun, Shin-Young; Kim, Yu Ri; Kim, Jin Seok; Min, Yoo Hong

2014-01-01

197

Monosomal and complex karyotypes as prognostic parameters in patients with International Prognostic Scoring System higher risk myelodysplastic syndrome treated with azacitidine  

PubMed Central

Background Azacitidine (AZA) is standard care for patients with myelodysplastic syndrome (MDS) who have not had allogeneic stem cell transplantation. Chromosomal abnormalities (CA) including complex karyotype (CK) or monosomal karyotype (MK) are associated with clinical outcome in patients with MDS. Methods We investigated which prognostic factors including CAs would predict clinical outcomes in patients with International Prognostic Scoring System (IPSS) higher risk MDS treated with AZA, retrospectively. CK was defined as the presence of three or more numerical or structural CAs. MK was defined as the presence of two or more distinct autosomal monosomies or single autosomal monosomy with at least one additional structural CA. Results A total of 243 patients who treated with AZA, were enrolled. CK was present in 124 patients and MK was present in 90 patients. Bone marrow blasts ?15% and CK were associated with poorer response (P=0.038, P=0.007) and overall survival (OS) (P<0.001, P<0.001) independently. Although MK in CK group was not associated with prognosis, non-MK status in non-CK group reflected favorable OS (P=0.005). The group including >3 CAs was associated with poorer OS (group including <3 CAs vs. only three CAs, P=0.001; group with >3 CAs vs. only three CAs, P=0.001). Conclusion CK was an important prognostic parameter associated with worse outcome. MK may predict poor survival in only non-CK status. The higher number of CAs was associated with poorer survival. PMID:25548756

Hwang, Kyung-Lim; Song, Moo-Kon; Shin, Ho-Jin; Na, Hae-Jung; Shin, Dong-Hun; Kim, Joong-Keun; Moon, Joon-Ho; Ahn, Jae-Sook; Song, Ik-Chan; Hong, Junshik; Lee, Gyeong-won

2014-01-01

198

Squamous cell carcinoma of the vagina: natural history, treatment modalities and prognostic factors.  

PubMed

Squamous cell carcinoma of the vagina accounts for less than 2% of all gynecologic malignancies. Surgery has a role in selected cases only. The standard treatment is radiotherapy, external beam radiation and/or brachytherapy, depending on the extent, thickness, location and morphology of the lesion. The role of chemotherapy is still under evaluation. Radiotherapy obtained 5-year overall survival rates ranged from 35% to 78%, with severe late complication rates of 9.4-23.1%. Tumor stage is the strongest prognostic factor. Tumor size >4cm, tumor location outside the upper third of the vagina, and old age at presentation are additional predictors of poor survival in most papers, whereas the prognostic value of histological grade, prior hysterectomy, and hemoglobin levels is controversial. High-risk HPV DNA and low MIB-1 index are associated with better clinical outcome. Because of the rarity of this tumor, future multicenter studies would be strongly warranted. PMID:25476235

Gadducci, Angiolo; Fabrini, Maria Grazia; Lanfredini, Nora; Sergiampietri, Claudia

2015-03-01

199

EZH2 is a negative prognostic factor and exhibits pro-oncogenic activity in glioblastoma.  

PubMed

The identification of single or less genes based on mRNA expression as clinical diagnostic markers for glioblastoma (GBM) remains a challenge. Recent data have shown the potential oncogenic role and prognostic significance of EZH2 in several human cancers. However, the clinical signature and further mechanisms of EZH2 function in gliomagenesis are still poorly understood. In this study, we found that increased EZH2 expression was associated with tumor grade. High expression of EZH2 in GBM was determined to be a strong and independent predictor of short overall survival. Further, we screened EZH2 targets and associated genes in GBM. Repression of EZH2 induced cell cycle arrest and inhibited tumor growth in vivo. This event represents a positive feedback loop with ?-catenin/TCF4 and STAT3 signaling. Taken together, EZH2 could be an independent prognostic factor and potential therapeutic target for GBM. PMID:25444902

Zhang, Junxia; Chen, Luyue; Han, Lei; Shi, Zhendong; Zhang, Jianning; Pu, Peiyu; Kang, Chunsheng

2015-01-28

200

FGF2 as a potential prognostic biomarker for proneural glioma patients.  

PubMed

Abstract Background. The survival of high-grade glioma patients is poor and the treatment of these patients can cause severe side effects. This fosters the necessity to identify prognostic biomarkers, in order to optimize treatment and diminish unnecessary suffering of patients. The aim of this study was to identify prognostic biomarkers for high-grade glioma patients. Methods. Eleven proteins were selected for analysis due to their suggested importance for survival of patients with other types of cancers and due to a high variation in protein levels between glioma patients (according to the Human Protein Atlas, www.proteinatlas.org ). Protein expression patterns of these 11 proteins were analyzed by immunohistochemistry in tumor samples from 97 high-grade glioma patients. The prognostic values of the proteins were analyzed with univariate and multivariate Cox regression analyses for the high-grade glioma patients, including subgroup analyses of histological subtypes and immunohistochemically defined molecular subtypes. Results. The proteins with the most significant (univariate and multivariate p < 0.05) correlations were analyzed further with cross-validated Kaplan-Meier analyses for the possibility of predicting survival based on the protein expression pattern of the corresponding candidate. Random Forest classification with variable subset selection was used to analyze if a protein signature consisting of any combination of the 11 proteins could predict survival for the high-grade glioma patients and the subgroup with glioblastoma patients. The proteins which correlated most significantly (univariate and multivariate p < 0.05) to survival in the Cox regression analyses were Myc for all high-grade gliomas and FGF2, CA9 and CD44 for the subgroup of proneural gliomas, with FGF2 having a strong negative predictive value for survival. No prognostic signature of the proteins could be found. Conclusion. FGF2 is a potential prognostic biomarker for proneural glioma patients, and warrants further investigation. PMID:25263081

Sooman, Linda; Freyhult, Eva; Jaiswal, Archita; Navani, Sanjay; Edqvist, Per-Henrik; Pontén, Fredrik; Tchougounova, Elena; Smits, Anja; Elsir, Tamador; Gullbo, Joachim; Lennartsson, Johan; Bergqvist, Michael; Ekman, Simon

2015-03-01

201

Prognostic factors in anal squamous carcinoma: a multivariate analysis of clinical, pathological and flow cytometric parameters in 235 cases.  

PubMed

Clinical, pathological and flow cytometric parameters have been analysed by univariate and multivariate analysis to define those parameters of important prognostic influence in 235 cases of surgically treated squamous carcinoma of the anus and perianal skin. Patients had been treated by anorectal excision (166 patients) or by local excision (69). Analyses were carried out on five data sets--the two surgical subgroups, two groups distinguished by site of tumour and on all 235 patients. Univariate analysis showed many parameters to be of prognostic influence, although histological typing of tumours into the more common histological subtypes was of no prognostic value. Parameters of independent prognostic significance in multivariate analysis were those indicating depth of spread, inguinal lymph node involvement and DNA-ploidy. In this study the subdivision of the rarer types of anal canal tumour, such as mucoepidermoid carcinoma, microcystic squamous carcinoma and small cell anaplastic carcinoma, was relevant confirming that these tumours have a poor prognosis. It is now felt that surgery should not be employed as primary treatment in most cases of anal cancer and the results of this study have to be interpreted with caution when applied to patients treated with radiotherapy with or without chemotherapy. Nevertheless, our findings suggest that the most useful prognostic information can be gleaned from accurate clinical staging and an assessment of DNA-ploidy status. PMID:2376397

Shepherd, N A; Scholefield, J H; Love, S B; England, J; Northover, J M

1990-06-01

202

Prognostic significance of spontaneous antibody responses against tumor-associated antigens in malignant melanoma patients.  

PubMed

Distribution, patterns and prognostic impact of spontaneous antibody responses against different tumor-associated antigens (TAAs) in malignant melanoma patients are unknown so far and were investigated in this study for the first time in a large cohort at different stages of the disease, identifying new prognostic biomarkers for malignant melanoma. Serum samples from 365 melanoma patients (97 Stage I melanoma patients, 87 Stage II, 92 Stage III and 89 Stage IV) and 100 age and gender matched healthy control donors were analyzed. Samples were drawn at the time of diagnosis (Stages I-III) or at time of diagnosis of distant metastasis (Stage IV). Applying a novel multiplex assay, humoral immune responses against 29 TAAs were determined and the association between response and patient survival was investigated. Antibody responses were mainly found in melanoma patients and all tested antigens elicited immune responses in all disease stages. Antibody responses against single antigens were either associated with poor prognosis and/or shorter progression-free survival (PFS) or had no influence. While in Stages I-III significant associations were observed between an antibody response and overall survival or PFS, among Stage IV patients, no significant association was found. Multivariate analyses identified specific humoral immune responses as prognostic factors independently of age, chemotherapy and immunotherapy. Antibody responses against specific TAA in Stage I-III melanoma patients correlate with poor prognosis and/or shorter PFS. These results may help to design clinical studies in order to evaluate the potential of these responses as prognostic serological biomarkers. PMID:24839182

Zörnig, Inka; Halama, Niels; Lorenzo Bermejo, Justo; Ziegelmeier, Claudia; Dickes, Elke; Migdoll, Alexander; Kaiser, Iris; Waterboer, Tim; Pawlita, Michael; Grabe, Niels; Ugurel, Selma; Schadendorf, Dirk; Falk, Christine; Eichmüller, Stefan B; Jäger, Dirk

2015-01-01

203

Fatal Prognostications and Messianic Faith: The Legend  

E-print Network

of the Catholic Monarchs Ángel Gómez Moreno Universidad Complutense July 26, 2011 To my friends at the University, the Great Captain, took over the city of Naples. At the same time, Ferdinand the Catholic decided in the European imagination thanks to works such as Historia Hierosolymitana 2 #12;Fatal Prognostications

Fiebig, Peter

204

A Neural Network Model for Prognostic Prediction  

Microsoft Academic Search

An important and difficult prediction taskin many domains, particularly medical decisionmaking, is that of prognosis. Prognosispresents a unique set of problems to alearning system when some of the outputsare unknown. This paper presents a new approachto prognostic prediction, using ideasfrom nonparametric statistics to fully utilizeall of the available information in a neural architecture.The technique is applied to breastcancer prognosis, resulting

1998-01-01

205

Systems Modeling for Prognostic Cancer Biology  

E-print Network

goal of this research is the development of personalized treatments in cancer, based on the genomic for various cancers, such as leukemia. In parallel with these efforts, cell line and mouse model experiments Systems Modeling for Prognostic Cancer Biology Xuefei Wang1 , BaiLian Li2 , Cheryl L. Willman

Maccabe, Barney

206

Discriminant analysis for helicopter rotor vibration prognostics  

Microsoft Academic Search

Traditionally, preventive maintenance has the drawback of being too expensive because of unnecessary replacements. Corrective maintenance involving replacement or repair after a failure is also expensive because of down time. In this paper, we present discriminant analysis and stepwise discriminant analysis for vibration prognostics. The goal is prediction of failures in drive train components of helicopters, specifically tail rotor drive

Ruben Avila; Pat Banerjee; D. He; E. Bechhoefer

2006-01-01

207

Prognostic Analysis of the Tactical Quiet Generator  

SciTech Connect

The U.S. Army needs prognostic analysis of mission-critical equipment to enable condition-based maintenance before failure. ORNL has developed and patented prognostic technology that quantifies condition change from noisy, multi-channel, time-serial data. This report describes an initial application of ORNL's prognostic technology to the Army's Tactical Quiet Generator (TQG), which is designed to operate continuously at 10 kW. Less-than-full power operation causes unburned fuel to accumulate on internal components, thereby degrading operation and eventually leading to failure. The first objective of this work was identification of easily-acquired, process-indicative data. Two types of appropriate data were identified, namely output-electrical current and voltage, plus tri-axial acceleration (vibration). The second objective of this work was data quality analysis to avoid the garbage-in-garbage-out syndrome. Quality analysis identified more than 10% of the current data as having consecutive values that are constant, or that saturate at an extreme value. Consequently, the electrical data were not analyzed further. The third objective was condition-change analysis to indicate operational stress under non-ideal operation and machine degradation in proportion to the operational stress. Application of ORNL's novel phase-space dissimilarity measures to the vibration power quantified the rising operational stress in direct proportion to the less-than-full-load power. We conclude that ORNL's technology is an excellent candidate to meet the U.S. Army's need for equipment prognostication.

Hively, Lee M [ORNL

2008-09-01

208

Prognostic factors in upper gastrointestinal bleeding  

Microsoft Academic Search

In this study we examined factors of possible prognostic value about outcome in a consecutive series of 2217 patients with hematemesis and melena. Death occurred in 189 (8.5%) patients, and 243 (11%) patients experienced rebleeding. Death was significantly associated with rebleeding, age over 60 years, and the finding of blood in the stomach at endoscopy. Rebleeding was significantly associated with

Bettina Katschinski; Richard Logan; Jackie Davies; Gail Faulkner; Jim Pearson; Michael Langman

1994-01-01

209

Sinonasal Tract Malignancies: Prognostic Factors and Surgery Outcomes  

PubMed Central

Background: Cancers of the sinonasal region are rare and its survival rate remains poor because most of the patients are asymptomatic and diagnosed in advanced stages with surrounding important structures. Objectives: This study attempted to analyze the clinical and histological features in addition to survival and prognostic factors of surgical treatment of sinonasal cancers. Patients and Methods: A retrospective cohort study, involving 36 patients with sinonasal cancer who were treated with surgery in our hospital between 2000 and 2010, was performed. Patients were selected based on the convenience sampling. Patients treated with radiotherapy and/or chemotherapy were excluded from the analysis. Clinical symptoms and histologic findings of patients as well as malignant tumor staging and its prognosis were collected from archives. Results: We found that overall 3 and 5-year survival rates of subjects were 52.8%, and 41.6%, respectively. There was a negative correlation between the clinical stage and survival. There was a significant difference between infrastructural and suprastructural localization in 5-year survival rate (P = 0.018). In the present study, there was a strong relationship between the local control and overall survival (P < 0.01). Overall 5-year survival rate was similar in patients both in the exenterated orbit and preserved orbit (P > 0.05). Conclusions: The present study has demonstrated that clinical stage, suprastructural tumor, and the presence of tumor- positive resection margins are the most significant prognostic factors affecting local tumor control and survival. As a result of this study, these tumors should be treated in early stages by surgical margin of resection followed by adjuvant radiotherapy. PMID:24693395

Bugra Cengiz, Abdurrahman; Uyar, Melek; Comert, Ela; Dursun, Engin; Eryilmaz, Adil

2013-01-01

210

Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma.  

PubMed

The aim of the present study was to determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). A retrospective chart review was performed for patients diagnosed with ICC between 2000 and 2009 at a single institution. We identified a total of 105 patients with ICC. Among them, 63.8% were older than 60 years of age, 50.5% were male and 88.6% were Caucasian. By preoperative imaging approximately half of the patients (50.5%) were surgical candidates and underwent resection. The other half of the patients (49.5%) were unresectable. The unresectable group received chemoradiotherapy (53%) and transarterial chemoembolization (7.7%) as palliative treatments while 23.0% of the patients (12/52) received best supportive care alone. The median survival rates were 16.1 months (13.1?19.2) for the entire cohort, 27.6 months (17.7-37.6) for curative resection, 12.9 months (6.5-19.2) for palliative chemoradiotherapy and 4.9 months (0.4-9.6) for best supportive care (p<0.001). Independent predictors on multivariate analysis were advanced stage at diagnosis and treatment received. In those patients who underwent resection, advanced AJCC stage and presence of microvascular invasion were also independent predictors of poor survival. We concluded that surgery offers the most beneficial curative option and outcome, emphasizing the importance of resectability as a major prognostic factor. The present study also revealed that use of chemoradiotherapy in the adjuvant setting failed to improve survival but its palliative use in those patients with unresectable ICC offered a modest survival advantage over best supportive care. The overriding factors influencing outcome were stage and the presence of microvascular invasion on pathology. PMID:23426976

Dhanasekaran, Renumathy; Hemming, Alan W; Zendejas, Ivan; George, Thomas; Nelson, David R; Soldevila-Pico, Consuelo; Firpi, Roberto J; Morelli, Giuseppe; Clark, Virginia; Cabrera, Roniel

2013-04-01

211

Are Poor Chinese Text Comprehenders Also Poor in Written Composition?  

ERIC Educational Resources Information Center

We studied the performance in three genres of Chinese written composition (narration, exposition, and argumentation) of 158 grade 4, 5, and 6 poor Chinese text comprehenders compared with 156 good Chinese text comprehenders. We examined text comprehension and written composition relationship. Verbal working memory (verbal span working memory and…

Guan, Connie Qun; Ye, Feifei; Meng, Wanjin; Leong, Che Kan

2013-01-01

212

Biological subtypes of breast cancer: Prognostic and therapeutic implications  

PubMed Central

Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors. PMID:25114856

Yersal, Ozlem; Barutca, Sabri

2014-01-01

213

EMMPRIN co-expressed with matrix metalloproteinases predicts poor prognosis in patients with osteosarcoma.  

PubMed

Several studies have focused on the relationships between the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and the prognosis of patients with malignant tumors. However, few of these have investigated the expression of EMMPRIN in osteosarcoma. We examined expression levels of EMMPRIN immunohistochemically in 53 cases of high-grade osteosarcoma of the extremities and analyzed the correlation of its expression with patient prognosis. The correlation between matrix metalloproteinases (MMPs) and EMMPRIN expression and the prognostic value of co-expression were also analyzed. Staining positivity for EMMPRIN was negative in 7 cases, low in 17, moderate in 19, and strong in 10. The overall and disease-free survivals (OS and DFS) in patients with higher EMMPRIN expression (strong-moderate) were significantly lower than those in the lower (weak-negative) group (0.037 and 0.024, respectively). In multivariate analysis, age (P=0.004), location (P=0.046), and EMMPRIN expression (P=0.038) were significant prognostic factors for overall survival. EMMPRIN expression (P=0.024) was also a significant prognostic factor for disease-free survival. Co-expression analyses of EMMPRIN and MMPs revealed that strong co-expression of EMMPRIN and membrane-type 1 (MT1)-MMP had a poor prognostic value (P=0.056 for DFS, P=0.006 for OS). EMMPRIN expression and co-expression with MMPs well predict the prognosis of patients with extremity osteosarcoma, making EMMPRIN a possible therapeutic target in these patients. PMID:24481662

Futamura, Naohisa; Nishida, Yoshihiro; Urakawa, Hiroshi; Kozawa, Eiji; Ikuta, Kunihiro; Hamada, Shunsuke; Ishiguro, Naoki

2014-06-01

214

The Biochemical Prognostic Factors of Subclinical Hypothyroidism  

PubMed Central

Background Patients with subclinical hypothyroidism (SHT) are common in clinical practice. However, the clinical significance of SHT, including prognosis, has not been established. Further clarifying SHT will be critical in devising a management plan and treatment guidelines for SHT patients. Thus, the aim of this study was to investigate the prognostic factors of SHT. Methods We reviewed the medical records of Korean patients who visited the endocrinology outpatient clinic of Severance Hospital from January 2008 to September 2012. Newly-diagnosed patients with SHT were selected and reviewed retrospectively. We compared two groups: the SHT maintenance group and the spontaneous improvement group. Results The SHT maintenance group and the spontaneous improvement group had initial thyroid-stimulating hormone (TSH) levels that were significantly different (P=0.035). In subanalysis for subjects with TSH levels between 5 to 10 µIU/mL, the spontaneous improvement group showed significantly lower antithyroid peroxidase antibody (anti-TPO-Ab) titer than the SHT maintenance group (P=0.039). Regarding lipid profiles, only triglyceride level, unlike total cholesterol and low density lipoprotein cholesterol, was related to TSH level, which is correlated with the severity of SHT. Diffuse thyroiditis on ultrasonography only contributed to the severity of SHT, not to the prognosis. High sensitivity C-reactive protein and urine iodine excretion, generally regarded as possible prognostic factors, did not show any significant relation with the prognosis and severity of SHT. Conclusion Only initial TSH level was a definite prognostic factor of SHT. TPO-Ab titer was also a helpful prognostic factor for SHT in cases with mildly elevated TSH. Other than TSH and TPO-Ab, we were unable to validate biochemical prognostic factors in this retrospective study for Korean SHT patients. PMID:25031888

Lee, Myung Won; Shin, Dong Yeob; Kim, Kwang Joon; Hwang, Sena

2014-01-01

215

Prognostic Relevance of Circulating Tumor Cells in Molecular Subtypes of Breast Cancer  

PubMed Central

Circulating tumor cells (CTCs) can be detected in the peripheral blood of breast cancer patients with early and metastatic disease. Recent data suggest that immune pathologic characteristics between the primary tumor, metastatic colonies and CTCs are discordant and that CTCs possess an independent phenotype that is associated with prognosis and treatment efficacy. Large scale gene expression analysis has provided the possibility to stratify breast cancer according to the gene expression fingerprint of primary tumor tissue into five intrinsic molecular subtypes which can be associated with different clinical outcome. As a consequence of the different prognostic power of primary tumors? characteristics and CTCs several groups have started to investigate if CTCs might be disseminated differentially within these breast cancer subtypes. They determined the CTC number in immunohistochemical subtypes to validate if CTCs may provide differential and more specific prognostic information within each subtype. This review provides an overview of the outcome of some recently published data gathered from early and metastatic breast cancer.

Banys-Paluchowski, M.; Schneck, H.; Blassl, C.; Schultz, S.; Meier-Stiegen, F.; Niederacher, D.; Krawczyk, N.; Ruckhaeberle, E.; Fehm, T.; Neubauer, H.

2015-01-01

216

Distributed Prognostic Health Management with Gaussian Process Regression  

NASA Technical Reports Server (NTRS)

Distributed prognostics architecture design is an enabling step for efficient implementation of health management systems. A major challenge encountered in such design is formulation of optimal distributed prognostics algorithms. In this paper. we present a distributed GPR based prognostics algorithm whose target platform is a wireless sensor network. In addition to challenges encountered in a distributed implementation, a wireless network poses constraints on communication patterns, thereby making the problem more challenging. The prognostics application that was used to demonstrate our new algorithms is battery prognostics. In order to present trade-offs within different prognostic approaches, we present comparison with the distributed implementation of a particle filter based prognostics for the same battery data.

Saha, Sankalita; Saha, Bhaskar; Saxena, Abhinav; Goebel, Kai Frank

2010-01-01

217

Metastatic Urothelial Cancer: Evaluation of Prognostic Factors and Change in Prognosis during the Last Twenty Years  

Microsoft Academic Search

Objective: This study was designed to establish prognostic factors for survival of patients with locally advanced or metastatic urothelial cancer. We have furthermore investigated changes in patient characteristics and treatment strategies during the last 20 years.Patients and Methods: Between 1992 and 1997, a total of 156 patients with newly diagnosed recurrent locally advanced disease (nonresectable, radioresistant) and/or metastatic transitional cell

Lisa Sengeløv; Claus Kamby; Hans von der Maase

2001-01-01

218

Prognostic Value of Discs Large Homolog 7 Transcript Levels in Prostate Cancer  

PubMed Central

Hypoxia has been associated with malignant progression, metastasis and resistance to therapy. Hence, we studied expression of hypoxia–regulated genes in 100 prostate cancer (CaP) bulk tissues and 71 adjacent benign tissues. We found 24 transcripts significantly overexpressed (p?0.02). Importantly, higher transcript levels of disc large (drosophila) homolog-associated protein 5 (DLGAP5)/discs large homolog 7 (DLG7)/hepatoma up-regulated protein (HURP), hyaluronan-mediated motility receptor (HMMR) and cyclin B1 (CCNB1) were associated with higher Gleason score and more advanced systemic progression. Since the products of HMMR and CCNB1 have been identified recently as molecular markers of CaP progression, we postulated that DLG7 has prognostic value too. To test this hypothesis, we measured transcript levels for DLG7 in a 150-pair case-control cohort. The cases (progression to systemic disease within six years of surgery) and controls (no progression within eight years) were matched for clinical and pathologic prognostic variables, including grade, stage, and preoperative serum levels of PSA. The overall prognostic ability of DLG7, as tested in receiver operating characteristic analysis was of 0.74 (95% CI, 0.68 to 0.8). Overall, our data indicate that expression of DLG7, a hypoxia-controlled gene, holds prognostic potential in high-risk CaP; this also demonstrates that variation of oxygen tension may constitute a tool for identification of novel biomarkers for CaP. PMID:24349376

Gomez, Christian R.; Kosari, Farhad; Munz, Jan-Marie; Schreiber, Claire A.; Knutson, Gaylord J.; Ida, Cristiane M.; El Khattouti, Abdelouahid; Karnes, R. Jeffrey; Cheville, John C.; Vasmatzis, George; Vuk-Pavlovi?, Stanimir

2013-01-01

219

Prospects for the Working Poor  

ERIC Educational Resources Information Center

Based on a chapter entitled "Barriers to Employment of the Disadvantaged by Martin Deutsch and S. M. Miller in "Manpower Report of the President, 1968. Discusses the Nixon proposals for remediating poverty in relation to the socioeconomic factors operating to maintain the condition of being poor while working. (JM)

Miller, S. M.

1970-01-01

220

Traumatic extremity arterial injury in children: Epidemiology, diagnostics, treatment and prognostic value of Mangled Extremity Severity Score  

Microsoft Academic Search

BACKGROUND: Traumatic paediatric arterial injuries are a great challenge due to low incidence and specific characteristics of paediatric anatomy and physiology. The aim of the present study was to investigate their epidemiology, diagnostic and therapeutic options and complications. Furthermore, the prognostic value of the Mangled Extremity Severity Score (MESS) was evaluated. METHODS: In a retrospective clinical study 44 children aged

Philipp Mommsen; Christian Zeckey; Frank Hildebrand; Michael Frink; Nawid Khaladj; Nadine Lange; Christian Krettek; Christian Probst

2010-01-01

221

Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia  

PubMed Central

Adult T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic tumor associated with poor outcome. In this study, we analyzed the prognostic relevance of genetic alterations, immunophenotypic markers, and microarray gene expression signatures in a panel of 53 adult T-ALL patients treated in the Eastern Cooperative Oncology Group E2993 clinical trial. An early immature gene expression signature, the absence of bi-allelic TCRG deletion, CD13 surface expression, heterozygous deletions of the short arm of chromosome 17, and mutations in IDH1/IDH2 and DNMT3A genes are associated with poor prognosis in this series. In contrast, expression of CD8 or CD62L, homozygous deletion of CDKN2A/CDKN2B, NOTCH1 and/or FBXW7 mutations, and mutations or deletions in the BCL11B tumor suppressor gene were associated with improved overall survival. Importantly, the prognostic relevance of CD13 expression and homozygous CDKN2A/CDKN2B deletions was restricted to cortical and mature T-ALLs. Conversely, mutations in IDH1/IDH2 and DNMT3A were specifically associated with poor outcome in early immature adult T-ALLs. This trial was registered at www.clinicaltrials.gov as #NCT00002514. PMID:23687089

Van Vlierberghe, Pieter; Ambesi-Impiombato, Alberto; De Keersmaecker, Kim; Hadler, Michael; Paietta, Elisabeth; Tallman, Martin S.; Rowe, Jacob M.; Forne, Carles; Rue, Montserrat

2013-01-01

222

Are poor Chinese text comprehenders also poor in written composition?  

PubMed

We studied the performance in three genres of Chinese written composition (narration, exposition, and argumentation) of 158 grade 4, 5, and 6 poor Chinese text comprehenders compared with 156 good Chinese text comprehenders. We examined text comprehension and written composition relationship. Verbal working memory (verbal span working memory and operation span working memory) and different levels of linguistic tasks-morphological sensitivity (morphological compounding and morphological chain), sentence processing (syntax construction and syntax integrity), and text comprehension (narrative and expository texts)-were used to predict separately narrative, expository, and argumentation written compositions in these students. Grade for grade, the good text comprehenders outperformed the poor text comprehenders in all tasks, except for morphological chain. Hierarchical multiple regression analyses showed differential contribution of the tasks to different genres of writing. In particular, text comprehension made unique contribution to argumentation writing in the poor text comprehenders. Future studies should ask students to read and write parallel passages in the same genre for better comparison and incorporate both instructional and motivational variables. PMID:23666849

Guan, Connie Qun; Ye, Feifei; Meng, Wanjin; Leong, Che Kan

2013-10-01

223

High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients  

PubMed Central

SIRT1, a NAD+ dependent class III deacetylase, takes part in many important biological processes. Previous studies show that SIRT1 is overexpressed in some cancers and plays an essential role in tumorigenesis. However, the association between SIRT1 and colorectal cancer (CRC) is still unclear. We found that many CRC specimens had strong SIRT1 expression, which had an obvious correlation with poor prognosis of CRC patients. Meanwhile, SIRT1 expression had a co-localization with CD133, a current universal marker to characterize colorectal cancer stem cells (CSCs). In vitro studies also revealed that SIRT1 was overexpressed in colorectal CSC-like cells. Moreover, SIRT1 deficiency decreased percentage of CD133+ cells, attenuated the abilities of colony and sphere formation, and inhibited tumorigenicity in vivo in CRC cells. Further study demonstrated that the expressions of several stemness-associated genes, including Oct4, Nanog, Cripto, Tert and Lin28, were reduced by SIRT1 knockdown in CRC cells. Taken together, our findings suggest that SIRT1 plays a crucial role in keeping the characteristics of CSCs cells. SIRT1 is a potential independent prognostic factor of CRC patients after tumor resection with curative intent, and will contribute to providing a promising new approach to target at CSCs in CRC treatment. PMID:25500546

Chen, Xiaojing; Sun, Kai; Jiao, Shufan; Cai, Ning; Zhao, Xue; Zou, Hanbing; Xie, Yuexia; Wang, Zhengshi; Zhong, Ming; Wei, Lixin

2014-01-01

224

What Number of Oocytes Is Appropriate for Defining Poor Ovarian Response?  

PubMed Central

Purpose This study attempted to derive an objective and sophisticated definition of poor ovarian response (POR). Materials and Methods A total of 176 consecutive in vitro fertilization (IVF) cycles (137 patients) with conventional ovarian stimulation during 2009 to 2012 were studied by retrospective analysis. Optimal oocyte number (total or mature) was determined by statistics-based (distribution of oocyte number) and prognosis-based approaches (prediction for IVF outcome). Receiver operating characteristics curve analysis was used to show what number of oocytes could predict IVF pregnancy and whether clinical and laboratory variables could predict newly defined POR. Results The 25th percentile of the distribution corresponded to total oocytes ?2 and mature oocyte ?1. The cut-off values for the prediction of IVF outcomes were total oocytes >5 and mature oocyte >1. Considering the incidence of POR (34.1%), a reasonable definition of POR was decided as total oocytes ?2 or mature oocyte ?1. For the prediction of this new definition, the extreme cut-off value (by setting a false positive rate of 5%) of serum anti-Mullerian hormone (AMH) was ?0.76 ng/mL, which was better than serum follicle stimulating hormone or age. A new simple definition of POR was derived as total oocytes ?2 or mature oocyte ?1 in a previous cycle or a serum AMH level of ?0.76 ng/mL. When this simple criterion was re-applied to our data, the predictive performance was similar to the Bologna criteria. Conclusion We here propose a new definition of POR, which is simple and supported by statistical and prognostic analyses. PMID:25683999

Kim, Seul Ki; Lee, Jung Ryeol; Suh, Chang Suk; Kim, Seok Hyun

2015-01-01

225

Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis  

PubMed Central

Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan–Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor. PMID:25197383

Kim, Sang Kyum; Song, Si Young; Kim, Sunghoon; Cho, Nam Hoon; Yim, Ga Won; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji

2014-01-01

226

Prognostic Significance and Treatment Implications of Minimal Residual Disease Studies in Philadelphia-Negative Adult Acute Lymphoblastic Leukemia  

PubMed Central

Acute lymphoblastic leukemia (ALL) is curable in about 40–50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates. PMID:25237475

Spinelli, Orietta; Tosi, Manuela; Peruta, Barbara; Montalvo, Marie Lorena Guinea; Maino, Elena; Scattolin, Anna Maria; Parolini, Margherita; Viero, Piera; Rambaldi, Alessandro; Bassan, Renato

2014-01-01

227

Distinct distribution and prognostic significance of molecular subtypes of breast cancer in Chinese women: a population-based cohort study  

Microsoft Academic Search

Background  Molecular classification of breast cancer is an important prognostic factor. The distribution of molecular subtypes of breast\\u000a cancer and their prognostic value has not been well documented in Asians.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 2,791 breast cancer patients recruited for a population-based cohort study were evaluated for molecular subtypes\\u000a of breast cancer by immunohistochemical assays. Data on clinicopathological characteristics were confirmed by

Yinghao Su; Ying Zheng; Wei Zheng; Kai Gu; Zhi Chen; Guoliang Li; Qiuyin Cai; Wei Lu; Xiao Ou Shu

2011-01-01

228

Meta-analysis confirms BCL2 is an independent prognostic marker in breast Cancer  

E-print Network

and poor prognostic groups independently of currently used standards or markers at stringent levels of statistical significance. With this in mind, we recently evaluated a findings in a second consecutive series of 983 cases on a tissue micro-array (TMA... / Abstract])' and also '(bcl-2 and breast) AND (incidence [MeSH:noexp] OR mortality [MeSH Terms] OR follow up studies [MeSH:noexp] OR prognos* [Title/Abstract] OR predict* [Title/Abstract] OR course* [Text Word])' limited to the English language. Three...

Callagy, Grace M; Webber, Mark J; Pharoah, Paul D P; Caldas, Carlos

2008-05-29

229

A Supervised Network Analysis on Gene Expression Profiles of Breast Tumors Predicts a 41-Gene Prognostic Signature of the Transcription Factor MYB across Molecular Subtypes  

PubMed Central

Background. MYB is predicted to be a favorable prognostic predictor in a breast cancer population. We proposed to find the inferred mechanism(s) relevant to the prognostic features of MYB via a supervised network analysis. Methods. Both coefficient of intrinsic dependence (CID) and Galton Pierson's correlation coefficient (GPCC) were combined and designated as CIDUGPCC. It is for the univariate network analysis. Multivariate CID is for the multivariate network analysis. Other analyses using bioinformatic tools and statistical methods are included. Results. ARNT2 is predicted to be the essential gene partner of MYB. We classified four prognostic relevant gene subpools in three breast cancer cohorts as feature types I–IV. Only the probes in feature type II are the potential prognostic feature of MYB. Moreover, we further validated 41 prognosis relevant probes to be the favorable prognostic signature. Surprisingly, two additional family members of MYB are elevated to promote poor prognosis when both levels of MYB and ARNT2 decline. Both MYBL1 and MYBL2 may partially decrease the tumor suppressive activities that are predicted to be up-regulated by MYB and ARNT2. Conclusions. The major prognostic feature of MYB is predicted to be determined by the MYB subnetwork (41 probes) that is relevant across subtypes. PMID:24639887

Liu, Li-Yu D.; Chang, Li-Yun; Kuo, Wen-Hung; Hwa, Hsiao-Lin; Chang, King-Jen; Hsieh, Fon-Jou

2014-01-01

230

Seven poor clusters of galaxies  

NASA Technical Reports Server (NTRS)

The measurement of 83 new redshifts from galaxies in the region of seven of the poor clusters of galaxies identified by Morgan et al (1975) and Albert et al (1977) has been followed by an estimation of cluster masses through the application of both the virial theorem and the projected mas method. For each system, these two estimates are consistent. For the two clusters with highest X-ray luminosities, the line-of-sight velocity dispersions are about 700 km/sec, while for the five other clusters, the dispersions are of the order of less than about 370 km/sec. The D or cD galaxy in each poor cluster is at the kinematic center of each system.

Beers, T. C.; Geller, M. J.; Huchra, J. P.; Latham, D. W.; Davis, R. J.

1984-01-01

231

The Poor Cartographer: Graph Coloring  

NSDL National Science Digital Library

In this activity, learners help a poor cartographer color in the countries on a map, making sure each country is colored a different color than any of its neighbors. Through this exercise, learners discover the "has-to-be" rule and the value of place-holders. This activity reveals the complexity of graph coloring algorithms in computer science. Variations, extensions, background information, and solutions are included in the PDF.

Tim Bell

1995-01-01

232

Stage-specific prognostic biomarkers in melanoma.  

PubMed

The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities. PMID:25784655

Cheng, Yabin; Lu, Jing; Chen, Guangdi; Ardekani, Gholamreza Safaee; Rotte, Anand; Martinka, Magdalena; Xu, Xuezhu; McElwee, Kevin J; Zhang, Guohong; Zhou, Youwen

2015-02-28

233

Cancer Patients’ Understanding of Prognostic Information  

PubMed Central

Prognostic information is necessary for cancer patients to be fully informed about the likely course of their disease. This information is needed for practical planning and treatment decisions. This study sought to examine how cancer patients understand the prognosis information available to them. The setting is an urban safety net hospital. Six focus groups with cancer patients (N=39) were digitally recorded and transcribed verbatim then analyzed using phases of content analysis. Participants in all groups discussed the prognosis almost exclusively in terms of mortality and reported that their physicians and nurses mostly provided prognostic information in terms of months or years for survival. This finding held across all cancer types and stages. Patients tend to think of prognosis information as being only estimated limited survival and find the idea upsetting. Due to this view on prognosis, patients need further explanation regarding where the prognosis information comes from and what prognostic information can tell them in order to make use of it. PMID:24402976

Dumenci, Levent; Siminoff, Laura A.; Matsuyama, Robin K.

2014-01-01

234

Prognostic factors for surgically managed patients with stage II non-small cell lung cancer  

PubMed Central

Background: To investigate the prognostic factors in surgically managed patients with stage II non-small cell lung cancer. Material and methods: A retrospective analysis of clinical data of surgically managed 93 patients with stage II non-small cell lung cancer in our hospital between May 2005 and November 2009 was conducted, and prognostic factors that may impact the postoperative 5-year survival rate were statistically analyzed. Results: Univariable survival analysis showed that new TNM staging, total number of dissected lymph nodes, number of dissected N1 and N2 lymph nodes and N1 lymph groups, metastasis rate of N1 lymph nodes, and 10th group of lymph nodes metastatic or not, were related to the postoperative 5-year survival rate in the patients. Multivariable survival analysis showed that the metastasis rate of N1 lymph nodes and 10th group of lymph nodes metastatic or not were independent prognostic factors for the postoperative 5-year survival rate in the patients. Conclusion: When patients with stage II non-small cell lung cancer are treated with surgery, the total number of dissected lymph nodes greater than 6, the number of dissected N1 lymph nodes over 5, N2 over 2, and the number of dissected N1 groups over 3, may improve their postoperative 5-year survival rate. The metastasis rate of N1 lymph nodes over 50%, and the metastasis of the 10th group of lymph nodes imply poor prognosis of the patients.

Wang, Liming; Liu, Yang; Xu, Shun

2015-01-01

235

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management  

SciTech Connect

For 43 medulloblatoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage, M-stage and histopathologic tumor score. Posterior fossa local control rates were also function of T-stage and TS. Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group, increasing the irradiation dose alone may improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.

Kopelson, G.; Linggood, R.M.; Kleinman, G.M.

1983-01-15

236

Drug holiday as a prognostic factor of medication-related osteonecrosis of the jaw  

PubMed Central

Objectives To identify post-treatment prognostic factors for medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods We evaluated 54 MRONJ patients who visited the Department of Dentistry, Ajou University Hospital, from May 2007 to March 2014. Twenty-one patients were surgically managed with debridement or sequestrectomy and 33 patients were conservatively managed using antibiotics. Correlations of age, sex, stage, bisphosphonate duration and type, and drug holiday with the prognosis of MRONJ were investigated. Correlations were verified by logistic regression analysis and t-tests with a significance level of 0.05. Results Clinical outcomes were evaluated on the basis of both clinical and radiographic findings. Twelve out of 21 surgically managed patients showed a favorable prognosis and nine patients relapsed. Thirty-one of the 33 conservatively managed patients showed no specific change in prognosis, and two patients worsened. Statistical analyses of the conservative management group did not reveal any correlation of the above factors with the prognosis of conservative management. Drug holiday was the only prognostic factor in the surgical management group (P=0.031 in logistic regression analysis, P=0.004 in t-test). Conclusion Drug holiday is a prognostic factor in the surgical management of MRONJ. Because the drug holiday in the patients of the poor prognosis group occurred 1.5 to 4 months prior to surgical management, we recommend a drug holiday more than 4 months before surgery. PMID:25368832

Kim, Yoon Ho; Lee, Ho Kyung; Song, Seung Il

2014-01-01

237

IMP3, a Promising Prognostic Marker in Clear Cell Renal Cell Carcinoma  

PubMed Central

Background Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported as a prognostic biomarker in various cancers. To validate IMP3 as a prognostic biomarker in renal cell carcinoma (RCC), we investigated the expression of IMP3, p53, and Ki-67, and their associations with clinicopathologic outcomes. Methods We studied 148 clear cell RCCs (CCRCCs) from patients who underwent radical nephrectomy. The expression levels of IMP3, p53, and Ki-67 were assessed by immunohistochemical staining and the clinical and pathologic parameters were retrospectively reviewed. Results Twenty-nine percent of CCRCCs expressed IMP3. Forty-one percent of IMP3-immunopositive tumors developed metastases, while only 11.4% of IMP3-negative tumors developed metastases (p<.001). A Kaplan-Meier curve showed that patients with IMP3-immunopositive tumors had lower metastasis-free survival and cancer-specific survival than did those with IMP3-immunonegative tumors (p<.001 and p<.001, respectively). Expression of high Ki-67 proliferation index was also associated with a higher metastatic rate. In the multivariate Cox regression analysis, pT stage and IMP3-positivity were independently associated with disease-specific survival. Conclusions IMP3 is an independent prognostic biomarker for patients with CCRCC to predict metastasis and poor outcome. PMID:24868223

Park, Ji Young; Kang, Yuna; Lee, Sang Sook

2014-01-01

238

Survival and prognostic factors in Malaysian acute myeloid leukemia patients after allogeneic haematopoietic stem cell transplantation.  

PubMed

Studies of survival outcomes in acute myeloid leukemia (AML) patients treated with allogeneic haematopoietic stem cell transplantation (HSCT) are essential for planning patient care. The objectives of the present study were to determine overall survival (OS) and disease-free survival (DFS) in AML patients treated with allogeneic HSCT, and to identify prognostic factors associated with poor outcome. This study was conducted retrospectively, using data from the Blood and Bone Marrow Transplant, National Transplant Registry, Malaysia. All cases of AML treated with allogeneic HSCT registered at the registry between 1st January 1987 and 31st December 2010 were included in the study. A total of 300 patients were included for final analysis. The Kaplan-Meier method and Cox proportional hazard regression were used for statistical analysis. The overall 10-year OS and DFS for Malaysian AML patients after allogeneic HSCT were 63 and 67 %, respectively. Donor gender, marrow status, and conditioning intensity were identified as important prognostic factors for overall survival, whereas the significant prognostic factors for disease-free survival were ethnic group, donor gender, marrow status, and conditioning intensity. In conclusion, the survival outcomes for Malaysian AML patients treated with allogeneic HSCT were good, and this treatment should be considered the standard therapeutic approach for suitable candidates. PMID:23719676

Mangantig, Ernest; Naing, Nyi Nyi; Norsa'adah, Bachok; Azlan, Husin

2013-08-01

239

Promoter DNA Methylation Pattern Identifies Prognostic Subgroups in Childhood T-Cell Acute Lymphoblastic Leukemia  

PubMed Central

Background Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. Design and Methods Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n?=?43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n?=?32). Results Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP? (low methylation). CIMP? T-ALL patients had significantly worse overall and event free survival (p?=?0.02 and p?=?0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. Conclusions We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL. PMID:23762353

Borssén, Magnus; Palmqvist, Lars; Karrman, Kristina; Abrahamsson, Jonas; Behrendtz, Mikael; Heldrup, Jesper; Forestier, Erik; Roos, Göran; Degerman, Sofie

2013-01-01

240

Prognostic Impact of Hypoxia-Inducible miRNA-210 in Patients with Lung Adenocarcinoma  

PubMed Central

Objective. The aim of this study was to investigate the prognostic value of MicroRNA-210 (miR-210) expression in patients with non-small-cell lung cancer (NSCLC). Methods. We examined the miR-210 expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship between miR-210 expression and clinicopathological factors as well as histological subtype was statistically analyzed. Results. miR-210 expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found between miR-210 expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated that miR-210 expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma. Conclusions. We showed that miR-210 may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma. PMID:25733977

Osugi, Jun; Kimura, Yuka; Owada, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Muto, Satoshi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Yonechi, Athushi; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Suzuki, Hiroyuki; Gotoh, Mitsukazu

2015-01-01

241

Prognostic and predictive response factors in colorectal cancer patients: Between hope and reality  

PubMed Central

Colorectal cancer (CRC) represents one of the most commonly diagnosed cancers worldwide. It is the second leading cause of cancer death in Western Countries. In the last decade the survival of patients with metastatic CRC has improved dramatically. Due to the advent of new drugs (irinotecan and oxaliplatin) and target therapies (i.e., bevacizumab, cetuximab and panitumab), the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently. Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy. Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings, and a greater emphasis on early detection, the outlook still remains poor for most patients. Molecular analyses have shown that the natural history of all CRCs is not the same. Individual patients with same stage tumours may have different long term prognosis and response to therapy. In addition, some prognostic variables are likely to be more important than others. Here we review the role of prognostic factors and predictive factors according to the recently published English literature. PMID:25386053

De Divitiis, Chiara; Nasti, Guglielmo; Montano, Massimo; Fisichella, Rossella; Iaffaioli, Rosario Vincenzo; Berretta, Massimiliano

2014-01-01

242

Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC  

PubMed Central

Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic modification in human cancer. Thus, detection of aberrant gene promoter methylation as a tool for diagnosis of tumors or as a prognostic marker has been widely described for many types of cancers, including nonsmall cell lung cancer (NSCLC). Emerging evidence indicates that CDH13 is a candidate tumor suppressor in several types of human tumors, including NSCLC. However, the correlation between CDH13 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In the current study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 803 NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, with the pooled odds ratio (OR) from seven studies including 448 NSCLC and 345 normal lung tissue (OR, 7.85; 95% confidence interval, 5.12–12.03; P<0.00001). CDH13 hypermethylation was also associated with pathological types. The pooled OR was obtained from four studies, including 111 squamous cell carcinoma and 106 adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19–0.66; P=0.001), which indicated that CDH13 hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13 hypermethylation had a lower survival rate than those without CDH13 hypermethylation. In addition, CDH13 mRNA high expression was found to correlate with better overall survival for all NSCLC patients followed for 20 years (hazard ratio, 0.81; P=0.0056). Interestingly, CDH13 mRNA overexpression was found to correlate with better overall survival only in adenocarcinoma patients (hazard ratio, 0.42; P=9.6e–09), not in squamous cell carcinoma patients (hazard ratio, 0.93; P=0.59). The results of this meta-analysis suggest that CDH13 hypermethylation is associated with an increased risk and worse survival in NSCLC. CDH13 hypermethylation and mRNA expression play an important role in carcinogenesis, progression, and development, as well as clinical outcomes. PMID:25382980

Xue, Ruilin; Yang, Cuili; Zhao, Fang; Li, Dejia

2014-01-01

243

Decreased semaphorin 3A expression is associated with a poor prognosis in patients with epithelial ovarian carcinoma.  

PubMed

Semaphorin 3A (SEMA3A) was initially identified to play an important role in axonal guidance. Recently, SEMA3A has also been considered as a candidate tumor suppressor, since it is often downregulated in numerous types of cancer, including prostate cancer, breast cancer and glioma. However, the biological role of SEMA3A in ovarian cancer is not clear. In the present study, the expression of SEMA3A in ovarian cancer and normal ovarian epithelial tissues was detected by immunofluorescence, reverse transcription?quantitative polymerase chain reaction (RT?qPCR) and western blotting, and the associations between the expression of SEMA3A with the development of ovarian cancer, clinicopathological characteristics and survival were also analyzed. Results from immunofluorescence, RT?qPCR and western blotting showed that SEMA3A is significantly downregulated in epithelial ovarian carcinoma compared to normal ovarian epithelial specimens (P<0.05). The expression levels of SEMA3A were lower in the cancer tissues with III/IV stage [the International Federation of Gynecology and Obstetrics (FIGO) stage], poor histological grade, lymph node metastasis and distant metastasis compared to that in the cancer tissues with I/II stage (FIGO), well histological grade, or without lymph node metastasis and distant metastasis (P<0.05). A decreased expression of SEMA3A is associated with a poor prognosis (P<0.001). The present findings suggest that decreased SEMA3A expression may be associated with the development of epithelial ovarian carcinoma, and therefore, SEMA3A may be a valuable prognostic marker, as well as a potential molecular therapy target for ovarian cancer patients. PMID:25812535

Jiang, Haiyan; Qi, Lei; Wang, Feiran; Sun, Zhichao; Huang, Zhongwei; Xi, Qinghua

2015-05-01

244

Neurofascin IgG4 antibodies in CIDP associate with disabling tremor and poor response to IVIg  

PubMed Central

Objective: To describe the frequency of antibodies against neurofascin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and the associated clinical features. Methods: Immunocytochemistry was used to identify antibodies to neurofascin 155 (NF155) and 186. Serum reactivity with paranodes and brain tissue was tested with immunohistochemistry of teased-nerve fibers and rat brain. Antibody titers and immunoglobulin (Ig) G isotypes were determined using ELISA. Clinical information was obtained retrospectively. Results: Two of 53 patients, but none of 204 controls, had antibodies to NF155 (p = 0.041). The 2 patients with NF155 antibodies developed severe polyradiculoneuropathy with predominant distal weakness that was refractory to IVIg. Eight additional patients with IVIg-refractory CIDP were then identified from a national database; 2 of them with the same clinical features also had NF155 antibodies. Overall, 3 of the 4 patients with NF155 antibodies had a disabling and characteristic tremor (high amplitude, low frequency, postural, and intention). Patients' antibodies reacted with the paranodes in teased-nerve fibers and with the neuropil of rat cerebellum, brain, and brainstem. Anti-NF155 antibodies were predominantly of the IgG4 isotype in all patients. Conclusion: Patients with CIDP positive for IgG4 NF155 antibodies constitute a specific subgroup with a severe phenotype, poor response to IVIg, and disabling tremor. Autoantibodies against paranodal structures associate with distinct clinical features in CIDP and their identification has diagnostic, prognostic, and therapeutic implications. Classification of evidence: This study provides Class IV evidence that autoantibodies to NF155 identify a CIDP subtype characterized by severe neuropathy, poor response to IVIg, and disabling tremor. PMID:24523485

Querol, Luis; Nogales-Gadea, Gisela; Rojas-Garcia, Ricardo; Diaz-Manera, Jordi; Pardo, Julio; Ortega-Moreno, Angel; Sedano, Maria Jose; Gallardo, Eduard; Berciano, Jose; Blesa, Rafael; Dalmau, Josep

2014-01-01

245

Stanniocalcin 2 expression predicts poor prognosis of hepatocellular carcinoma  

PubMed Central

Previous studies have shown that the expression level of stanniocalcin 2 (STC2) is associated with tumor progression. However, to date, the association between STC2 and clinicopathological factors in hepatocellular carcinoma (HCC) has not been investigated. The clinical significance of STC2 was investigated in 30 fresh HCC samples using western blot analysis and in 240 HCC tissues using immunohistochemical analysis. The level of STC2 in cancerous tissue was higher than in the matched non-cancerous tissues. Using immunohistochemistry, the STC2-positive group exhibited a higher incidence of lymph node metastasis and venous invasion compared with the STC2-negative group. Kaplan-Meier survival analysis revealed that the positive expression of STC2 correlated with poor overall survival (OS) and disease-free survival of HCC patients (P<0.01). STC2 expression was observed to be an independent prognostic factor for OS in HCC patients by multivariate analysis (hazard ratio, 2.39; 95% confidence interval, 1.04–5.89; P=0.013). These data suggest that STC2 expression may be a useful indicator of poor prognosis in HCC patients. PMID:25289096

ZHANG, ZHEN-HAI; WU, YA-GUANG; QIN, CHENG-KUN; RONG, ZHONG-HOU; SU, ZHONG-XUE; XIAN, GUO-ZHE

2014-01-01

246

Prognostic Impact of the 6th and 7th American Joint Committee on Cancer TNM Staging Systems on Esophageal Cancer Patients Treated With Chemoradiotherapy  

SciTech Connect

Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.

Nomura, Motoo, E-mail: excell@hkg.odn.ne.jp [Department of Clinical Oncology, Aichi Cancer Center Hospital (Japan); Department of Radiation Oncology, Aichi Cancer Center Hospital (Japan); Shitara, Kohei [Department of Clinical Oncology, Aichi Cancer Center Hospital (Japan); Kodaira, Takeshi [Department of Radiation Oncology, Aichi Cancer Center Hospital (Japan); Hatooka, Shunzo [Department of Thoracic Surgery, Aichi Cancer Center Hospital (Japan); Mizota, Ayako; Kondoh, Chihiro; Yokota, Tomoya; Takahari, Daisuke; Ura, Takashi; Muro, Kei [Department of Clinical Oncology, Aichi Cancer Center Hospital (Japan)

2012-02-01

247

Direct multiangle solution for poorly stratified atmospheres.  

PubMed

The direct multiangle solution is considered, which allows improving the scanning lidar-data-inversion accuracy when the requirement of the horizontally stratified atmosphere is poorly met. The signal measured at zenith or close to zenith is used as a core source for extracting optical characteristics of the atmospheric aerosol loading. The multiangle signals are used as auxiliary data to extract the vertical transmittance profile from the zenith signal. Details of the retrieval methodology are considered that eliminate, or at least soften, some specific ambiguities in the multiangle measurements in horizontally heterogeneous atmospheres. Simulated and experimental elastic lidar data are presented that illustrate the essentials of the data-processing technique. Finally, the prospects of the utilization of high-spectral-resolution lidar in the multiangle mode are discussed. PMID:22945162

Kovalev, Vladimir; Wold, Cyle; Petkov, Alexander; Hao, Wei Min

2012-09-01

248

Periostin is a new potential prognostic biomarker for glioma.  

PubMed

The objective of this study is to investigate the expression level of periostin in cancer stem cells as well as in the glioma tissues and the relationship between periostin expression and clinical and pathological characteristics and prognosis of gliomas. ESA+/CD133+/lin- tumor cells were selected by flow cytometry from glioma tissues, and the periostin expression in ESA+/CD133+/lin- tumor cells and non-ESA+/CD133+/lin- tumor cells was detected by quantitative real-time polymerase chain reaction (RT-PCR) and Western blot analysis. The expression status of periostin in glioma tissues was analyzed by immunohistochemistry staining, and the relationship between periostin and clinicopathological parameters of gliomas was determined. It showed that periostin is expressed higher in ESA+/CD133+/lin- tumor cells compared to non-ESA+/CD133+/lin- tumor cells in both mRNA and protein levels. One hundred eighteen (37.82 %) glioma patients were observed with highly expressed periostin protein in immunohistochemistry. Moreover, we observed that the expression of periostin protein was related to Karnofsky performance scale score (KPS), extent of resection, Ki67, and WHO grade of gliomas in universal analysis (P=0.008, 0.045, 0.001, and 0.001, respectively). However, only WHO grade was identified to be related to periostin expression in gliomas after multivariate analysis. After survival analysis, the cases with highly expressed periostin protein attained a significantly poorer postoperative disease-specific survival and distant metastasis than those with none/low expressed periostin protein (P=0.001 and 0.002). In the Cox regression test, KPS, extent of resection, Ki67, WHO grade, and periostin were detected as the independent prognostic factors (P=0.008, 0.007, 0.032, 0.001, and 0.001, respectively). Periostin can be an important prognostic marker for gliomas, which may present a new therapeutic target for glioma patients. PMID:24719188

Tian, Buxian; Zhang, Yuhong; Zhang, Jing

2014-06-01

249

Bcl2 and Ki67 refine prognostication in luminal breast cancers.  

PubMed

Combined B-cell lymphoma 2 (Bcl2) and Ki67 expression for breast cancer prognostication has been proposed recently. However, the combinatorial relationship with patient outcome, clinico-pathologic features, and various biomarkers has not been fully explored. Bcl2 and Ki67 expression were examined in a large cohort of breast cancers. Differential Bcl2 and Ki67 combinatorial analysis, particularly in luminal cancers, were evaluated with respect to the clinico-pathologic features, biomarkers profile and outcome. Combined Bcl2/Ki67 phenotypes classified by Bcl2 and Ki67 cutoffs showed a better correlation with outcome. Multivariate analysis revealed this to be an independent prognostic factor in luminal cancers. Both Ki67 and Bcl2 contributed to the prognostic implications of different subgroups defined by Bcl2/Ki67 combination phenotypes with clinico-pathologic features and biomarkers profile. Ki67low/Bcl2high cases showed better DFS (HR = 2.17, P = 0.015) and OS (HR = 3.217, P = 0.015) compared to Ki67high/Bcl2low cases. Interestingly, Ki67low/Bcl2high cases also showed better outcome than other phenotypes in grade 2 cancers (log-rank = 4.844, P = 0.028) and TNM stage 2 cancers (log-rank = 8.161, P = 0.004). This classification by Bcl2/Ki67 combination phenotypes, together with PR expression, can also refine luminal A cancers prognostication. Not all PR low luminal A cases had poorer outcome compared to the PR high luminal A cases; poor prognosis was only limited to those with also low Bcl2 (log-rank = 23.568, P < 0.001 compared to PR high Bcl2 high cases). The combined Ki67/Bcl2 phenotyping was useful in luminal cancers prognostication. It also refined prognostication in intermediate groups (grade 2 and stage 2 cancers) of luminal cancers; and aided in further classification of luminal A cancers. PMID:25648135

Chen, Lin-Ying; Tsang, Julia Y S; Ni, Yun-Bi; Chan, Siu-Ki; Chan, Kui-Fat; Zhang, Sheng; Tse, Gary M

2015-02-01

250

The Royal Free Hospital Score: A Calibrated Prognostic Model for Patients With Cirrhosis Admitted to Intensive Care Unit. Comparison With Current Models and CLIF-SOFA Score  

PubMed Central

OBJECTIVES: Prognosis for patients with cirrhosis admitted to intensive care unit (ICU) is poor. ICU prognostic models are more accurate than liver-specific models. We identified predictors of mortality, developed a novel prognostic score (Royal Free Hospital (RFH) score), and tested it against established prognostic models and the yet unvalidated Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) model. METHODS: Predictors of mortality were defined by logistic regression in a cohort of 635 consecutive patients with cirrhosis admitted to ICU (1989–2012). The RFH score was derived using a 75% training and 25% validation set. Predictive accuracy and calibration were evaluated using area under the receiver operating characteristic (AUROC) and goodness-of-fit ?2 for the RFH score, as well as for SOFA, Model for End-Stage Liver Disease (MELD), Acute Physiology and Chronic Health Evaluation (APACHE II), and Child-Pugh. CLIF-SOFA was applied to a recent subset (2005–2012) of patients. RESULTS: In-hospital mortality was 52.3%. Mortality improved over time but with a corresponding reduction in acuity of illness on admission. Predictors of mortality in training set, which constituted the RFH score, were the following: bilirubin, international normalized ratio, lactate, alveolar arterial partial pressure oxygen gradient, urea, while variceal bleeding as indication for admission conferred lesser risk. Classification accuracy was 73.4% in training and 76.7% in validation sample and did not change significantly across different eras of admission. The AUROC for the derived model was 0.83 and the goodness-of-fit ?2 was 3.74 (P=0.88). AUROC for SOFA was 0.81, MELD was 0.79, APACHE II was 0.78, and Child-Pugh was 0.67. In 2005–2012 cohort, AUROC was: SOFA: 0.74, CLIF-SOFA: 0.75, and RFH: 0.78. Goodness-of-fit ?2 was: SOFA: 6.21 (P=0.63), CLIF-SOFA: 9.18 (P=0.33), and RFH: 2.91 (P=0.94). CONCLUSIONS: RFH score demonstrated good discriminative ability and calibration. Internal validation supports its generalizability. CLIF-SOFA did not perform better than RFH and the original SOFA. External validation of our model should be undertaken to confirm its clinical utility. PMID:24492755

Theocharidou, Eleni; Pieri, Giulia; Mohammad, Ali Omar; Cheung, Michelle; Cholongitas, Evangelos; Banwari, Agarwal; Burroughs, Andrew K

2014-01-01

251

Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy  

ERIC Educational Resources Information Center

Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

2007-01-01

252

Outcome and Prognostic Factors of Radiation Therapy for Medulloblastoma  

SciTech Connect

Purpose: To investigate treatment outcome and prognostic factors after radiation therapy in patients with medulloblastomas (MB). Methods and Materials: Sixty-six patients with histologically confirmed MB were treated at University Hospital of Heidelberg between 1985 and 2009. Forty-two patients (64%) were pediatric ({<=}18 years), and 24 patients (36%) were adults. Tumor resection was performed in all patients and was complete in 47%. All patients underwent postoperative craniospinal irradiation (CSI) delivering a median craniospinal dose of 35.5 Gy with additional boosts to the posterior fossa up to 54.0 Gy. Forty-seven patients received chemotherapy, including 21 in whom chemotherapy was administered before CSI. Statistical analysis was performed using the log-rank test and the Kaplan-Meier method. Results: Median follow-up was 93 months. Overall survival (OS) and local and distant progression-free survival (LPFS and DPFS) were 73%, 62%, and 77% at 60 months. Both local and distant recurrence predisposed for significantly reduced OS. Macroscopic complete tumor resection, desmoplastic histology and early initiation of postoperative radiation therapy within 28 days were associated with improved outcome. The addition of chemotherapy did not improve survival rates. Toxicity was moderate. Conclusions: Complete resection of MB followed by CSI yields long survival rates in both children and adults. Delayed initiation of CSI is associated with poor outcome. Desmoplastic histology is associated with improved survival. The role of chemotherapy, especially in the adult population, must be further investigated in clinical studies.

Rieken, Stefan, E-mail: Stefan.Rieken@med.uni-heidelberg.de [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany); Mohr, Angela; Habermehl, Daniel; Welzel, Thomas; Lindel, Katja [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany); Witt, Olaf; Kulozik, Andreas E. [Department of Pediatric Oncology, Hematology, Immunology, and Pneumatology, University of Heidelberg, Heidelberg (Germany); Wick, Wolfgang [Department of Neurooncology, University of Heidelberg, Heidelberg (Germany); Debus, Juergen; Combs, Stephanie E. [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany)

2011-11-01

253

Prognostic Factors for Myositis-Associated Interstitial Lung Disease  

PubMed Central

Background Interstitial lung disease (ILD) is a common manifestation of polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM); however, little is known about the factors influencing the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the present study is to assess prognostic factors for PM/DM/CADM-ILD. Methods The clinical features and survival of 114 consecutive patients diagnosed with PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed retrospectively. Results The study group included 30 PM-associated ILD, 41 DM-associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55 patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever. High-resolution computed tomography frequently revealed ground-glass opacities, traction bronchiectasis, and consolidation. Most of the patients were treated with corticosteroids or corticosteroids in combination with immunosuppressive agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in univariate Cox proportional hazards models. Multivariate Cox proportional hazards analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM) as significant predictors of overall mortality. Patients with acute/subacute ILD had a much lower survival rate than those with the chronic form (p<0.001). Patients with CADM-ILD had a lower survival rate than those with PM-ILD (p?=?0.034). Conclusions Acute/subacute form, older age, lower level of FVC and diagnosis of CADM predict poor outcome in PM/DM/CADM-ILD. PMID:24905449

Fujisawa, Tomoyuki; Hozumi, Hironao; Kono, Masato; Enomoto, Noriyuki; Hashimoto, Dai; Nakamura, Yutaro; Inui, Naoki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Shirai, Toshihiro; Yasuda, Kazumasa; Hayakawa, Hiroshi; Suda, Takafumi

2014-01-01

254

Prognostic value of bone marrow involvement by clonal immunoglobulin gene rearrangements in follicular lymphoma  

PubMed Central

Aims We aimed to evaluate the prognostic value of routine use of PCR amplification of immunoglobulin gene rearrangements in bone marrow (BM) staging in patients with follicular lymphoma (FL). Methods Clonal rearrangements were assessed by immunoglobulin heavy and light-chain gene rearrangement analysis in BM aspirates from 96 patients diagnosed with FL and related to morphological detection of BM involvement in biopsies. In 71 patients, results were also compared with concurrent flow cytometry analysis. Results BM involvement was detected by PCR in 34.4% (33/96) of patients. The presence of clonal rearrangements by PCR was associated with advanced clinical stage (I–III vs IV; p<0.001), high FL International Prognostic Index (FLIPI) score (0–1, 2 vs ?3; p=0.003), and detection of BM involvement by morphology and flow cytometry analysis (p<0.001 for both). PCR-positive patients had a significantly poorer survival than PCR-negative patients (p=0.001, log-rank test). Thirteen patients positive by PCR but without morphologically detectable BM involvement, had significantly poorer survival than patients with negative morphology and negative PCR result (p=0.002). The poor survival associated with BM involvement by PCR was independent of the FLIPI score (p=0.007, Cox regression). BM involvement by morphology or flow cytometry did not show a significant impact on survival. Conclusions Our results showed that routine use of PCR-based clonality analysis significantly improved the prognostic impact of BM staging in patients with FL. BM involvement by PCR was also an independent adverse prognostic factor. PMID:25233852

Berget, Ellen; Helgeland, Lars; Liseth, Knut; Løkeland, Turid; Molven, Anders; Vintermyr, Olav Karsten

2014-01-01

255

New prognostic factors and scoring system for patients with skeletal metastasis  

PubMed Central

The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ?7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ?3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment. PMID:25044999

Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

2014-01-01

256

Evaluation of prognostic factors in patients with therapy-related acute myeloid leukemia  

PubMed Central

Background Therapy-related AML (t-AML) occurs as a late complication of chemotherapy administered to treat a prior disorder. Prognostic factors affecting the clinical outcome in t-AML have not yet been clearly defined; therefore, we evaluated these factors in this study. Methods Forty-eight patients diagnosed with t-AML within the past 10 years were enrolled, and their chemotherapy regimens categorized into 4 groups: alkylating agents (AK) only, topoisomerase II inhibitors (TI) and AK, TI only, and others. The prognostic factors affecting clinical outcome were evaluated. Results Five (10.4%), 21 (43.8%), 9 (18.8%), and 13 (27.0%) patients were treated with AK only, AK and TI, TI only, and others, respectively. Patients with an AML M3 phenotype showed significantly longer overall survival (OS; 55.1 vs. 14.3 months, P=0.040) and disease-free survival (DFS; 61.2 vs. 17.5 months, P=0.049) than other phenotypes. In contrast, patients with a complex karyotype showed significantly shorter OS (7.9 vs. 31.3 months, P=0.008) and DFS (9.5 vs. 38.6 months, P=0.046); additionally, patients with chromosome 5 or 7 abnormalities showed significantly shorter OS (9.1 vs. 30.7 months, P=0.011) than other phenotypes. Only the presence of a complex karyotype or AML M3 phenotype retained prognostic impact in a multivariate analysis. Conclusion Only the AML M3 phenotype was identified as having a good prognosis, and this might suggest that it exhibits unique clinical features in t-AML patients. Moreover, our findings indicated that karyotype was the strongest prognostic indicator and predicted a poor prognosis for t-AML patients with a complex karyotype. PMID:24086938

Park, Sang Hyuk; Cho, Young-Uk; Jang, Seongsoo; Park, Chan-Jeoung

2013-01-01

257

A possible role of the P53 gene deletion as a prognostic factor in multiple myeloma.  

PubMed

The role of P53 gene abnormalities in the pathogenesis of multiple myeloma (MM) and their potential use as prognostic indicators remain uncertain. To further define this question, we studied genomic DNA from 50 MM and one plasma cell leukemia patients by polymerase chain reaction single-strand conformation polymorphism and sequencing, and fluorescence in situ hybridization in order to detect P53 mutation and deletion, respectively. Kaplan-Meier survival curves and the log-rank test were used to analyze the survival data. No P53 mutation was detected in our patients. In contrast, P53 deletion, predominantly monoallelic, was detected in 8 of 51 (15.7%) patients. Similar frequencies of P53 deletion were observed in patients stratified by age ( P=0.71), gender ( P=0.44), status, and stage of the disease ( P=0.70 and P=0.23, respectively). However, patients with P53 deletion had significantly shorter median overall survival compared with those without a deletion (7.4 vs 139.0 months, P<0.0001). On univariate regression analysis, P53 deletion was a parameter for predicting shortened survival ( P=0.02). We concluded that P53 mutation may be seen as a prognostic indicator of limited value in MM. In contrast, P53 deletion may be seen as a prognostic indicator of poor outcome. However, as the cohort of patients is rather limited for a prognostic analysis, these results should be confirmed by further studies with larger sized samples. PMID:12783209

Ortega, M M; Melo, M B; De Souza, C A; Lorand-Metze, I; Costa, F F; Lima, C S P

2003-07-01

258

The Prognostic Significance of HbF in Childhood Haematological Malignancies.  

PubMed

The degree of increase in foetal haemoglobin (HbF) synthesis in haematological malignancies may be associated with the degree of malignancy. The aim of the present study was to quantify HbF levels in various childhood haematological malignancies and also, to ascertain its prognostic significance by comparing the results with the already established standard prognostic factors. Newly diagnosed cases of haematological malignancies in the paediatric age group were included in the study. HbF levels were estimated in each case of the study group along with HbF levels of control group comprising healthy children of same age group. The estimation was done by HPLC and Modified Betke's method. 50 cases of newly diagnosed haematological malignancies were studied out of which most of the cases were of acute lymphoblastic leukaemia (ALL) [n = 30(60 %)] followed by acute myeloid leukaemia (AML) [n = 8(16 %)], Hodgkin's lymphoma [n = 7(14%)], non-Hodgkin's lymphoma [n = 5(10 %)]. Raised HbF levels were found in 43.3 % cases of ALL (13/30) and 37.5 % cases of AML (3/8). No significant rise in HbF level was found in cases of lymphomas. There was correlation between raised HbF level and poor prognostic factors in cases of ALL but no such correlation was found in cases of AML. HbF levels are often elevated in childhood leukaemias as compared to childhood lymphomas. Thus, the concentration of HbF in acute childhood leukaemia may be considered as a prognostic factor. PMID:25548456

Mallick, Debjani; Karmakar, Rupam; Barui, Gopinath; Gon, Sonia; Chakrabarti, Sudipta

2015-03-01

259

Osteopontin is a prognostic biomarker in non-small cell lung cancer  

PubMed Central

Background In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the -443 position of the OPN promoter were analyzed. Methods Associations between immunohistochemical expression of S100A4, OPN and ephrin-A1 and relapse free and overall survival were examined using univariate and multivariate analyses. Serum OPN was measured by ELISA, polymorphisms in the -443 position of the tumor OPN promoter were analyzed by PCR, and associations between OPN levels and promoter polymorphisms and clinicopathological parameters and patient outcome were investigated. Results High expression of OPN in NSCLC tumors was associated with poor patient outcome, and OPN was a strong, independent prognostic factor for both relapse free and overall survival. Serum OPN levels increased according to tumor pT classification and tumor size, and patients with OPN-expressing tumors had higher serum levels than patients with OPN-negative tumors. S100A4 was a negative prognostic factor in several subgroups of adenocarcinoma patients, but not in the overall patient cohort. There was no association between ephrin-A1 expression and patient outcome. Conclusions OPN is a promising prognostic biomarker in NSCLC, and should be further explored in the selection of patients for adjuvant treatment following surgical resection. PMID:24215488

2013-01-01

260

Prognostic value of histologic grading for feline mammary carcinoma: a retrospective survival analysis.  

PubMed

Feline mammary carcinoma is highly malignant and generally associated with a poor prognosis, although studies suggest the range of survival times in affected cats is broad. Histologic grading of these tumors is achieved using the Elston and Ellis system, originally developed for human breast cancer. In cats, however, classification using this method has variable prognostic value. Therefore, objectives of this study were (1) to evaluate the Elston and Ellis grading system for feline mammary carcinoma in a predominantly spayed population and (2) to determine whether modification of this system or development of a novel system improved the prognostic value of histologic grading. Survey data and histologic features for 108 carcinomas from 97 cats were analyzed with respect to overall survival. Elston and Ellis grading failed to correlate significantly with overall survival. Using multivariable analysis, lymphovascular invasion, nuclear form, and mitotic count each demonstrated independent prognostic significance (P = .008, <.001, and .004, respectively). Modifications of the Elston and Ellis system and a novel grading system were proposed based on these results; all showed significant correlation with overall survival (P < .001). Median survival times were 27, 29, or 31 months for grade I; 14, 12, or 14 months for grade II; and 13, 5, or 8 months for grade III carcinomas using the mitotic-modified Elston and Ellis, the revised Elston and Ellis, or the novel grading system, respectively. Based on this retrospective study, adoption of the species-specific systems as proposed here may improve the prognostic value of histologic grading for feline mammary carcinoma. PMID:25060990

Mills, S W; Musil, K M; Davies, J L; Hendrick, S; Duncan, C; Jackson, M L; Kidney, B; Philibert, H; Wobeser, B K; Simko, E

2015-03-01

261

Stress testing on silicon carbide electronic devices for prognostics and health management.  

SciTech Connect

Power conversion systems for energy storage and other distributed energy resource applications are among the drivers of the important role that power electronics plays in providing reliable electricity. Wide band gap semiconductors such as silicon carbide (SiC) and gallium nitride (GaN) will help increase the performance and efficiency of power electronic equipment while condition monitoring (CM) and prognostics and health management (PHM) will increase the operational availability of the equipment and thereby make it more cost effective. Voltage and/or temperature stress testing were performed on a number of SiC devices in order to accelerate failure modes and to identify measureable shifts in electrical characteristics which may provide early indication of those failures. Those shifts can be interpreted and modeled to provide prognostic signatures for use in CM and/or PHM. Such experiments will also lead to a deeper understanding of basic device physics and the degradation mechanisms behind failure.

Kaplar, Robert James; Brock, Reinhard C.; Marinella, Matthew; King, Michael Patrick; Smith, Mark A.; Atcitty, Stanley

2011-01-01

262

Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade  

PubMed Central

Purpose Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas; the prognostic impact of grade in localized disease, and the validity of the AJCC Cancer Staging Manual 7th edition decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known. Methods Patients with adenocarcinoma of the appendix diagnosed between 1988-2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage and grade were calculated; and Cox proportional hazards regression analyses were performed. Results We analyzed a total of 2,469 appendiceal adenocarcinomas, of which 1,375 had mucinous histology and 860 had non-mucinous histology. Though overall CSS was similar for mucinous and nonmucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female gender, stage IV disease, and well differentiated histology were more common for mucinous adenocarcinomas. Histological grade had a strong prognostic impact, especially in patients with stage IV mucinous adenocarcinoma. The adjusted hazard ratios for stage IV moderately and poorly differentiated histological grade were 1.63 (95%CI: 1.14-2.34) and 4.94 (95%CI: 3.32-7.35) for mucinous histology, in comparison to 1.44 (95%CI: 0.82-2.52) and 1.90 (95%CI: 0.95-3.80) for non-mucinous histology, respectively. Conclusion The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and this data does not support the combination of these two histological grades in the recent AJCC 7th edition. PMID:23001080

Overman, Michael J.; Fournier, Keith; Hu, Chung-Yuan; Eng, Cathy; Taggart, Melissa; Royal, Richard; Mansfield, Paul; Chang, George J.

2013-01-01

263

Livestock services and the poor.  

PubMed

This paper reviews the economic framework for the delivery of livestock services to the poor. It is argued that the demand for livestock products is likely to increase rapidly and the ability of the poor to participate in the opportunities presented by this growth is linked critically to the availability of good service support, both on the input and output side. Governments therefore have a responsibility to supply the necessary public goods (including the institutions and legal frameworks), and the market infrastructure for facilitating the emergence of efficient markets for livestock services. The paper further argues that the dynamics of public policy in developing countries are much more complex than the simple application of economic logic. It is the larger political economy that often dictates policy choices. It is therefore important to integrate political economy and governance issues into the economic debate on livestock service delivery. The paper also reviews the context in which the markets for livestock services will need to function. Different countries are facing very different sets of issues, and the identification of possible interventions in livestock service markets would require careful field research and analysis. In this context, the paper suggests the elements of a research agenda for the next few years. PMID:15080541

Ahuja, V; Redmond, E

2004-04-01

264

Loss of p27 Expression Is Associated with Poor Prognosis in Stage I–II Pancreatic Cancer  

Microsoft Academic Search

Objective: p27 is a cyclin-dependent kinase inhibitor that prevents progression of the cell cycle from G1 phase. Postranscriptional loss of p27 correlates with poor prognosis in various solid tumors. In pancreatic cancer, the loss of p27 expression has been correlated with high tumor grade and advanced clinical stage, but data on its prognostic value are lacking. Method: In this retrospective

A. Juuti; S. Nordling; J. Louhimo; J. Lundin; K. von Boguslawski; C. Haglund

2003-01-01

265

C-reactive protein in the very early phase of acute ischemic stroke: association with poor outcome and death  

Microsoft Academic Search

Acute ischemic stroke may trigger an inflammatory response that leads to increased levels of C-reactive protein (CRP). High\\u000a levels of CRP may be associated with poor outcome because they reflect either an inflammatory reaction or tissue damage. We\\u000a evaluated the prognostic value of CRP within 12 h of onset of ischemic stroke. Levels of CRP were routinely obtained within\\u000a 12 h of

H. M. den Hertog; J. A. van Rossum; H. B. van der Worp; H. M. A. van Gemert; R. de Jonge; P. J. Koudstaal; D. W. J. Dippel

2009-01-01

266

Technical Needs for Prototypic Prognostic Technique Demonstration for Advanced Small Modular Reactor Passive Components  

SciTech Connect

This report identifies a number of requirements for prognostics health management of passive systems in AdvSMRs, documents technical gaps in establishing a prototypical prognostic methodology for this purpose, and describes a preliminary research plan for addressing these technical gaps. AdvSMRs span multiple concepts; therefore a technology- and design-neutral approach is taken, with the focus being on characteristics that are likely to be common to all or several AdvSMR concepts. An evaluation of available literature is used to identify proposed concepts for AdvSMRs along with likely operational characteristics. Available operating experience of advanced reactors is used in identifying passive components that may be subject to degradation, materials likely to be used for these components, and potential modes of degradation of these components. This information helps in assessing measurement needs for PHM systems, as well as defining functional requirements of PHM systems. An assessment of current state-of-the-art approaches to measurements, sensors and instrumentation, diagnostics and prognostics is also documented. This state-of-the-art evaluation, combined with the requirements, may be used to identify technical gaps and research needs in the development, evaluation, and deployment of PHM systems for AdvSMRs. A preliminary research plan to address high-priority research needs for the deployment of PHM systems to AdvSMRs is described, with the objective being the demonstration of prototypic prognostics technology for passive components in AdvSMRs. Greater efficiency in achieving this objective can be gained through judicious selection of materials and degradation modes that are relevant to proposed AdvSMR concepts, and for which significant knowledge already exists. These selections were made based on multiple constraints including the analysis performed in this document, ready access to laboratory-scale facilities for materials testing and measurement, and potential synergies with other national laboratory and university partners.

Meyer, Ryan M.; Coble, Jamie B.; Hirt, Evelyn H.; Ramuhalli, Pradeep; Mitchell, Mark R.; Wootan, David W.; Berglin, Eric J.; Bond, Leonard J.; Henager, Charles H.

2013-05-17

267

Inflammatory and microRNA Gene Expression as Prognostic Classifiers of Barrett's Associated Esophageal Adenocarcinoma  

PubMed Central

Purpose Esophageal cancer is one of the most aggressive and deadly forms of cancer; highlighting the need to identify biomarkers for early detection and prognostic classification. Our recent studies have identified inflammatory gene and microRNA signatures derived from tumor and nontumor tissues as prognostic biomarkers of hepatocellular, lung, and colorectal adenocarcinoma. Here, we examine the relationship between expression of these inflammatory genes and miRNA expression in esophageal adenocarcinoma and patient survival. Experimental Design We measured the expression of 23 inflammation-associated genes in tumors and adjacent normal tissues from 93 patients (58 Barrett's and 35 Sporadic adenocarcinomas) by quantitative reverse transcription-polymerase chain reaction. These data were used to build an inflammatory risk model, based on multivariate Cox regression, to predict survival in a training cohort (n=47). We then determined if this model could predict survival in a cohort of 46 patients. Expression data for miRNA-375 was available for these patients and was combined with inflammatory gene expression. Results IFN?, IL-1?, IL-8, IL-21, IL-23, and PRG expression in tumor and nontumor samples were each associated with poor prognosis based on Cox regression ([Z-score]>1.5) and therefore, were used to generate an inflammatory risk score (IRS). Patients with a high IRS had poor prognosis compared to those with a low IRS in the training (P=0.002) and test (P=0.012) cohorts. This association was stronger in the group with Barrett's history. When combining with miRNA-375, the combined IRS/miR signature was an improved prognostic classifier than either one alone. Conclusion Transcriptional profiling of inflammation-associated genes and miRNA expression in resected esophageal Barrett's associated adenocarcinoma tissues may have clinical utility as predictors of prognosis. PMID:20947516

Nguyen, Giang Huong; Schetter, Aaron J.; Chou, David B.; Bowman, Elise D.; Zhao, Ronghua; Hawkes, Jason E.; Mathe, Ewy A.; Kumamoto, Kensuke; Zhao, Yiqiang; Budhu, Anuradha; Hagiwara, Nobutoshi; Wang, Xin Wei; Miyashita, Masao; Casson, Alan G.; Harris, Curtis C.

2010-01-01

268

Meta-Analysis: Prognostic Value of Survivin in Patients with Hepatocellular Carcinoma  

PubMed Central

Background The expression of survivin is a promising prognostic indicator for some carcinomas. However, evidence for the prognostic value of survivin with respect to survival in hepatocellular carcinoma remains controversial. Aim To conduct a systematic review of studies evaluating survivin expression in hepatocellular carcinoma as a prognostic indicator. Methods The relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases, and two meta-analyses were performed. One studied the association between survivin expression and the overall survival of patients with hepatocellular carcinoma, whereas the other studied the association between survivin expression and disease-free survival. Studies were pooled, and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted. Results Fourteen eligible studies with a total of 890 patients were included in this study. Two meta-analyses were performed according to the different outcomes by which prognosis was valued. The combined HR of the overall survival studies was 2.33 (95% CI: 1.65–3.31). The combined HR of disease-free survival studies was 2.13 (95% CI: 1.65–2.75). These data appeared to be significant when stratified by detection method, the language of publication, and HR estimate. The heterogeneities were highly significant (I2>50%) when subgroup analyses of overall survival rate were conducted, whereas little heterogeneity was found when subgroup analyses of disease-free survival rate were carried out. The positive expression of survivin in the cytoplasm was significantly correlated with poor prognosis in HCC (HR>1). Conclusions This study showed that survivin expression was correlated with poor prognosis in patients with hepatocellular carcinoma, regardless whether they were assessed by overall survival or disease-free survival. PMID:24386184

Liu, Jin Long; Zhang, Xue Jun; Zhang, Zhao; Zhang, An Hong; Wang, Wei; Dong, Jia Hong

2013-01-01

269

Cytogenetic polyclonality of breast carcinomas: association with clinico-pathological characteristics and outcome.  

PubMed

Routinely used prognostic factors fail to predict clinical outcome in a significant proportion of breast cancer patients, implying that they can not detect some important biological characteristics. Chromosomal changes have been described in breast carcinomas for many years but their significance is not clear. We compared chromosomal changes with clinico-pathological characteristics and clinical outcome in 203 breast cancer patients with a follow-up of 9-18 years. Combining data from classical cytogenetics and flow cytometry revealed chromosomal abnormalities in 142 cases (70%). Of these, 51 (35.9%) contained two or more cytogenetically abnormal clones. Polyclonality was significantly associated with poor breast-cancer-specific survival (P = 0.03) within 5 years, independent of tumor size, lymph node metastases, and hormone receptors. Specific changes were similar to those previously described, but a new finding was a significant association between del 3p12p21 and poor survival. Polyclonality was significantly associated with TP53-mutations but not with a germline BRCA2 mutation. Less than one third of the polyclonal samples were identified by flow cytometry alone. Cytogenetic changes were detected in 17 out of 114 samples from non-tumorous tissue (15%), two of them identical with a clone in the corresponding tumor. Several samples contained clearly unrelated clones within the tumor and outside, implying either multifocal origin or early divergence. In conclusion, the common deletion on Chromosome 3p12p21 was associated with poor clinical outcome. Chromosomal polyclonality is common in breast carcinomas and predicts poor survival. Polyclonality was poorly detected by one-sample flow cytometry. Multiple sampling might improve the detection rate. PMID:21910159

Steinarsdottir, Margret; Gudmundsson, Ingi Hrafn; Jonasson, Jon Gunnlaugur; Olafsdottir, Elinborg J; Eyfjörd, Jorunn E; Ogmundsdottir, Helga M

2011-11-01

270

Prognostic value of LAMP3 and TP53 overexpression in benign and malignant gastrointestinal tissues  

PubMed Central

Lysosomal associated membrane protein 3 (LAMP3) is a newly identified tumor-specific protein. It is a downstream target gene of tumor suppressor TP53 and its expression has been associated with hypoxia-induced metastasis and poor overall survival in cervical and breast cancers. However, little is known of LAMP3 protein expression in gastrointestinal cancer and its prognostic value. We determined protein expression of LAMP3 and TP53 in both gastric (n=750) and colorectal (n=479) tissues by immunohistochemistry analysis on tissue microarray (TMA), their expression was correlated with patients' clinical parameters. LAMP3 and TP53 protein expression was significantly higher in cancerous tissues compared to normal and benign tissues. In both gastric and colorectal cancers, high LAMP3 protein expression (LAMP3+) was significantly associated with tumor stage (P=0.014 and P<0.001). No correlation between LAMP3 and TP53 expression was observed. Patients with high LAMP3 expression but not high TP53 expression had a poor overall survival (for gastric cancer P<0.001, CI: 1.762-4.567; for colorectal cancer P=0.036, CI: 1.062-5.980). Our data suggest that epithelial LAMP3 expression is an independent prognostic marker for gastrointestinal cancer. PMID:25362357

Zhu, Huijun; Mei, Haijun; Wang, Wei; Zhang, Shu; Huang, Jianfei

2014-01-01

271

Increased expression of SOX4 is a biomarker for malignant status and poor prognosis in patients with non-small cell lung cancer.  

PubMed

The aim of the present study was to analyze the expression of sex-determining region Y-related high mobility group box 4 (SOX4) in non-small cell lung cancer (NSCLC) and its correlation with clinicopathologic characteristics, including the survival of NSCLC patients. To observe initially the expression status of SOX4 in lung squamous cell carcinoma and adenocarcinoma at gene expression omnibus. The expression of SOX4 mRNA and protein was examined in NSCLC tissues and normal lung tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of SOX4 expression levels with clinical characteristics of 168 NSCLC patients was analyzed by immunohistochemistry. Univariate and multivariate analyses were performed to determine the association between SOX4 expression and prognosis of NSCLC patients. In our results, SOX4 expression was increased in NSCLC tissues compared with paired normal lung tissues in microarray data (GSE3268). SOX4 mRNA and protein expression were markedly higher in NSCLC tissues than in normal lung tissues (P = 0.001 and P = 0.001, respectively). Using immunohistochemistry, high levels of SOX4 protein were positively correlated with status of differentiated degree (high vs. middle, P = 0.004; high vs. low, P < 0.001), clinical stage (I-II vs. III-IV, P < 0.001), T classification (T1-T2 vs. T3-T4, P = 0.004), N classification (N0-N1 vs. N2-N3, P = 0.002), and M classification (M0 vs. M1, P = 0.011) in NSCLC. Moreover, the higher level of SOX4 expression was markedly correlated with poor overall survival in NSCLC patients (P < 0.001). Multivariate analysis suggested that increased SOX4 expression was a poor independent prognostic predictor for NSCLC patients (P = 0.002). In conclusion, SOX4 plays an important role on NSCLC progression and prognosis and may serve as a convictive prognostic biomarker for NSCLC patients. PMID:25567207

Wang, Dingmiao; Hao, Ting; Pan, Yang; Qian, Xiaowei; Zhou, Daixing

2015-04-01

272

Computational prognostic indicators for breast cancer  

PubMed Central

Breast cancer remains the leading cause of cancer-related mortality in women. Comprehensive genomics, proteomics, and metabolomics studies are emerging that offer an opportunity to model disease biology, prognosis, and response to specific therapies. Although many biomarkers have been identified through advances in data mining techniques, few have been applied broadly to make patient-specific decisions. Here, we review a selection of breast cancer prognostic indicators and their implications. Our goal is to provide clinicians with a general evaluation of emerging computational methodologies for outcome prediction. PMID:25050076

Yang, Xinan; Ai, Xindi; Cunningham, John M

2014-01-01

273

Tumor signatures of PTHLH overexpression, high serum calcium, and poor prognosis were observed exclusively in clear cell but not non clear cell renal carcinomas  

PubMed Central

High serum calcium (Ca) due to aberrant secretion of tumor parathyroid hormone-like hormone (PTHLH) is a well-known paraneoplastic sign and is associated with poor prognosis in patients with renal cell carcinoma (RCC). However, the status of serum Ca and tumor PTHLH expression have not been verified using the 2004 World Health Organization (WHO) renal tumor classification. We retrospectively reviewed corrected serum Ca levels at initial onset (n = 683) and/or as of recurrence (n = 71) in patients with RCC. We also examined a total of 623 renal parenchymal tumor samples for PTHLH mRNA expressions by quantitative real-time PCR. High serum Ca concomitant with PTHLH overexpression in tumors was observed exclusively in clear cell RCC but not in other non clear cell subtype tumors, including papillary, chromophobe, collecting-duct, unclassified, and other rare subtype RCCs or in benign oncocytomas and angiomyolipomas. In clear cell RCC, PTHLH expression was significantly high in male patients, and was associated with a symptomatic presentation, higher grade, and higher stage cases, whereas it was not associated with VHL gene status. Univariate analyses demonstrated that high PTHLH expression was strongly associated with poor outcome both in overall survival (OS) and disease-free survival (DFS) for patients who underwent standard nephrectomy. Further multivariate Cox analyses revealed that the PTHLH expressions remained as independent prognostic parameters for OS but not for DFS. These data suggest that the previously characterized tumor signatures of high serum Ca due to high PTHLH expression and poor prognosis are clear cell RCC-specific features, whereas these characteristics are rare in non clear cell RCCs. PMID:24861371

Yao, Masahiro; Murakami, Takayuki; Shioi, Koichi; Mizuno, Nobuhiko; Ito, Hiroki; Kondo, Keiichi; Hasumi, Hisashi; Sano, Futoshi; Makiyama, Kazuhide; Nakaigawa, Noboru; Kishida, Takeshi; Nagashima, Yoji; Yamanaka, Shoji; Kubota, Yoshinobu

2014-01-01

274

Explaining the Role of Proximate Determinants on Fertility Decline among Poor and Non-Poor in Asian Countries  

PubMed Central

Objectives We examined the overall contributions of the poor and non-poor in fertility decline across the Asian countries. Further, we analyzed the direct and indirect factors that determine the reproductive behaviour of two distinct population sub-groups. Design Data from several new rounds of DHS surveys are available over the past few years. The DHS provides cross-nationally comparable and useful data on fertility, family planning, maternal and child health along with the other information. Six selected Asian countries namely: Bangladesh, India, Indonesia, Nepal, Philippines, and Vietnam are considered for the purpose of the study. Three rounds of DHS surveys for each country (except Vietnam) are considered in the present study. Methods Economic status is measured by computing a “wealth index”, i.e. a composite indicator constructed by aggregating data on asset ownership and housing characteristics using principal components analysis (PCA). Computed household wealth index has been broken into three equal parts (33.3 percent each) and the lowest and the highest 33.3 percent is considered as poor and non-poor respectively. The Bongaarts model was employed to quantify the contribution of each of the proximate determinants of fertility among poor and non-poor women. Results Fertility reduction across all population subgroups is now an established fact despite the diversity in the level of socio-economic development in Asian countries. It is clear from the analysis that fertility has declined irrespective of economic status at varying degrees within and across the countries which can be attributed to the increasing level of contraceptive use especially among poor women. Over the period of time changing marriage pattern and induced abortion are playing an important role in reducing fertility among poor women. Conclusions Fertility decline among majority of the poor women across the Asian countries is accompanied by high prevalence of contraceptive use followed by changing marriage pattern and induced abortion. PMID:25689843

Majumder, Nabanita; Ram, Faujdar

2015-01-01

275

Prognostic Models in Medicine: Artificial Intelligence and Decision Analytic Approaches  

E-print Network

Prognostic Models in Medicine: Artificial Intelligence and Decision Analytic Approaches Peter Lucas to the workshop on Prognostic Models in Medicine: Artificial Intelligence and Decision Analytic Approaches held. This view may explain why progno­ sis, despite its central role in medicine, is not clearly recognised

Lucas, Peter

276

Prognostic stratification of diabetic patients by exercise echocardiography  

Microsoft Academic Search

OBJECTIVESThe aim of this study was to assess the incremental value of exercise echocardiography for the risk stratification of diabetic patients.BACKGROUNDThere are currently insufficient outcome data in diabetic patients to define the role of stress echocardiography as a prognostic tool.METHODSWe studied the prognostic value of exercise echocardiography in 563 patients with diabetes mellitus (mean age 64 ± 11 years, 336

Abdou Elhendy; Adelaide M Arruda; Douglas W Mahoney; Patricia A Pellikka

2001-01-01

277

The prognostic importance of anemia in patients with heart failure  

Microsoft Academic Search

PurposePhysiologic studies have suggested that anemia could adversely affect the cardiovascular condition of patients with heart failure. Yet, the prognostic importance of this treatable condition is not well established by epidemiologic studies. We sought to determine the prognostic value of hematocrit level in a cohort of elderly patients hospitalized with heart failure.

Mikhail Kosiborod; Grace L Smith; Martha J Radford; JoAnne M Foody; Harlan M Krumholz

2003-01-01

278

High mobility group-box 3 overexpression is associated with poor prognosis of resected gastric adenocarcinoma  

PubMed Central

AIM: To elucidate high mobility group-box 3 (HMGB3) protein expression in gastric adenocarcinoma, its potential prognostic relevance, and possible mechanism of action. METHODS: Ninety-two patients with gastric adenocarcinomas surgically removed entered the study. HMGB3 expression was determined by immunohistochemistry through a tissue microarray procedure. The clinicopathologic characteristics of all patients were recorded, and regular follow-up was made for all patients. The inter-relationship of HMGB3 expression with histological and clinical factors was analyzed using nonparametric tests. Survival analysis was carried out by Kaplan-Meier (log-rank) and multivariate Cox (Forward LR) analyses between the group with overexpression of HMGB3 and the group with low or no HMGB3 expression to determine the prognosis value of HMGB3 expression on overall survival. Further, HMGB3 expression was knocked down by small hairpin RNAs (shRNAs) in the human gastric cancer cell line BGC823 to observe its influence on cell biological characteristics. The MTT method was utilized to detect gastric cancer cell proliferation changes, and cell cycle distribution was analyzed by flow cytometry. RESULTS: Among 92 patients with gastric adenocarcinomas surgically removed in this study, high HMGB3 protein expression was detected in the gastric adenocarcinoma tissues vs peritumoral tissues (P < 0.001). Further correlation analysis with patients’ clinical and histology variables revealed that HMGB3 overexpression was obviously associated with extensive wall penetration (P = 0.005), a positive nodal status (P = 0.004), and advanced tumor-node-metastasis (TNM) stage (P = 0.001). But there was no correlation between HMGB3 overexpression and the age and gender of the patient, tumor localization or histologic grade. Statistical Kaplan-Meier survival analysis disclosed significant differences in overall survival between the HMGB3 overexpression group and the HMGB3 no or low expression group (P = 0.006). The expected overall survival time was 31.00 ± 3.773 mo (95%CI = 23.605-38.395) for patients with HMGB3 overexpression and 49.074 ± 3.648 mo (95%CI = 41.925-57.311) for patients with HMGB3 no and low-level expression. Additionally, older age (P = 0.040), extensive wall penetration (P = 0.008), positive lymph node metastasis (P = 0.005), and advanced TNM tumor stage (P = 0.007) showed negative correlation with overall survival. Multivariate Cox regression analysis indicated that HMGB3 overexpression was an independent variable with respect to age, gender, histologic grade, extent of wall penetration, lymph nodal metastasis, and TNM stage for patients with resectable gastric adenocarcinomas with poor prognosis (hazard ratio = 2.791, 95%CI = 1.233-6.319, P = 0.019). In the gene function study, after HMGB3 was knocked down in the gastric cell line BGC823 by shRNA, the cell proliferation rate was reduced at 24 h, 48 h and 72 h. Compared to BGC823 shRNA-negative control (NC) cells, the cell proliferation rate in cells that had HMGB3 shRNA transfected was significantly decreased (P < 0.01). Finally, cell cycle analysis by FACS showed that BGC823 cells that had HMGB3 knocked down were blocked in G1/G0 phase. The percentage of cells in G1/G0 phase in BGC823 cells with shRNA-NC and with shRNA-HMGB3 was 46.84% ± 1.7%, and 73.03% ± 3.51% respectively (P = 0.001), whereas G2/M cells percentage decreased from 26.51% ± 0.83% to 17.8% ± 2.26%. CONCLUSION: HMGB3 is likely to be a useful prognostic marker involved in gastric cancer disease onset and progression by regulating the cell cycle. PMID:23326140

Tang, Hua-Rong; Luo, Xian-Qin; Xu, Gang; Wang, Yan; Feng, Zhi-Jun; Xu, Hui; Shi, Ya-Wei; Zhang, Qin; Wu, Li-Guang; Xue, Chun-Quan; Wang, Cheng-Wei; Wu, Chao-Yang

2012-01-01

279

Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review  

SciTech Connect

The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in {>=}50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1{alpha}). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank; Graeff, Pauline de [Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Pras, Elisabeth [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Schuuring, Ed [Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Wisman, G. Bea A. [Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Bock, Geertruida H. de [Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Zee, Ate G.J. van der, E-mail: a.g.j.van.der.zee@og.umcg.n [Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

2011-02-01

280

Loss of stromal caveolin-1 expression in colorectal cancer predicts poor survival  

PubMed Central

AIM: To investigate the clinicopathological signi?cance and prognostic value of caveolin-1 (CAV-1) in both tumor and stromal cells in colorectal cancer (CRC). METHODS: A total of 178 patients with CRC were included in this study. The correlation between CAV-1 expression and clinicopathologic features and survival was studied. RESULTS: CAV-1 expression was detected in tumor and stromal cells. The expression of stromal CAV-1 was closely associated with histological type (P = 0.022), pathologic tumor-node-metastasis stage (P = 0.047), pathologic N stage (P = 0.035) and recurrence (P = 0.000). However, tumor cell CAV-1 did not show any correlation with clinical parameters. Additionally, the loss of stromal CAV-1 expression was associated with shorter disease-free survival (P = 0.000) and overall survival (P = 0.000). Multivariate analysis revealed that the loss of stromal CAV-1 expression was an independent prognostic factor for both overall survival (P = 0.014) and disease-free survival (P = 0.006). CONCLUSION: The loss of stromal CAV-1 expression in CRC was associated with poor prognosis and could be a prognostic factor for CRC patients. PMID:25632186

Zhao, Zhi; Han, Fang-Hai; Yang, Shi-Bin; Hua, Li-Xin; Wu, Jian-Hai; Zhan, Wen-Hua

2015-01-01

281

Decreased expression of uroplakin Ia is associated with colorectal cancer progression and poor survival of patients  

PubMed Central

Aim: The present study was to investigate the clinical significance of Uroplakins Ia (UPKIa) in the development of colorectal cancer. Methods: mRNA levels of UPKIa in paired colorectal cancer lesions and the adjacent noncancerous tissues were examined using real-time PCR. The expression and prognostic value of UPKIa were examined in 125 colorectal cancer patients after resection. Statistical analyses were applied to derive prognostic associations. Results: UPKIa mRNA level was down-regulated in colorectal cancer lesions compared with that in the paired adjacent noncancerous tissues. Reduced expression of UPKIa was significantly associated with clinical staging (P = 0.038), and tumor size (P = 0.035) of the disease. Moreover, low expression of UPKIa was significantly associated with poorer overall (OS) and recurrent free (RFS) survival (P = 0.017 and P = 0.007, respectively) of colorectal cancer patients. Multivariate analysis suggested that reduced expression of UPK1a was an independent prognostic marker of colorectal cancer (P = 0.047). Conclusions: Low expression of UPKIa was a promising predictor for poor outcome of colorectal cancer patients. Further studies on the potential use of UPKIa as a therapeutic targetis are still needed. PMID:25197375

He, Yongzhong; Kong, Fandong; Du, Hanpeng; Wu, Mingjian

2014-01-01

282

Increased frequency of minimal homozygous deletions is associated with poor prognosis in primary malignant melanoma patients.  

PubMed

Identification of prognostic melanoma-associated copy number alterations (CNAs) is still an area of active research. Here, we investigated by high-resolution array comparative genomic hybridization (aCGH) a cohort of 31 paraffin-preserved primary malignant melanomas (MMs), whose prognosis was not predictable on the basis of conventional histopathological parameters. Although we identified a variety of highly recurrent sites of genomic lesions, the total number of CNAs per patient was not a discriminator of MM outcome. Furthermore, validation of aCGH by quantitative PCR on an extended population of 65 MM samples confirmed the absence of predictive value for the most recurrent CNA loci. Instead, our analysis revealed specific prognostic potential of the frequency of homozygous deletions (representing less than 3% of the total CNAs on average per sample), which was strongly associated with sentinel lymph node (SLN) invasion (P?=?0.003), and distant metastasis (P?=?0.003). Increased number of homozygous deletions was also indicative of poor patient survival (P?=?0.01), both in our samples and in an independent validation of public dataset of primary and metastatic MMs. Moreover, we identified 77 hotspots of minimal common homozygous deletions, enriched in genes involved in cell adhesion processes and cell-communication functions, which preferentially accumulated in primary MMs showing the most severe outcome. Therefore, specific loss of gene loci in regions of minimal homozygous deletion may represent a pivotal type of genomic alteration accumulating during MM progression with potential prognostic implication. PMID:24615732

Boi, Sebastiana; Tebaldi, Toma; Re, Angela; Cantaloni, Chiara; Adami, Valentina; Barbareschi, Mattia; Cristofolini, Mario; Pasini, Luigi; Quattrone, Alessandro

2014-06-01

283

Epidemiologic and molecular prognostic review of glioblastoma.  

PubMed

Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system malignancy with a median survival of 15 months. The average incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis is 64 years. Incidence is higher in men and individuals of white race and non-Hispanic ethnicity. Many genetic and environmental factors have been studied in GBM, but the majority are sporadic, and no risk factor accounting for a large proportion of GBMs has been identified. However, several favorable clinical prognostic factors are identified, including younger age at diagnosis, cerebellar location, high performance status, and maximal tumor resection. GBMs comprise of primary and secondary subtypes, which evolve through different genetic pathways, affect patients at different ages, and have differences in outcomes. We report the current epidemiology of GBM with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival. We also provide a concise review on molecular markers in GBM that have helped distinguish biologically similar subtypes of GBM and have prognostic and predictive value. PMID:25053711

Thakkar, Jigisha P; Dolecek, Therese A; Horbinski, Craig; Ostrom, Quinn T; Lightner, Donita D; Barnholtz-Sloan, Jill S; Villano, John L

2014-10-01

284

Prognostic variables in canine multicentric lymphosarcoma.  

PubMed

This paper presents the results of a prospective study to investigate the prognostic value of clinical staging, histological grading, immunophenotype, mitotic count and average numbers of argyrophilic nucleolar organiser region counts in dogs with multicentric lymphosarcoma treated with a standard chemotherapy protocol comprising vincristine, cyclophosphamide and prednisolone. Forty-nine dogs were treated according to the study protocol. Univariate and multivariate analysis with regression modelling was used to evaluate the prognostic importance of patient and tumour variables upon tumour response and relapse-free survival. Thirty-seven dogs (76 per cent) achieved a complete remission, seven (14 per cent) a partial remission and five (10 per cent) failed to respond to treatment. None of the variables examined had a statistically significant effect upon tumour response. Tumour immunophenotype was the only parameter found to have a significant influence on patient survival, the hazard ratio for T-cell versus B-cell immunophenotype was 3.99 with 95 per cent confidence interval from 1.399 to 11.372, P = 0.035. PMID:11518416

Dobson, J M; Blackwood, L B; McInnes, E F; Bostock, D E; Nicholls, P; Hoather, T M; Tom, B D

2001-08-01

285

Prognostic intraoperative factors in severe acute pancreatitis  

PubMed Central

Acute pancreatitis is a serious disease. Triggered by the local inflammation of the pancreas, it can cause inflammation in various organs and systems in the body. It is important to identify severe forms of acute pancreatitis with an increased morbidity and mortality rate. Lately, internationally, numerous clinical and paraclinical factors predicting the severity of acute pancreatitis have been proposed. The purpose of the study is to identify the prognostic intraoperative factors of severity. The prospective study was conducted over a period of four years, between 2007 and 2010 and included 238 patients treated in a surgical clinic in Bucharest. 103 patients experienced a severe form of acute pancreatitis, which means 67.95% of all operations practiced. We monitored intraoperative factors, in particular: the presence and/ or the extent of pancreatic necrosis, common bile duct lithiasis and intraperitoneal fluid, parameters proposed to become statistically prognostic factors in the development and long-term morbidity of acute pancreatitis. The presence and/ or extension of necrosis was identified in the histopathology only in patients with severe acute pancreatitis. 71.43% of the patients with common bile duct lithiasis and 73.91% of the patients with inflammatory intraperitoneal fluid had severe acute pancreatitis. Most patients who developed postoperative complications (86.49%) or who required a surgical intervention (85.71%), presented a severe form of the disease. Conclusions: pancreatic necrosis, common bile duct lithiasis and intraperitoneal fluid may contribute to a more precise prediction of severity, as confirmed by international literature.

Popa, CC

2014-01-01

286

Nuclear-cytoplasmic PARP-1 expression as an unfavorable prognostic marker in lymph node?negative early breast cancer: 15-year follow-up.  

PubMed

PARP-1 plays an important role in DNA damage repair and maintaining genome integrity by repairing DNA single-strand breaks (SSBs) by base excision repair (BER). The aim of the present study was to examine the expression of PARP-1 in breast cancer (BC) patients and to assess the relationship between the subcellular localization of this protein and clinicopathological characteristics. The reactivity of PARP-1 was analyzed by immunohistochemistry in a homogeneous group of 83 stage II ductal BC patients with a 15-year follow-up. Immunostaining of PARP-1 was also evaluated in 4 human BC cell lines and resistance prediction profile for 11 anticancer agents was performed using 3 models of drug-resistant cell lines. Nuclear-cytoplasmic expression (NCE) was associated with shorter overall survival, which was not statistically significant during the 10-year follow-up but became statistically significant after 10 years of observation, during the 15-year follow-up (P=0.015). Analysis performed in subgroups of patients with (N+) and without (N-) nodal metastases showed that NCE was associated with poor clinical outcome in N- patients (P=0.017). Multivariate analysis confirmed a significant impact of NCE on unfavorable prognosis in N- early BC. The presence of PARP-1 NCE may be a new potential unfavorable prognostic factor in lymph node- negative early BC. PMID:24535158

Donizy, Piotr; Pietrzyk, Grazyna; Halon, Agnieszka; Kozyra, Cyprian; Gansukh, Tserenchunt; Lage, Hermann; Surowiak, Pawel; Matkowski, Rafal

2014-04-01

287

Prognostic Accuracy of Immunologic and Metabolic Markers for Type 1 Diabetes in a High-Risk Population  

PubMed Central

OBJECTIVE To establish and compare the prognostic accuracy of immunologic and metabolic markers in predicting onset of type 1 diabetes in those with high risk in a prospective study. RESEARCH DESIGN AND METHODS A total of 339 subjects from the Diabetes Prevention Trial–Type 1 (DPT-1) parenteral study, who were islet cell antibody (ICA)-positive, with low first-phase insulin response (FPIR) and/or abnormal glucose tolerance at baseline, were followed until clinical diabetes onset or study end (5-year follow-up). The prognostic performance of biomarkers was estimated using receiver operating characteristic (ROC) curve analysis and compared with nonparametric testing of ROC curve areas. Pearson correlation was used to assess the relationship between the markers. RESULTS Individually, insulin autoantibody titer, ICA512A titer, peak C-peptide, 2-h glucose, FPIR, and FPIR/homeostasis model assessment of insulin resistance provided modest but significant prognostic values for 5-year risk with a similar level of area under ROC curve ranging between 0.61 and 0.67. The combination of 2-h glucose, peak C-peptide, and area under the curve C-peptide significantly improved the prognostic accuracy compared with any solitary index (P < 0.05) with an area under ROC curve of 0.76 (95% CI 0.70–0.81). The addition of antibody titers and/or intravenous glucose tolerance test (IVGTT) markers did not increase the prognostic accuracy further (P = 0.46 and P = 0.66, respectively). CONCLUSIONS The combination of metabolic markers derived from the oral glucose tolerance test improved accuracy in predicting progression to type 1 diabetes in a population with ICA positivity and abnormal metabolism. The results indicate that the autoimmune activity may not alter the risk of type 1 diabetes after metabolic function has deteriorated. Future intervention trials may consider eliminating IVGTT measurements as an effective cost-reduction strategy for prognostic purposes. PMID:22787174

Xu, Ping; Beam, Craig A.; Cuthbertson, David; Sosenko, Jay M.; Skyler, Jay S.; Krischer, Jeffrey P.

2012-01-01

288

7 CFR 51.779 - Poorly colored.  

Code of Federal Regulations, 2012 CFR

...VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) United States Standards for Grades of Florida Grapefruit Definitions § 51.779 Poorly colored. Poorly colored means that not more than 25 percent of the surface may...

2012-01-01

289

7 CFR 51.779 - Poorly colored.  

Code of Federal Regulations, 2010 CFR

...VEGETABLES AND OTHER PRODUCTS 1,2 (INSPECTION, CERTIFICATION, AND STANDARDS) United States Standards for Grades of Florida Grapefruit Definitions § 51.779 Poorly colored. Poorly colored means that not more than 25 percent of the surface may...

2010-01-01

290

7 CFR 51.1166 - Poorly colored.  

Code of Federal Regulations, 2010 CFR

...AND STANDARDS) United States Standards for Grades of Florida Oranges and Tangelos Definitions § 51.1166 Poorly colored. Poorly colored as applied to common oranges means that not more than 25 percent of the surface may be solid...

2010-01-01

291

Improvement of CRB-65 as a prognostic tool in adult patients with community-acquired pneumonia  

PubMed Central

Background Patients with community-acquired pneumonia (CAP) often require hospitalisation. CRB-65 is a simple and useful scoring system to predict mortality. However, prognostic factors such as underlying disease and blood oxygenation are not included despite their potential to increase the performance of CRB-65. Methods The study included 1172 consecutive patients (830 inpatients, 342 outpatients) with CAP. Mortality, sensitivity, specificity, positive predictive value and negative predictive value, and the area under the receiver operating characteristic (ROC) curve with 95% CI were calculated. Prognostic accuracy was evaluated after adding coexisting illnesses according to the Pneumonia Severity Index (malignancy, heart failure, hepatic, renal and cerebrovascular disease) and pulse oximetry (SpO2). Results Mean age was 65?years, 30-day mortality 7% (inpatients 9%, outpatients 1%). Addition of one point for the presence of ?1 coexisting condition and one point for SpO2 <90% increased the area under the ROC curve of CRB-65 from 0.82 (95% CI 0.77 to 0.85) to 0.87 (95% CI 0.84 to 0.90; p<0.0001). Conclusions Modification of CRB-65 by including hypoxaemia and presence of specified underlying diseases increased the scoring system’s prognostic accuracy while retaining its independence of laboratory tests. DS CRB-65 may have the potential to further facilitate site of care decision for patients with CAP. PMID:25478185

Dwyer, Richard; Hedlund, Jonas; Henriques-Normark, Birgitta; Kalin, Mats

2014-01-01

292

Ploidy and DNA index as prognostic factors in resected pancreatic ductal adenocarcinoma – a review of the literature  

PubMed Central

In Poland, pancreatic cancer is the seventh most common cause of cancer-related death amongst men and the sixth amongst women. Pancreatic cancer has an extremely poor prognosis. Radical surgery still remains the only way of curing pancreatic cancer, and this is possible to perform in just 20% of cases, i.e. those that present localised disease upon diagnosis. An average survival of ?20 months post-resection and adjuvant chemotherapy has been observed in 10–15% of patients with tumours limited to the pancreas at the time of presentation. It is necessary to define strong prognostic factors to determine individual treatment and prognosis. In this paper we submit a review of the literature concerning the prognostic impact of the ploidy and the DNA index on the survival of patients who underwent resection of pancreatic ductal adenocarcinoma. However, the presented studies have produced conflicting results. Pancreatic cancer still remains a great challenge in medicine. PMID:25653724

Tuchalska-Czuro?, Julia

2014-01-01

293

Predicting stabilizing treatment outcomes for complex posttraumatic stress disorder and dissociative identity disorder: an expertise-based prognostic model.  

PubMed

The purpose of this study was to develop an expertise-based prognostic model for the treatment of complex posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID). We developed a survey in 2 rounds: In the first round we surveyed 42 experienced therapists (22 DID and 20 complex PTSD therapists), and in the second round we surveyed a subset of 22 of the 42 therapists (13 DID and 9 complex PTSD therapists). First, we drew on therapists' knowledge of prognostic factors for stabilization-oriented treatment of complex PTSD and DID. Second, therapists prioritized a list of prognostic factors by estimating the size of each variable's prognostic effect; we clustered these factors according to content and named the clusters. Next, concept mapping methodology and statistical analyses (including principal components analyses) were used to transform individual judgments into weighted group judgments for clusters of items. A prognostic model, based on consensually determined estimates of effect sizes, of 8 clusters containing 51 factors for both complex PTSD and DID was formed. It includes the clusters lack of motivation, lack of healthy relationships, lack of healthy therapeutic relationships, lack of other internal and external resources, serious Axis I comorbidity, serious Axis II comorbidity, poor attachment, and self-destruction. In addition, a set of 5 DID-specific items was constructed. The model is supportive of the current phase-oriented treatment model, emphasizing the strengthening of the therapeutic relationship and the patient's resources in the initial stabilization phase. Further research is needed to test the model's statistical and clinical validity. PMID:21240739

Baars, Erik W; van der Hart, Onno; Nijenhuis, Ellert R S; Chu, James A; Glas, Gerrit; Draijer, Nel

2011-01-01

294

?2microglobulin mRNA expression levels are prognostic for lymph node metastasis in colorectal cancer patients  

PubMed Central

Colorectal cancer (CRC) is the fourth most common non-cutaneous malignancy in the United States and the second most frequent cause of cancer-related death. One of the most important determinants of CRC survival is lymph node metastasis. To determine whether molecular markers might be prognostic for lymph node metastases, we measured by quantitative real-time RT–PCR the expression levels of 15 cancer-associated genes in formalin-fixed paraffin-embedded primary tissues derived from stage I–IV CRC patients with (n=20) and without (n=18) nodal metastases. Using the mean of the 15 genes as an internal reference control, we observed that low expression of ?2microglobulin (B2M) was a strong prognostic indicator of lymph node metastases (area under the curve (AUC)=0.85; 95% confidence interval (CI)=0.69–0.94). We also observed that the expression ratio of B2M/Spint2 had the highest prognostic accuracy (AUC=0.87; 95% CI=0.71–0.96) of all potential two-gene combinations. Expression values of Spint2 correlated with the mean of the entire gene set at an R2 value of 0.97, providing evidence that Spint2 serves not as an independent prognostic gene, but rather as a reliable reference control gene. These studies are the first to demonstrate a prognostic role of B2M at the mRNA level and suggest that low B2M expression levels might be useful for identifying patients with lymph node metastasis and/or poor survival. PMID:18506145

Shrout, J; Yousefzadeh, M; Dodd, A; Kirven, K; Blum, C; Graham, A; Benjamin, K; Hoda, R; Krishna, M; Romano, M; Wallace, M; Garrett-Mayer, E; Mitas, M

2008-01-01

295

Serum albumin retains independent prognostic significance in diffuse large B-cell lymphoma in the post-rituximab era.  

PubMed

Serum albumin (SA) has been shown to be a prognostic marker in many hematological malignancies and in diffuse large B-cell lymphoma (DLBCL) prior to chemo-immunotherapy. SA may be a surrogate for age, comorbid status, and disease severity. Here, we aimed to assess whether SA can be an independent prognostic marker in patients with newly diagnosed DLBCL treated with rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP). Patients who presented at the Moffitt Cancer Center from 2007 to 2010 for DLBCL diagnosis or treatment were identified using our institutional database. Clinical and treatment data were recorded, including SA levels at diagnosis. Survival time was estimated using the Kaplan-Meier method, with Cox proportional hazard model used to identify potential risk factors for time-to-event data. From 295 identified patients, 171 were excluded for not having primary treatment at our institution or not having R-CHOP treatment. In 124 included patients (mean age at diagnosis of 58 years, 91 % Caucasian), 25 % were categorized as poor by the revised International Prognostic Index. Overall and progression-free survival at 4 years were 65 % (95 % CI 57-75) and 58 % (95 % CI 0.49-0.69), respectively. Using multivariate analysis, we found that the hazard index of death of patients with SA ?3.7 g/dL was 26 % (95 % CI 13-53) of the hazard for those patients who had SA <3.7 g/dL when controlling for the revised International Prognostic Index risk and initial lymphocyte count. Our study shows that SA ?3.7 g/dL is an independent prognostic marker in DLBCL patients treated with R-CHOP. PMID:24590536

Dalia, Samir; Chavez, Julio; Little, Bryan; Bello, Celeste; Fisher, Kate; Lee, Ji-Hyun; Chervenick, Paul; Sokol, Lubomir; Sotomayor, Eduardo; Shah, Bijal

2014-08-01

296

Risk stratification using a new prognostic score for patients with secondary acute myeloid leukemia: results of the prospective AML96 trial.  

PubMed

Patients with secondary acute myeloid leukemia (sAML) are generally thought to have a poor prognosis. As there are no prognostic risk stratification models for patients with sAML available, the aim of this study was to obtain a scoring system. Prognostic factors influencing overall survival (OS) and event-free survival (EFS) were analyzed in 305 sAML patients treated in the prospective AML96 trial. The obtained prognostic scoring system was then validated in an independent patient cohort included in the AML2003 and AML60+ trials. In addition to the known risk factors for AML, age and karyotype, we identified the absolute platelet count and the Nucleophosmin 1 mutational status at diagnosis as prognostic factors of sAML patients. A pronounced distribution of sAML patients into three score groups was achieved showing a 2-year OS/EFS of 52/44% for patients in the low-risk group, 21/12% in the intermediate-risk group and 7/3% in the high-risk group (both P<0.001). Validation of this scoring system in a second independent set of sAML patients revealed similar significantly different survival results. In conclusion, for the first time, a prognostic scoring system is provided for sAML patients, allowing differential treatment strategies in the future. PMID:21135859

Stölzel, F; Pfirrmann, M; Aulitzky, W E; Kaufmann, M; Bodenstein, H; Bornhäuser, M; Röllig, C; Kramer, M; Mohr, B; Oelschlägel, U; Schmitz, N; Soucek, S; Thiede, C; Ehninger, G; Schaich, M

2011-03-01

297

Low expression of TFPI-2 associated with poor survival outcome in patients with breast cancer  

PubMed Central

Background The purpose of this study is to evaluate the prognostic value of TFPI-2 expression in breast cancer patients through examining the correlation between TFPI-2 expression and breast cancer clinicopathologic features. Methods Immunohistochemical staining combined with digital image analysis was used to quantify the expression of TFPI-2 protein in breast tumor tissues. For evaluation of the prognostic value of TFPI-2 expression to each clinicopathologic factor, Kaplan-Meier method and COX’s Proportional Hazard Model were employed. Results TFPI-2 expression was significantly correlated with tumor size, lymph node metastasis, histologic grade, clinical stage, and vessel invasion. More importantly, TFPI-2 expression was also associated with disease-free survival (DFS) of breast cancer patients. We found that patients with high TFPI-2 expression had longer DFS compared with those with low or negative expression of TFPI-2 (P <0.05, log-rank test). Cox’s regression analysis indicated that TFPI-2 expression, histologic grade, and vessel invasion might be significant prognostic factors for DFS, while TFPI-2 expression and histologic grade were the most significant independent predictors for tumor recurrence. Compared with the group with low/high TFPI-2 expression, the TFPI-2 negative group was more likely to have tumor relapse. The hazard ratio of DFS is 0.316 (P <0.01). Conclusions Low or negative expression of TFPI-2 is associated with breast cancer progression, recurrence and poor survival outcome after breast cancer surgery. TFPI-2 expression in breast tumors is a potential prognostic tool for breast cancer patients. PMID:23497249

2013-01-01

298

Looking for prognostic information in the ST-T segment--is it really worth it?  

PubMed

The West of Scotland Coronary Prevention Study (WOSCOPS) provided baseline electrocardiograms (ECGs) on 6,595 men without a previous myocardial infarction who were followed for a mean of 4.9 years during which time all events, cardiovascular or otherwise, were recorded. Half of the study group was treated with a lipid lowering drug while the other half was randomly assigned to placebo. This study cohort afforded the opportunity to look at ECG morphology as a marker of risk. All 12-lead ECGs in the study were processed by the Glasgow Program and automated Minnesota Coding was also undertaken. All computer outputs were reviewed to exclude errors due to technically unsatisfactory recordings. Multiple variables were studied. Univariate and multivariate logistic regression analyses were undertaken to determine those electrocardiographic and clinical parameters of predictive value with respect to the primary endpoint of fatal or non fatal myocardial infarction. Those ST-T variables with additional prognostic value in the multivariate analysis, which included the clinical parameters, were used to develop a risk score. Although many ECG measures were of prognostic value in a univariate analysis, only rate, frontal T axis and T+ amplitude in lead I were of significance in a multivariate analysis which included clinical data. With respect to QT dispersion, while it was shown that there was an increased risk for those with QT dispersion exceeding 44 ms (RR 1.38, CI 1.02 - 1.81 P = 0.034) the receiver operating characteristic curve was virtually a straight line. The risk equation also demonstrated that there was as much prognostic value in the use of age and smoking history alone as there was in ECG plus age combined. The conclusion drawn is that the prognostic value of ECG variables has to be considered carefully in the light of other available data. PMID:15534843

Macfarlane, Peter W; Norrie, John

2004-01-01

299

Prognostic analysis and comparison of colon cancer in Han and Hui patients  

PubMed Central

AIM: To investigate the relevant prognostic factors and their differences between colorectal cancer (CRC) patients of Chinese Han and Hui ethnicities in the Beijing region. METHODS: A retrospective analysis of 880 patients diagnosed with CRC at Xuanwu Hospital, Capital Medical University between September 2001 and September 2011 was performed. Among the 880 patients, 398 and 482 were Hui and Han, respectively. Characteristics including sex, age, diet, tumor size, primary tumor site, Dukes’ stage and degree of differentiation were analyzed for their influence on prognosis. Data on dietary structures were recorded through a questionnaire survey conducted during the patient’s first visit, return visit or follow-up checkups. RESULTS: Among patients with colon cancer, the 5-year survival rate for patients of Hui ethnicity was lower than that for Han patients (P = 0.025). Six risk factors (age of onset, dietary structure, tumor size, Dukes’ stage, location of cancer and degree of differentiation) in both Han and Hui patients were identified as prognostic factors (P < 0.05). Multivariate analysis showed that age of onset (P = 0.002), diet (P = 0.000), Dukes’ stage (P = 0.000) and degree of differentiation (P = 0.000) are prognostic factors affecting both ethnic groups. Comparison of prognostic factors between Han and Hui patients with CRC showed that dietary structure was a statistically significant factor, and diet varied significantly between the two ethnic groups. CONCLUSION: Dietary structure has a significant influence on colon cancer prognosis among Han and Hui patients with colon cancer in Beijing, which may cause a difference in their survival rates. PMID:24803822

Zhang, Mei; Zhao, Qu-Chuan; Liu, Yan-Peng; Yang, Lei; Zhu, Hong-Ming; Chhetri, Jagadish K

2014-01-01

300

miR-320a is an independent prognostic biomarker for invasive breast cancer  

PubMed Central

Breast cancer is one of the most common malignancies worldwide and is the second leading cause of cancer-related mortality among females. miRNAs are a class of small noncoding RNAs that are aberrantly expressed in human cancers. Due to their small size and stability, miRNAs have the potential to be efficacious clinical targets. MicroRNA-320a (miR-320a) has been shown to be dysregulated in multiple malignancies. In the present study, the expression levels of miR-320a were investigated in 15 paraffin-embedded in situ breast carcinoma and 130 invasive breast cancer tissues, and the prognostic value for breast cancer patients was assessed. Chromogenic in situ hybridization revealed that 60/130 (46%) invasive breast cancer tissues exhibited high expression levels of miR-320a (staining index score of ?4). Furthermore, miR-320a staining was found to significantly correlate with tumor size (P=0.046), clinical stage (P<0.001), lymph node metastasis (P<0.001) and distant metastasis (P=0.006). In addition, patients exhibiting low miR-320a expression levels had shorter overall survival times (P<0.001). Univariate and multivariate analyses revealed that miR-320a was an independent prognostic biomarker for invasive breast cancer (hazard ratio, 0.221; 95% confidence interval, 0.050–0.979; P=0.047). Receiver operator characteristic curves revealed that the prognostic value of miR-320a was enhanced when compared with the widely used prognostic biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor-2) in invasive breast cancer. The results of the present study suggest that miR-320a presents a potential biomarker for the prognosis of invasive breast cancer, and dysregulation of miR-320a may be involved in invasive breast cancer progression. PMID:25120655

YANG, HAIPING; YU, JUAN; WANG, LEI; DING, DI; ZHANG, LEI; CHU, CHENGYU; CHEN, QI; XU, ZUDE; ZOU, QIANG; LIU, XIUPING

2014-01-01

301

High expression of phosphorylated 4E-binding protein 1 is an adverse prognostic factor in esophageal squamous cell carcinoma.  

PubMed

Cell signaling pathways play important roles in oncogenesis. Among a large number of signaling regulators in different pathways, 4E-binding protein 1 (4E-BP1) was found to be a key factor, which converges several oncogenic signals, phosphorylates the molecules, and drives the downstream proliferative signals. Recent studies showed that high expression of phosphorylated 4E-BP-1 (p-4E-BP1) is associated with poor prognosis, tumor progression, or nodal metastasis in different human cancers, but its prognostic significance in esophageal cancer remains undefined. In this study, we investigated the expression levels of p-4E-BP1 with two different phosphorylation sites Thr(37/46) and Thr(70) by immunohistochemistry and their prognostic significance in 78 cases of surgically resected esophageal squamous cell carcinoma (SCC) for the first time. We found no correlation of p-4E-BP1 expression with age, gender, preoperative concurrent chemoradiotherapy, tumor grade, pT classification, pN, pM, or pStage. Multivariate Cox regression analysis showed that high expression of p-4E-BP-1 Thr(37/46) was an independent adverse prognostic factor, with a hazard ratio of 1.73 (95% confidence interval?=?1.03-2.90) and a p value of 0.038. Stratifying the patients with other prognostic factors, we found that the effect of p-4E-BP1 Thr(37/46) on survival was significant only in patients with relatively early stage disease (pT1/pT2, pN0, or pStage I/II; p?=?0.0047, 0.012, and 0.011, respectively). Our data suggest that assessment of p-4E-BP1 expression could identify a subpopulation of earlier stage esophageal SCC patients with poor prognosis. These patients could be possible candidates for future studies on more aggressive treatment or target therapy. PMID:21046149

Yeh, Chi-Ju; Chuang, Wen-Yu; Chao, Yin-Kai; Liu, Yun-Hen; Chang, Yu-Sun; Kuo, Shao-Yun; Tseng, Chen-Kan; Chang, Hsien-Kun; Hsueh, Chuen

2011-02-01

302

Disease recurrence patterns and analysis of clinicopathological prognostic factors for recurrence after resection for distal bile duct cancer.  

PubMed

Surgical resection is the treatment of choice for bile duct cancers. The aim of this study was to investigate disease recurrence patterns and prognostic factors for recurrence of distal bile duct cancers after surgical resection. A retrospective study was performed on 122 patients with distal bile duct cancers who underwent R0 or R1 surgical resection at Korea University Guro Hospital from 1991 to 2010. Sites of initial disease recurrence were classified as locoregional or distant. Univariate and multivariate analyses were performed to investigate the factors affecting recurrence. Of the 122 patients, 80 patients developed recurrence. The disease-free survival rate was 63.1 per cent at one year and 36.4 per cent at three years. The patterns of recurrence at diagnosis were locoregional in 25 patients, locoregional and distant metastasis in 14 patients, and distant metastasis in 41 patients. Multivariate analyses revealed that recurrence pattern, lymph node metastasis, and differentiation are independent prognostic factors affecting disease-free survival. R status (marginal significance) and tumor differentiation were independent prognostic factors associated with locoregional recurrence. Differentiation and lymph node metastasis were independent prognostic factors associated with distant metastasis. The prognosis after recurrence was poor with a 1-year survival rate after recurrence of 26.1 per cent. Adjuvant chemo- or radiation therapy, delivered in patients mainly with R1 resection or with presence of lymph node metastasis, did not demonstrate the survival benefit. Significant factors for recurrence were tumor differentiation and lymph node metastasis. Therefore, close follow-up and adjuvant therapy will be necessary in patients with lymph node metastasis or poorly differentiated tumor. PMID:25760206

Choi, Sae Byeol; Han, Hyung Joon; Park, Pyoung Jae; Kim, Wan Bae; Song, Tae Jin; Kim, Jae Seon; Suh, Sung Ock; Choi, Sang Yong

2015-03-01

303

Reproducibility of an imaging based prostate cancer prognostic assay  

NASA Astrophysics Data System (ADS)

The Prostate Px prognostic assay offered by Aureon Biosciences is designed to predict progression post primary treatment for prostate cancer patients based on their diagnostic biopsy specimen. The assay is driven by the automated image analysis of biological specimens. Three different histological sections are analyzed for morphometric as well as immunofluorescence protein expression properties within areas of tumor digitally masked by expert pathologists. The assay was developed on a multi-institution cohort of up to 9 images from each of 1027 patients. The variation in histological sections, staining, pathologist tumor masking and the region of image acquisition all have the potential to significantly impact imaging features and consequently the reproducibility of the assay's results for the same patient. This study analyzed the reproducibility of the assay in 50 patients who were re-processed within 3 months in a blinded fashion as de-novo patients. The key assay results reported were in agreement in 94% of the cases. The two independent endpoints of risk classification reproduced results in 90% and 92% of the predictions. This work presents one of the first assessments of the reproducibility of a commercial assay's results given the inherent variations in images and quantitative imaging characteristics in a commercial setting.

Khan, Faisal M.; Powell, Douglas; Bayer-Zubek, Valentina; Soares, Rui; Mott, Allison; Fernandez, Gerardo; Mesa-Tejada, Ricardo; Donovan, Michael J.

2011-03-01

304

Predictors of Poor Outcome in Patients with Acute Cerebral Infarction  

PubMed Central

Background and Purpose Plasma D-dimer levels are elevated during the acute phase of cerebral infarction (CI). We investigated whether the D-dimer level on admission and other clinical characteristics could be used to predict the poor outcome of patients with acute CI. Methods The clinical characteristics and plasma D-dimer levels measured within 3 days of onset were compared according to outcome among patients with acute CI. Results In total, 359 consecutive patients (mean age, 71.8 years) were examined, of which 174 had a poor outcome [score on the modified Rankin scale (mRS) ?3] at 30 days after hospitalization. The mean mRS score was higher and a poor outcome was observed more frequently among women than among men (p<0.001 for each). The proportions of women, cardioembolism, atrial fibrillation, advanced age (?75 years), prior history of CI or transient ischemic attack, and elevated D-dimer level (?1.0 µg/mL) were significantly higher among patients with a poor outcome than among those with a good outcome. A multivariate analysis showed that elevated D-dimer level [?1.0 µg/mL; odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.52-3.89; p<0.01], advanced age (OR, 1.93; 95% CI, 1.21-3.07; p<0.01), and female gender (OR, 1.75; 95% CI, 1.08-2.83; p=0.02) were independent predictors of a poor outcome. Conclusions Certain clinical characteristics (gender and advanced age) and an elevated D-dimer level upon admission can be used to predict the outcome of patients with acute CI at 30 days after hospitalization. PMID:22259615

Takashima, Shutaro; Sasahara, Etsuko; Taguchi, Yoshiharu; Toyoda, Shigeo; Hirai, Tadakazu; Nozawa, Takashi; Tanaka, Kortaro; Inoue, Hiroshi

2011-01-01

305

Prognostic significance of CUB domain containing protein expression in endometrioid adenocarcinoma.  

PubMed

CDCP1, a transmembrane protein with intracellular tyrosine residues which are phosphorylated upon activation, is supposed to be engaged in proliferative activities and resistance to apoptosis of cancer cells. High level of CDCP1 expression proved to be a poor prognosticator for lung adenocarcinoma. Here, expression level of CDCP1 was immunohistochemically examined in 110 cases (median age of 54.7 years) of endometrioid adenocarcinoma, and its clinical implications were evaluated. Tumor stage was stage I in 71 cases (64.5%), II in 5 (4.5%), III in 28 (25.5%), and IV in 6 (5.5%). Staining intensity of tumor cells was divided into two categories; tumor cells with no to weak and moderate to strong membrane staining. The intensity of CDCP1 expression in each case was defined by the staining of major population of cells as follows; cases with tumor cells showing no to weak and moderate to high membrane staining were categorized as CDCP1-low and CDCP1-high, respectively. Eighty-seven of 110 cases were categorized as CDCP1-high, and the remaining as CDCP1-low. Significant positive correlation was observed between low CDCP1 expression and stage (p=0.0091), relapse rate (p=0.0017), and poor prognosis (p=0.0009). Multivariate analysis revealed that low CDCP1 and advanced stage were independent poor prognostic factors for both OS and DFS. As compared to cancer cells, normal endometrium continuously expressed CDCP1. These suggested that the attitude of CDCP1 in cancers of lung and endometrium was different. Different role of CDCP1 by tissues and cancers is discussed. PMID:20372833

Mamat, Suhana; Ikeda, Jun-Ichiro; Enomoto, Takayuki; Ueda, Yutaka; Rahadiani, Nur; Tian, Tian; Wang, Yi; Qiu, Ying; Kimura, Tadashi; Aozasa, Katsuyuki; Morii, Eiichi

2010-05-01

306

Obstructive Jaundice in Hepatocellular Carcinoma: Response after Percutaneous Transhepatic Biliary Drainage and Prognostic Factors  

SciTech Connect

Purpose: To evaluate the therapeutic effect of percutaneous transhepatic biliary drainage (PTBD) in patients with obstructive jaundice caused by biliary involvement of hepatocellular carcinomas (HCC) and to determine the prognostic factors. Methods: We retrospectively analyzed the data of 22 consecutive patients (M:F = 20:2, mean age 52.8 years).Inclusion criteria were the patient having obstructive jaundice caused by HCC that invaded the bile ducts and having at least 4 weeks of follow-up data after the PTBD. We defined 'good response' and 'poor response' as whether the level of total bilirubin decreased more than 50% in 4 weeks or not. Total bilirubin level (T-bil),Child-Pugh score and the location of biliary obstruction for the two groups were compared. In addition, the interval between clinical onset of jaundice and PTBD, the degree of parenchymal atrophy and the size of the primary tumor were compared. Results: Of the 22 patients, 13 (59.1%) showed good response. T-bil was significantly lower in the good response group than in the poor (14.2 {+-} 6 mg/dlvs 25.9 {+-} 13.8 mg/dl, p = .017). In the five patients with T-bil <10 mg/dl, four (80%) showed good response,while in nine patients with T-bil > 20 mg/dl, only three (33%)showed good response. Although statistically not significant, patients with Child score <10 showed better results [good response rate of 66.7% (12/18)] than patients with Child score ?10 [good response rate of 25% (1/4)]. Involvement of secondary confluence of the bile duct also served as a poor prognostic factor (p =0.235). The interval between clinical onset of jaundice and PTBD, the presence of parenchymal atrophy and the size of the tumor did not show significant effect. Conclusion: Early and effective biliary drainage might be necessary in this group of patients with limited hepatic function.

Lee, Joon Woo; Han, Joon Koo; Kim, Tae Kyoung; Choi, Byung Ihn; Park, Seong Ho; Ko, Young Hwan; Yoon, Chang Jin; Yeon, Kyung-Mo [Department of Radiology and the Institute of Radiation Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744 (Korea, Republic of)

2002-06-15

307

Vitamin D deficiency and prognostics among patients with pancreatic adenocarcinoma  

PubMed Central

Background The prevalence of vitamin D deficiency among patients with cancer has been previously reported. Because vitamin D is fat soluble, patients with pancreatic adenocarcinoma may have an especially high risk of vitamin D deficiency in association with ongoing and varying degrees of malabsorption. However, little is known about the correlation between vitamin D status and prognosis in these patients. Methods We conducted a retrospective review of vitamin D status in patients with pancreatic adenocarcinoma who were treated at Siteman Cancer Center. Patients’ demographic information, clinical staging at the time of vitamin D assessment, vitamin D levels, and survival data were collected. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25[OH]D) level of less than 20 ng/mL, and vitamin D insufficiency was defined as a 25(OH)D level of between 20 ng/mL and 30 ng/mL. Results Between December 2007 and June 2011, 178 patients with pancreatic adenocarcinoma had their vitamin D levels checked at the time of initial visit at this center. Of these 178 patients, 87 (49%) had vitamin D deficiency, and 44 (25%) had vitamin D insufficiency. The median 25(OH)D level was significantly lower among nonwhite patients and among patients with stage I and II disease. A 25(OH)D level of less than 20 ng/mL was found to be associated with poor prognosis (p?=?0.0019) in patients with stage III and IV disease. Conclusions Vitamin D insufficiency and deficiency were prevalent among patients with pancreatic adenocarcinoma. The vitamin D level appears to be prognostic for patients with advanced pancreatic adenocarcinoma, and its effects should be further examined in a prospective study. PMID:24011168

2013-01-01

308

Prognostic impact of stress testing in coronary artery disease  

SciTech Connect

Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and {sup 201}Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing.47 references.

Severi, S.; Michelassi, C. (CNR Clinical Physiology Institute, Pisa, (Italy))

1991-05-01

309

Accelerated Aging in Electrolytic Capacitors for Prognostics  

NASA Technical Reports Server (NTRS)

The focus of this work is the analysis of different degradation phenomena based on thermal overstress and electrical overstress accelerated aging systems and the use of accelerated aging techniques for prognostics algorithm development. Results on thermal overstress and electrical overstress experiments are presented. In addition, preliminary results toward the development of physics-based degradation models are presented focusing on the electrolyte evaporation failure mechanism. An empirical degradation model based on percentage capacitance loss under electrical overstress is presented and used in: (i) a Bayesian-based implementation of model-based prognostics using a discrete Kalman filter for health state estimation, and (ii) a dynamic system representation of the degradation model for forecasting and remaining useful life (RUL) estimation. A leave-one-out validation methodology is used to assess the validity of the methodology under the small sample size constrain. The results observed on the RUL estimation are consistent through the validation tests comparing relative accuracy and prediction error. It has been observed that the inaccuracy of the model to represent the change in degradation behavior observed at the end of the test data is consistent throughout the validation tests, indicating the need of a more detailed degradation model or the use of an algorithm that could estimate model parameters on-line. Based on the observed degradation process under different stress intensity with rest periods, the need for more sophisticated degradation models is further supported. The current degradation model does not represent the capacitance recovery over rest periods following an accelerated aging stress period.

Celaya, Jose R.; Kulkarni, Chetan; Saha, Sankalita; Biswas, Gautam; Goebel, Kai Frank

2012-01-01

310

Poor Facial Affect Recognition Among Boys with Duchenne Muscular Dystrophy  

Microsoft Academic Search

Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria\\u000a for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine\\u000a whether comprehension of facial affect is compromised in boys with MD, children were given a matching-to-sample test with\\u000a four types of visual recognition (Object, Face,

V. J. Hinton; R. J. Fee; D. C. De Vivo; E. Goldstein

2007-01-01

311

Urban trees and the risk of poor birth outcomes  

Microsoft Academic Search

This paper investigated whether greater tree-canopy cover is associated with reduced risk of poor birth outcomes in Portland, Oregon. Residential addresses were geocoded and linked to classified-aerial imagery to calculate tree-canopy cover in 50, 100, and 200m buffers around each home in our sample (n=5696). Detailed data on maternal characteristics and additional neighborhood variables were obtained from birth certificates and

Geoffrey H. Donovan; Yvonne L. Michael; David T. Butry; Amy D. Sullivan; John M. Chase

2011-01-01

312

Prognostic factors in soft tissue sarcoma.  

PubMed

Despite major advances in the knowledge of soft tissue sarcoma (STS) during the last decades, no significant improvement in survival has been observed. Detailed data on the prognosis of STS are crucial in order to identify patients who might benefit from more aggressive treatment. Such data can be obtained from properly designed databases; however, the validation of data is crucial in order to obtain valid, reliable results. Furthermore, the majority of prognostic studies in STS have been limited by potential selection bias, low power, and biased estimates due to the statistical methods used, e.g., dichotomizing continuous variables, censoring competing events, as well as not adjusting for important confounders. The overall aim of this thesis was to investigate the prognosis of STS patients using data from the Aarhus Sarcoma Registry (ASR), covering western Denmark in the period from 1979 to 2008. In study I, we systematically validated data in the ASR and evaluated the validity, including completeness of patient registration and accuracy of data. In study II, we investigated the prognostic impact of patient-, tumor-, and treatment-related factors on local recurrence and disease-specific mortality. These were analyzed in a competing risk model in which continuous variables were included as cubic splines and possible confounders were selected based on directed acyclic graphs. In study III, we examined the impact of comorbidity on overall and disease-specific mortality. In study IV, we compared mortality in patients with abnormal biomarkers to those with normal values, assessed the significance of adjusting for comorbidity, as well as constructed a prognostic biomarker score. In study V, we described the relative mortality, i.e., the mortality in STS patients compared with the mortality in a general population, and compared relative and disease-specific estimates. The mortality in the general population was determined using an individually age- and sex-matched comparison cohort. All five studies were conducted in western Denmark within a population of approximately 2.5 million. Individual linkage between the ASR and national registries was made possible by the unique Danish civil registration number. The National Patient Registry and the LABKA research database were used to obtain data on comorbidity and biomarkers. In studies II to V we used a time-to-event-analysis approach that included cumulative incidence functions as well as crude and confounder adjusted Cox proportional hazard regression. In study I, we established that the overall validity of data in the ASR, after validation, was satisfactory and that the ASR included 85.3% of sarcoma patients from western Denmark between 1979 and 2008. In study II, we found a five-year local recurrence and disease-specific mortality of 16% and 24%, respectively. We excluded depth as a prognostic factor, and established that age, duration of symptoms, tumor size, anatomical and compartmental location, as well as radiotherapy were important prognostic factors for disease-specific mortality. In study III, we found that the level of comorbidity before or at diagnosis was an independent prognostic factor for both overall and disease-specific mortality, even after adjustment for age. In study IV, we showed that pretreatment levels of albumin, hemoglobin, and neutrophil to lymphocyte ratios were independently correlated with disease-specific mortality, and that adjusting for comorbidity was significant. In study V, we found five- and ten-year relative mortalities of 32.8% and 36.0%, respectively. The mortality in patients with low-grade STS was not significantly increased compared with the general population. The five- and ten-year disease-specific mortalities were underestimated by 3.1 and 1.9 percentage points compared to the relative mortality, respectively. We showed that relative mortality provided an accurate method to differentiate between cancer-specific and non-cancer-specific deaths. In conclusion, we showed that the ASR is a valid source of population-based data on STS. Impro

Maretty-Nielsen, Katja

2014-11-01

313

Increased expression of MMP14 correlates with the poor prognosis of Chinese patients with gastric cancer.  

PubMed

The role of matrix metalloproteinase 14 (MMP14) has been identified to involve tumor progression and prognosis. The purpose of this study is to investigate the role of MMP14 in tumor progression and prognosis of gastric cancer. This study indicated that MMP14 mRNA and protein were overexpressed in gastric cancer tissue (P<0.001 and P=0.037, respectively) and significantly associated with clinical stage (P=0.005), lymph node metastasis (P=0.003), and distant metastasis (P=0.017). Moreover, we found that the overexpression of MMP14 was a significant predictor of poor prognosis for gastric cancer patients (P<0.001). Furthermore, we performed a meta-analysis which included 594 cases from 3 studies and showed that MMP14 overexpression was a significantly poor prognostic factor in Chinese patients with gastric cancer and HR (95% CI) was 2.17 (1.64-2.86). In conclusion, MMP14 plays an important role on gastric cancer progression and prognosis and acts as a convictive biomarker for prognostic prediction for Chinese patients with gastric cancer. PMID:25748728

Dong, Yichen; Chen, Guohua; Gao, Mingming; Tian, Xia

2015-05-25

314

Prognostic role of MR imaging in nonischemic myocardial disease.  

PubMed

The role of cardiac magnetic resonance (MR) imaging as a prognostic tool in patients with ischemic heart disease is well established. However, an increasing body of data now demonstrates that cardiac MR imaging can provide prognostic information in a variety of nonischemic and diffuse myocardial diseases including myocarditis, dilated and hypertrophic cardiomyopathies, sarcoidosis, amyloidosis, and arrhythmogenic right ventricular cardiomyopathy. Cardiac MR imaging can also supply incremental information above established prognostic indicators, providing an additional tool for use in the prediction of disease progression, response to treatment, and risk stratification. PMID:25476677

Kallianos, Kimberly; Moraes, Gustavo L; Ordovas, Karen G

2015-02-01

315

Low GILT Expression is Associated with Poor Patient Survival in Diffuse Large B-Cell Lymphoma  

PubMed Central

The major histocompatibility complex (MHC) class II-restricted antigen processing pathway presents antigenic peptides acquired in the endocytic route for the activation of CD4+ T cells. Multiple cancers express MHC class II, which may influence the anti-tumor immune response and patient outcome. Low MHC class II expression is associated with poor survival in diffuse large B-cell lymphoma (DLBCL), the most common form of aggressive non-Hodgkin lymphoma. Therefore, we investigated whether gamma-interferon-inducible lysosomal thiol reductase (GILT), an upstream component of the MHC class II-restricted antigen processing pathway that is not regulated by the transcription factor class II transactivator, may be important in DLBCL biology. GILT reduces protein disulfide bonds in the endocytic compartment, exposing additional epitopes for binding to MHC class II and facilitating antigen presentation. In each of four independent gene expression profiling cohorts with a total of 585 DLBCL patients, low GILT expression was significantly associated with poor overall survival. In contrast, low expression of a classical MHC class II gene, HLA-DRA, was associated with poor survival in one of four cohorts. The association of low GILT expression with poor survival was independent of established clinical and molecular prognostic factors, the International Prognostic Index and the cell of origin classification, respectively. Immunohistochemical analysis of GILT expression in 96 DLBCL cases demonstrated variation in GILT protein expression within tumor cells which correlated strongly with GILT mRNA expression. These studies identify a novel association between GILT expression and clinical outcome in lymphoma. Our findings underscore the role of antigen processing in DLBCL and suggest that molecules targeting this pathway warrant investigation as potential therapeutics. PMID:24409177

Phipps-Yonas, Hannah; Cui, Haiyan; Sebastiao, Noemi; Brunhoeber, Patrick S.; Haddock, Ellen; Deymier, Martin J.; Klapper, Wolfram; Lybarger, Lonnie; Roe, Denise J.; Hastings, Karen Taraszka

2013-01-01

316

Image Analyzer-Based Assessment of Tumor-Infiltrating T Cell Subsets and Their Prognostic Values in Colorectal Carcinomas  

PubMed Central

To find useful tools to evaluate the prognosis in colorectal carcinoma (CRC) patients, we investigated the prognostic values of tumor-infiltrating T lymphocyte subsets according to intratumoral subsites as well as clinical or molecular characteristics. Immunohistochemistry for CD8, CD45RO, and FOXP3 was performed, and densities of the T cell subsets in each tissue microarray core (cells/mm2) were measured by image analysis. In the training set (n = 218) of CRC, T cell subset densities in the invasion front were more strongly associated with patient outcome than those in the tumor center. In the validation set (n = 549), T cell subset densities in the invasion front were evaluated. Univariate analysis showed that all three T cell subset densities were significantly associated with longer progression free survival and overall survival time (p < 0.001). In multivariate analysis, a high CD45RO density correlated independently with longer progression free survival (p = 0.011) and overall survival time (p = 0.007) in CRC patients, regardless of tumor location or adjuvant chemotherapy status. Our results showed that CD45RO density in the invasion front was the only independent prognostic factor regarding CRC. However, CD8 and FOXP3 densities were also independent prognostic factors in certain clinical settings. Thus, image analysis of tissue microarray cores in the invasion front of CRC could be used as a valid method for evaluating the prognostic significance of T cell subset densities. PMID:25875774

Kim, Younghoon; Bae, Jeong Mo; Li, Gang; Cho, Nam Yun; Kang, Gyeong Hoon

2015-01-01

317

Defining Human Embryo Phenotypes by Cohort-Specific Prognostic Factors  

PubMed Central

Background Hundreds of thousands of human embryos are cultured yearly at in vitro fertilization (IVF) centers worldwide, yet the vast majority fail to develop in culture or following transfer to the uterus. However, human embryo phenotypes have not been formally defined, and current criteria for embryo transfer largely focus on characteristics of individual embryos. We hypothesized that embryo cohort-specific variables describing sibling embryos as a group may predict developmental competence as measured by IVF cycle outcomes and serve to define human embryo phenotypes. Methodology/Principal Findings We retrieved data for all 1117 IVF cycles performed in 2005 at Stanford University Medical Center, and further analyzed clinical data from the 665 fresh IVF, non-donor cycles and their associated 4144 embryos. Thirty variables representing patient characteristics, clinical diagnoses, treatment protocol, and embryo parameters were analyzed in an unbiased manner by regression tree models, based on dichotomous pregnancy outcomes defined by positive serum ß-human chorionic gonadotropin (ß-hCG). IVF cycle outcomes were most accurately predicted at ?70% by four non-redundant, embryo cohort-specific variables that, remarkably, were more informative than any measures of individual, transferred embryos: Total number of embryos, number of 8-cell embryos, rate (percentage) of cleavage arrest in the cohort and day 3 follicle stimulating hormone (FSH) level. While three of these variables captured the effects of other significant variables, only the rate of cleavage arrest was independent of any known variables. Conclusions/Significance Our findings support defining human embryo phenotypes by non-redundant, prognostic variables that are specific to sibling embryos in a cohort. PMID:18596962

Shahine, Lora; Westphal, Lynn M.; Behr, Barry; Reijo Pera, Renee A.; Wong, Wing H.; Yao, Mylene W. M.

2008-01-01

318

Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index.  

PubMed

Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis. PMID:24249260

Sarkozy, Clémentine; Terré, Christine; Jardin, Fabrice; Radford, Isabelle; Roche-Lestienne, Catherine; Penther, Dominique; Bastard, Christian; Rigaudeau, Sophie; Pilorge, Sylvain; Morschhauser, Franck; Bouscary, Didier; Delarue, Richard; Farhat, Hassan; Rousselot, Philippe; Hermine, Olivier; Tilly, Hervé; Chevret, Sylvie; Castaigne, Sylvie

2014-01-01

319

Hyaluronan expression as a significant prognostic factor in patients with malignant peripheral nerve sheath tumors.  

PubMed

Hyaluronan (HA) regulates malignant tumor growth, invasion, and metastasis. However, few studies have focused on the roles of HA in tumorigenicity in malignant peripheral nerve sheath tumors (MPNST). In this study, we sought to clarify the prognostic value of HA in patients with MPNST. Specimens obtained from 15 patients with neurofibroma and 30 with MPNST were subjected to HA staining and scored as three grades. Protein expressions of HA synthase 1-3 were examined in the 22 MPNST tissue samples available. Statistically higher HA positivity was observed in MPNST as compared with neurofibroma (P = 0.020). The univariate analysis revealed that increased HA expression, age, neurofibromatosis type 1 (NF1) status, large tumor size, and histological grade were significantly associated with reduced overall survival of patients with MPNST; while increased HA expression, NF1 status, tumor size, and histological grade were correlated with disease-free survival. However, HA synthase 1-3 expression related to neither overall survival nor disease-free survival of these patients. In multivariate analysis, large tumor size (P = 0.022) was an independent prognostic factor for overall survival, and HA expression (P = 0.028) and tumor size (P = 0.002) were independent prognostic factors for disease-free survival. Statistically higher levels of HA in the human MPNST cells were observed compared with neurofibroma cells in vitro. Our results demonstrate that HA expression can be a useful marker in differentiating MPNST from neurofibroma, and in identifying patients with a poor prognosis. Hyaluronan-targeting therapy for patients with MPNST may have potential as a therapeutic tool. PMID:24957185

Ikuta, Kunihiro; Urakawa, Hiroshi; Kozawa, Eiji; Arai, Eisuke; Zhuo, Lisheng; Futamura, Naohisa; Hamada, Shunsuke; Kimata, Koji; Ishiguro, Naoki; Nishida, Yoshihiro

2014-08-01

320

Prognostic Value of Long Non-Coding RNA HOTAIR in Various Cancers  

PubMed Central

Long non-coding RNA has been involved in cancer progression, and high HOX transcript antisense intergenic RNA (HOTAIR) is thought to be a poor prognostic indicator in tumorigenesis of multiple types of cancer. Hence, the present study further reveals its prognostic value in tumor malignancy. A systematic review of PubMed and Web of Science was carried out to select literatures relevant to the correlation between HOTAIR expression levels and clinical outcome of various tumors. Overall survival (OS), metastasis-free survival (MFS), recurrence-free survival (RFS), and disease-free survival (DFS) were subsequently analyzed. Data from studies directly reporting a hazard ratio (HR) and the corresponding 95% confidence interval (CI) or a P value as well as survival curves were pooled in the current meta-analysis. A total of 2255 patients from 19 literatures almost published in 2011 or later were included in the analysis. The results suggest that HOTAIR was highly associated with HR for OS of 2.33 (95%CI?=?1.77-3.09, Pheterogeneity?=?0.016). Stratified analyses indicate that elevated levels of HOTAIR appears to be a powerful prognostic biomarker for patients with colorectal cancer (HR?=?3.02, 95CI%?=?1.84-4.95, Pheterogeneity?=?0.699) and esophageal squamous cell carcinomas (HR?=?2.24, 95CI%?=?1.67-3.01, Pheterogeneity?=?0.711), a similar effect was also observed in analysis method and specimen, except for ethnicity. In addition, Hazard ratios for up-regulation of HOTAIR for MFS, RFS, and DFS were 2.32 (P<0.001), 1.98 (P?=?0.369), and 3.29 (P?=?0.001), respectively. In summary, the high level of HOTAIR is intimately associated with an adverse OS in numerous cancers, suggesting that HOTAIR may act as a potential biomarker for the development of malignancies. PMID:25303230

Pan, Yuqin; Gao, Tianyi; Chen, Jie; Ying, Houqun; Liu, Xian; Wang, Feng; Xu, Yong; Wang, Shukui

2014-01-01

321

Low SOX17 expression is a prognostic factor and drives transcriptional dysregulation and esophageal cancer progression.  

PubMed

The transcriptional network of the SRY (sex determining region Y)-box 17 (SOX17) and the prognostic impact of SOX17 protein expression in human cancers remain largely unclear. In this study, we evaluated the prognostic effect of low SOX17 protein expression and its dysregulation of transcriptional network in esophageal squamous cell carcinoma (ESCC). Low SOX17 protein expression was found in 47.4% (73 of 154) of ESCC patients with predicted poor prognosis. Re-expression of SOX17 in ESCC cells caused reduced foci formation, cell motility, decreased ESCC xenograft growth and metastasis in animals. Knockdown of SOX17 increased foci formation in ESCC and normal esophageal cells. Notably, 489 significantly differential genes involved in cell growth and motility controls were identified by expression array upon SOX17 overexpression and 47 genes contained putative SRY element in their promoters. Using quantitative chromatin immunoprecipitation-PCR and promoter activity assays, we confirmed that MACC1, MALAT1, NBN, NFAT5, CSNK1A1, FN1 and SERBP1 genes were suppressed by SOX17 via the SRY binding-mediated transcriptional regulation. Overexpression of FN1 and MACC1 abolished SOX17-mediated migration and invasion suppression. The inverse correlation between SOX17 and FN1 protein expression in ESCC clinical samples further strengthened our conclusion that FN1 is a transcriptional repression target gene of SOX17. This study provides compelling clinical evidence that low SOX17 protein expression is a prognostic biomarker and novel cell and animal data of SOX17-mediated suppression of ESCC metastasis. We establish the first transcriptional network and identify new suppressive downstream genes of SOX17 which can be potential therapeutic targets for ESCC. PMID:24407731

Kuo, I-Ying; Wu, Ching-Chi; Chang, Jia-Ming; Huang, Yu-Lin; Lin, Chien-Hsun; Yan, Jing-Jou; Sheu, Bor-Shyang; Lu, Pei-Jung; Chang, Wei-Lun; Lai, Wu-Wei; Wang, Yi-Ching

2014-08-01

322

P36. The prognostic potential of circulating and tissue activin A level in malignant pleural mesothelioma  

PubMed Central

Background Malignant pleural mesothelioma (MPM) is an aggressive malignancy characterized by poor outcome and there is a lack of prognostic biomarkers to estimate prognosis. Previously we have shown that suppression of activin A can interfere with MPM tumor growth. In the current study, we compare the circulating and tissue expression level of activin A as a prognostic biomarker in MPM. Methods In a cohort of 53 MPM patients, plasma samples were collected between 2010 and 2014. Controls consisted of age-matched healthy individuals (n=46) and patients with pleuritis or pleural fibrosis (n=16). Circulating activin A was measured by ELISA and correlated to clinicopathological data. Furthermore, activin A expression in the tumor tissue was semiquantitatively measured by immunohistochemistry in 24 patients. Results Plasma activin A level was significantly elevated in MPM patients (n=53, 843±122 pg/mL) when compared to healthy controls (452±144 pg/mL, P=0.0039). Non-malignant pleuritis or pleural fibrosis patients only showed a modest, non-significant increase (625±95 pg/mL, P=0.093). Circulating activin A levels were slightly increased in cases with non-epitheloid morphology (n=16, 1101±183) when compared to epithelioid (n=37, 732±153 pg/mL, P=0.13). MPM patients with below median activin A concentrations had a modestly and non-significantly longer overall survival when compared to the high activin A level patients (469 vs. 271 days, P=0.4751). Interestingly, there was no correlation between circulating and tissue expression level of activin A in 17 patients where both parameters could have been analyzed. Conclusions Our findings suggest that the measurement of circulating activin A may support the diagnosis and prognosis of MPM but additional patient cohorts need to be analyzed to establish the diagnostic and prognostic value of this non-invasive biomarker.

Dong, Yawen; Hoda, Mir Alireza; Schelch, Karin; Rozsas, Anita; Laszlo, Viktoria; Dome, Balazs; Grusch, Michael; Berger, Walter; Klepetko, Walter; Hegedus, Balazs

2014-01-01

323

DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes  

PubMed Central

DNA repair pathways can enable tumor cells to survive DNA damage induced by chemotherapy and thus provide prognostic and/or predictive value. We evaluated Affymetrix gene expression profiles for 145 DNA repair genes in untreated breast cancer (BC) patients (n = 684) and BC patients treated with regimens containing neoadjuvant taxane/anthracycline (n = 294) or anthracycline (n = 210). We independently assessed estrogen receptor (ER)-positive/HER2-negative, HER2-positive, and ER-negative/HER2-negative subgroups for differential expression, bimodal distribution, and the prognostic and predictive value of DNA repair gene expression. Twenty-two genes were consistently overexpressed in ER-negative tumors, and five genes were overexpressed in ER-positive tumors, but no differences in expression were associated with HER2 status. In ER-positive/HER2-negative tumors, the expression of nine genes (BUB1, FANCI, MNAT1, PARP2, PCNA, POLQ, RPA3, TOP2A, and UBE2V2) was associated with poor prognosis, and the expression of one gene (ATM) was associated with good prognosis. Furthermore, the prognostic value of specific genes did not correlate with proliferation. A few genes were associated with chemotherapy response in BC subtypes and treatment-specific manner. In ER-negative/HER2-negative tumors, the MSH2, MSH6, and FAN1 (previously MTMR15) genes were associated with pathological complete response and residual invasive cancer in taxane/anthracycline-treated patients. Conversely, PMS2 expression was associated with residual invasive cancer in treatments using anthracycline as a single agent. In HER2-positive tumors, TOP2A was associated with patient response to anthracyclines but not to taxane/anthracycline regimens. In genes expressed in a bimodal fashion, RECQL4 was significantly associated with clinical outcome. In vitro studies showed that defects in RECQL4 impair homologous recombination, sensitizing BC cells to DNA-damaging agents. PMID:24072219

Iwamoto, Takayuki; Di Leo, Angelo; Hayashi, Naoki; Bottai, Giulia; Stampfer, Martha; André, Fabrice; Turner, Nicholas C.; Symmans, W. Fraser; Hortobágyi, Gabriel N.; Pusztai, Lajos; Bianchini, Giampaolo

2013-01-01

324

Development and External Validation of a Prognostic Nomogram for Metastatic Uveal Melanoma  

PubMed Central

Background Approximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians. Patients and Methods Two cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram. Results The median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated. Conclusions The nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials. PMID:25780931

Valpione, Sara; Moser, Justin C.; Parrozzani, Raffaele; Bazzi, Marco; Mansfield, Aaron S.; Mocellin, Simone; Pigozzo, Jacopo; Midena, Edoardo; Markovic, Svetomir N.; Aliberti, Camillo; Campana, Luca G.; Chiarion-Sileni, Vanna

2015-01-01

325

A profile of prognostic and molecular factors in European and M?ori breast cancer patients  

PubMed Central

Background New Zealand M?ori have a poorer outcome from breast cancer than non-M?ori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared M?ori and European breast cancer patients from Christchurch, New Zealand. Methods and Results Clinicopathological and survival data from 337 consecutive breast cancer patients (27 M?ori, 310 European) were evaluated. Fewer tumours were high grade in M?ori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 M?ori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1?), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1? correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. Conclusions In this Christchurch cohort of breast cancer patients, M?ori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences. PMID:20932344

2010-01-01

326

Overexpression of CARM1 in breast cancer is correlated with poorly characterized clinicopathologic parameters and molecular subtypes  

PubMed Central

Background Coactivator-associated arginine methyltransferase 1 (CARM1) belongs to the protein arginine methyltransferase family. CARM1 has been reported to be associated with high grade tumors in breast cancer. It still remains unknown the expression pattern of CARM1 in breast cancer and its relationships with clinicopathological characteristics and molecular subtypes. Methods Two hundred forty-seven invasive breast cancer cases were collected and prepared for tissue array. There were thirty-seven tumors with benign glandular epithelium adjacent to the tumors among these cases. Molecular subtype and CARM1 expression were investigated using immunohistochemistry. Results Cell staining was observed in the cytoplasm and/or nucleus. Staining for CARM1 was significantly stronger in adenocarcinoma compared with adjacent benign epithelium. There is a significant correlation between CARM1 overexpression with young age, high grade, estrogen receptor (ER) and progesterone receptor (PR) negative, increased p53 expression, and high Ki-67 index. Our study demonstrated CARM1 overexpression was associated with an increase in the protein expression of HER2. Furthermore, our data indicated CARM1-overexpression rate were remarkably higher in HER2 subtype (69.6%), luminal B subtype (59.6%) and TN subtype (57.1%) compared with luminal A subtype (41.3%). Conclusions CARM1 expression was increased in invasive breast cancer. CARM1 overexpression was associated with poorly characterized clinicopathologic parameters and HER2 overexpression. There were significant differences between different molecular subtypes in their relationship to CARM1 overexpression. Our results support the value of using CARM1 in prognostic stratification of breast cancer patients and its potential therapeutic implications in targeting treatment. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4116338491022965 PMID:23915145

2013-01-01

327

Characteristics and outcomes of fall-related open-globe injuries in pseudophakic patients  

PubMed Central

Aim We aimed to identify the characteristics and prognostic indicators of poor visual and anatomic outcome in pseudophakic patients with fall-related open-globe (OG) injuries. We used a case series design, for a total of 26 patients. Methods Charts of consecutive pseudophakic patients with fall-related OG injury at a single institution were reviewed. Demographics, ophthalmic history, circumstances of injury, initial best-corrected visual acuity (BCVA), examination findings, surgical interventions, and follow-up BCVA were tabulated for statistical analysis with unpaired t-tests and Fisher’s exact tests. Results Nineteen patients (73%) were women. Mean (± standard deviation) age was 80.6±4.6 years (range: 61–97 years). Initial BCVA was <20/400 in 24 of 25 patients (96%). Mean ocular trauma score (OTS) was 38.54±10.95. OTS was lower (P=0.0017, P<0.0001, and P=0.0240) and wound size was larger (P=0.0440, 0.0145, and 0.0026) in patients with final BCVA <20/40, <20/400, and phthisis at final follow-up, respectively; compared to patients with BCVA ?20/40, 20/400, and no phthisis at final follow-up, respectively. Final BCVA <20/400 was associated with 360° subconjunctival hemorrhage (SCH), retinal detachment, and proliferative vitreoretinopathy (P=0.0498, 0.0181, and 0.0310, respectively). Total hyphema, intraocular lens (IOL) damage, and IOL expulsion were associated with needing multiple surgical interventions (P=0.0345, P<0.0001, and P=0.0023, respectively). Conclusion Large wound size, low OTS, 360° SCH, total hyphema, posterior injury, and IOL damage are common findings that are also prognostic of poor visual and anatomic outcome in pseudophakic patients with fall-related OG injuries. Ophthalmologists dealing primarily with geriatric populations should contribute to the discussion of fall risk. PMID:25784783

Kavoussi, Shaheen C; Slade, Martin D; Meskin, Seth W; Adelman, Ron A

2015-01-01

328

p53 mutation is a poor prognostic indicator for survival in patients with hepatocellular carcinoma undergoing surgical tumour ablation.  

PubMed Central

Forty-two patients with hepatocellular carcinoma (HCC) were resected and their tumours were analysed for p53 mutations by GC-clamped denaturing gradient gel electrophoresis (DGGE), single-strand conformation polymorphism (SSCP) and gene sequencing. All the exons have been analysed in this study. Eight of 12 HCCs with cirrhosis due to viral hepatitis and the two patients with sarcomatoid changes displayed p53 mutations. In contrast, no mutation was observed in the fibrolamellar variant (n = 9), non-cirrhotics (n = 13) and alcoholic cirrhosis (n = 6). The mutations observed were in exons 5-8. Two mutations were observed in codons 136 and 213 as well as a T insertion between residues 156 and 157 (exon 5) and these are reported for the first time in HCC. Likewise, the silent mutation polymorphism in codon 213 was noticed in 3 of the 42 patients. Survival analysis of these patients after surgery showed the mean and median survival in patients with wild-type p53 to be 60 and 43 months respectively. In the group with p53 mutations, the mean and median survival was 15 and 12 months. The difference was statistically significant (P= 0.003). Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9514057

Honda, K.; Sbisà, E.; Tullo, A.; Papeo, P. A.; Saccone, C.; Poole, S.; Pignatelli, M.; Mitry, R. R.; Ding, S.; Isla, A.; Davies, A.; Habib, N. A.

1998-01-01

329

A Poor Man's Evolving Algebra Compiler  

E-print Network

leanEA A Poor Man's Evolving Algebra Compiler Bernhard Beckert Joachim Posegga Interner Bericht 25/95 Universitat Karlsruhe Fakultat fur Informatik #12;#12;leanEA: A Poor Man's Evolving Algebra Compiler Bernhard://www.engin.umich.edu/~huggins/EA. 1 #12;2 leanEA: A Poor Man's Evolving Algebra Compiler APE (Borger et al., 1994b). EA speci cations

Posegga, Joachim

330

Roswell Park researchers find prognostic biomarker candidates for ovarian cancer  

Cancer.gov

Cancer researchers at Roswell Park Cancer Institute have identified two independent classes of novel candidate prognostic markers for ovarian cancer, advancing efforts to develop targeted therapies for the disease.

331

Novel Prognostic and Therapeutic Biomarker for Cancer and Inflammatory Diseases  

Cancer.gov

There remains a significant unmet need for diagnostics, prognostics, and therapeutics for conditions that involve inflammation and the formation of blood clots such as bleeding disorders, trauma, and diseases such as sepsis, cardiovascular disease, stroke, and cancer.

332

Accelerated Aging with Electrical Overstress and Prognostics for Power MOSFETs  

NASA Technical Reports Server (NTRS)

Power electronics play an increasingly important role in energy applications as part of their power converter circuits. Understanding the behavior of these devices, especially their failure modes as they age with nominal usage or sudden fault development is critical in ensuring efficiency. In this paper, a prognostics based health management of power MOSFETs undergoing accelerated aging through electrical overstress at the gate area is presented. Details of the accelerated aging methodology, modeling of the degradation process of the device and prognostics algorithm for prediction of the future state of health of the device are presented. Experiments with multiple devices demonstrate the performance of the model and the prognostics algorithm as well as the scope of application. Index Terms Power MOSFET, accelerated aging, prognostics

Saha, Sankalita; Celaya, Jose Ramon; Vashchenko, Vladislav; Mahiuddin, Shompa; Goebel, Kai F.

2011-01-01

333

Multivariate and subgroup analyses of a randomized, multinational, phase 3 trial of decitabine vs treatment choice of supportive care or cytarabine in older patients with newly diagnosed acute myeloid leukemia and poor- or intermediate-risk cytogenetics  

PubMed Central

Background Compared with younger patients, older adults with acute myeloid leukemia (AML) generally have poorer survival outcomes and less benefit from clinical trials. A recent phase 3 trial demonstrated a trend toward improved overall survival (OS) with decitabine, a hypomethylating agent, compared with treatment choice of either cytarabine or supportive care (7.7 months, 95% CI: 6.2–9.2 vs 5.0 months, 95% CI: 4.3–6.3, respectively) in older adults with newly diagnosed AML. The current analyses investigated prognostic factors for outcomes in this trial and examined OS and responses in prespecified subgroups. Methods A multivariate Cox proportional hazards model was used to investigate effects of demographic and baseline characteristics, including age, sex, cytogenetic risk, AML type, ECOG Performance Status, geographic region, bone marrow blasts, platelets, and white blood cells on OS, based on mature data. Similar analyses were conducted with a logistic regression model to predict response rates. Prespecified subgroup analyses were performed for OS and response rates, also using mature data. Results Patient characteristics that appeared to negatively influence OS included more advanced age (hazard ratio [HR] 1.560 for ?75 vs <70 years; p?=?0.0010), poorer performance status at baseline (HR 0.771 for 0 or 1 vs 2; p?=?0.0321), poor cytogenetics (HR 0.699 for intermediate vs poor; p?=?0.0010), higher bone marrow blast counts (HR 1.355 for >50% vs ?50%; p?=?0.0045), low baseline platelet counts (HR 0.775 for each additional 100?×?109/L; p?=?0.0015), and high white blood cell counts (HR 1.256 for each additional 25?×?109/L; p?=?0.0151). Regarding geographic regions, patients from Western Europe had the longest median OS. Response rates favored decitabine for all subgroups investigated, including patients ?75 years (odds ratio 5.94, p?=?0.0006). Conclusion Response to decitabine in AML is associated with known prognostic factors related to both patient demographics and disease characteristics. Trial registration ClinicalTrials.gov identifier NCT00260832 PMID:24498872

2014-01-01

334

The Prognostic Value of Plasma Soluble ST2 in Hospitalized Chinese Patients with Heart Failure  

PubMed Central

Background sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF. Methods and Results We consecutively enrolled 1528 hospitalized patients with HF. Receiver operating characteristic (ROC) and multivariable Cox proportional hazards analysis were used to assess the prognostic values of sST2. Adverse events were defined as all-cause death and cardiac transplantation. During a median follow-up of 19.1 months, 325 patients experienced adverse events. Compared with patients free of events, sST2 concentrations were significantly higher in patients with events (P<0.001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with adverse events (per 1 log unit, adjusted hazard ratio 1.52, 95% confidence interval: 1.30 to 1.78, P<0.001). An sST2 concentration in the highest quartiles (>55.6 ng/mL) independently predicted events in comparison to the lowest quartile (?25.2 ng/mL) when adjusted by multivariable model. In ROC analysis, the area under the curve for sST2 was not different from that for NT-proBNP in short and longer term. Over time, sST2 also improved discrimination and reclassification of risk beyond NT-proBNP. Conclusions sST2 is a strong independent risk predictor in Chinese patients hospitalized with HF and can significantly provide additional prognostic value to NT-proBNP in risk prediction. PMID:25347817

Zhang, Rongcheng; Zhang, Yuhui; Zhang, Jian; An, Tao; Huang, Yan; Guo, Xiao; Januzzi, James L.; Cappola, Thomas P.; Yin, Shijie; Wang, Yunhong; Zhou, Qiong; Zou, Changhong; Ji, Shiming; Lv, Rong

2014-01-01

335

Reinforced HEAV'D therapy for adult acute lymphoblastic leukemia: improved results and revised prognostic criteria.  

PubMed

Thirty-six adults with acute lymphoblastic leukemia (ALL) were treated with adriamycin, vincristine, prednisolone, and asparaginase for remission induction, followed by vincristine-adriamycin-cyclophosphamide consolidation courses, cranial irradiation, a short ara-C plus VM-26 pulse, and vincristine plus cyclophosphamide rotating weekly with ara-C plus VM-26 for three months (reinforced HEAV'D). Thirty-one patients achieved a complete remission (86 per cent). Compared with historical results from a prior study, age > 30 years, absolute blast count > 15 x 10(9)/l, and CD10-negative immunophenotype were not associated with higher relapse rate and shorter survival, suggesting a positive effect from intensification therapy with ara-C and VM-26 in these poor prognostic categories. However, patients with an abnormal karyotypic pattern or a positive molecular study for BCR-ABL rearrangement detecting t(9;22) had a far greater likelihood of treatment failure (probability of remission at 3 years 0.10) than those with normal karyotype or negative molecular study (probability 0.70), and those not studied or with insufficient methaphases (probability 0.50) (p < 0.05 by log-rank test). These results underline the prognostic importance of chromosomal abnormalities and the usefulness of ara-C and VM-26 in the management of adult ALL. PMID:8144131

Bassan, R; Battista, R; Montaldi, A; Rambaldi, A; D'Emilio, A; Viero, P; Borleri, G; Buelli, M; Dini, E; Barbui, T

1993-01-01

336

Prognostic value of preoperative inflammatory markers in Chinese patients with breast cancer  

PubMed Central

Cancer-associated inflammation is a key determinant of disease progression and survival in most cancers. The aim of our study was to assess the predictive value of preoperative inflammatory markers, such as the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio, red cell distribution width (RDW), and mean platelet volume, for survival in breast cancer patients. In total, 608 breast cancer patients operated on between January 2009 and December 2011 were included in this observational study. The association between preoperative inflammatory markers and survival outcomes was analyzed. Patients with high NLR (>2.57) or high RDW (>13.45%) showed a significantly lower overall survival rate than those with lower NLR (?2.57) or lower RDW (?13.45%). NLR and RDW, along with node stage and molecular subtypes, were independent prognostic factors. There was a significant survival difference according to NLR in the luminal A and triple-negative subtypes (93.3% versus 99.3%, P=0.001; 68.8% versus 95.1%, P=0.000, respectively). The triple-negative subtype was the only subtype in which higher RDW patients showed significantly poor prognosis (81.3% versus 95.5%, P=0.025). Pre-operation NLR and RDW is a convenient, easily measured prognostic indicator for patients with breast cancer, especially in patients with the triple-negative subtype. PMID:25328407

Yao, Minya; Liu, Yu; Jin, Hailong; Liu, Xiaojiao; Lv, Kezhen; Wei, Haiyan; Du, Chengyong; Wang, Shuqian; Wei, Bajin; Fu, Peifen

2014-01-01

337

Prognostic Impact of HOTAIR Expression is Restricted to ER-Negative Breast Cancers.  

PubMed

Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects. RNA-ISH analysis was successful in 94 cases (17% cases scored 0, 32.9% scored 1, 30.8% scored 2, and 19.1% scored 3). The expression of HOTAIR did not correlate with nodal metastasis regardless of the scoring intensity or with other study parameters (age, tumor size and grade, expression status). Further analysis of TCGA dataset showed that HOTAIR expression was lower in ductal carcinomas but higher in ER-negative tumors. Overexpression of HOTAIR was not associated with nodal metastases or prognosis in ER-positive patients. Its function as a poor prognostic indicator in ER-negative patients was restricted to node-positive patients. HOTAIR appears to be a marker for lymphatic metastases rather than hematogenous metastases in ER-negative patients. PMID:25739705

Gökmen-Polar, Yesim; Vladislav, I Tudor; Neelamraju, Yaseswini; Janga, Sarath C; Badve, Sunil

2015-01-01

338

FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma.  

PubMed

F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS. PMID:25622249

Li, Zhanchun; Xiao, Jie; Hu, Kongzu; Wang, Gang; Li, Maoqiang; Zhang, Jidong; Cheng, Guangqi

2015-01-01

339

Urokinase plasminogen activator receptor on invasive cancer cells: a prognostic factor in distal gastric adenocarcinoma.  

PubMed

Gastric cancer is the second cancer causing death worldwide. The five-year survival for this malignancy is below 25% and few parameters have shown an impact on the prognosis of the disease. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Using immunohistochemistry, the prognostic significance of uPAR was evaluated in tissue samples from a retrospective series of 95 gastric cancer patients. uPAR was expressed by neoplastic cells, macrophages, myofibroblasts and neutrophils in both intestinal and diffuse subtypes. No association was demonstrated between the expression of uPAR on cancer cells and histological subtype (p = 0.64) or TNM stage (p = 0.75). Univariate analysis revealed a significant association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor for overall survival in gastric cancer (HR = 2.39; 95% CI: 1.22-4.69; p = 0.011). In consequence, scoring of uPAR-positive cancer cells may be a direct measure for the invasive potential of gastric adenocarcinomas. PMID:21901747

Alpízar-Alpízar, Warner; Christensen, Ib Jarle; Santoni-Rugiu, Eric; Skarstein, Arne; Ovrebo, Kjell; Illemann, Martin; Laerum, Ole Didrik

2012-08-15

340

Cathepsin B as a potential prognostic and therapeutic marker for human lung squamous cell carcinoma  

PubMed Central

Background The lung squamous cell carcinoma survival rate is very poor despite multimodal treatment. It is urgent to discover novel candidate biomarkers for prognostic assessment and therapeutic targets to lung squamous cell carcinoma (SCC). Results Herein a two-dimensional gel electrophoresis and ESI-Q-TOF MS/MS-based proteomic approach was used to identify differentially expressed proteins between lung SCC and adjacent normal tissues. 31 proteins with significant alteration were identified. These proteins were mainly involved in metabolism, calcium ion binding, signal transduction and so on. Cathepsin B (CTSB) was one of the most significantly altered proteins and was confirmed by western blotting. Immunohistochemistry showed the correlation between higher CTSB expression and lower survival rate. No statistically significant difference between CTSB-shRNA treated group and the controls was observed in tumor volume, tumor weight, proliferation and apoptosis. However, the CTSB-shRNA significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. Moreover, CTSB, Shh and Ptch were up-regulated in patients with metastatic lung SCC, suggesting that hedgehog signaling might be activated in metastatic lung SCC which could affect the expression of CTSB that influence the invasive activity of lung SCC. Conclusions These data suggested that CTSB might serve as a prognostic and therapeutic marker for lung SCC. PMID:24139065

2013-01-01

341

Prognostic Impact of HOTAIR Expression is Restricted to ER-Negative Breast Cancers  

PubMed Central

Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects. RNA-ISH analysis was successful in 94 cases (17% cases scored 0, 32.9% scored 1, 30.8% scored 2, and 19.1% scored 3). The expression of HOTAIR did not correlate with nodal metastasis regardless of the scoring intensity or with other study parameters (age, tumor size and grade, expression status). Further analysis of TCGA dataset showed that HOTAIR expression was lower in ductal carcinomas but higher in ER-negative tumors. Overexpression of HOTAIR was not associated with nodal metastases or prognosis in ER-positive patients. Its function as a poor prognostic indicator in ER-negative patients was restricted to node-positive patients. HOTAIR appears to be a marker for lymphatic metastases rather than hematogenous metastases in ER-negative patients. PMID:25739705

Gökmen-Polar, Yesim; Vladislav, I. Tudor; Neelamraju, Yaseswini; Janga, Sarath C.; Badve, Sunil

2015-01-01

342

Prognostic Value of Combined Aquaporin 3 and Aquaporin 5 Overexpression in Hepatocellular Carcinoma  

PubMed Central

Background. Aquaporin (AQP) 3 and AQP 5 are involved in tumorigenesis and tumor progression of several tumor types. Aim. To investigate expression patterns and clinical significance of AQP3 and AQP5 in hepatocellular carcinoma (HCC). Methods. Immunohistochemistry was performed to detect the expression of AQP3 and AQP5 in HCC tissues. Results. Immunohistochemistry analysis showed the increased expression of AQP3 and AQP5 protein levels in HCC tissues compared with their adjacent nonneoplastic tissues (both P < 0.001). In addition, combined AQP3 and AQP5 protein expression was significantly associated with serum AFP (P = 0.008), tumor stage (P = 0.006), and tumor grade (P = 0.006). Moreover, HCC patients highly expressing both AQP3 and AQP5 proteins had worse 5-year disease-free survival and 5-year overall survival (P = 0.002 and 0.005, resp.). Furthermore, the Cox proportional hazards model showed that combined AQP3 and AQP5 protein expression was an independent poor prognostic factor for both 5-year disease-free survival (P = 0.009) and 5-year overall survival (P = 0.01) in HCC. Conclusion. Our data suggest for the first time that the aberrant expression of AQP3 and AQP5 proteins may be strongly related to tumor progression and prognosis in patients with HCC. The overexpression of AQP3 in combination with upregulation of AQP5 may be an unfavorable prognostic factor for HCC. PMID:24224160

Guo, Xiaodong; Sun, Ting; Yang, Mei; Li, Zhiyan; Li, Zhiwei; Gao, Yuejuan

2013-01-01

343

Prognostic value of proliferating cell nuclear antigen in parotid gland cancer.  

PubMed

Although cell proliferation is related to tumour aggressiveness and prognosis, there are few studies describing the expression of proliferative markers in salivary gland cancer. Our aim was to assess the long-term prognostic value of the proliferating cell nuclear antigen (PCNA) in a large group of histologically different salivary gland cancers. We analysed the expression of PCNA in 159 patients with parotid gland cancer by means of immunohistochemistry. The mean follow-up time was 56.6 months. A high expression of PCNA showed a significant correlation to the patients' pathological lymph node stage (p = 0.004). A high PCNA expression significantly indicated a poor 5-year disease-free (p = 0.046) and overall survival rate (p = 0.018). The PCNA expression was the only prognostic factor for a worse 5-year disease-free and overall survival in acinic cell carcinomas (p = 0.004, p = 0.022). The correlation between PCNA expression and survival probabilities of salivary gland cancer might make proliferation markers helpful tools in patient follow-up, prognosis and targeted therapy in salivary gland cancer in future. PMID:21874325

Stenner, Markus; Demgensky, Ariane; Molls, Christoph; Hardt, Aline; Luers, Jan C; Grosheva, Maria; Huebbers, Christian U; Klussmann, Jens P

2012-04-01

344

Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course  

PubMed Central

Pulmonary arterial hypertension (PAH) is a rapidly progressive pulmonary vascular disease with a multifactorial etiopathogenesis that can result in right-sided heart failure and death. A number of studies indicate that an early therapeutic intervention yields better results on disease progression as compared to delayed treatment. In this review, we will analyze treatment strategies that may be used for monitoring disease progression and for guiding treatment decisions. Several factors (ie, symptoms, functional class, exercise capacity as assessed by a walking test and cardiopulmonary stress testing, hemodynamic parameters, cardiac magnetic resonance imaging, and plasma levels of biochemical markers) have been prognostic of survival. These indicators may be used both at the time of diagnosis and during treatment follow-up. No resolutive therapy is currently available for PAH; however, in the last decade, the advent of specific pharmacological treatments has given new hope to patients suffering from this debilitating disease with a poor prognosis. Combination drug therapies offer increased benefits over monotherapy, and current guidelines recommend a sequential “add on” design approach for patients in functional class II–IV. The goal-oriented “treat to target” therapy sets the timing for treatment escalation in case of inadequate response to currently known prognostic indicators. To date, further longitudinal studies should be urgently conducted to identify new goals that may improve therapeutic strategies in order to optimize personalized treatment in PAH patients. PMID:25328398

Baldi, Fabiana; Fuso, Leonello; Arrighi, Eugenio; Valente, Salvatore

2014-01-01

345

Monosomal karyotypes among 1147 Chinese patients with acute myeloid leukemia: prevalence, features and prognostic impact.  

PubMed

A monosomal karyotype (MK), defined as ?2 autosomal monosomies or a single monosomy in the presence of additional structural abnormalities, was recently identified as an independent prognostic factor conveying an extremely poor prognosis in patients with acute myeloid leukemia (AML). In the present study, after excluding patients with t(15;17), t(8;21), inv(16) and normal karyotypes, 324 AML patients with cytogenetic abnormalities were the main subject of analysis. The incidences of MK were 13% in patients aged 15 to 60 years and 18% in those between 15 and 88 years old. MK was much more prevalent among elderly patients (p<0.001) and was significantly associated with the presence of -7, -5, del(5q), abn12p, abn17p, -18 or 18q-, -20 or 20q- and CK (for all p<0.001 except for abn12p p=0.009), and +8 or +8q was less frequent in MK+ AML(p=0.007). No correlation was noted between monosomal karyotype and FAB subtype (p>0.05); MK remained significantly associated with worse overall survival among patients with complex karyotype (p=0.032); A single autosomal monosomy contributed an additional negative effect in OS of patients with structural cytogenetic abnormalities (P=0.008). This report presents the prevalence, feature and prognostic impact of MK among a large series of Chinese AML patients from a single center for the first time. PMID:23317194

Yang, Xiao-Fei; Sun, Ai-Ning; Yin, Jia; Cai, Cheng-Sen; Tian, Xiao-Peng; Qian, Jun; Chen, Su-Ning; Wu, De-Pei

2012-01-01

346

Prognostic value of SATB2 expression in patients with esophageal squamous cell carcinoma  

PubMed Central

SATB2, a member of the family of special AT-rich binding proteins, has been shown to affect numerous tumorigenesis. However, the role of SATB2 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, the SATB2 expression was examined at mRNA and protein levels by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry in ESCC tissues and adjacent non-cancerous tissues. Statistical analyses were applied to test the associations between SATB2 expression, clinicopathologic factors, and prognosis. Western blotting and qRT-PCR showed that the expression levels of SATB2 mRNA and protein were both significantly lower in SATB2 tissues than those in non-cancerous tissues. Immunohistochemistry analysis showed that SATB2 expression was significantly correlated with clinical stage and Histological differentiation. The results of Kaplan-Meier analysis indicated that a low expression level of SATB2 resulted in a significantly poor prognosis of ESCC patients. Importantly, multivariate analysis showed that low SATB2 expression was an independent prognostic factor for ESCC patients. In sum, our data suggest that SATB2 plays an important role in ESCC progression, and that decreased expression of SATB2 in tumor tissues could be used as a potential prognostic marker for patients with ESCC. PMID:25755730

Geng, Guo-Jun; Li, Ning; Mi, Yan-Jun; Yu, Xiu-Yi; Luo, Xian-Yang; Gao, Jing; Luo, Qi-Cong; Xie, Jing-Dun; Fa, Xian-En; Jiang, Jie

2015-01-01

347

The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers  

PubMed Central

Triple negative breast cancer (TNBC) is one type of breast cancer (BC), which is defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her2). Its origins and development seem to be elusive. And for now, drugs like tamoxifen or trastuzumab which specifically apply to ER, PR or Her2 positive BC seem unforeseeable in TNBC clinical treatment. Due to its extreme malignancy, high recurrence rate and poor prognosis, a lot of work on the research of TNBC is needed. This review aims to summarize the latest findings in TNBC in risk factors, possible therapeutic targets and possible prognostic makers. PMID:25276378

Jiao, Qingli; Shao, Guoli; Peng, Haoyu; Wang, Mengchuan; Ji, Shufeng; Liu, Peng; Zhang, Jian

2014-01-01

348

Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: A meta-analysis  

PubMed Central

AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer. METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters. RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009). CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients.

Yang, Jian-Jun; Hu, Zhi-Gao; Shi, Wu-Xiang; Deng, Te; He, Song-Qing; Yuan, Sheng-Guang

2015-01-01

349

Lifecycle Prognostics Architecture for Selected High-Cost Active Components  

SciTech Connect

There are an extensive body of knowledge and some commercial products available for calculating prognostics, remaining useful life, and damage index parameters. The application of these technologies within the nuclear power community is still in its infancy. Online monitoring and condition-based maintenance is seeing increasing acceptance and deployment, and these activities provide the technological bases for expanding to add predictive/prognostics capabilities. In looking to deploy prognostics there are three key aspects of systems that are presented and discussed: (1) component/system/structure selection, (2) prognostic algorithms, and (3) prognostics architectures. Criteria are presented for component selection: feasibility, failure probability, consequences of failure, and benefits of the prognostics and health management (PHM) system. The basis and methods commonly used for prognostics algorithms are reviewed and summarized. Criteria for evaluating PHM architectures are presented: open, modular architecture; platform independence; graphical user interface for system development and/or results viewing; web enabled tools; scalability; and standards compatibility. Thirteen software products were identified and discussed in the context of being potentially useful for deployment in a PHM program applied to systems in a nuclear power plant (NPP). These products were evaluated by using information available from company websites, product brochures, fact sheets, scholarly publications, and direct communication with vendors. The thirteen products were classified into four groups of software: (1) research tools, (2) PHM system development tools, (3) deployable architectures, and (4) peripheral tools. Eight software tools fell into the deployable architectures category. Of those eight, only two employ all six modules of a full PHM system. Five systems did not offer prognostic estimates, and one system employed the full health monitoring suite but lacked operations and maintenance support. Each product is briefly described in Appendix A. Selection of the most appropriate software package for a particular application will depend on the chosen component, system, or structure. Ongoing research will determine the most appropriate choices for a successful demonstration of PHM systems in aging NPPs.

N. Lybeck; B. Pham; M. Tawfik; J. B. Coble; R. M. Meyer; P. Ramuhalli; L. J. Bond

2011-08-01

350

Molecular-pathological prognostic factors of gastric cancer: a review  

Microsoft Academic Search

Invasion and metastasis are critical determinants of cancer morbidity. Genes and molecules participating in these steps must be regarded as potential prognostic factors. Growth factors and their receptors, cell-cycle regulators, cell-adhesion molecules and matrix-degrading enzymes are those to be used as prognostic factors, including epidermal growth factor (EGF), EGF receptor, K-sam, HER-2, interleukin (IL)-8, vascular endothelial growth factor (VEGF), cyclin

Wataru Yasui; Naohide Oue; Phyu Phyu Aung; Shunji Matsumura; Mariko Shutoh; Hirofumi Nakayama

2005-01-01

351

Demographic and Prognostic Factors of 455 Patients with Acute Leukemia Admitted to Two Referral Hospitals in Tehran-Iran During Ten Years (2001-2011)  

PubMed Central

Background Global death toll of Acute Leukemia (AL), as a heterogeneous group of hematopoietic malignancies, is rather high, i.e. almost 74% of 300,000 new cases die every year. This reflects a poor prognosis of this malignancy in most parts of the world, where contemporary and rather complex remedies are not available. There are a few well documented reports about the epidemiologic features of AL at national level in Iran. This retrospective study demonstrates demographic and laboratory features of Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) patients admitted to the main referral oncology hospitals in the ex-Iran University of Medical Sciences in Tehran (Firoozgar and Rasoul-Akram hospitals) during the last decade (2001-2011). Methods Medical records of all patients admitted to the both hospitals diagnosed with AML and ALL were reviewed during the study period for demographic, biological and clinical characteristics at diagnosis. Results Four-hundred fifty five patients were diagnosed with AML and ALL, who admitted to the both hospitals during ten years, of whom 59.6 % (271 patients) were male. Fifty five percent of patients had AML and 44.6 % had ALL, both significantly dominated in men (p<0.001). AML patients died more significantly (p<0.05) and the most deaths occurred in older patients (p<0.001). Initial WBC count was significantly related to death (p= 0.001), where the least death (13%) occurred in the group with initial WBC between 5-10×103/?L and most of deceased had an initial WBC more than 10×103/?L. Logistic regression showed that age, fever and WBC were significant prognostic factors. Conclusion Demographic characteristics of AL patients were almost the same as other global reports. Most deaths occurred in older patients, those who had fever, and patients with higher WBC count at first admission, which warrants more investigations accurately and also improvements in hospital records. PMID:25628835

Ayremlou, Parvin; Razavi, Seyed Mohsen; Solaymani-Dodaran, Masoud; Vakili, Masoud; Asadi-Lari, Mohsen

2012-01-01

352

Diagnostic and Prognostic Models for Generator Step-Up Transformers  

SciTech Connect

In 2014, the online monitoring (OLM) of active components project under the Light Water Reactor Sustainability program at Idaho National Laboratory (INL) focused on diagnostic and prognostic capabilities for generator step-up transformers. INL worked with subject matter experts from the Electric Power Research Institute (EPRI) to augment and revise the GSU fault signatures previously implemented in the Electric Power Research Institute’s (EPRI’s) Fleet-Wide Prognostic and Health Management (FW-PHM) Suite software. Two prognostic models were identified and implemented for GSUs in the FW-PHM Suite software. INL and EPRI demonstrated the use of prognostic capabilities for GSUs. The complete set of fault signatures developed for GSUs in the Asset Fault Signature Database of the FW-PHM Suite for GSUs is presented in this report. Two prognostic models are described for paper insulation: the Chendong model for degree of polymerization, and an IEEE model that uses a loading profile to calculates life consumption based on hot spot winding temperatures. Both models are life consumption models, which are examples of type II prognostic models. Use of the models in the FW-PHM Suite was successfully demonstrated at the 2014 August Utility Working Group Meeting, Idaho Falls, Idaho, to representatives from different utilities, EPRI, and the Halden Research Project.

Vivek Agarwal; Nancy J. Lybeck; Binh T. Pham

2014-09-01

353

Prognostic stratification of colorectal cancer patients: current perspectives  

PubMed Central

Tumor staging according to the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis (TNM) system is currently regarded as the standard for staging of patients with colorectal cancer. This system provides the strongest prognostic information for patients with early stage disease and those with advanced disease. For patients with intermediate levels of disease, it is less able to predict disease outcome. Therefore, additional prognostic markers are needed to improve the management of affected patients. Ideal markers are readily assessable on hematoxylin and eosin-stained tumor slides, and in this way are easily applicable worldwide. This review summarizes the histological features of colorectal cancer that can be used for prognostic stratification. Specifically, we refer to the different histological variants of colorectal cancer that have been identified, each of these variants carrying distinct prognostic significance. Established markers of adverse outcomes are lymphatic and venous invasion, as well as perineural invasion, but underreporting still occurs in the routine setting. Tumor budding and tumor necrosis are recent advances that may help to identify patients at high risk for recurrence. The prognostic significance of the antitumor inflammatory response has been known for quite a long time, but a lack of standardization prevented its application in routine pathology. However, scales to assess intra- and peritumoral inflammation have recently emerged, and can be expected to strengthen the prognostic significance of the pathology report. PMID:25061338

Schneider, Nora I; Langner, Cord

2014-01-01

354

Prognostic Significance of Erythropoietin in Pancreatic Adenocarcinoma  

PubMed Central

Background Erythropoietin (Epo) administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC). Methodology The clinico-pathological relevance of hemoglobin (Hb, n?=?150), serum Epo (sEpo, n?=?87) and tissue expression of Epo/Epo receptor (EpoR, n?=?104) was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. Results Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05) and PDAC (p<0.001), reaching anemic grade in one third of patients. While inversely correlating to Hb (r?=??0.46), 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P?=?0.99) but not in PDAC (O/P?=?0.85). Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P?=?0.82 vs. 0.96; p<0.01)—although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ?16 mU/ml) were not significantly different in M0 (20%) and M1 (30%) groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05). The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. Conclusion/Significance Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold ?16 mU/ml by endogenous or exogenous means may predispose to or promote metastatic progression. PMID:21829709

Becker, Verena; Giese, Thomas; Bergmann, Frank; Hinz, Ulf; Keleg, Shereen; Heller, Anette; Sipos, Bence; Klingmüller, Ursula; Büchler, Markus W.; Werner, Jens; Giese, Nathalia A.

2011-01-01

355

Elucidating poor decision-making in a rat gambling task.  

PubMed

Although poor decision-making is a hallmark of psychiatric conditions such as attention deficit/hyperactivity disorder, pathological gambling or substance abuse, a fraction of healthy individuals exhibit similar poor decision-making performances in everyday life and specific laboratory tasks such as the Iowa Gambling Task. These particular individuals may provide information on risk factors or common endophenotypes of these mental disorders. In a rodent version of the Iowa gambling task--the Rat Gambling Task (RGT), we identified a population of poor decision makers, and assessed how these rats scored for several behavioral traits relevant to executive disorders: risk taking, reward seeking, behavioral inflexibility, and several aspects of impulsivity. First, we found that poor decision-making could not be well predicted by single behavioral and cognitive characteristics when considered separately. By contrast, a combination of independent traits in the same individual, namely risk taking, reward seeking, behavioral inflexibility, as well as motor impulsivity, was highly predictive of poor decision-making. Second, using a reinforcement-learning model of the RGT, we confirmed that only the combination of extreme scores on these traits could induce maladaptive decision-making. Third, the model suggested that a combination of these behavioral traits results in an inaccurate representation of rewards and penalties and inefficient learning of the environment. Poor decision-making appears as a consequence of the over-valuation of high-reward-high-risk options in the task. Such a specific psychological profile could greatly impair clinically healthy individuals in decision-making tasks and may predispose to mental disorders with similar symptoms. PMID:24339988

Rivalan, Marion; Valton, Vincent; Seriès, Peggy; Marchand, Alain R; Dellu-Hagedorn, Françoise

2013-01-01

356

Elucidating Poor Decision-Making in a Rat Gambling Task  

PubMed Central

Although poor decision-making is a hallmark of psychiatric conditions such as attention deficit/hyperactivity disorder, pathological gambling or substance abuse, a fraction of healthy individuals exhibit similar poor decision-making performances in everyday life and specific laboratory tasks such as the Iowa Gambling Task. These particular individuals may provide information on risk factors or common endophenotypes of these mental disorders. In a rodent version of the Iowa gambling task – the Rat Gambling Task (RGT), we identified a population of poor decision makers, and assessed how these rats scored for several behavioral traits relevant to executive disorders: risk taking, reward seeking, behavioral inflexibility, and several aspects of impulsivity. First, we found that poor decision-making could not be well predicted by single behavioral and cognitive characteristics when considered separately. By contrast, a combination of independent traits in the same individual, namely risk taking, reward seeking, behavioral inflexibility, as well as motor impulsivity, was highly predictive of poor decision-making. Second, using a reinforcement-learning model of the RGT, we confirmed that only the combination of extreme scores on these traits could induce maladaptive decision-making. Third, the model suggested that a combination of these behavioral traits results in an inaccurate representation of rewards and penalties and inefficient learning of the environment. Poor decision-making appears as a consequence of the over-valuation of high-reward-high-risk options in the task. Such a specific psychological profile could greatly impair clinically healthy individuals in decision-making tasks and may predispose to mental disorders with similar symptoms. PMID:24339988

Seriès, Peggy; Marchand, Alain R.; Dellu-Hagedorn, Françoise

2013-01-01

357

Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study  

PubMed Central

Minimal residual disease (MRD) is an important predictor of relapse in acute lymphoblastic leukemia (ALL), but its relationship to other prognostic variables has not been fully assessed. The Children's Oncology Group studied the prognostic impact of MRD measured by flow cytometry in the peripheral blood at day 8, and in end-induction (day 29) and end-consolidation marrows in 2143 children with precursor B-cell ALL (B-ALL). The presence of MRD in day-8 blood and day-29 marrow MRD was associated with shorter event-free survival (EFS) in all risk groups; even patients with 0.01% to 0.1% day-29 MRD had poor outcome compared with patients negative for MRD patients (59% ± 5% vs 88% ± 1% 5-year EFS). Presence of good prognostic markers TEL-AML1 or trisomies of chromosomes 4 and 10 still provided additional prognostic information, but not in National Cancer Insitute high-risk (NCI HR) patients who were MRD+. The few patients with detectable MRD at end of consolidation fared especially poorly, with only a 43% plus or minus 7% 5-year EFS. Day-29 marrow MRD was the most important prognostic variable in multi-variate analysis. The 12% of patients with all favorable risk factors, including NCI risk group, genetics, and absence of days 8 and 29 MRD, had a 97% plus or minus 1% 5-year EFS with nonintensive therapy. These studies are registered at www.clinicaltrials.gov as NCT00005585, NCT00005596, and NCT00005603. PMID:18388178

Borowitz, Michael J.; Devidas, Meenakshi; Hunger, Stephen P.; Bowman, W. Paul; Carroll, Andrew J.; Carroll, William L.; Linda, Stephen; Martin, Paul L.; Pullen, D. Jeanette; Viswanatha, David; Willman, Cheryl L.; Winick, Naomi; Camitta, Bruce M.

2008-01-01

358

WPSS is a strong prognostic indicator for clinical outcome of allogeneic transplant for myelodysplastic syndrome in Southeast Asian patients.  

PubMed

To better understand the predictive factors and improve clinical outcome of allogeneic transplant for patients with myelodysplastic syndrome (MDS), we retrospectively analyzed the post-transplant outcome of 60 Southeast Asian patients with MDS. Multivariate analysis showed that WHO classification-based Prognostic Scoring System (WPSS) significantly affect overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), and cumulative incidence of non-relapse mortality (CINRM). Stratified by WPSS into very low/low, intermediate, high, and very high-risk categories, 3-year OS was 100, 61, 37, and 18 % (p?=?0.02); PFS was 100, 55, 32, and 18 % (p?=?0.014); CIR was 12, 24, 38, and 59 % (p?=?0.024); CINRM was 0, 6, 12, and 26 % (p?=?0.037), respectively. WHO classification, Revised International Prognostic Scoring System (IPSS-R), IPSS-R-defined cytogenetic risk groups, donor gender, and acute and chronic graft vs host disease (GVHD) also influenced different aspects of transplant outcome. We found that WPSS is a powerful predictor of post-transplant outcome. WPSS provides an important model not only for prognostication but also for exploration of further post-transplant measures such as immunological maneuvers or novel therapy to improve the poor outcome of high-risk patients. PMID:25519475

Ma, Liyuan; Hao, Siguo; Diong, Colin; Goh, Yeow-Tee; Gopalakrishnan, Sathish; Ho, Aloysius; Hwang, William; Koh, Liang-Piu; Koh, Mickey; Lim, Zi-Yi; Loh, Yvonne; Poon, Michelle; Tan, Lip-Kun; Tan, Patrick; Linn, Yeh-Ching

2015-05-01

359

Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma.  

PubMed

Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature within the TBX21 subgroup also showed poor clinical outcome (P = .05). In AITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004). PMID:24632715

Iqbal, Javeed; Wright, George; Wang, Chao; Rosenwald, Andreas; Gascoyne, Randy D; Weisenburger, Dennis D; Greiner, Timothy C; Smith, Lynette; Guo, Shuangping; Wilcox, Ryan A; Teh, Bin Tean; Lim, Soon Thye; Tan, Soon Yong; Rimsza, Lisa M; Jaffe, Elaine S; Campo, Elias; Martinez, Antonio; Delabie, Jan; Braziel, Rita M; Cook, James R; Tubbs, Raymond R; Ott, German; Geissinger, Eva; Gaulard, Philippe; Piccaluga, Pier Paolo; Pileri, Stefano A; Au, Wing Y; Nakamura, Shigeo; Seto, Masao; Berger, Francoise; de Leval, Laurence; Connors, Joseph M; Armitage, James; Vose, Julie; Chan, Wing C; Staudt, Louis M

2014-05-01

360

CD14+HLA-DRlow/? expression: A novel prognostic factor in chronic lymphocytic leukemia  

PubMed Central

Currently, no prognostic factors exist for determining the host immune status of chronic lymphocytic leukemia (CLL) patients. Therefore, the present report analyzed cluster of differentiation 14 (CD14)+ human leukocyte antigen (HLA)-DRlow/? myeloid-derived suppressor cells (MDSC) from 49 CLL patients and demonstrated that these cells were significantly expanded in all CLL patients when compared with monoclonal B cell lymphocytosis patients and healthy volunteers. Furthermore, upregulation of CD14+HLA-DRlow/? MDSCs was correlated with CLL tumor progression and a poor prognosis for CLL patients, and CD14+HLA-DRlow/? MDSCs were significantly correlated with the presence of CD4+ T and CD5+CD19+ cells in CLL patients, which could significantly inhibit the CD4+ T-cell immune response, contributing to CLL cell progression in CLL patients. PMID:25663875

LIU, JINLIN; ZHOU, YONGLIE; HUANG, QIANG; QIU, LIANNV

2015-01-01

361

BIRTH CONTROL, CULTURE AND THE POOR.  

ERIC Educational Resources Information Center

EVIDENCE FROM STUDIES INDICATE THAT THE POOR DESIRE TO CONTROL THEIR FAMILY SIZE AND PREFER TO USE BIRTH CONTROL DEVICES (PILLS OR INTERUTERINE DEVICES) WHICH ARE NOT COITUS-CONNECTED AND ANTITHETICAL TO THEIR SEXUAL ATTITUDES AND TRADITIONS. CONTRARY TO THE BELIEF THAT THE POOR ARE LESS LIKELY TO UTILIZE EXISTING HEALTH FACILITIES OR TO TAKE PART…

RIESSMAN, CATHERINE KOHLER

362

Heritability of Poor Language Achievement among Twins.  

ERIC Educational Resources Information Center

To examine the basis of familiar associations with poor language achievement, 62 twin pairs and 3 triplet sets were studied in which at least one member presented poor oral-language status in the absence of other impairments. The language status of monozygotic pairs was highly similar. (Author/CR)

Tomblin, J. Bruce; Buckwalter, Paula R.

1998-01-01

363

Testing for Poor Responsiveness in Android Applications  

E-print Network

Testing for Poor Responsiveness in Android Applications Shengqian Yang Dacong Yan Atanas Rountev,yan,rountev}@cse.ohio-state.edu Abstract--An important category of defects in Android appli- cations are related to poor responsiveness responsiveness in Android software. When test cases are executed against the application GUI, artificial long

Rountev, Atanas "Nasko"

364

Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma  

PubMed Central

SUMMARY Purpose Lung cancer is the leading cause of cancer related mortality in the world. BAC is a subset of NSCLC that has recently gained attention because of distinct biologic and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods 46 cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. Results Age and histology (mucinous vs. non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95% CI 1.07-4.71, p=0.032), advanced stage (III or IV) (HR 2.17, 95% CI 1.004-4.71, p=0.049), and smoking status (HR 6.89, 95% CI 1.49-31.88, p=0.013) were associated with a worse prognosis. Conclusions Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients. PMID:17097759

Tsurutani, Junji; Steinberg, Seth M.; Ballas, Marc; Robertson, Matthew; LoPiccolo, Jaclyn; Soda, Hiroshi; Kohno, Shigeru; Egilsson, Valgardur; Dennis, Phillip A.

2007-01-01

365

Damage Propagation Modeling for Aircraft Engine Prognostics  

NASA Technical Reports Server (NTRS)

This paper describes how damage propagation can be modeled within the modules of aircraft gas turbine engines. To that end, response surfaces of all sensors are generated via a thermo-dynamical simulation model for the engine as a function of variations of flow and efficiency of the modules of interest. An exponential rate of change for flow and efficiency loss was imposed for each data set, starting at a randomly chosen initial deterioration set point. The rate of change of the flow and efficiency denotes an otherwise unspecified fault with increasingly worsening effect. The rates of change of the faults were constrained to an upper threshold but were otherwise chosen randomly. Damage propagation was allowed to continue until a failure criterion was reached. A health index was defined as the minimum of several superimposed operational margins at any given time instant and the failure criterion is reached when health index reaches zero. Output of the model was the time series (cycles) of sensed measurements typically available from aircraft gas turbine engines. The data generated were used as challenge data for the Prognostics and Health Management (PHM) data competition at PHM 08.

Saxena, Abhinav; Goebel, Kai; Simon, Don; Eklund, Neil

2008-01-01

366

Prognostics for advanced compressor health monitoring  

NASA Astrophysics Data System (ADS)

Axial flow compressors are subjected to demands for ever-increasing levels of pressure ratio at a compression efficiency that augments the overall cycle efficiency. However, unstable flow may develop in the compressor, which can lead to a stall or surge and subsequently to gas turbine failure resulting in significant downtime and cost to repair. To protect against these potential aerodynamic instabilities, compressors are typically operated with a stall margin. This means operating the compressor at less than peak pressure rise which results in a reduction in operating efficiency and performance. Therefore, it is desirable to have a reliable method to determine the state of a compressor by detecting the onset of a damaging event prior to its occurrence. In this paper, we propose a health monitoring scheme that gathers and combines the results of different diagnostic tools to maximize the advantages of each one while at the same time minimizing their disadvantages. This fusion scheme produces results that are better than the best result by any one tool used. In part this is achieved because redundant information is available that when combined correctly improves the estimate of the better tool and compensates for the shortcomings of the less capable tool. We discuss the usage of diagnostic information fusion for a compressor event coupled with proactive control techniques to support improved compressor performance while at the same time avoid the increased damage risk due to stall margin reduction. Discretized time to failure windows provide event prediction in a prognostic sense.

Krok, Michael J.; Goebel, Kai F.

2003-08-01

367

Integrating genomics into prognostic models for AML.  

PubMed

The use of genomic profiling in acute myeloid leukemia (AML) has led to an improved understanding of disease pathogenesis. Genomic profiling has given rise to fundamental observations about the biology of AML and has served to better define clinical outcomes for patients based on somatic mutational status. As additional mutations are identified with a known or postulated role in AML pathogenesis, the challenge ahead will be learning how to integrate these findings into clinical practice in such a way that they have a meaningful impact on patient care and, ultimately, on patient outcomes. Potential goals include using genomic information for refined risk stratification and clinical decision making, and to identify genetic lesions that guide the use of molecularly targeted therapies. The development of next-generation sequencing technologies has made genomic profiling a viable option for use in clinical practice because it can provide robust, high-coverage sequencing data for multiple genes in 1 assay, within a clinically reasonable time frame. The present article discusses recent candidate gene sequencing studies, the development of prognostic models based on these studies, and the current and potential future uses of next-generation sequencing technologies in making treatment decisions for patients with AML. PMID:25311742

Sanchez, Matias; Levine, Ross L; Rampal, Raajit

2014-10-01

368

Clinical Outcomes and Prognostic Factors of Empirical Antifungal Therapy with Itraconazole in the Patients with Hematological Malignancies: A Prospective Multicenter Observational Study in Korea  

PubMed Central

Purpose To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies. Materials and Methods Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled. Results The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) ?2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (?4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity. Conclusion We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole. PMID:24339281

Kim, Jin Seok; Cheong, June-Won; Shin, Ho Jin; Lee, Jong Wook; Lee, Je-Hwan; Yang, Deok-Hwan; Lee, Won Sik; Kim, Hawk; Park, Joon Seong; Kim, Sung-Hyun; Kim, Yang Soo; Kwak, Jae-Yong; Chae, Yee Soo; Park, Jinny; Do, Young Rok

2014-01-01

369

Prognostic values of chromosome 18q microsatellite alterations in stage II colonic carcinoma  

PubMed Central

AIM: To investigate the prognostic value of chromosome 18q microsatellite alterations (MA) in stage II colon cancer. METHODS: One hundred and six patients with sporadic stage II colon cancer were enrolled in this study. DNA was extracted from formalin-fixed, paraffin-embedded tumor and adjacent normal mucosal tissue samples. MA, including loss of heterozygosity (LOH) and microsatellite instability (MSI), was analyzed by polymerase chain reaction, polyacrylamide gel-electrophoresis and DNA sequencing at 5 microsatellite loci on chromosome 18q (D18S474, D18S55, D18S58, D18S61 and D18S64). RESULTS: Among the 102 patients eligible for MA information, the overall frequencies of LOH, high and low frequency MSI/microsatellite stable were 49.0%, 17.6% and 82.4%, respectively. The high frequency of 18q-LOH was significantly associated with the poor 5-year overall survival (OS) (P = 0.008) and disease free survival (P = 0.006). High levels of MSI were significantly associated with a longer 5-year OS (P = 0.045) while the higher frequency of 18q-LOH at the loci of D18S474 and D18S61 was significantly associated with a poorer 5-year OS (P = 0.010 and 0.005, respectively). But multivariate analysis showed that only the frequency of 18q-LOH was significantly associated with the prognosis of the disease. CONCLUSION: High frequency of 18q-LOH is an independent prognostic factor indicating poor prognosis of the patients with stage II colon cancer. PMID:21157981

Wang, Wei; Wang, Guo-Qiang; Sun, Xiao-Wei; Chen, Gong; Li, Yuan-Fang; Zhang, Li-Yi; Qiu, Hai-Bo; Huang, Chun-Yu; Zhan, You-Qing; Zhou, Zhi-Wei

2010-01-01

370

Correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma  

PubMed Central

Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman’s rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma. PMID:25755762

Zhai, Lu-Lu; Cai, Chong-Yang; Wu, Yang; Tang, Zhi-Gang

2015-01-01

371

Expression and prognostic value of estrogen receptor beta in breast cancer patients  

PubMed Central

This study is to determine the expression of estrogen receptor beta (ER?) in breast cancer patients and to evaluate its relationship with clinicopathological parameters of breast cancer and its effects on the prognosis of breast cancer patients. Paraffin-embedded primary tumor tissue sections from 490 breast cancer patients were collected consecutively from January 2000 to December 2010. They had complete clinical data and follow-up records. Immunohistochemical staining was conducted to determine ER? expression. The Kaplan-Meier method was used for survival analysis. Difference in survival was analyzed by the Log-Rank test. The Cox proportional hazard model was performed to evaluate the prognostic value of ER? expression in breast cancer patients. The ER? high and over expression rate in 490 breast patients was 22.4% (110/490). ER? expression was not associated with clinicopathological parameters of breast cancer. The mean survival time in patients with ER? negative expression, ER? low expression, ER? high expression and ER? over expression was 9.9 years, 9.2 years, 8.6 years and 5.6 years. Statistically, patients with ER? high and over expression had significantly shorter disease-free survival (DFS) time compared with the patients with ER? negative and low expression. The Cox multivariate analysis revealed that ER? high and over expression, the pathologic stages of tumor and chemotherapy were the independent predictors for poor DFS in breast cancer patients. ER? expression is an independent prognostic factor of breast cancer patients and its high and over expression indicates poor prognosis of breast cancer. There was no correlation between ER? expression and clinicopathological parameters in breast cancer. PMID:25419426

Guo, Liying; Zhu, Qianwen; Yilamu, Dilimina; Jakulin, Adina; Liu, Sha; Liang, Ting

2014-01-01

372

Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients  

PubMed Central

Background An imbalance between cell proliferation and programmed cell death can result in tumor growth. Although most systemic cytotoxic agents induce apoptosis in tumor cells, a high apoptotic rate in primary breast cancer correlates with poor prognosis. The aim of this study was to investigate the incidence and the prognostic significance of apoptotic disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients who either underwent primary surgery or primary systemic chemotherapy (PST). Methods A total of 383 primary breast cancer patients with viable DTC in the BM were included into this study. Eighty-five patients were initially treated with primary systemic chemotherapy whereas 298 patients underwent surgery first. Detection of apoptotic DTC were performed by immunocytochemistry using the M30 antibody which detects a neo-epitope expressed after caspase cleavage of cytokeratin 18 during early apoptosis. The median follow up was 44 months (range 10–88 months). Results Eighty-two of 298 (27%) primary operated patients and 41 of 85 (48%) patients treated with primary systemic systemic therapy had additional apoptotic DTC (M30 positive). In the neoadjuvant group M30-positive patients were less likely to suffer relapse than those without apoptotic DTC (7% vs. 23% of the events, p?=?0.049). In contrast, the detection of apoptotic DTC in patients treated by primary surgery was significantly associated with poor overall survival (5% vs. 12% of the events, p?=?0.008). Conclusions Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in patients with PST may be induced by the cytotoxic agents. Thus, both spontaneous and chemotherapy-induced apoptosis may have different prognostic significance. PMID:24894702

2014-01-01

373

Prognostic significance of the degree of extranodal extension in patients with penile carcinoma.  

PubMed

This study sought to assess the prognostic significance of the degree of extranodal extension (ENE) and several other risk factors in pathological ENE penile carcinoma. We analyzed prospectively collected data on a consecutive series of 31 chemotherapy-naive patients with proven ENE who underwent therapeutic regional lymphadenectomy. Postoperative external radiotherapy was then performed. We studied the extent of ENE utilizing a novel grading system and correlated patient grades with their outcome measures. ENE was graded as 1 - if the capsule of the lymph node (LN) was ruptured less than one-third of its circumference or 2 - if the capsule was disrupted more than one-third of its circumference or the entire LN was disrupted. We estimated overall survival (OS) using the Kaplan-Meier method. Multivariate analysis was performed according to the Cox proportional hazards model using factors that were identified as statistically significant in univariate analysis. The incidence rate of ENE was 51.8% in patients with pathological node-positive carcinoma of the penis. The median OS and 5-year survival were 18 months (95% confidence interval (CI), 14.4-21.6) and 23%, respectively. Prognostic variables on univariate analysis were ENE grade 2, ? 3 LNs with ENE, maximal LN ? 35 mm, ? 5 positive LNs and pelvic LN involvement. On multivariate analysis, only ENE grade 2 remained associated with decreased OS (hazard ratio (HR): 6.50). In conclusion, patients with ENE have a poor outcome, and ENE grade 2 is an independent predictive factor of poor OS in patients with pathological ENE penile carcinoma. PMID:24480925

Wang, Jin-You; Zhu, Yao; Tang, Shao-Xian; Zhang, Hai-Liang; Qin, Xiao-Jian; Zhang, Shi-Lin; Dai, Bo; Ye, Ding-Wei

2014-01-01

374

Prognostic value of KRAS and BRAF mutations in curatively resected colorectal cancer  

PubMed Central

AIM: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability (MSI) status in Japanese colorectal cancer (CRC) population. METHODS: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage?I-III CRC and examined associations of these mutations with disease-free survival (DFS) and overall survival (OS) using uni- and multivariate Cox proportional hazards models. RESULTS: KRAS and BRAF mutations were detected in 312 (38%) of 812 and 40 (5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males (P = 0.02), while the presence of BRAF mutations was significantly associated with the female gender (P = 0.006), proximal tumor location (P < 0.001), mucinous or poorly differentiated histology (P < 0.001), and MSI-high tumors (P < 0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS (HR = 1.35; 95%CI: 1.03-1.75) and OS (HR = 1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS (HR = 2.20; 95%CI: 1.19-4.06) and OS (HR = 2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS. CONCLUSION: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected CRC. PMID:25632202

Kadowaki, Shigenori; Kakuta, Miho; Takahashi, Shuhei; Takahashi, Akemi; Arai, Yoshiko; Nishimura, Yoji; Yatsuoka, Toshimasa; Ooki, Akira; Yamaguchi, Kensei; Matsuo, Keitaro; Muro, Kei; Akagi, Kiwamu

2015-01-01

375

Causes of death and prognostic factors in multiple endocrine neoplasia type 1: a prospective study: comparison of 106 MEN1/Zollinger-Ellison syndrome patients with 1613 literature MEN1 patients with or without pancreatic endocrine tumors.  

PubMed

Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking.To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%-14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled literature series, the main causes of MEN1-related deaths were due to the malignant nature of the PETs, followed by the malignant nature of thymic carcinoid tumors. These results differ from the results of a number of the literature series, especially those reported before the 1990s. The causes of non-MEN1-related death for the 2 series, in decreasing frequency, were cardiovascular disease, other nonendocrine tumors > lung diseases, cerebrovascular diseases. The most frequent non-MEN1-related tumor deaths were colorectal, renal > lung > breast, oropharyngeal. Although both overall and disease-related survival are better than in the past (30-yr survival of NIH series: 82% overall, 88% disease-related), the mean age at death was 55 years, which is younger than expected for the general population.Detailed analysis of causes of death correlated with clinical, laboratory, and tumor characteristics of patients in the 2 series allowed identification of a number of prognostic factors. Poor prognostic factors included higher fasting gastrin levels, presence of other functional hormonal syndromes, need for >3 parathyroidectomies, presence of liver metastases or distant metastases, aggressive PET growth, large PETs, or the development of new lesions.The results of this study have helped define the causes of death of MEN1 patients at present, and have enabled us to identify a number of prognostic factors that should be helpful in tailoring treatment for these patients for both short- and long-term management, as well as in directing research efforts to better define the natural history of the disease and the most important factors determining long-term survival at present. PMID:23645327