WorldWideScience

Sample records for prognosis remains poor

  1. Data-driven remaining useful life prognosis techniques stochastic models, methods and applications

    CERN Document Server

    Si, Xiao-Sheng; Hu, Chang-Hua

    2017-01-01

    This book introduces data-driven remaining useful life prognosis techniques, and shows how to utilize the condition monitoring data to predict the remaining useful life of stochastic degrading systems and to schedule maintenance and logistics plans. It is also the first book that describes the basic data-driven remaining useful life prognosis theory systematically and in detail. The emphasis of the book is on the stochastic models, methods and applications employed in remaining useful life prognosis. It includes a wealth of degradation monitoring experiment data, practical prognosis methods for remaining useful life in various cases, and a series of applications incorporated into prognostic information in decision-making, such as maintenance-related decisions and ordering spare parts. It also highlights the latest advances in data-driven remaining useful life prognosis techniques, especially in the contexts of adaptive prognosis for linear stochastic degrading systems, nonlinear degradation modeling based pro...

  2. RSPF-based Prognosis Framework for Estimation of Remaining Useful Life in Energy Storage Devices

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper presents a case study where a RSPF-based prognosis framework is applied to estimate the remaining useful life of an energy storage device (Li-Ion...

  3. Why does Bangladesh remain so poor? Part II: eight answers.

    Science.gov (United States)

    Maloney, C

    1985-01-01

    Bangladeshis of varying background all over the country were asked why they think poverty persists to such an extent in Bangladesh. Their answers provide a new perspective on the situation. The initial response often blames outside and natural causes -- floods, droughts, lack of resources, low demand for the country's exports, or historic exploitation. It is true that Bangladesh has virtually no mineral resources except gas. Yet, the soil, water, and human labor add up to a huge potential. The Third Five Year Plan emphasizes use of the soil, irrigation, tanks, rivers, and human labor. These provide the only hope for reducing poverty a little during the next 5 years. Bangladeshis as well as foreign observers most commonly cite overpopulation as the cause of poverty. Population growth is a cause of present poverty in Bangladesh but is not the only cause of poverty. The Third Five Year Plan goal to reduce annual growth to 1.8% is ambitious, but even if it is achieved the population will double in a few decades. As it would most likely be impossible for Bangladesh to support such numbers and maintain political and economic stability, such growth will have to be prevented. Poverty in Bangladesh is party a result of the long history of low urbanization, weak institutions, spotty and inadequate physical infrastructure, and insufficient entrapreneurship. Other reasons cited as causes of persisting poverty include illiteracy, idleness, class exploitation, the selfishness of individuals, and a lack of trust among people. All of the efforts of the poor themselves, various agencies, and the government, as examined in the 1st part of this discussion, fail to indicate any reason to hope that poverty in Bangladesh can be dramatically reduced any time soon. The Third Five Year Plan foresees a possible reduction of the number of those in poverty by 10%. According to the Plan itself, those in or near poverty comprise 85% of the people. The conditions under which the people of some

  4. Poor Prognosis in Acute Myeloid Leukemia Patients with Monosomal Karyotype

    Directory of Open Access Journals (Sweden)

    Junqing Xu

    2017-06-01

    Full Text Available Objective: This study aimed to investigate the clinical characteristics and prognostic significance of monosomal karyotypes (MKs in patients with acute myeloid leukemia (AML. Materials and Methods: We retrospectively analyzed the clinical data for 498 patients with AML, of whom 233 (46.8% had an abnormal karyotype, including 42 with MKs (8.4% and 70 with a complex karyotype (CK (14.1%. Results: Patients with MKs were older (median age 62.5 vs. 52 years, p=0.003 and had lower median hemoglobin levels (62.5 vs. 77 g/L, p=0.009 and lower white blood cell counts (7.0×109/L vs. 11.7×109/L, p=0.008. Univariate analysis showed that patients with MKs or CKs had shorter overall survival than patients without these karyotypes (median survival time 7.3 vs. 26.3 months for MK, p<0.001, and 14.8 vs. 26.3 months for CK, p<0.001. In multivariable analysis for overall survival, MK and National Comprehensive Cancer Network prognostic group were the only significant factors. Conclusion: MK is an independent risk factor for poor prognosis in AML patients.

  5. Apathy is associated with poor prognosis in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Caga, J; Turner, M R; Hsieh, S; Ahmed, R M; Devenney, E; Ramsey, E; Zoing, M C; Mioshi, E; Kiernan, M C

    2016-05-01

    Apathy is the most commonly reported behavioural change in amyotrophic lateral sclerosis (ALS). However, the degree to which it affects prognosis and overlaps with depression in this population is unknown. The present study examined the relationship between level of apathy, mortality and survival time and whether apathy was linked to specific symptom clusters of depression. A cohort of 76 consecutive ALS patients attending specialized multidisciplinary clinics were classified according to level of apathy. The effects of clinical factors and apathy on survival time were analysed using univariate and multivariate methods. The majority of patients with moderate to severe apathy died during the study (P = 0.003) and had a median survival time of 21.7 months, considerably shorter than patients with mild apathy (46.9 months) and no apathy (51.9 months) (P = 0.0001). Apathy remained a significant predictor of survival even after controlling for clinical factors and symptom duration at the time of study entry (hazard ratio 3.8, 95% confidence interval 1.9-7.5, P = 0.0001). Depression with demoralization was not associated with level of apathy (P = 0.172) whereas depression with anhedonia was more common in patients with apathy than in those without apathy (P = 0.006). The presence of severe apathy is an independent, negative prognostic factor in ALS. © 2016 EAN.

  6. [Congenital anomalies of poor prognosis. Genetics Consensus Committee].

    Science.gov (United States)

    Pardo Vargas, Rosa A; Aracena, Mariana; Aravena, Teresa; Cares, Carolina; Cortés, Fanny; Faundes, Víctor; Mellado, Cecilia; Passalacqua, Cristóbal; Sanz, Patricia; Castillo Taucher, Silvia

    The Genetic Branch of the Chilean Society of Paediatrics, given the draft Law governing the decriminalisation of abortion on three grounds, focusing on the second ground, which considers the "embryo or foetus suffering from a congenital structural anomaly or a genetic disorder incompatible with life outside the womb", met to discuss the scientific evidence according to which congenital anomalies (CA) may be included in this draft law. Experts in clinical genetics focused on 10 CA, reviewed the literature evidence, and met to discuss it. It was agreed not to use the term "incompatible with life outside the womb", as there are exceptions and longer survivals, and change to "congenital anomaly of poor prognosis (CAPP)". Ten CA were evaluated: serious defects of neural tube closure: anencephaly, iniencephaly and craniorachischisis, pulmonary hypoplasia, acardiac foetus, ectopia cordis, non-mosaic triploidy, "limb body wall" complex, "body stalk" anomaly, trisomy 13, trisomy 18, and bilateral renal agenesis. Findings on the prevalence, natural history, prenatal diagnostic methods, survival, and reported cases of prolonged survival were analysed. Post-natal survival, existence of treatments, and outcomes, as well as natural history without intervention, were taken into account in classifying a CA as a CAPP. A CAPP would be: anencephaly, severe pulmonary hypoplasia, acardiac foetus, cervical ectopia cordis, non-mosaic triploidy, limb body wall complex, body stalk anomaly, non-mosaic trisomy 13, non-mosaic trisomy 18, and bilateral renal agenesis. For their diagnosis, it is required that all pregnant women have access to assessments by foetal anatomy ultrasound and occasionally MRI, and cytogenetic and molecular testing. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Risk Factors of Poor Prognosis after Whiplash Injury

    Directory of Open Access Journals (Sweden)

    Samy Suissa

    2003-01-01

    and symptoms that were found to be independently associated with a slower recovery from whiplash, besides female gender and older age, were neck pain on palpation; muscle pain; pain or numbness radiating from neck to arms, hands or shoulders; and headache. Together, the presence of all these factors in females aged 60 predicted a median recovery time of 262 days, compared with 17 days for younger males aged 20 who do not have any of these factors. In contrast, using the Quebec classification of signs and symptoms, the median recovery time varied from 17 to 123 days. We conclude that several socio-demographic and crash-related factors, as well as several signs and symptoms, including a combination of specific musculoskeletal and neurological ones that whiplash patients present with, are predictive of a longer recovery period. These patients should be targeted for an early intervention programme aimed at managing whiplash patients with a poor prognosis.

  8. Genetic Predictors of Poor Prognosis in Portuguese Patients with Juvenile Idiopathic Arthritis: Data from Reuma.pt

    Science.gov (United States)

    Mourão, Ana Filipa; Santos, Maria José; Mendonça, Sílvia; Oliveira-Ramos, Filipa; Salgado, Manuel; Estanqueiro, Paula; Melo-Gomes, José; Martins, Fernando; Lopes, Ana; Bettencourt, Bruno Filipe; Bruges-Armas, Jácome; Costa, José; Furtado, Carolina; Figueira, Ricardo; Brito, Iva; Branco, Jaime; Fonseca, João Eurico; Canhão, Helena

    2015-01-01

    Introduction. This study aimed to assess the genetic determinants of poor outcome in Portuguese patients with juvenile idiopathic arthritis (JIA). Methods. Our study was conducted in Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA. We collected prospectively patient and disease characteristics and a blood sample for DNA analysis. Poor prognosis was defined as CHAQ/HAQ >0.75 at the last visit and/or the treatment with biological therapy. A selected panel of single nucleotide polymorphisms (SNPs) associated with susceptibility was studied to verify if there was association with poor prognosis. Results. Of the 812 patients with JIA registered in Reuma.pt, 267 had a blood sample and registered information used to define “poor prognosis.” In univariate analysis, we found significant associations with poor prognosis for allele A of TNFA1P3/20 rs6920220, allele G of TRAF1/C5 rs3761847, and allele G of PTPN2 rs7234029. In multivariate models, the associations with TRAF1/C5 (1.96 [1.17–3.3]) remained significant at the 5% level, while TNFA1P3/20 and PTPN2 were no longer significant. Nevertheless, none of associations found was significant after the Bonferroni correction was applied. Conclusion. Our study does not confirm the association between a panel of selected SNP and poor prognosis in Portuguese patients with JIA. PMID:26504858

  9. Claudin-1 correlates with poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Sun, Bing-Sheng; Yao, Yi-Qun; Pei, Bao-Xiang; Zhang, Zhen-Fa; Wang, Chang-Li

    2016-09-01

    This study was conducted to investigate the clinical significance of claudin-1 (CLDN1) expression in patients with lung adenocarcinoma. We examined CLDN1 protein expression by immunohistochemistry in a tissue microarray from 258 patients with lung adenocarcinoma. We investigated messenger ribonucleic acid (mRNA) expression in H358 (formerly bronchioloalveolar carcinoma) and lung adenocarcinoma cell lines (A549) by real-time reverse transcriptase-polymerase chain reaction. Multivariate analysis showed that prognostic factors for lung adenocarcinoma were histologic type, CLDN1, T stage and N stage. Patients with positive CLDN1 expression had a poorer prognosis than patients with negative CLDN1 expression. CLDN1 expression was correlated with Ras and epidermal growth factor receptor (EGFR) expression. Patients with positive expressions of both CLDN1 and Ras/EGFR had a poorer prognosis than patients with CLDN1 (+) Ras/EGFR(-) or CLDN1 (-) Ras/EGFR(+) and patients with negative expressions of both CLDN1 and Ras/EGFR. CLDN1 mRNA expression was lower in the H358 compared with the lung adenocarcinoma cell line (A549). The combination of CLDN1 and Ras/EGFR is a valuable independent prognostic predictor for lung adenocarcinoma. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  10. High YBX1 expression indicates poor prognosis and promotes cell migration and invasion in nasopharyngeal carcinoma.

    Science.gov (United States)

    Zhou, Lei-Lei; Ni, Jie; Feng, Wan-Ting; Yao, Rong; Yue, Shun; Zhu, Ya-Ning; Tang, Hai-Yan; Lv, Ling-Yun; Feng, Ji-Feng; Zhu, Wei-Guo

    2017-12-01

    Y-box binding protein-1 (YBX1) is a multifunctional protein and often acts as an indicator of poor prognosis in cancers. Increasing evidence has shown that the levels of YBX1 protein were closely associated with multidrug resistance, relapse, metastasis and poor prognosis in cancers. However, its role in nasopharyngeal carcinoma (NPC) metastasis remains unknown. In our study, we discovered that the expression of YBX1 was increased in nasopharyngeal carcinoma tissues. YBX1 protein levels positively correlated with T stage and metastasis of NPC patients. Moreover, expression of YBX1 was negatively correlated with membrane E-cadherin levels and positively correlated with Vimentin expression. In vitro, the expression of YBX1 was closely related to the invasive and migratory ability of nasopharyngeal carcinoma cells. Knockdown of YBX1 inhibited migration and invasion in 5-8F cells, and over-expression of YBX1 promoted CNE1 cells migration and invasion. Transforming growth factor-β1 (TGF-β1) treatment led to epithelial-to-mesenchymal transition (EMT) in CNE1 cells accompanied by elevated YBX1 expression. On the contrary, knockdown of YBX1 partially inhibited the TGF-β1-induced CNE1 cell migration, together with changes of EMT-associated markers. Our study revealed that TGF-β1/YBX1 signaling might be one of novel mechanisms mediating EMT in NPC, providing a new target for the treatment of nasopharyngeal carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Increased PTOV1 expression is related to poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Guo, Fei; Feng, Liu; Hu, Ji-Long; Wang, Mei-Ling; Luo, Peng; Zhong, Xiao-Ming; Deng, An-Mei

    2015-01-01

    Altered expression of prostate tumor overexpressed-1 (PTOV1) is observed in various types of human cancers. However, the role of PTOV1 in epithelial ovarian cancer (EOC) remains unclear. PTOV1 messenger (m)RNA expression in EOC patients was evaluated by quantitative real-time PCR (qRT-PCR). PTOV1 protein expression was also analyzed in archived paraffin-embedded EOC tissues using immunohistochemistry (IHC), and its association with overall survival of patients was analyzed by statistical analysis. Results from qRT-PCR analysis show that the expression level of PTOV1 mRNA was significantly higher in tumor tissues of EOC, compared to that in adjacent noncancerous tissues (P IHC staining showed that high expression of PTOV1 was detected in 57.2 % (87/152) of EOC cases. High expression of PTOV1 was significantly associated with pathological grade (P = 0.029) and clinical stage (P = 0.001). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of PTOV1 resulted in a significantly poor prognosis of EOC patients. Multivariate analysis showed that high expression of PTOV1 was an independent prognostic factor for overall survival (P < 0.001). In conclusion, PTOV1 protein abnormal expression might contribute to the malignant progression of EOC. High expression of PTOV1 predicts poor prognosis in patients with EOC.

  12. Progression of urinary protein excretion after kidney transplantation: A marker for poor long-term prognosis

    Directory of Open Access Journals (Sweden)

    Josefa Borrego Hinojosa

    2015-07-01

    Conclusions: Proteinuria after transplantation, essentially when it progresses, is a marker of a poor prognosis and a predictor for graft survival. Progression of proteinuria is associated with poorer renal function and lower graft survival rates.

  13. Discovery of dachshund 2 protein as a novel biomarker of poor prognosis in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Nodin Björn

    2012-01-01

    Full Text Available Abstract Background The Dachshund homolog 2 (DACH2 gene has been implicated in development of the female genital tract in mouse models and premature ovarian failure syndrome, but to date, its expression in human normal and cancerous tissue remains unexplored. Using the Human Protein Atlas as a tool for cancer biomarker discovery, DACH2 protein was found to be differentially expressed in epithelial ovarian cancer (EOC. Here, the expression and prognostic significance of DACH2 was further evaluated in ovarian cancer cell lines and human EOC samples. Methods Immunohistochemical expression of DACH2 was examined in tissue microarrays with 143 incident EOC cases from two prospective, population-based cohorts, including a subset of benign-appearing fallopian tubes (n = 32. A nuclear score (NS, i.e. multiplier of staining fraction and intensity, was calculated. For survival analyses, cases were dichotomized into low (NS 3 using classification and regression tree analysis. Kaplan Meier analysis and Cox proportional hazards modelling were used to assess the impact of DACH2 expression on survival. DACH2 expression was analysed in the cisplatin sensitive ovarian cancer cell line A2780 and its cisplatin resistant derivative A2780-Cp70. The specificity of the DACH2 antibody was tested using siRNA-mediated silencing of DACH2 in A2780-Cp70 cells. Results DACH2 expression was considerably higher in the cisplatin resistant A2780-Cp70 cells compared to the cisplatin-sensitive A2780 cells. While present in all sampled fallopian tubes, DACH2 expression ranged from negative to strong in EOC. In EOC, DACH2 expression correlated with several proteins involved in DNA integrity and repair, and proliferation. DACH2 expression was significantly higher in carcinoma of the serous subtype compared to non-serous carcinoma. In the full cohort, high DACH2 expression was significantly associated with poor prognosis in univariable analysis, and in carcinoma of the serous subtype

  14. High expression of Ki-67 acts a poor prognosis indicator in locally advanced nasopharyngeal carcinoma.

    Science.gov (United States)

    Zhao, Yajie; Shen, Lin; Huang, Xinqiong; Jing, Di; Huang, David; Fu, Jun; Li, Zhanzhan; Zhang, Guangying; Shen, Liangfang

    2017-12-09

    Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy in Southern China and Southeast Asia compared with Western countries. The standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to satisfactory treatment, it can cause local recurrence and distant metastases in some patients after treatment by radiation. We retrospectively reviewed 108 NPC patients (7th AJCC Ⅲ-Ⅳa) who have received intensity modulated radiation therapy (IMRT) between August 2008 and January 2012 at Xiangya Hospital of Central South University. Ninety-eight patients with >60% reduction of tumor size after radiation treatment were regarded as radiation sensitive, Ten patients with carcinoma patients [Hazard ratio (95% CI), 2.098(1.101, 3.996); p = 0.024]. These results demonstrate that high expression of Ki-67 contributes to radiation resistance and acts a poor prognosis indicator in patients with locally advanced nasopharyngeal carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Decreased FOXD3 Expression Is Associated with Poor Prognosis in Patients with High-Grade Gliomas.

    Directory of Open Access Journals (Sweden)

    Wei Du

    Full Text Available The transcription factor forkhead box D3 (FOXD3 plays important roles in the development of neural crest and has been shown to suppress the development of various cancers. However, the expression and its potential biological roles of FOXD3 in high-grade gliomas (HGGs remain unknown.The mRNA and protein expression levels of FOXD3 were examined using real-time quantitative PCR and western blotting in 23 HGG and 13 normal brain samples, respectively. Immunohistochemistry was used to validate the expression FOXD3 protein in 184 HGG cases. The association between FOXD3 expression and the prognosis of HGG patients were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression models. In addition, we further examined the effects of FOXD3 on the proliferation and serum starvation-induced apoptosis of glioma cells.In comparison to normal brain tissues, FOXD3 expression was significantly decreased in HGG tissues at both mRNA and protein levels. Immunohistochemistry further validated the expression of FOXD3 in HGG tissues. Moreover, low FOXD3 expression was significantly associated with poor prognosis in HGG patients. Depletion of FOXD3 expression promoted glioma cell proliferation and inhibited serum starvation-induced apoptosis, whereas overexpression of FOXD3 inhibited glioma cell proliferation and promoted serum starvation-induced apoptosis.Our results indicated that FOXD3 might serve as an independent prognostic biomarker and a potential therapeutic target for HGGs, which warrant further investigation.

  16. Oral cavity tumors in younger patients show a poor prognosis and do not contain viral RNA.

    Science.gov (United States)

    Brägelmann, J; Dagogo-Jack, I; El Dinali, M; Stricker, T; Brown, C D; Zuo, Z; Khattri, A; Keck, M; McNerney, M E; Longnecker, R; Bieging, K; Kocherginsky, M; Alexander, K; Salgia, R; Lingen, M W; Vokes, E E; White, K P; Cohen, E E W; Seiwert, T Y

    2013-06-01

    Oral cavity and in particular oral tongue cancers occur with a rising incidence in younger patients often lacking the typical risk factors of tobacco use, alcohol use, and human papilloma virus (HPV) infection. Their prognosis when treated with chemoradiation has not been well studied and responsible risk factors remain elusive. A viral etiology (other than HPV) has been hypothesized. First we analyzed outcomes from 748 head and neck cancer patients with locoregionally advanced stage tumors treated with curative-intent chemoradiation by anatomic site. Second, we analyzed seven oral tongue (OT) tumors from young, non-smokers/non-drinkers for the presence of viral mRNA using short-read massively-parallel sequencing (RNA-Seq) in combination with a newly-developed digital subtraction method followed by viral screening and discovery algorithms. For positive controls we used an HPV16-positive HNC cell line, a cervical cancer, and an EBV-LMP2A transgene lymphoma. Younger patients with oral cavity tumors had worse outcomes compared to non-oral cavity patients. Surprisingly none of the seven oral tongue cancers showed significant presence of viral transcripts. In positive controls the expected viral material was identified. Oral cavity tumors in younger patients have a poor prognosis and do not appear to be caused by a transcriptionally active oncovirus. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

    Directory of Open Access Journals (Sweden)

    Fabien Vidal

    Full Text Available Early recurrence (ER after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS at 12 months after relapse and determined parameters associated to poor prognosis.The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months and 65 survived after one year (mean OS = 26.9 months. Residual disease (RD after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively. The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5.ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters.

  18. High plasma interleukin-6 levels associated with poor prognosis of patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Shao, Yu-Yun; Lin, Hang; Li, Yong-Shi; Lee, Ying-Hui; Chen, Ho-Min; Cheng, Ann-Lii; Hsu, Chih-Hung

    2017-10-01

    Antiangiogenic therapy is crucial for advanced hepatocellular carcinoma (HCC) treatment. Interleukin (IL)-6 is an inflammatory response mediator that can promote angiogenesis. We explored its prognostic role in patients with advanced HCC. We had two patient cohorts, both comprising patients who received sorafenib-containing therapy as the first-line treatment for advanced HCC. We explored the best cut point for pretreatment plasma IL-6 levels in the exploration cohort and then confirmed it in the validation cohort. In total, 55 and 73 patients constituted the exploration and validation cohorts, respectively. In the exploration cohort, a cut point of 4.28 pg/ml was the best for defining high and low IL-6 levels because it could most effectively differentiate overall survival (OS). On application of this cut point to the validation cohort, patients with high plasma IL-6 levels, compared with patients with low IL-6 levels, exhibited significantly poorer OS (median, 8.0 vs 13.9 months, P = 0.031) but similar progression-free survival or treatment response. After adjusting for patient demographics and tumor characteristics, a high plasma IL-6 level remained an independent predictor of poor OS (hazard ratio 2.594, P = 0.005). High pretreatment plasma IL-6 levels were associated with poor prognosis of patients with advanced HCC.

  19. CREPT expression correlates with poor prognosis in patients with retroperitoneal leiomyosarcoma

    Science.gov (United States)

    She, Yaoguang; Liang, Jiao; Chen, Lin; Qiu, Ying; Liu, Na; Zhao, Xudong; Huang, Xiaohui; Wang, Yinyin; Ren, Fangli; Chang, Zhijie; Li, Peiyu

    2014-01-01

    Retroperitoneal leiomyosarcomas (LMSs) are rare gynecological malignancies that display poor prognosis and high mortality. Cell cycle-related and expression-elevated protein in tumor (CREPT) is an oncogene that is involved in the regulation of many cell cycle-related proteins. However, its distribution and clinical significance in retroperitoneal LMS remains poorly understood. This study assessed the histological classifications of postoperative tumor samples from 71 cases of retroperitoneal LMS that were collected at The General Hospital of the People’s Liberation Army from January 1998 to December 2012. We found that more than half of the patients displayed positive expressions of CREPT, Ki-67 and PCNA via immunohistochemical analysis. The expression of CREPT correlated with histological grade (P = 0.044), and the PCNA expression level correlated with the differentiation of tumor cells and histological grade (P retroperitoneal LMS tumor tissue than in paired control tissue. Based on the above data, we concluded that CREPT displays unique immunostaining for retroperitoneal LMS tissue and can be used to supplement other currently available retroperitoneal LMS markers. PMID:25400738

  20. Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma

    Science.gov (United States)

    Sung, Pi-Lin; Jan, Yi-Hua; Lin, Shih-Chieh; Huang, Chao-Cheng; Lin, Hao; Wen, Kuo-Chang; Chao, Kuan-Chong; Lai, Chiung-Ru; Wang, Peng-Hui; Chuang, Chi-Mu; Wu, Hua-Hsi; Twu, Nae-Fang; Yen, Ming-Shyen; Hsiao, Michael; Huang, Chi-Ying F.

    2016-01-01

    The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics. PMID:26716408

  1. Allergens associated with severe symptoms of hand eczema and a poor prognosis

    DEFF Research Database (Denmark)

    Hald, Marianne; Agner, Tove; Blands, Jette

    2009-01-01

    BACKGROUND: Contact allergy is frequent among persons with hand eczema and may be associated with a poor prognosis. OBJECTIVES: To identify allergens associated with the most severe initial clinical symptoms and the worst prognosis in a cohort of hand eczema patients followed for 6 months. METHODS......: The study population comprised 799 consecutive hand eczema patients enrolled during January 2006-February 2007. All patients were patch tested with the European baseline series. Severity assessment of the hand eczema was performed initially and at the 6-month follow-up using a validated scoring system...... (HECSI). With logistic regression analyses, associations of severe hand eczema or a poor prognosis with 15 individual allergens were analysed and adjusted for by sex, age, atopic dermatitis and other allergens. RESULTS: At baseline, greater severity of hand eczema was associated with a positive patch...

  2. Deregulation of COMMD1 Is Associated with Poor Prognosis in Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Taskinen, M.; Louhimo, R.; Koivula, S.

    2014-01-01

    Background: Despite improved survival for the patients with diffuse large B-cell lymphoma (DLBCL), the prognosis after relapse is poor. The aim was to identify molecular events that contribute to relapse and treatment resistance in DLBCL. Methods: We analysed 51 prospectively collected pretreatme...

  3. Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chenchen; Yue, Ben; Yuan, Chenwei; Zhao, Senlin; Fang, Changyi; Yu, Yang; Yan, Dongwang, E-mail: yandw70@163.com

    2015-12-04

    The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.

  4. WDR62 overexpression is associated with a poor prognosis in patients with lung adenocarcinoma.

    Science.gov (United States)

    Shinmura, Kazuya; Kato, Hisami; Kawanishi, Yuichi; Igarashi, Hisaki; Inoue, Yusuke; Yoshimura, Katsuhiro; Nakamura, Satoki; Fujita, Hidehiko; Funai, Kazuhito; Tanahashi, Masayuki; Niwa, Hiroshi; Ogawa, Hiroshi; Sugimura, Haruhiko

    2017-08-01

    Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test). An immunohistochemical analysis for LAC (n = 237) showed that WDR62 proteins were also significantly overexpressed in LAC (P lung cancer cell line H1299. WDR62-overexpressing lung cancer cells exhibited an increase in cell growth. Moreover, the concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in LAC, induced centrosome amplification in the lung cells. Finally, we disclosed that the concurrent overexpression of WDR62 and TPX2 is common in diverse human cancers, using data from the Cancer Genome Atlas. These results suggested that WDR62 overexpression is associated with a poor prognosis in patients with LAC and leads to an increase in the malignant potential of lung cells. © 2017 Wiley Periodicals, Inc.

  5. HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

    LENUS (Irish Health Repository)

    2012-02-01

    p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

  6. HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

    LENUS (Irish Health Repository)

    2011-06-01

    p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

  7. Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review.

    Science.gov (United States)

    Chmielewski, Piotr Paweł; Strzelec, Bartłomiej

    2017-10-24

    Total leukocyte count increases significantly in response to infection, trauma, inflammation, and certain diseases. Factors affecting leukocyte count in healthy adults include sex, hormonal milieu, genetic inheritance, stress level, diet, nutrition, and lifestyle (e.g. tobacco-induced inflammatory changes, chronic psychological stress, etc.). To date, numerous studies have reported that high but normal leukocyte counts at baseline predict increased cardiovascular and noncardiovascular mortality in older adults. Recent findings suggest that elevated leukocyte count within the normal range, but especially neutrophil and monocyte counts, may be a harbinger of increased systemic inflammation and subclinical disease. Moreover, elderly people who tend to have high but normal leukocyte counts are at greater risk of cancer, cardiovascular disease, type 2 diabetes, some other age-related conditions, and they also have increased all-cause mortality. These results indicate that strong and reliable inflammatory markers, such as leukocyte count, may reflect the rate of ageing and therefore can predict long-term survival in the elderly. Remarkably, leukocyte count correlates positively with genuine markers of systemic inflammation like C-reactive protein and interleukin 6. Interestingly, some authors conclude that leukocyte counts have a stronger prognostic ability with regard to total and cardiovascular mortality than total cholesterol or low-density lipoproteins. The fact that these inflammatory markers are clinically useful predictors of long-term survival in the elderly is quite remarkable as these blood parameters are included in routine medical check-ups. Therefore, they can be used as simple and reliable morphological indicators of chronic systemic inflammation, disease progression, and poor prognosis, especially among individuals who are likely to develop age-related conditions. Nevertheless, the pathomechanism that links elevated but normal leukocyte counts to increased

  8. Extraction the First Permanent Molar With Poor Prognosis in Mixed Dentition Period

    Directory of Open Access Journals (Sweden)

    B Seraj

    2002-02-01

    Full Text Available Whenever the first permanent molar is extracted or its long- term prognosis is poor, before taking any steps, a full clinical and radiographic evaluation associated with patients dental models investigation is necessary to determine the following cases:The quality and quantity of dentition, teeth missing, occlusion, buds position, orthodontic problems, the level of parents and patient cooperation for future long term orthodontic treatment and finally patient's oral hygiene. On the basis of this information, a decision is taken about the first permanent molar extraction with poor prognosis, either of balancing or compensatory type, especially when future orthodontic treatment is improbable. The aim of this article is to explain the principles of time and sequence of first permanent molar extraction.

  9. Rosai-Dorfman Disease Involving Multiple Organs: An Unusual Case with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Fandresena Arilala Sendrasoa

    2016-01-01

    Full Text Available Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder that usually affects the lymph nodes. Although extranodal involvement has been reported in diverse sites, manifestation in the cardiovascular system is extremely rare. Specifically, cardiac involvement in Rosai-Dorfman disease is an extraordinarily infrequent event. We describe a case of a 36-year-old female who presented Rosai-Dorfman disease of multiple organs including the heart, with poor prognosis.

  10. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Diego Sanchez-Martinez

    2016-10-01

    Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

  11. Low SIRT3 expression correlates with poor differentiation and unfavorable prognosis in primary hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Chris Zhiyi Zhang

    Full Text Available SIRT3, a mitochondrial sirtuin belonging to nicotinamide adenine nucleotide (NAD dependent deacetylases, is implicated in metabolism, longevity and carcinogenesis. SIRT3 expression and its significance in hepatocellular carcinoma (HCC remain largely unclear. In this study, we demonstrated that SIRT3 expression in HCC tissue was much lower than that in paracarcinoma tissue, at both mRNA and protein levels. The cutoff value for low SIRT3 expression in HCC was defined according to receiver operating characteristic curve (ROC analysis. As disclosed by immunohistochemistry (IHC results, low SIRT3 expression was present in 67.3% (167/248 of HCC cases. Furthermore, low expression of SIRT3 was significantly correlated to differentiation (P = 0.013, clinical stage (P = 0.005, serum AFP level (P<0.01, tumor multiplicity (P = 0.026 and relapse (P = 0.028. Moreover, Kaplan-Meier analysis indicated that low SIRT3 expression associated with unfavorable overall survival (P<0.01 and recurrence-free survival (P = 0.004. The prognostic impact of SIRT3 was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low SIRT3 expression was an independent poor prognostic marker for overall survival (Hazard Ratio (HR 0.555, 95% confidence interval (95% CI 0.344-0.897, P = 0.016. Collectively, we conclude that SIRT3 is decreased in HCC and is a novel unfavorable marker for prognosis of patients with this fatal disease.

  12. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer.

    Directory of Open Access Journals (Sweden)

    Peter Arner

    Full Text Available Cancer cachexia (CC is linked to poor prognosis. Although the mechanisms promoting this condition are not known, several circulating proteins have been proposed to contribute. We analyzed the plasma proteome in cancer subjects in order to identify factors associated with cachexia.Plasma was obtained from a screening cohort of 59 patients, newly diagnosed with suspected gastrointestinal cancer, with (n = 32 or without (n = 27 cachexia. Samples were subjected to proteomic profiling using 760 antibodies (targeting 698 individual proteins from the Human Protein Atlas project. The main findings were validated in a cohort of 93 patients with verified and advanced pancreas cancer.Only six proteins displayed differential plasma levels in the screening cohort. Among these, Carnosine Dipeptidase 1 (CNDP1 was confirmed by sandwich immunoassay to be lower in CC (p = 0.008. In both cohorts, low CNDP1 levels were associated with markers of poor prognosis including weight loss, malnutrition, lipid breakdown, low circulating albumin/IGF1 levels and poor quality of life. Eleven of the subjects in the discovery cohort were finally diagnosed with non-malignant disease but omitting these subjects from the analyses did not have any major influence on the results.In gastrointestinal cancer, reduced plasma levels of CNDP1 associate with signs of catabolism and poor outcome. These results, together with recently published data demonstrating lower circulating CNDP1 in subjects with glioblastoma and metastatic prostate cancer, suggest that CNDP1 may constitute a marker of aggressive cancer and CC.

  13. Mast Cells Comprise the Major of Interleukin 17-Producing Cells and Predict a Poor Prognosis in Hepatocellular Carcinoma

    Science.gov (United States)

    Tu, Jian-Fei; Pan, Hong-Ying; Ying, Xi-Hui; Lou, Jian; Ji, Jian-Song; Zou, Hai

    2016-01-01

    Abstract IL-17 and IL-17-producing cells have been found in many types of human cancers and murine models. However, the source of tumor-infiltrating IL-17 and IL-17-producing cells in HCC and the prognostic values remain poorly understood. A total of 57 HCC patients were enrolled in this study, and immunofluorescence double stain was used to evaluate the colocalization of CD3+ T cells, CD4+ T cells, CD56+ NK cells, CD20+ B cells, CD68+ Macrophages, and MCT+ mast cells with IL-17. The prognostic value of IL-17-producing cells was evaluated by Kaplan–Meier analysis and Cox regression model. MCT+ mast cells, but not other cells, were the predominant IL-17-producing cell type. Overall survival analysis revealed that the increasing intratumoral-infiltrated MCT+ mast cells were significantly associated with poor prognosis. Immunofluorescence double stain showed a positive correlation between the number of MCT+ mast cells and MCVs. These findings indicated the major IL-17-producing cells in HCC were MCT+ mast cells and these cells infiltration may promote tumor progression by angiogenesis. Increased MCT+ mast cells was associated with a poor prognosis, indicating therapy targeting MCT+ mast cells might be an effective strategy in controlling intratumor IL-17 infiltration and MCVs. PMID:27043690

  14. Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer.

    Science.gov (United States)

    Jorissen, Robert N; Christie, Michael; Mouradov, Dmitri; Sakthianandeswaren, Anuratha; Li, Shan; Love, Christopher; Xu, Zheng-Zhou; Molloy, Peter L; Jones, Ian T; McLaughlin, Stephen; Ward, Robyn L; Hawkins, Nicholas J; Ruszkiewicz, Andrew R; Moore, James; Burgess, Antony W; Busam, Dana; Zhao, Qi; Strausberg, Robert L; Lipton, Lara; Desai, Jayesh; Gibbs, Peter; Sieber, Oliver M

    2015-09-15

    APC mutations (APC-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. APC prognostic value was evaluated in 746 stage I-IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify APC mutation status, and classifier ability to predict prognosis was examined in an independent cohort. Wild-type APC microsatellite stable (APC-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than APC-mt/MSS proximal, APC-wt/MSS distal and APC-mt/MSS distal tumours (OS HR⩾1.79, P⩽0.015; RFS HR⩾1.88, P⩽0.026). APC was a stronger prognostic indicator than BRAF, KRAS, PIK3CA, TP53, CpG island methylator phenotype or chromosomal instability status (P⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an APC-wt-like signature (P=0.019). APC status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer, APC-wt-like signature MSS cases showed poorer survival than APC-mt-like signature MSS or MSI cases (OS HR⩾2.50, P⩽0.010; RFS HR⩾2.14, P⩽0.025). Poor prognosis APC-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (P⩽0.016). APC-wt status is a marker of poor prognosis in MSS proximal colon cancer.

  15. Long noncoding RNA CCAT2 can predict metastasis and poor prognosis: A meta-analysis.

    Science.gov (United States)

    Fan, Yang-Hua; Fang, Hua; Ji, Chen-Xing; Xie, Huan; Xiao, Bing; Zhu, Xin-Gen

    2017-03-01

    It has been reported that Colon cancer-associated transcript 2 (CCAT2) is dysregulated in various cancers. We performed this meta-analysis to clarify its promising functions as a prognosis marker in malignant tumors. Electronic databases, including PubMed, Medline, OVID, Cochrane Library, and Web of Science, were searched from inception to October 20, 2016. The hazard ratio (HR) and 95% confidence interval (CI) were calculated to explore the relationship between CCAT2 expression and survival, which were extracted from the eligible studies. The odds ratio (OR) was calculated to assess the association between CCAT2 expression and pathological parameters using RevMan5.3 software. Six original studies were included in this meta-analysis including 725 cancer patients. The pooled HR suggested that high CCAT2 expression was significantly correlated with overall survival (OS) (HR=2.30, 95% CI: 1.62-3.25, panalysis revealed a significant association between CCAT2 and OS in urogenital system (HR=1.70, 95% CI: 1.27-2.26, panalysis demonstrated that high CCAT2 expression significantly predicts poor OS, poor PFS, LNM, DM and tumor stage, suggesting that high CCAT2 expression may serve as a novel biomarker for poor prognosis and metastasis in cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Online Remaining Fatigue Life Prognosis for Composite Materials Based on Strain Data and Stochastic Modeling

    NARCIS (Netherlands)

    Eleftheroglou, N.; Zarouchas, D.; Loutas, T.; Alderliesten, R.C.; Benedictus, R.

    2016-01-01

    The present study utilizes a state-of-the-art stochastic modeling with structural health monitoring (SHM) data derived from strain measurements, in order to assess the remaining useful life (RUL) online in composite materials under fatigue loading. Non-Homogenous Hidden Semi Markov model (NHHSMM) is

  17. Nuclear Ep-ICD expression is a predictor of poor prognosis in "low risk" prostate adenocarcinomas.

    Directory of Open Access Journals (Sweden)

    Jasmeet Assi

    Full Text Available Molecular markers for predicting prostate cancer (PCa that would have poor prognosis are urgently needed for a more personalized treatment for patients. Regulated intramembrane proteolysis of Epithelial cell adhesion molecule results in shedding of the extracellular domain (EpEx and release of its intracellular domain (Ep-ICD which triggers oncogenic signaling and might correlate to tumor aggressiveness. This study aimed to explore the potential of Ep-ICD and EpEx to identify PCa that have poor prognosis.Immunohistochemical analysis of Ep-ICD and EpEx was carried out in normal prostate tissues (n = 100, benign prostate hyperplasia (BPH, n = 83, and prostate cancer (n = 249 using domain specific antibodies. The expression of Ep-ICD and EpEx was correlated with clinico- pathological parameters and disease free survival (DFS.Reduced expression of nuclear Ep-ICD and membrane EpEx was observed in PCa in comparison with BPH and normal prostate tissues (p = 0.006, p < 0.001 respectively. For patients who had PCa with Gleason Score less than 7, preserved nuclear Ep-ICD emerged as the most significant marker in multivariate analysis for prolonged DFS, where these patients did not have recurrence during follow up of up to 12 years (p = 0.001.Reduced expression of nuclear Ep-ICD was associated with shorter disease free survival in patients with a Gleason Score less than 7 and may be useful in identifying patients likely to have aggressive tumors with poor prognosis. Furthermore, nuclear Ep-ICD can differentiate between normal and prostate cancer tissues for ambiguous cases.

  18. Overexpression of the metastasis-associated gene MTA3 correlates with tumor progression and poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Chuanxi; Li, Guanzhen; Li, Jiamei; Li, Jie; Li, Tao; Yu, Jinyu; Qin, Chengyong

    2017-08-01

    Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers in the world. However, there remains a lack of effective diagnostic and treatment markers. We aimed to explore metastasis-associated protein 3 (MTA3) expression and function in HCC and its relationship with clinicopathological factors. We investigated the expression pattern and clinicopathological significance of MTA3 in 90 patients with HCC via immunohistochemistry and explored MTA3 function via gene knockdown of MTA3. MTA3 was overexpressed in HCC cell nuclei and downregulated in HCC cell cytoplasm. The former finding correlated with metastasis (P = 0.010) and poor prognosis (P = 0.018). In addition, deleting MTA3 inhibited HCC cell growth, invasion, and metastasis in vitro, as shown in the colony formation, migration, and wound-healing assays. These results indicate that MTA3 is an oncogene of HCC, predicts poor prognosis of HCC, and may be a future marker of HCC treatment. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  19. Microscopic residual disease after resection for lung cancer: a multifaceted but poor factor of prognosis.

    Science.gov (United States)

    Riquet, Marc; Achour, Karima; Foucault, Christophe; Le Pimpec Barthes, Françoise; Dujon, Antoine; Cazes, Aurélie

    2010-03-01

    Many studies focus on bronchial microscopic residual disease (R1) after resection for lung cancer, although R1 also concerns vascular and soft tissues. Our purpose was to study the R1 prognosis at different resection margins and to compare it with the prognosis for those having complete resection (R0). We reviewed the clinical records of 4,026 patients from two centers who underwent surgery in view of cure. Despite perioperative frozen section, 216 patients (5.4%) proved R1 and were classified into seven types according to R1 anatomic site: bronchus, peribronchus, great vessels and atrium, mediastinum and pericardium, chest wall, lung tissue, and lymph nodes. Patients who were classified as R0 and R1 were compared, and R1 patients were further studied according to R1 margins. Frequency of R1 increased with the T and N values and type of resection (lobectomies, 3.3% [70 of 2,041 patients]; pneumonectomies, 8.8% [126 of 1,308 patients]; p < 10(-6)). Five-year survival rates for R1 patients were lower than those for R0 patients (20% versus 46%; p < 10(-6)), and were not modified by the degree of T and N involvement or adjuvant therapy, but were better in bronchial and peribronchial (48.4% of R1 patients) than in extrabronchial R1 (26.3% versus 15.6%; p = 0.023). Multivariate analysis confirmed R1 to be an independent factor of poor prognosis (p = 0.0008), after N, T, and age. Long-term survival is possible in case of an R1 margin, but 5-year survival rates are jeopardized. Poor efficacy of adjuvant therapy and global outcome indicate advanced disease or reflect tumor cell aggressiveness, rather than surgical insufficiency, when prevention of R1 margins is guided by frozen-section examination and scrupulously respected. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  20. MGMT and CALCA promoter methylation are associated with poor prognosis in testicular germ cell tumor patients.

    Science.gov (United States)

    Martinelli, Camila Maria da Silva; Lengert, André van Helvoort; Cárcano, Flavio Mavignier; Silva, Eduardo Caetano Albino; Brait, Mariana; Lopes, Luiz Fernando; Vidal, Daniel Onofre

    2017-08-01

    Testicular germ cell tumors (TGCT) represent the second main cause of cancer-related death in young men. Despite high cure rates, refractory disease results in poor prognosis. Epigenetic reprogramming occurs during the development of seminomas and non-seminomas. Understanding the molecular and genetic basis of these tumors would represent an important advance in the search for new TGCT molecular markers. Hence the frequency of methylation of a gene panel (VGF, MGMT, ADAMTS1, CALCA, HOXA9, CDKN2B, CDO1 and NANOG) was evaluated in 72 primary TGCT by quantitative methylation specific PCR. A high frequency of MGMT (90.9%, 20/22; p=0.019) and CALCA (90.5%, 19/21; p<0.026) methylation was associated with non-seminomatous tumors while CALCA methylation was also associated with refractory disease (47.4%, 09/19; p=0.005). Moreover, promoter methylation of both genes predicts poor clinical outcome for TGCT patients (5-year EFS: 50.5% vs 77.1%; p=0.032 for MGMT and 51.3% vs 77.0%; p=0.029 for CALCA). The findings of this study indicate that methylation of MGMT and CALCA are frequent and could be used as new molecular markers of prognosis in TGCT.

  1. Increased lysyl oxidase-like 2 associates with a poor prognosis in non-small cell lung cancer.

    Science.gov (United States)

    Zhan, Ping; Lv, Xiao-Jing; Ji, Ya-Nan; Xie, Haiyan; Yu, Li-Ke

    2016-11-18

    Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and is associated with invasiveness and metastasis in breast cancer. However, its relevance in non-small cell lung cancer (NSCLC) remained largely unknown. LOXL2 protein levels in a cohort of NSCLC and adjacent normal lung tissues were evaluated and analyzed their clinicopathologic and prognostic significance. It was found that cytoplasmic and nuclear LOXL2 levels were higher in lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) tissues than in paired adjacent normal tissues. High LOXL2 levels were associated with p-TNM stage, and cytoplasmic, but not nuclear, LOXL2 levels were an independent prognostic factor in lung AD and SCC patients. These results demonstrate that elevated LOXL2 levels are positively associated with poor prognosis in NSCLC patients. LOXL2 might, therefore, serve as a novel prognostic biomarker and potential therapeutic target in NSCLC patients. © 2016 John Wiley & Sons Ltd.

  2. Upregulation of B23 promotes tumor cell proliferation and predicts poor prognosis in glioma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jianguo [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China); Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Sun, Jie; Yang, Liu; Yan, Yaohua; Shi, Wei; Shi, Jinlong; Huang, Qingfeng; Chen, Jian [Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Lan, Qing, E-mail: lanqingsj@163.com [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China)

    2015-10-09

    B23 (also known as Nucleophosmin, NPM, numatrin or NO38) is a ubiquitously expressed phosphoprotein belonging to the nucleoplasmin family of chaperones. In this study we intended to investigate the clinical significance of B23 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that B23 was overexpressed in glioma tissues and glioma cell lines. In addition, the expression level of B23 was positively correlated with glioma pathological grade and Ki-67 expression. Kaplan–Meier analysis revealed that a higher B23 expression in patients with glioma was associated with a poorer prognosis. In vitro, after the release of glioma cell lines from serum starvation, the expression of B23 was upregulated, as well as PCNA (Proliferating Cell Nuclear Antigen) and cyclin A. In addition, knockdown of B23 by small interfering RNA transfection diminished the expression of PCNA, cyclin D1 and arrested cell growth at G1 phase. Taken together, our results implied that B23 could be a candidate prognostic biomarker as well as a potential therapeutical target of glioma. - Highlights: • B23 expression increased as the malignant degree of glioma increased, which was consistent with Ki-67 expression. • High expression of B23 could be a strong determinant of poor prognosis in glioma. • B23 may be involved in the proliferation of glioma in a cell-cycle-dependent pathway. • Knockdown of B23 expression by siRNA could affect the progression of glioma. • B23 may be a potential prognosis biomarker and a possible therapeutic target for glioma.

  3. Overexpression of ezrin and galectin-3 as predictors of poor prognosis of cervical cancer

    Directory of Open Access Journals (Sweden)

    M. Li

    Full Text Available The aim of this study was to explore the correlation of ezrin and galectin-3 expressions with prognosis in cervical cancer. The immunohistochemical method was applied to detect ezrin and galectin-3 expressions in normal cervix tissues (n=30, cervicitis tissues (n=28, cervical intraepithelial neoplasia (CIN tissues (classified as I-III, n=89, and cervical carcinoma tissues (n=84. Follow-up was conducted for 5 to 78 months to analyze the correlation of protein expressions with prognosis. Ezrin and galectin-3 expressions in cervical cancer were significantly higher than in normal cervix, cervicitis and CIN (all P<0.05, and expressions in CIN were significantly higher than in normal cervix and cervicitis (both P<0.05. The expressions of ezrin and galectin-3 were both related with histological grade, deep myometrial invasion and lymph node metastasis (all P<0.05. Spearman analysis showed that ezrin expression was positively correlated with galectin-3 expression in cervical cancer (r=0.355, P<0.05. The survival rate of patients with high expressions of ezrin and galectin-3 was significantly lower than those with low expressions of proteins (both P<0.05. The expressions of ezrin and galectin-3, histological grade, depth of stromal invasion, and lymph node metastasis are risk factors affecting the survival rate of patients with cervical cancer. The expressions of ezrin and galectin-3 were correlated with the development of cervical cancer, and overexpressions of those proteins were indicative of poor prognosis in patients with cervical cancer.

  4. Tumor budding is associated with an increased risk of lymph node metastasis and poor prognosis in superficial esophageal adenocarcinoma.

    Science.gov (United States)

    Landau, Michael S; Hastings, Steven M; Foxwell, Tyler J; Luketich, James D; Nason, Katie S; Davison, Jon M

    2014-12-01

    The treatment approach for superficial (stage T1) esophageal adenocarcinoma critically depends on the pre-operative assessment of metastatic risk. Part of that assessment involves evaluation of the primary tumor for pathologic characteristics known to predict nodal metastasis: depth of invasion (intramucosal vs submucosal), angiolymphatic invasion, tumor grade, and tumor size. Tumor budding is a histologic pattern that is associated with poor prognosis in early-stage colorectal adenocarcinoma and a predictor of nodal metastasis in T1 colorectal adenocarcinoma. In a retrospective study, we used a semi-quantitative histologic scoring system to categorize 210 surgically resected, superficial (stage T1) esophageal adenocarcinomas according to the extent of tumor budding (none, focal, and extensive) and also evaluated other known risk factors for nodal metastasis, including depth of invasion, angiolymphatic invasion, tumor grade, and tumor size. We assessed the risk of nodal metastasis associated with tumor budding in univariate analyses and controlled for other risk factors in a multivariate logistic regression model. In all, 41% (24 out of 59) of tumors with extensive tumor budding (tumor budding in ≥3 20X microscopic fields) were metastatic to regional lymph nodes, compared with 10% (12 out of 117) of tumors with no tumor budding, and 15% (5 out of 34) of tumors with focal tumor budding (Ptumor budding remains an independent risk factor for lymph node metastasis in superficial esophageal adenocarcinoma associated with a 2.5-fold increase (95% CI=1.1-6.3, P=0.039) in the risk of nodal metastasis. Extensive tumor budding is also a poor prognostic factor with respect to overall survival and time to recurrence in univariate and multivariate analyses. As an independent risk factor for nodal metastasis and poor prognosis after esophagectomy, tumor budding should be evaluated in superficial (T1) esophageal adenocarcinoma as a part of a comprehensive pathologic risk

  5. Autophagy may promote carcinoma cell invasion and correlate with poor prognosis in cholangiocarcinoma

    Science.gov (United States)

    Nitta, Takeo; Sato, Yasunori; Ren, Xiang Shan; Harada, Kenichi; Sasaki, Motoko; Hirano, Satoshi; Nakanuma, Yasuni

    2014-01-01

    The role of autophagy in cholangiocarcinoma is poorly understood. This study investigated its involvement in cholangiocarcinoma, focusing on carcinoma cell invasion and prognostic significance using cholangiocarcinoma cell lines, CCKS1 and HuCCT1, and human tissues of hilar and extrahepatic cholangiocarcinoma. Nutrient starvation induced the expression of LC3-II and the formation of LC3 puncta in both CCKS1 and HuCCT1, suggesting the occurrence of autophagy. The induction of autophagy was accompanied by the increased expression of an autophagy-related protein, Ambra1, in the cells. Under starvation conditions, the invasive activity of both cells was significantly increased, and a lysosomal inhibitor, chloroquine, attenuated this increased invasive activity. Transforming growth factor-β1 (TGF-β1), known as an inducer of epithelial-mesenchymal transition (EMT), increased the invasive activity of both cells, and chloroquine also significantly reduced TGF-β1-induced cell invasion. Immunohistochemical staining using cholangiocarcinoma tissues showed that the expression of Ambra1 positively correlated with the expression of Snail, one of the major transcriptional factors of EMT. In addition, overexpression of Ambra1 significantly correlated with lymph node metastasis and poor survival rate of the patients. These results suggest that the occurrence of autophagy may be associated with a malignant phenotype and poor prognosis in cholangiocarcinoma, and autophagy is possibly involved in EMT-related cholangiocarcinoma cell invasion. PMID:25197362

  6. Identification and targeting of a TACE-dependent autocrine loopwhich predicts poor prognosis in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, Paraic A.; Bissell, Mina J.

    2005-06-15

    The ability to proliferate independently of signals from other cell types is a fundamental characteristic of tumor cells. Using a 3D culture model of human breast cancer progression, we have delineated a protease-dependent autocrine loop which provides an oncogenic stimulus in the absence of proto-oncogene mutation. Inhibition of this protease, TACE/ADAM17, reverts the malignant phenotype by preventing mobilization of two crucial growth factors, Amphiregulin and TGF{alpha}. We show further that the efficacy of EGFR inhibitors is overcome by physiological levels of growth factors and that successful EGFR inhibition is dependent on reducing ligand bioavailability. Using existing patient outcome data, we demonstrate a strong correlation between TACE and TGF{alpha} expression in human breast cancers that is predictive of poor prognosis.

  7. High copy number of mitochondrial DNA predicts poor prognosis in patients with advanced stage colon cancer.

    Science.gov (United States)

    Wang, Yun; He, Shuixiang; Zhu, Xingmei; Qiao, Wei; Zhang, Juan

    2016-12-23

    The aim of this investigation was to determine whether alterations in mitochondrial DNA (mtDNA) copy number in colon cancer were associated with clinicopathological parameters and postsurgical outcome. By quantitative real-time PCR assay, the mtDNA copy number was detected in a cohort of colon cancer and matched adjacent colon tissues (n = 162). The majority of patients had higher mtDNA content in colon cancer tissues than matched adjacent colon tissues. Moreover, high mtDNA content in tumor tissues was associated with larger tumor size, higher serum CEA level, advanced TNM stage, vascular emboli, and liver metastases. Further survival curve analysis showed that high mtDNA content was related to the worst survival in patients with colon cancer at advanced TNM stage. High mtDNA content is a potential effective factor of poor prognosis in patients with advanced stage colon cancer.

  8. Pretreatment circulating monocyte count associated with poor prognosis in patients with oral cavity cancer.

    Science.gov (United States)

    Tsai, Yu-Duan; Wang, Chao-Ping; Chen, Chih-Yu; Lin, Li-Wen; Hwang, Tzer-Zen; Lu, Li-Fen; Hsu, Hsia-Fen; Chung, Fu-Mei; Lee, Yau-Jiunn; Houng, Jer-Yiing

    2014-07-01

    The purpose of this study was to investigate whether the pretreatment total and differential leukocyte counts can predict the prognosis of patients with oral cavity cancer. In a retrospective analysis of patients treated between 2004 and 2011, medical records of 202 patients with oral cavity cancer were evaluated. Patients with oral cavity cancer, the peripheral total white blood cell (WBC) count, monocyte, and neutrophil counts and neutrophil lymphocyte ratio increased with the advancement of clinical stage. In contrast, the lymphocyte count decreased. Further, total WBC, monocyte, and neutrophil counts were increased in those with pathologic stage T4 and poor tumor differentiation, and the monocyte count was also increased in those with lymph node metastasis. Moreover, the pretreatment circulating monocyte count was an independent prognostic factor for cancer-specific survival. A higher pretreatment circulating monocyte count can be considered as a useful prognostic marker in patients with oral cavity cancer. Copyright © 2014 Wiley Periodicals, Inc.

  9. SIRT1 expression is associated with poor prognosis of lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Li C

    2015-04-01

    Full Text Available Chong Li,1,2,* Lingling Wang,3,* Liang Zheng,4 Xianghong Zhan,4 Bin Xu,1,2 Jingting Jiang,1,2 Changping Wu1,2 1Department of Tumor Biological Treatment, the Third Affiliated Hospital, Soochow University, Changzhou, 2Cancer Immunotherapy Engineering Research Center of Jiangsu Province, Changzhou, 3Department of Medical Education, Jinling Hospital, Medical School of Nanjing University, Nanjing, 4Department of Thoracic Surgery, the Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Several studies have reported that the overexpression of Sirtuin 1 (SIRT1 was associated with poor prognosis in various human cancers. However, little is known regarding the prognostic value of SIRT1 in lung adenocarcinoma. Therefore, the aim of this study is to evaluate the role of SIRT1 in the prognosis of lung adenocarcinoma patients. Using a tissue microarray, we detected SIRT1 expression by immunohistochemistry in lung adenocarcinoma tissue, as well as in corresponding noncancerous tissues (NCTs. A high expression level of SIRT1 was observed in 74.7% (56/75 of patients with lung adenocarcinoma and 6.7% (5/75 of NCTs (P<0.001. SIRT1 expression was significantly associated with high pathological stage. Importantly, we found that SIRT1 expression was associated with worse overall survival in these lung adenocarcinoma patients (67.0 months vs 104.5 months; P=0.005. In addition, anaplastic lymphoma kinase, epidermal growth factor receptor, vascular endothelial growth factor (VEGF, and Survivin expression were evaluated by fluorescent in situ hybridization or immunohistochemistry, respectively. We found that VEGF and Survivin were both highly expressed in the lung adenocarcinoma tissues, as compared to NCTs. Moreover, the SIRT1 and VEGF expression statuses were significantly positively correlated (r=0.238, P=0.039, while SIRT1 and Survivin expression status were not

  10. Tbx2 confers poor prognosis in glioblastoma and promotes temozolomide resistance with change of mitochondrial dynamics

    Science.gov (United States)

    Yi, Fuxin; Du, Jianzhou; Ni, Weimin; Liu, Weixian

    2017-01-01

    Tbx2 is a cancer-related protein that was found to be overexpressed in several human malignancies. The present study aims to investigate the clinical significance and biological role of Tbx2 in human astrocytoma. We examined its protein expression in 102 cases of astrocytoma tissues using immunohistochemical staining. Negative Tbx2 staining was observed in normal astrocytes, and positive nuclear staining was found in 41 out of 102 astrocytoma specimens. The rate of Tbx2 overexpression in pylocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma multiform (GBM) were 0%, 26.1%, 40%, and 52%, respectively. Tbx2 overexpression correlated with poor prognosis in patients with astrocytoma or GBM. Tbx2 plasmid transfection was performed in A172 cells, and Tbx2 siRNA knockdown was carried out in U251 cells. Cell Counting Kit-8, cell cycle analysis, and matrigel invasion assay showed that Tbx2 overexpression upregulated cell proliferation, G1-S transition, and invasion, with corresponding change of cyclin D1, p21, and MMP 2 and 9. Importantly, we demonstrated that Tbx2 reduced apoptosis and conferred resistance to temozolomide in GBM cell lines. Further experiments showed that Tbx2 could regulate mitochondrial fission/fusion balance. Western blot showed that Tbx2 overexpression reduced caspase 3 cleavage, while it induced Bcl-2 and p-Drp1 upregulation. In conclusion, our results indicated that Tbx2 might serve as an indicator for poor prognosis and also be useful as an important therapeutic in human GBM, which inhibits apoptosis through regulation of mitochondrial function. PMID:28260920

  11. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies.

    Science.gov (United States)

    Wu, Jiayuan; Hu, Liren; Chen, Manyu; Cao, Wenjun; Chen, Haicong; He, Taiping

    2016-01-01

    The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; Pdigestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers.

  12. Opacity of big toenail predicts poor prognosis in patients with end-stage renal disease on hemodialysis.

    Science.gov (United States)

    Soma, Osamu; Hatakeyama, Shingo; Matsumoto, Teppei; Tanaka, Toshikazu; Tanaka, Yoshimi; Hosogoe, Shogo; Kodama, Hirotake; Horiguchi, Hirotaka; Kubota, Yuka; Kido, Koichi; Momota, Masaki; Anan, Go; Narita, Ikuyo; Kitahara, Ryuji; Saitoh, Hisao; Suzuki, Tadashi; Ohyama, Chikara

    2017-10-25

    The impact of nail abnormalities on prognosis in hemodialysis patients is unknown. This study investigated whether toenail opacity as a readout of nail abnormalities predicted prognosis in hemodialysis patients. In this observational study, 494 eligible hemodialysis patients who received hemodialysis at Oyokyo Kidney Research Institute between September 2010 and December 2015 were included. The presence of nail abnormalities was objectively evaluated by big toenail opacity ratio measurement. Primary endpoint was overall survival, and secondary endpoints were lower limb amputation and determination of risk factors for poor prognosis among patient demographics, comorbidities, blood tests, and big toenail opacity. Overall survival and lower limb survival were evaluated using the Kaplan-Meier method with log-rank test. Multivariate Cox regression analyses assessed predictors for poor prognosis. Big toenail opacity was found in 259 (52%) patients. Patients with big toenail opacity were significantly older, had shorter duration of dialysis, higher prevalence rates of diabetes mellitus (DM), cardiovascular disease (CVD), and higher mortality rates than those without opacity. Presence of big toenail opacity predicted poor prognosis for both overall and lower limb survival. Multivariate Cox regression analyses revealed serum albumin, the presence of DM and big toenail opacity were independent risk factors for both poor overall and lower limb survivals. The prevalence of big toenail opacity was high in hemodialysis patients. Despite the short observation period, our findings indicated that big toenail opacity had significant predictive power for poor overall and lower limb survival.

  13. IVF outcomes in average- and poor-prognosis infertile women according to the number of embryos transferred.

    Science.gov (United States)

    Vega, Mario G; Gleicher, Norbert; Darmon, Sarah K; Weghofer, Andrea; Wu, Yan-Guang; Wang, Qi; Zhang, Lin; Albertini, David F; Barad, David H; Kushnir, Vitaly A

    2016-09-01

    Outcome measures of IVF success, which account for effectiveness of IVF and perinatal outcome risks, have recently been described. The association between number of embryos transferred in average and poor-prognosis IVF patients, and the chances of having good or poor IVF and perinatal outcomes, was investigated. Good IVF and perinatal outcome was defined as the birth of a live, term, normal-weight infant (≥2500 g). Poor IVF and perinatal outcome was defined as no live birth or birth of a very low weight neonate (IVF cycles in 504 average and poor-prognosis patients from January 2010 to December 2013 were identified. The odds of having good IVF and perinatal outcomes increased by 28% for each additional embryo transferred. The odds of poor IVF and perinatal outcome decreased by 32% with an additional embryo transferred. The likelihood of live birth with good perinatal outcome in average- and poor-prognosis patients after IVF increases with additional embryos being transferred. These data add to recently reported evidence in favour of multiple embryo transfer in older women and those with average or poor IVF prognosis. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  14. Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) for the treatment of children with poor-prognosis acute leukemia: the Hacettepe experience.

    Science.gov (United States)

    Tavil, Betul; Aytac, Selin; Balci, Yasemin Isik; Unal, Sule; Kuskonmaz, Barıs; Yetgin, Sevgi; Gurgey, Aytemiz; Tuncer, Murat; Gumruk, Fatma; Uckan, Duygu; Cetin, Mualla

    2010-10-01

    Fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin (FLAG-IDA) regimen has been proven to be a potentially useful chemotherapy regimen for relapsed or poor-prognosis childhood leukemia. The aim of the study was to evaluate complete remission (CR) rate, toxicity, and overall survival of children with poor-prognosis acute leukemia who received the FLAG-IDA regimen. Furthermore, the authors investigated the children who achieved CR following FLAG-IDA treatment regarding their eligibility for allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2002 and April 2007, 25 children with poor-prognosis acute leukemia were treated with FLAG-IDA regimen in our center. Of the 25 children (16 AML, 9 ALL) with poor-prognosis acute leukemia, 7 (28.0%) received 1 cycle, 17 (68.0%) received 2 cycles, and 1 (4%) received 3 cycles of FLAG or FLAG-IDA regimen. After 44 cycles of FLAG-IDA or FLAG regimen, 10/25 (40%) children were nonresponders, 15/25 (60.0%) showed CR. Five (20%) of these patients in CR who underwent allogeneic HSCT are still in remission. The remaining 20 (80.0%) children were lost due to infection or relapse of the primary diseases. The overall survival of patients who are still alive and underwent allogeneic HSCT (mean: 40.6 ± 4.7, median: 40, range: 34-46 months) was longer than that of patients (mean: 5.5 ± 4.3, median: 4, range: 1-15 months) who did not undergo allogeneic HSCT. The CR rate was quite high in the present study using the FLAG-IDA regimen, and the authors believe this regimen is a possible option prior to allogeneic HSCT in children with poor-prognosis acute leukemia.

  15. Putative risk factors for postoperative pneumonia which affects poor prognosis in patients with gastric cancer.

    Science.gov (United States)

    Kiuchi, Jun; Komatsu, Shuhei; Ichikawa, Daisuke; Kosuga, Toshiyuki; Okamoto, Kazuma; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Yasuda, Tomoyo; Otsuji, Eigo

    2016-10-01

    Several recent studies identified that postoperative infectious complications contribute to recurrence and poor outcome in patients with gastric cancer. This study was designed to investigate the prognostic impact of postoperative pneumonia, and to identify the putative risk factors for its occurrence. We retrospectively analyzed 1,415 consecutive patients who underwent curative gastrectomy for gastric cancer between 1997 and 2013. A total of 31 (2.2 %) patients developed postoperative pneumonia (Clavien-Dindo classification ≥II). Patients with postoperative pneumonia showed a significantly poorer prognosis than patients without (P pneumonia, univariate and multivariate analyses identified older age (≥65 years; P = 0.010; odds ratio [OR] 3.59), lower nutritious status (albumin pneumonia was shown to be associated with long-term poor outcome in patients with gastric cancer. Care should be taken for patients with clinical factors such as older age, lower nutritional status, advanced stage, concurrent hypertension, and total gastrectomy.

  16. Overexpression of Fli-1 in astrocytoma is associated with poor prognosis.

    Science.gov (United States)

    Tsai, Hung-Pei; Tsai, Tai-Hsin; Hsieh, Ya-Ju; Chen, Yi-Ting; Lee, Chih-Ling; Tsai, Yi-Cheng; She, Ting-Chang; Lin, Chih-Lung; Chai, Chee-Yin; Kwan, Aij-Lie

    2017-04-25

    Astrocytoma, a common and highly malignant type of brain tumor, is associated with poor overall survival despite advances in surgical treatment, radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been shown to increase cellular proliferation and tumorigenesis in many types of cancer; however, previous reports have not described a correlation between clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to elucidate the clinical role of Fli-1 in astrocytoma. High-level of Fli-1 protein expression was significantly association with World Health Organization (WHO) high grade and poor prognosis. A multivariate analysis revealed that the WHO grade and Fli-1 protein expression were independent factor of prognostic factors of patients with astrocytoma. In addition, Fli-1 silencing inhibited proliferation, migration, and invasion and led to the downregulation of Ki-67, VEGF, and cyclin D1 expression in the astrocytoma cells. Fli-1 protein expression in astrocytoma tissue samples were detected via immunohistochemistry, and potential correlations between clinical parameters and Fli-1 expression were assessed in patients with astrocytoma. Additionally, proliferation, invasion, and migration assays of astrocytoma cell lines were conducted to evaluate the effects of short interfering RNA (siRNA) on these processes; in addition, these cells were subjected to western blotting to detect the expression levels of Fli-1, Ki-67, VEGF, and Cyclin D1. Fli-1 shows promise as a potential prognostic biomarker and therapeutic molecular target for astrocytoma patients.

  17. Downregulated Ku70 and ATM associated to poor prognosis in colorectal cancer among Chinese patients

    Directory of Open Access Journals (Sweden)

    Lu YF

    2014-10-01

    Full Text Available Yuanfang Lu,1,2 Jingyan Gao,1,3 Yuanming Lu,1 1Department of Toxicology, School of Public Health, Guilin Medical University, Guangxi, People's Republic of China; 2Department of Clinical Research Center, Affiliated 2nd Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3Department of Human Anatomy and Histo-Embryology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Background: Double-strand DNA breaks (DSBs are a key factor in carcinogenesis. The necessary repair of DSBs is pivotal in maintaining normal cell division. To address the relationship between altered expression of DSB repair of proteins Ku70 and ataxia-telangiectasia mutated (ATM in colorectal cancer (CRC, we examined the expression levels and patterns of Ku70 and ATM in CRC samples. Methods: Expression and coexpression of Ku70 and ATM were investigated by using real-time quantitative polymerase chain reaction assays and confirmed further with fluorescent immunohistochemistry in CRC and pericancerous samples from 112 Chinese patients. Results: Downexpression patterns for both Ku70 and ATM were found in the CRC samples and were significantly associated with advanced tumor node metastasis stage and decreased 5-year overall survival rate. Conclusion: Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in patients with CRC. Keywords: DNA double-strand breaks, ataxia-telangiectasia mutated, Ku70, colorectal cancer

  18. High Expression of Glypican-1 Predicts Dissemination and Poor Prognosis in Glioblastomas.

    Science.gov (United States)

    Saito, Taiichi; Sugiyama, Kazuhiko; Hama, Seiji; Yamasaki, Fumiyuki; Takayasu, Takeshi; Nosaka, Ryo; Onishi, Shumpei; Muragaki, Yoshihiro; Kawamata, Takakazu; Kurisu, Kaoru

    2017-09-01

    Glioblastoma (GBM) relapses locally or in a disseminated pattern and is highly resistant to chemoradiotherapy. Although dissemination is associated with poor prognosis for patients with GBM, the clinicopathologic factors that promote dissemination have not been elucidated. Glypican-1 (GPC-1) is a heparin sulfate proteoglycan that is attached to the extracytoplasmic surface of the cell membrane and regulates cell motility. The aim of this study was to determine whether GPC-1 expression correlated with GBM dissemination and patient prognosis. GPC-1 expression was examined by immunohistochemistry in 53 patients with GBM who received radiotherapy and temozolomide treatment. We assessed the relationship between dissemination and clinicopathologic factors, including GPC-1 expression. We also evaluated the relationship between GPC-1 expression and overall survival (OS) by uni- and multivariate analyses of a range of clinicopathologic factors, including age, Karnofsky Performance Status, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) status. Logistic regression analysis revealed that GPC-1 expression correlated with dissemination (P = 0.0116). Log-rank tests revealed that age, Karnofsky Performance Status, extent of resection, MGMT status, dissemination (P = 0.0008) and GPC-1 expression (P = 0.0011) were significantly correlated with OS. Multivariate analysis indicated that age, MGMT status, and GPC-1 expression were significantly correlated with OS. GPC-1 expression had the highest hazard ratio (2.392) among all regressors. GPC-1 expression significantly correlated with OS in patients with GBM who received radiotherapy and temozolomide treatment. GPC-1 expression can help predict the occurrence of dissemination and shorter OS in patients with GBM. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Combined Intratympanic and Systemic Steroid Therapy for Poor-Prognosis Sudden Sensorineural Hearing Loss

    Directory of Open Access Journals (Sweden)

    Shima Arastou

    2012-12-01

    Full Text Available Introduction: The aim of this study was to evaluate the efficacy of combined intratympanic and systemic steroid therapy compared with systemic steroid therapy alone in idiopathic sudden sensorineural hearing loss (ISSNHL patients with poor prognostic factors.     Materials and Methods: Seventy-seven patients with sudden sensorineural hearing loss (SSNHL who had at least one poor prognostic factor (age greater than 40 years, hearing loss more than 70 db, or greater than a 2-week delay between the onset of hearing loss and initiation of therapy were included in this study. Patients were randomized to the intervention group (combined intratympanic and systemic steroid therapy or the control group (systemic steroid therapy alone. All patients received oral treatment with systemic prednisolone (1 mg/kg/day for 10 days, acyclovir (2 g/day for 10 days, divided into four doses, triamterene H (daily, and omeprazole (daily, during steroid treatment, and were advised to follow a low salt diet. The intervention group also received intratympanic dexamethasone injections (0.4 ml of 4 mg/ml dexamethasone two times a week for two consecutive weeks (four injections in total. A significant hearing improvement was defined as at least a 15-db decrease in pure tone average (PTA.  Results: Among all participants, 44 patients (57.14% showed significant improvement in hearing evaluation. More patients showed hearing improvement in the intervention group than in the control group (27 patients (75% versus 17 patients (41.4%, respectively; P = 0.001.  Conclusion:  The combination of intratympanic dexamethasone and systemic prednisolone is more effective than systemic prednisolone alone in the treatment of poor-prognosis SSNHL.

  20. Natural progression of renal function in the elderly: analysis of poor prognosis factors associated with chronic kidney disease.

    Science.gov (United States)

    Heras, Manuel; García-Cosmes, Pedro; Fernández-Reyes, María J; Sánchez, Rosa

    2013-01-01

    In the last few years a debate has emerged on the range of normal renal function and the rate at which renal disease progresses in the elderly. In this review we analysed, on the basis of the results of the study Ancianos con enfermedad renal crónica del Hospital General de Segovia (Elderly people with chronic kidney disease of the Hospital General de Segovia), the poor prognosis factors associated with this disease: proteinuria, episodes of acute renal failure and heart failure, and the role of uric acid. Elderly people with chronic kidney disease who present these poor prognosis factors may benefit from follow-up by Nephrology.

  1. Deregulated HOXB7 expression predicts poor prognosis of patients with malignancies of digestive system.

    Science.gov (United States)

    Liu, Fang-Teng; Chen, Han-Min; Xiong, Ying; Zhu, Zheng-Ming

    2017-07-26

    Numerous studies have investigated the relationship between deregulated HOXB7 expression with the clinical outcome in patients with digestive stem cancers, HOXB7 has showed negative impacts but with varying levels. We aimed to comprehensively evaluate the prediction and prognostic value of HOXB7 in digestive stem cancers. Electronic databases updated to December 1, 2016 were retrieved to collect relevant eligible studies to quantitatively explore the potential roles of HOXB7 as a prognostic indicator in digestive system cancers. A total of 9 studies (n = 1298 patients) was included in this synthetical meta-analysis. The pooled hazard ratios suggested that high expression of HOXB7 protein was associated with poor prognosis of OS in patients with digestive system cancers (HR = 1.97, 95% CI: 1.65-2.28, p= 0.000), and HOXB7 protein could act as an independent prognostic factor for predicting OS of patients with digestive system cancers (HR: 2.02, 95% CI: 1.69-2.36, p = 0.000). Statistical significance was also observed in subgroup meta-analysis based on the cancer type, histology type, country, sample size and publication date. Furthermore, we examined the correlations between HOXB7 protein and clinicopathological features. It showed that altered expression of HOXB7 protein was correlated with tumor invasion (p = 0.000), lymph node status (p = 0.000), distant metastasis (p = 0.001) and TNM stage (p = 0.000). However, the expression of HOXB7 protein was not associated with age (p = 0.64), gender (p = 0.40) or levels of differentiation (p = 0.19). High expression of HOXB7 protein was associated with poor prognosis of patients with digestive system cancers, as well as clinicopathologic characteristics, including the tumor invasion, lymph node status, distant metastasis and TNM stage. The expression of HOXB7 protein was not associated with age, gender or levels of differentiation. HOXB7 protein expression level in tumor tissue might serve as a novel prognostic marker for

  2. Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Rongna Wei

    2016-01-01

    Conclusions: High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.

  3. Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer.

    Science.gov (United States)

    Irshad, Shazia; Bansal, Mukesh; Guarnieri, Paolo; Davis, Hayley; Al Haj Zen, Ayman; Baran, Brygida; Pinna, Claudia Maria Assunta; Rahman, Haseeb; Biswas, Sujata; Bardella, Chiara; Jeffery, Rosemary; Wang, Lai Mun; East, James Edward; Tomlinson, Ian; Lewis, Annabelle; Leedham, Simon John

    2017-06-01

    The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase-independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal-subtype tumours, where it interacts with Notch to induce an epithelial-mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP-Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal-subtype tumours promotes a synergistic BMP-Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal-subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley

  4. Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

    Science.gov (United States)

    Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

    2016-01-01

    Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

  5. ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Miao Yun

    Full Text Available 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.

  6. PHGDH Defines a Metabolic Subtype in Lung Adenocarcinomas with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Boxi Zhang

    2017-06-01

    Full Text Available Molecular signatures are emerging determinants of choice of therapy for lung adenocarcinomas. An evolving therapeutic approach includes targeting metabolic dependencies in cancers. Here, using an integrative approach, we have dissected the metabolic fingerprints of lung adenocarcinomas, and we show that Phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme in serine biosynthesis, is highly expressed in a adenocarcinoma subset with poor prognosis. This subset harbors a gene signature for DNA replication and proliferation. Accordingly, models with high levels of PHGDH display rapid proliferation, migration, and selective channeling of serine-derived carbons to glutathione and pyrimidines, while depletion of PHGDH shows potent and selective toxicity to this subset. Differential PHGDH protein levels were defined by its degradation, and the deubiquitinating enzyme JOSD2 is a regulator of its protein stability. Our study provides evidence that a unique metabolic program is activated in a lung adenocarcinoma subset, described by PHGDH, which confers growth and survival and may have therapeutic implications.

  7. High expression of BAG3 predicts a poor prognosis in human medulloblastoma.

    Science.gov (United States)

    Yang, Dong; Zhou, Ji; Wang, Hao; Wang, Yutao; Yang, Ge; Zhang, Yundong

    2016-10-01

    Bcl2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock protein (Hsp) 70, regulates various physiological and pathological processes. However, its role in human medulloblastoma has not been clarified. First of all, the expression of BAG3 was examined in formalin-fixed, paraffin-embedded specimens by immunohistochemical staining. And then, the prognostic role of BAG3 was analyzed in 51 medulloblastoma samples. Finally, the roles of BAG3 in the proliferation, migration, and invasion of Daoy medulloblastoma cell were investigated using a specific short hairpin RNA (shRNA). The expression of BAG3 in medulloblastoma tissues was higher than nontumorous samples. Furthermore, BAG3 overexpression significantly correlated with poor prognosis of patients with medulloblastoma. The overall survival and tumor-free survival in patients with BAG3 low expression were higher than high expression. Univariate and multivariate analysis showed that BAG3 overexpression was an independent prognostic marker for medulloblastoma. After the BAG3 knockdown, the Daoy cells exhibited decreased the ability to proliferate and form neurosphere. The preliminary mechanism study showed that overexpression of BAG3 might facilitate the cell cycle transition from G1 to S phase by modulating the cyclin-dependent kinase 2 (CDK2) and cyclin E expression. Additionally, we found that BAG3 might enhance the medulloblastoma cell migratory and invasive ability. In summary, BAG3 overexpression may regulate the survival and invasive properties of medulloblastoma and may serve as a potential therapy target for medulloblastoma.

  8. High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma.

    Science.gov (United States)

    Li, Xiaoxian; Wei, Bo; Sonmez, Ceyda; Li, Zaibo; Peng, Limin

    2017-08-01

    This study is to address the significance of tumor budding (TB) in breast carcinoma. Totally 244 estrogen receptor-positive (ER+)/HER2-negative (HER2-) and 131 triple-negative breast carcinoma (TNBC) diagnosed from 2004 to 2014 were analyzed. TB (cluster of up to 5 tumor cells at the invasive front) was evaluated using five 200× high-power fields (HPF) at the hotspot. The highest TB (H-TB) in 1 HPF and average TB (A-TB) in 5 HPFs were correlated with lymph node and distant metastasis, lymphovascular invasion (LVI), local recurrence, overall survival (OS), and disease-free survival (DFS). In ER+/HER2- cancer, H-TB and A-TB were significantly associated with distant metastasis. In TNBC, H-TB was associated with distant metastasis by univariate but not multivariate analysis; H-TB and A-TB were associated with LVI and worse OS (all P < .05). TB is associated with poor prognosis in ER+/HER2- and TNBC cancer. Evaluation of H-TB may be sufficient in breast carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Correlation Between Poor Prognosis and Lower TPPP Gene Expression in Hepatocellular Carcinoma.

    Science.gov (United States)

    Inokawa, Yoshikuni; Sonohara, Fuminori; Kanda, Mitsuro; Hayashi, Masamichi; Nishikawa, Yoko; Sugimoto, Hiroyuki; Kodera, Yasuhiro; Nomoto, Shuji

    2016-09-01

    Post-resection recurrence of hepatocellular carcinoma (HCC) tends to derive from multicentric origins, which indicates that the background liver microenvironment affects carcinogenesis. We obtained control liver samples [super normal (SN)] from 11 patients with secondary metastatic liver malignancies and used expression and methylation arrays to compare them with non-cancerous liver tissue from a patient with typical HCC with chronic hepatitis C (corresponding normal (CN)]. The expression array showed that gene expression of tubulin polymerization-promoting protein (TPPP) was lower in CN compared with SN. The methylation array showed a greater TPPP methylation index for CN than for SN. Transcripts of TPPP differed significantly among SN (n=11), CN (n=179), and tumor tissue of HCC (n=179) (median of 116, 4.60, and 2.63, respectively, pexpression in tumor than in normal tissue (ratio expression was found in HCC and CN tissue compared to SN and indicated poor prognosis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Correlation of Altered Expression of the Autophagy Marker LC3B with Poor Prognosis in Astrocytoma

    Directory of Open Access Journals (Sweden)

    Daniel Winardi

    2014-01-01

    Full Text Available Glioblastoma multiforme is one of the most serious malignant brain tumors and is characterized by resistance to chemotherapy and radiation therapy. Recent studies suggest that autophagy may play an important role not only in the regulation of cancer development and progression but also in determining the response of cancer cells to anticancer therapy. The purpose of the present study was to assess the relationship between protein expressions of two autophagy markers, LC3B and Beclin-1, with clinical parameters in astrocytoma patients. Furthermore, the expression of CD133, a marker of the cancer stem-like cells, in astrocytoma patients was also investigated. A total of 106 thin-section slides were retrospectively collected from astrocytoma patients. LC3B, but not Beclin-1, protein expression was found to significantly correlate with resistance to radiation- or chemotherapy. In addition, high intensity of LC3B staining was predictive of poor prognosis. Furthermore, survival time of patients with high-level expression in both CD133 and LC3B was significantly shorter than those with weak expression in both CD133 and LC3B. These results suggest that astrocytoma cancer stem-like cells together with enhanced autophagy may cause resistance to radiation therapy/chemotherapy and that targeting the cancer stem-like cell in astrocytoma may offer a viable therapeutic approach.

  11. Overexpression of OLC1 in Lung Squamous Cell Carcinoma Tissues is Associated with Poor Prognosis of Patients

    Directory of Open Access Journals (Sweden)

    Kunpeng ZHANG

    2017-05-01

    Full Text Available Background and objective OLC1 (overexpressed in lung cancer 1, screened out and cloned in our previous research, is a new gene associated with lung cancer. It is highly expressed in lung cancer and many other malignant tumors, and is associated with poor prognosis of esophageal squamous cell carcinoma, ovarian cancer, breast cancer and colorectal cancer. The aim of this research was to detect the expression level of OLC1 in the tumor tissues of lung adenocarcinoma (ADC and squamous cell carcinoma (SCC and explore its relationship with the prognosis of lung cancer patients. Methods Lung cancer tissues of 108 SCC and 90 ADC was dealed with immunohistochemical staining to detect the expression level of OLC1. The relationship between the expression level of OLC1 and clinical parameters and prognosis was analyzed. Results The rate of high expression of OLC1 staining in ADC was significantly higher than that in SCC (87.5% vs 55.3%, P<0.001. The overexpression of OLC1 in tumor tissues did not have a significant relationship with the prognosis of patients with ADC, but it was related with a poor prognosis of SCC patients as the univariate analysis showed. However the multivariate regression analysis showed that correlation between the overexpression of OLC1 and poor prognosis of SCC patients did not have a statistical significance (P=0.05. Conclusion The expression of OLC1 in ADC might be higher than that in SCC. A higher score of OLC1 staining in tumor tissue was associated with a poorer prognosis of patients with SCC, but could not be an independent predictor for a shorter overall survival in patients with SCC.

  12. Decreased expression of the GATA3 gene is associated with poor prognosis in primary gastric adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Rajiv Prasad Keshari

    Full Text Available BACKGROUND: GATA binding protein 3 (GATA3 was recently proposed to function as a tumor suppressor gene in some types of human cancer. This study aims to investigate GATA3 expression and its prognostic significance in primary gastric adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time quantitative PCR (RT-qPCR and immunohistochemical staining methods, GATA3 expression was analyzed in tissue samples from a consecutive series of 402 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between GATA3 expression, clinicopathological factors, and patient survival was investigated. The expression status of GATA3 was shown to be clearly reduced in the tumor tissue samples compared with that in the matched adjacent non-tumor tissue samples by RT-qPCR (P = 0.0014. Immunohistochemistry analysis indicated that GATA3 expression was significantly decreased in 225 of the 402 (56% gastric adenocarcinoma cases. Reduced GATA3 expression was also observed in patients with large tumors (P = 0.017, signet ring cell carcinoma or mucinous carcinoma (P = 0.005 and tumors with lymphatic or venous invasion (P = 0.040. Additionally, reduced expression of GATA3 was more commonly observed in tumors that were staged as T4a/b (P<0.001, N3 (P<0.001, or M1 (P<0.001. Kaplan-Meier survival curves revealed that reduced expression of GATA3 was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001. Multivariate Cox analysis identified GATA3 expression as an independent prognostic factor for overall survival (HR = 5.375, 95% CI = 3.647-7.921, P<0.001. To investigate the predictive ability of the models with and without containing GATA3 gene expression, Harrell's c-index was calculated as a measure of predictive accuracy of survival outcome. The c-index values revealed that model containing GATA3 expression (c-index = 0.897 had superior discrimination ability to the model without containg it (c-index = 0

  13. ASPM is a novel marker for vascular invasion, early recurrence, and poor prognosis of hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Shih-Yeh; Pan, Hung-Wei; Liu, Shu-Hsiang; Jeng, Yung-Ming; Hu, Fu-Chang; Peng, Shian-Yang; Lai, Po-Lin; Hsu, Hey-Chi

    2008-08-01

    Abnormal spindle-like microcephaly associated (ASPM) plays an important role in neurogenesis and cell proliferation. This study is to elucidate its role in hepatocellular carcinoma (HCC), particularly early tumor recurrence (ETR) and prognosis. We used reverse transcription-PCR assays to measure the ASPM mRNA levels in 247 HCC and correlated with clinicopathologic and molecular features. ASPM mRNA levels were high in fetal tissues but very low in most adult tissues. ASPM mRNA was overexpressed in 162 HCC (66%) but not in benign liver tumors. ASPM overexpression correlated with high alpha-fetoprotein (P = 1 x 10(-8)), high-grade (grade II-IV) HCC (P = 2 x 10(-6)), high-stage (stage IIIA-IV) HCC (P = 1 x 10(-8)), and importantly ETR (P = 1 x 10(-8)). ETR is the most critical unfavorable clinical prognostic factor. Among the various independent histopathologic (tumor size, tumor grade and tumor stage) and molecular factors (p53 mutation, high alpha-fetoprotein, and ASPM overexpression), tumor stage was the most crucial histologic factor (odds ratio, 14.7; 95% confidence interval, 6.65-33.0; P = 1 x 10(-8)), whereas ASPM overexpression (odds ratio, 6.49; P = 1 x 10(-8)) is the most important molecular factor associated with ETR. ASPM overexpression was associated with vascular invasion and ETR in both p53-mutated (all P values = 1 x 10(-8)) and non-p53-mutated HCC (P = 1 x 10(-8) and 0.00088, respectively). Hence, patients with APSM-overexpressing HCC had lower 5-year survival (P = 0.000001) in both p53-mutated (P = 0.00008) and non-p53-mutated HCC (P = 0.0027). In low-stage (stage II) HCC, ASPM overexpression also correlated with higher ETR (P = 0.008). ASPM overexpression is a molecular marker predicting enhanced invasive/metastatic potential of HCC, higher risk of ETR regardless of p53 mutation status and tumor stage, and hence poor prognosis.

  14. Behavioral health care for adolescents with poorly controlled diabetes via Skype: does working alliance remain intact?

    Science.gov (United States)

    Freeman, Kurt A; Duke, Danny C; Harris, Michael A

    2013-05-01

    Increasingly various technologies are being tested to deliver behavioral health care. Delivering services via videoconferencing shows promise. Given that the patient-provider relationship is a strong predictor of patient adherence to medical regimens, addressing relationship quality when services are not delivered face-to-face is critical. To that end, we compared the therapeutic alliance when behavioral health care was delivered to youth with poorly controlled type 1 diabetes mellitus (T1DM) and their caregivers in-clinic with the same services delivered via Internet-based videoconferencing (i.e., Skype™). Seventy-one adolescents with poorly controlled T1DM (hemoglobin A1c ≥9%) and one of their caregivers received up to 10 sessions of a family-based behavioral health intervention previously shown to improve adherence to diabetes regimens and family functioning; 32 were randomized to the Skype condition. Youth and caregivers completed the working alliance inventory (WAI), a 36-item measure of therapeutic alliance, at the end of treatment. Additionally, the number of behavioral health sessions completed was tracked. No significant differences in WAI scores were found for those receiving behavioral health care via Skype versus in-clinic. Youth WAI goal and total scores were significantly associated with the number of sessions completed for those in the clinic group. Behavioral health can be delivered to youth with T1DM via Internet-based videoconferencing without significantly impacting the therapeutic relationship. Thus, for those adolescents with T1DM who require specialized behavioral health care that targets T1DM management, Internet-based teleconferencing represents a viable alternative to clinic-based care. © 2013 Diabetes Technology Society.

  15. Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Nicola Ferrari

    Full Text Available The RUNX1 transcription factor is widely recognised for its tumour suppressor effects in leukaemia. Recently a putative link to breast cancer has started to emerge, however the function of RUNX1 in breast cancer is still unknown. To investigate if RUNX1 expression was important to clinical outcome in primary breast tumours a tissue microarray (TMA containing biopsies from 483 patients with primary operable invasive ductal breast cancer was stained by immunohistochemistry. RUNX1 was associated with progesterone receptor (PR-positive tumours (P<0.05, more tumour CD4+(P<0.05 and CD8+(P<0.01 T-lymphocytic infiltrate, increased tumour CD138+plasma cell (P<0.01 and more CD68+macrophage infiltrate (P<0.001. RUNX1 expression did not influence outcome of oestrogen receptor (ER-positive or HER2-positive disease, however on univariate analysis a high RUNX1 protein was significantly associated with poorer cancer-specific survival in patients with ER-negative (P<0.05 and with triple negative (TN invasive breast cancer (P<0.05. Furthermore, multivariate Cox regression analysis of cancer-specific survival showed a trend towards significance in ER-negative patients (P<0.1 and was significant in triple negative patients (P<0.05. Of relevance, triple negative breast cancer currently lacks good biomarkers and patients with this subtype do not benefit from the option of targeted therapy unlike patients with ER-positive or HER2-positive disease. Using multivariate analysis RUNX1 was identified as an independent prognostic marker in the triple negative subgroup. Overall, our study identifies RUNX1 as a new prognostic indicator correlating with poor prognosis specifically in the triple negative subtype of human breast cancer.

  16. p53 protein expression in nephroblastomas: a predictor of poor prognosis.

    Science.gov (United States)

    Govender, D; Harilal, P; Hadley, G P; Chetty, R

    1998-01-01

    Alteration of the tumour-suppressor gene p53 is the commonest genetic change encountered in human malignant tumours. A study was undertaken to ascertain the prognostic value of p53 immunoexpression in nephroblastomas. A series of 93 consecutive cases was analysed. Archival formalin-fixed, paraffin wax-embedded tissue sections were stained with monoclonal anti-p53 antibody (DO-7, Dako) using a peroxidase-labelled streptavidin biotin kit. Five of seven tumours (71.4%) with unfavourable histology, but only 3 of 86 favourable histology tumours, showed 'high' p53 immunoexpression (P < 0.001). p53 expression in unfavourable histology tumours was present in both anaplastic and non-anaplastic components. Moreover, there was uniform staining of blastema, epithelium and stroma in unfavourable histology tumours. No statistical difference in p53 expression was found between patients who had received and those who had not received preoperative chemotherapy (P = 0.678). Similarly, no statistical difference was found in the groups of patients who were disease free, who had residual/recurrent disease or who had died (P = 0.238). The mean survival period for patients with tumours that had 'low' and 'high' expressions was 24.8 months and 12.6 months respectively (P = 0.0003). In conclusion, p53 immunoexpression in nephroblastomas was found to be an important determinant of poor prognosis as it identifies those patients with a shorter survival period and also those with unfavourable histology tumours. It may also be of practical value to the practising pathologist by identifying those tumours that require careful assessment for the presence of anaplasia.

  17. Elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma.

    Science.gov (United States)

    Fan, Weibing; Fan, Shuang-Shi; Feng, Juan; Xiao, Desheng; Fan, Songqing; Luo, Jiadi

    2017-01-01

    elevated expression of HSP10 protein inhibits apoptosis and associates with poor prognosis of astrocytoma.

  18. Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Huanwen Wu

    Full Text Available Epidermal growth factor receptor (EGFR is highly expressed in pancreatic ductal adenocarcinoma (PDAC and is involved in tumorigenesis and development. However, EGFR expression alone has limited clinical and prognostic significance. Recently, the cross-talk between EGFR and G-protein-coupled chemokine receptor CXCR4 has become increasingly recognized.In the present study, immunohistochemical staining of EGFR and CXCR4 was performed on paraffin-embedded specimens from 131 patients with surgically resected PDAC. Subsequently, the associations between EGFR expression, CXCR4 expression, EGFR/CXCR4 coexpression and clinicopathologic factors were assessed, and survival analyses were performed.In total, 64 (48.9% patients expressed EGFR, 68 (51.9% expressed CXCR4, and 33 (25.2% coexpressed EGFR and CXCR4. No significant association between EGFR and CXCR4 expression was observed (P = 0.938. EGFR expression significantly correlated with tumor differentiation (P = 0.031, whereas CXCR4 expression significantly correlated with lymph node metastasis (P = 0.001. EGFR/CXCR4 coexpression was significantly associated with lymph node metastasis (P = 0.026, TNM stage (P = 0.048, and poor tumor differentiation (P = 0.004. By univariate survival analysis, both CXCR4 expression and EGFR/CXCR4 coexpression were significant prognostic factors for poor disease-free survival (DFS and overall survival (OS. Moreover, EGFR/CXCR4 coexpression significantly increased the hazard ratio for both recurrence and death compared with EGFR or CXCR4 protein expression alone. Multivariate survival analysis demonstrated that EGFR/CXCR4 coexpression was an independent prognostic factor for DFS (HR = 2.33, P<0.001 and OS (HR = 2.48, P = 0.001.In conclusion, our data indicate that although EGFR expression alone has limited clinical and prognostic significance, EGFR/CXCR4 coexpression identified a subset of PDAC patients with more aggressive tumor characteristics and a significantly worse

  19. STAT3 signaling drives EZH2 transcriptional activation and mediates poor prognosis in gastric cancer.

    Science.gov (United States)

    Pan, Yuan-Ming; Wang, Cheng-Gang; Zhu, Min; Xing, Rui; Cui, Jian-Tao; Li, Wen-Mei; Yu, De-Dong; Wang, Shu-Bin; Zhu, Wei; Ye, Ying-Jiang; Wu, Yun; Wang, Shan; Lu, You-Yong

    2016-12-09

    STAT3 signaling plays the pivotal role in tumorigenesis through EZH2 epigenetic modification, which enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. Here, another possible feedback mechanism and clinical significance of EZH2 and STAT3 were investigated in gastric cancer (GC). STAT3, p-STAT3 (Tyr 705) and EZH2 expression were examined in 63 GC specimens with matched normal tissues by IHC staining. EZH2 and STAT3 were also identified in five GC cell lines using RT-PCR and western blot analyses. p-STAT3 protein was detected by western blotting. In order to investigate whether EZH2 expression was directly regulated by STAT3, EZH2 expression was further detected using siRNA for STAT3 or IL-6 stimulation, with dual luciferase reporter analyses, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. The clinical significance of STAT3, p-STAT3 and EZH2 expression was evaluated by multi-factor COX regression and Kaplan-Meier analyses. Hyper-activation of STAT3, p-STAT3 and EZH2 expression were observed in GC cells and tissues. STAT3 signaling was correlated with EZH2 expression in GC (R = 0.373, P = 0.003), which was consistent with our data showing that STAT3 as the transcriptional factor enhanced EZH2 transcriptional activity by binding the relative promoter region (-214 ~ -206). STAT3 was an independent signature for poor survival (P = 0.002). Patients with STAT3(+)/EZH2(+) or p-STAT3(+)/EZH2(+) had a worse outcome than others (P EZH2 was associated with advanced TNM staging (P = 0.017). Moreover, treatment with a combination of siSTAT3 and EZH2-specific inhibitor, 3-deazaneplanocin A (DZNEP), increased the apoptotic ratio of cells. It is benefit for targeting STAT3-EZH2 interplay in GC treatment. Our results indicate that STAT3 status mediated EZH2 upregulation, associated with advanced TNM stage and poor prognosis, suggesting that combination with knockdown of STAT3 and EZH2 inhibitor

  20. Non-Hodgkin's lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis.

    Science.gov (United States)

    Mossafa, H; Damotte, D; Jenabian, A; Delarue, R; Vincenneau, A; Amouroux, I; Jeandel, R; Khoury, E; Martelli, J M; Samson, T; Tapia, S; Flandrin, G; Troussard, X

    2006-09-01

    Out of 344 patients with newly diagnosed non-Hodgkin's lymphoma (NHL), this study identified 16 patients presenting Burkitt-like cells (BLCs) after cytological and/or histological review. Conventional cytogenetic analysis showed at diagnosis complex chromosomal abnormalities in 13 cases and a normal karyotype in three cases. However, neither t(8;14)(q24;q32) nor the variants t(2;8)(p12;q24) or t(8;22)(q24;q11) was detected. FISH studies showed c-MYC amplification in all cases with four to more than seven copies in 10 - 77% metaphase or inter-phase cells. This study did not observe any gene fusion signal for c-MYC/IgH excluding a t(8;14) translocation and partial tri or polysomy of chromosome 8. It also excluded in that cases a break apart for the c-MYC locus. This study also never detected IgL/c-MYC, IgK/c-MYC or X-c-MYC. The BLCs were present whatever the lymphoma sub-type: follicular lymphoma (FL) was diagnosed in six out of 16 patients, mantle cell lymphoma (MCL) in four out of 16 patients, marginal zone lymphoma (MZL) in two out of 16 patients and diffuse large B-cell lymphomas (DLBCL) in three out of 16 patients. One additional patient presented a T-cell lymphoma. The clinical course was aggressive with a poor prognosis, as death occurred in nine patients, within 6 months after diagnosis for eight of them. These data could suggest a sub-group of NHL patients (15 B-NHL, 1 T-NHL) have been identified with a poor prognosis characterized by the association of Burkitt-like cells and c-MYC amplification without t(8;14)(q24;q32) or its variants. The possibility that this profile may represent a distinct morphologic NHL sub-set remains to be determined on a large cohort of patients.

  1. Reduced myocardial carbon-11 hydroxyephedrine retention is associated with poor prognosis in chronic heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Pietilae, M.; Ukkonen, H. [Dept. of Medicine, Turku University Central Hospital (Finland); Turku PET Centre, Turku (Finland); Malminiemi, K. [Dept. of Clinical Chemistry, Tampere University Hospital (Finland); Saraste, M. [Dept. of Clinical Physiology, Turku University Central Hospital (Finland); Naagren, K.; Lehikoinen, P. [Turku PET Centre, Turku (Finland); Voipio-Pulkki, L.-M. [Dept. of Medicine, Turku University Central Hospital (Finland); Dept. of Medicine, Helsinki University Central Hospital (Finland)

    2001-03-01

    Abnormalities of the autonomic nervous system are known to be of prognostic significance in chronic heart failure (CHF). The prognostic value of positron emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not been explored previously. We retrospectively studied the survival data of 46 NYHA class II-III CHF patients (mean LVEF 35%{+-}8%) who had undergone carbon-11 hydroxyephedrine ({sup 11}C-HED) studies at the Turku PET Centre between August 1992 and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46 patients and coronary artery disease with at least one prior myocardial infarction in the remaining 33. Data on causes of death and heart transplantation were collected, and the statistically significant predictors of prognosis were analysed using Cox's proportional hazards regression. During the mean follow-up period of 55{+-}19 months, 11 deaths occurred and two patients underwent heart transplantation successfully. Eleven end-points were classified as cardiac (nine sudden cardiac deaths and two deaths due to progressive heart failure) and two as non-cardiac. When divided into two groups based on the median of {sup 11}C-HED retention (mean 0.184{+-}0.061, median 0.183), eight end-points (death or cardiac transplantation) were reached in the group with {sup 11}C-HED retention below the median and three in the group with {sup 11}C-HED retention above the median (P<0.02). In proportional hazards regression analysis, only peak oxygen uptake (peak VO{sub 2}), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that {sup 11}C-HED PET provides independent prognostic information in patients with CHF. (orig.)

  2. Loss of SFRP1 Expression Is Associated with Poor Prognosis in Hepatocellular Carcinoma.

    Science.gov (United States)

    Davaadorj, Mandakhnaran; Imura, Satoru; Saito, Y U; Morine, Yuji; Ikemoto, Tetsuya; Yamada, Shinichiro; Takasu, Chie; Hiroki, Teraoku; Yoshikawa, Masato; Shimada, Mitsuo

    2016-02-01

    Secreted frizzled-related protein-1 (SFRP1) is a well-known inhibitor of the wingless type (WNT)-β-catenin signaling pathway and its inactivation plays an important role in the development and progression of various types of cancer. However, the clinical significance of SFRP1 expression in patients with hepatocellular carcinoma (HCC) remains unknown. A total of 63 patients with HCC who underwent hepatectomy at our Institution were enrolled in this study. A quantitative real-time polymerase chain reaction (RT-PCR) was performed to determine the SFRP1 mRNA expression level in both the tumorous and non-tumorous tissues of HCC. The patients were divided into low and high gene-expression groups based on the SFRP1 gene expression level in their tumor tissues. We analyzed the differences in clinicopathological characteristics between these two groups of patients. The expression level of SFRP1 was significantly lower in tumor tissue than in non-tumor tissue (pexpression of SFRP1 in tumor tissue and older than 65 years (p=0.030), tumor size less than 5 cm (p=0.011); and no vascular invasion (p=0.004). Patients with high SFRP1 expression in tumor tissue had a significantly better overall survival rate (p=0.040). However, the SFRP1 expression level was not defined as an independent risk factor for patient survival based on results of multivariate analysis. SFRP1 may play a role in the development and progression of HCC. Therefore, more studies are required to investigate a potential role of SFRP1 in HCC prognosis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. PTEN gene mutations correlate to poor prognosis in glioma patients: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Han F

    2016-06-01

    Full Text Available Feng Han,1,* Rong Hu,2,* Hua Yang,1 Jian Liu,1 Jianmei Sui,1 Xin Xiang,1 Fan Wang,1 Liangzhao Chu,1 Shibin Song1 1Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, 2Department of Histology and Embryology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China *These authors contributed equally to this work Background: We conducted this meta-analysis based on eligible trials to investigate the relationship between phosphatase and tensin homolog (PTEN genetic mutation and glioma patients’ survival. Methods: PubMed, Web of Science, and EMBASE were searched for eligible studies regarding the relationship between PTEN genetic mutation and glioma patients’ survival. The primary outcome was the overall survival of glioma patient with or without PTEN genetic mutation, and second outcome was prognostic factors for the survival of glioma patient. A fixed-effects or random-effects model was used to pool the estimates according to the heterogeneity among the included studies. Results: Nine cohort studies, involving 1,173 patients, were included in this meta-analysis. Pooled results suggested that glioma patients with PTEN genetic mutation had a significant shorter overall survival than those without PTEN genetic mutation (hazard ratio [HR] =2.23, 95% confidence interval [CI]: 1.35, 3.67; P=0.002. Furthermore, subgroup analysis indicated that this association was only observed in American patients (HR =2.19, 95% CI: 1.23, 3.89; P=0.008, but not in Chinese patients (HR =1.44, 95% CI: 0.29, 7.26; P=0.657. Histopathological grade (HR =1.42, 95% CI: 0.07, 28.41; P=0.818, age (HR =0.94, 95% CI: 0.43, 2.04; P=0.877, and sex (HR =1.28, 95% CI: 0.55, 2.98; P=0.564 were not significant prognostic factors for the survival of patients with glioma. Conclusion: Current evidence indicates that PTEN genetic mutation is associated with poor prognosis in glioma patients. However, this

  4. Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Kuai W

    2012-09-01

    Full Text Available Jin Bai,1 Aiping Guo,2 Ze Hong,3 Wenxia Kuai31Department of Pediatrics, Huai'an Hospital to Xuzhou Medical College and Huai'an Second People's Hospital, Huai'an, China; 2Department of Pediatrics, Chuzhou Hospital, Huai'an, China; 3Department of Pediatrics, Huai'an First People's Hospital, Huai'an, ChinaObjective: MicroRNA-100 (miR-100, a small noncoding RNA molecule, acts as a tumor suppressor or an oncogene in different cancers. The aberrant expression of this microRNA has been demonstrated as a frequent event in adult patients with acute myeloid leukemia (AML, but little is known for pediatric AML. The aim of this study was to investigate the expression and clinical significance of miR-100 in pediatric AML.Methods: The expression levels of miR-100 in bone marrow mononuclear cells were detected by real-time quantitative polymerase chain reaction in a cohort of 106 patients with de novo pediatric AML. The prognostic values of miR-100 in pediatric AML were also analyzed.Results: Compared with normal controls, upregulation of miR-100 in the bone marrow of pediatric AML patients with statistically significant differences (P < 0.001 was found. The expression levels of miR-100 were found to be significantly higher in pediatric AML patients with extramedullary disease, with the French–American–British classification subtype M7, and with unfavorable day 7 response to induction chemotherapy (P = 0.008, 0.001 and 0.01, respectively. Moreover, both univariate and multivariate analyses revealed that miR-100 upregulation was associated with poorer relapse-free and overall survival in pediatric AML patients.Conclusion: This is the first report demonstrating the upregulation of miR-100 in pediatric AML, and its association with poor relapse-free and overall survival. These results suggest that miR-100 upregulation may be used as an unfavorable prognostic marker in pediatric AML.Keywords: pediatric acute myeloid leukemia, microRNA-100, real

  5. Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Weiyuan Wang

    expression of p-4EBP1 and p-p70S6K proteins were the independent poor prognostic factors for NPC (P = 0.043, P = 0.027, respectively. Taken together, high expression of p-p70S6K and p-4EBP1 proteins may act as valuable independent biomarkers to predict a poor prognosis of NPC.

  6. Overexpression of EZH2 is associated with the poor prognosis in osteosarcoma and function analysis indicates a therapeutic potential

    OpenAIRE

    Sun, Ranran; Shen,Jacson; Gao, Yan; Zhou, Yubing; Yu, Zujiang; Hornicek, Francis; Kan, Quancheng; Duan, Zhenfeng

    2016-01-01

    Osteosarcoma is a primary malignant bone tumor that has a poor prognosis due to local recurrence, metastasis, and chemotherapy resistance. Therefore, there is an urgent need to develop novel potential therapeutic targets for osteosarcoma. Enhancer of zeste homologue 2 (EZH2) is a member of the polycomb group of proteins, which has important functions in epigenetic silencing and cell cycle regulation. Overexpression of EZH2 has been found in several malignancies, however, its expression and th...

  7. Nerve growth factor receptor (p75 NTR) and pattern of invasion predict poor prognosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Søland, T M; Brusevold, I J; Koppang, H S; Schenck, K; Bryne, M

    2008-07-01

    To evaluate the expression of p75 neurotrophin receptor (p75(NTR)) in oral squamous cell carcinoma (OSCC). The results were related to tumour node metastasis (TNM) stage, World Health Organization (WHO) grade, invasive front grading (IFG) and prognosis. Immunohistochemically, the expression of p75(NTR) was assessed in 53 T1-T2 OSCCs. Clinical data were recorded prospectively. The end-point was disease-free survival. All tumours expressed p75(NTR), and this expression, both in central/superficial tumour areas and at the invasive front, was associated with poor prognosis (P = 0.03 and P = 0.02) (log rank test). Tumours with marked cellular dissociation (IFG parameter) had more recurrences than tumours with collective tumour cell invasion (P = 0.03). In tumours showing both p75(NTR) at the invasive front and marked tumour cell dissociation, the average risk of recurrence was increased about 17 times (Cox regression analysis) compared with tumours with low p75(NTR) expression and collective invasion. Traditional prognostic systems were of no prognostic significance. p75(NTR) was expressed in all OSCCs. p75(NTR) expression and the pattern of invasion were significantly associated with a poor prognosis in OSCCs, and both were better prognostic factors than traditional prognostic parameters. The combination of p75(NTR) expression and the pattern of invasion strongly increased precision in the identification of tumours with poor disease-free survival.

  8. Obvious emphysema on computed tomography during an acute exacerbation of chronic obstructive pulmonary disease predicts a poor prognosis.

    Science.gov (United States)

    Cheng, T; Wan, H Y; Cheng, Q J; Guo, Y; Qian, Y R; Fan, L; Feng, Y; Song, Y Y; Zhou, M; Li, Q Y; Shi, G C; Huang, S G

    2015-05-01

    Emphysematous change on computed tomography (CT) during the stable phase of chronic obstructive pulmonary disease (COPD) is reported to correlate with COPD prognosis. Acute exacerbation of COPD (AECOPD) is associated with a high risk of mortality and a poor prognosis. This study aims to study the relationship between prognosis and emphysematous changes on CT during an AECOPD. Histories were recorded, and CT acquired for 106 patients who visited the emergency department for an AECOPD. Emphysematous change was quantified by measuring the percentage of low-attenuation areas (LAA%) in the entire lung on CT images with a threshold of -950 Hounsfield units. Other factors that could influence AECOPD prognosis were also recorded on admission and analysed. At follow ups conducted in 1 year, patient survival, the modified Medical Research Council (mMRC) Dyspnoea Scale, and performance status (PS) were evaluated, and a COPD Assessment Test (CAT) was completed. The 1-year follow up was completed by 103 of 106 patients. The median LAA% was significantly higher in non-survivors (11%, n = 16) than in survivors (5.69%, n = 87) (P = 0.006) at the 1-year follow up. LAA% was significantly correlated with mMRC grade (r = 0.285, P = 0.008), PS (r = 0.397, P 7.5% was a significant predictor of 1-year mortality, higher mMRC and PS at the 3-month and 1-year follow ups, after adjustment for other prognostic predictors. Obvious emphysematous changes on CT (LAA% > 7.5%) during an AECOPD predicts a poor prognosis independent of other known indicators. © 2015 Royal Australasian College of Physicians.

  9. EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

    Directory of Open Access Journals (Sweden)

    MacMillan Christina

    2010-06-01

    Full Text Available Abstract Background Proteolytic cleavage of the extracellular domain (EpEx of Epithelial cell adhesion molecule (EpCAM and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. Methods EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. Results The anaplastic (ATC and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p Conclusion We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC.

  10. Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer.

    Science.gov (United States)

    Okumura, Shinya; Kaido, Toshimi; Hamaguchi, Yuhei; Kobayashi, Atsushi; Shirai, Hisaya; Yao, Siyuan; Yagi, Shintaro; Kamo, Naoko; Hatano, Etsuro; Okajima, Hideaki; Takaori, Kyoichi; Uemoto, Shinji

    2017-11-01

    Visceral fat accumulation and muscle depletion have been identified as poor prognostic factors for various cancers. However, the significance of visceral adiposity and sarcopenic visceral obesity on outcomes after resection of pancreatic cancer remains unclear. A retrospective analysis of 301 patients who underwent resection for localized pancreatic cancer between 2004 and 2015 was performed. The extent of visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] and visceral obesity [visceral fat area (VFA)] were measured on preoperative computed tomography images, together with skeletal muscle index (SMI) and muscle attenuation (MA). The impacts of these body composition parameters on outcomes after pancreatic resection were investigated. The overall survival (OS) and recurrence-free survival (RFS) rates in patients with high VSR were significantly lower than those in patients with low VSR (P = 0.001, P = 0.007, respectively). There were no differences in OS and RFS between high VFA and low VFA group; however, when analyzed together with sarcopenic factors, OS and RFS rates of the patients with sarcopenic visceral obesity were significantly lower compared with those of the others. Multivariate analyses revealed that high VSR was an independent risk factor for mortality (hazard ratio (HR) 1.58, P = 0.009) and recurrence (HR 1.41, P = 0.026) together with low SMI, low MA, high CA19-9, microvascular invasion, and nodal metastasis. Visceral adiposity and sarcopenic visceral obesity, as well as low muscle mass and quality, were closely associated with mortality and recurrence after resection of pancreatic cancer.

  11. Increased expression of interleukin-6 predicts poor response to chemoradiotherapy and unfavorable prognosis in oral squamous cell carcinoma

    Science.gov (United States)

    JINNO, TEPPEI; KAWANO, SHINTARO; MARUSE, YASUYUKI; MATSUBARA, RYOTA; GOTO, YUICHI; SAKAMOTO, TAIKI; HASHIGUCHI, YUMA; KANEKO, NAOKI; TANAKA, HIDEAKI; KITAMURA, RYOJI; TOYOSHIMA, TAKESHI; JINNO, AKIKO; MORIYAMA, MASAFUMI; OOBU, KAZUNARI; KIYOSHIMA, TAMOTSU; NAKAMURA, SEIJI

    2015-01-01

    Recent studies have revealed that cancer cells are exacerbated by chronic inflammation. The present study examined the immunohistochemical expression for interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, in oral squamous cell carcinoma (OSCC) to elucidate the association of IL-6 expression with tumor progression, chemoresistance and prognosis. Seventy-eight patients with primary OSCC were analyzed by immunohistochemical staining for IL-6. These labeling indexes (LIs) were calculated and evaluated in association with the clinicopathologic characteristics and prognosis in the OSCC patients. The patients were divided into three groups as follows: negative group = LI <5%; low IL-6 group = 5% ≤ LI <30%; high IL-6 group = LI ≥30%. The patient numbers of the negative, low and high expression groups were 24, 22 and 32, respectively. In the high IL-6 expression group, IL-6 receptor (IL-6R), phospho-signal tranducer and activator of transcription 3 (p-STAT3) were also detected in almost all the cancer cells. The prevalence of the cervical lymph node or the distant metastasis in the high expression group was significantly higher than those in the negative and low expression groups. Furthermore, the high expression group had a significantly poorer tumor response to the preoperative chemoradiotherapy and a more unfavourable prognosis than the negative and the low expression groups. Interestingly, IL-6, IL-6R and p-STAT3 were expressed in the residual cancer cells of all the patients in the high expression group with poor response to chemoradiotherapy. These results suggested that IL-6 signaling possibly is involved in the progression and treatment-resistance of OSCC and IL-6 expression in cancer cells could be a useful predictive factor of poor response to chemoradiotherapy and unfavorable prognosis. PMID:25761055

  12. EMAST is associated with a poor prognosis in microsatellite instable metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Sabine Venderbosch

    Full Text Available To determine the frequency and prognostic value of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST in metastatic colorectal cancer (mCRC patients in relation to microsatellite instability (MSI status and MSH3 protein expression.The frequency of EMAST was evaluated in mCRC patients with MSI tumors and microsatellite stable (MSS tumors. A literature overview was performed to compare the frequency of EMAST in our study with existing data. Immunohistochemistry for MSH3 was compared with EMAST status. Outcome was studied in terms of overall survival (OS of mCRC patients with MSI and MSS tumors.EMAST was evaluated in 89 patients with MSI tumors (including 39 patients with Lynch syndrome and 94 patients with MSS tumors. EMAST was observed in 45.9% (84 out of 183 of patients, with an increased frequency in MSI tumors (79.8% versus 13.8%, p < 0.001. We found no correlation between EMAST and MSH3 protein expression. There was no effect of EMAST on prognosis in patients with MSS tumors, but patients with MSI / non-EMAST tumors had a significantly better prognosis than patients with MSI / EMAST tumors (OS: HR 3.22, 95% CI 1.25-8.30.Frequency of EMAST was increased in mCRC patients with MSI tumors, compared to MSS tumors. Our data suggest that the presence of EMAST correlates with worse OS in these patients. There was no effect of EMAST on the prognosis of patients with MSS tumors. A limitation of our study is the small number of patients in our subgroup analysis.

  13. EMAST is associated with a poor prognosis in microsatellite instable metastatic colorectal cancer.

    Science.gov (United States)

    Venderbosch, Sabine; van Lent-van Vliet, Shannon; de Haan, Anton F J; Ligtenberg, Marjolijn J; Goossens, Monique; Punt, Cornelis J A; Koopman, Miriam; Nagtegaal, Iris D

    2015-01-01

    To determine the frequency and prognostic value of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in metastatic colorectal cancer (mCRC) patients in relation to microsatellite instability (MSI) status and MSH3 protein expression. The frequency of EMAST was evaluated in mCRC patients with MSI tumors and microsatellite stable (MSS) tumors. A literature overview was performed to compare the frequency of EMAST in our study with existing data. Immunohistochemistry for MSH3 was compared with EMAST status. Outcome was studied in terms of overall survival (OS) of mCRC patients with MSI and MSS tumors. EMAST was evaluated in 89 patients with MSI tumors (including 39 patients with Lynch syndrome) and 94 patients with MSS tumors. EMAST was observed in 45.9% (84 out of 183) of patients, with an increased frequency in MSI tumors (79.8% versus 13.8%, p < 0.001). We found no correlation between EMAST and MSH3 protein expression. There was no effect of EMAST on prognosis in patients with MSS tumors, but patients with MSI / non-EMAST tumors had a significantly better prognosis than patients with MSI / EMAST tumors (OS: HR 3.22, 95% CI 1.25-8.30). Frequency of EMAST was increased in mCRC patients with MSI tumors, compared to MSS tumors. Our data suggest that the presence of EMAST correlates with worse OS in these patients. There was no effect of EMAST on the prognosis of patients with MSS tumors. A limitation of our study is the small number of patients in our subgroup analysis.

  14. Liver Angiosarcoma: Rare tumour associated with a poor prognosis, literature review and case report.

    Science.gov (United States)

    Millan, Mauricio; Delgado, Alejandro; Caicedo, Luis A; Arrunategui, Ana M; Meneses, Carlos A; Villegas, Jorge I; Serrano, Oscar; Caicedo, Liliana; Duque, Mauricio; Echeverri, Gabriel J

    2016-01-01

    Liver angiosarcoma is a very uncommon tumour of mesenchymal origin, representing between 0.1-2% of all primary tumours of the liver, affecting mainly men in their sixth or seventh decade of life, with a high mortality in the first years (Chaudhary et al., 2015). Literature reports of its surgical treatment vary from a total or partial hepatectomy with or without liver transplant. A 37year old male, with a 7year history of a fatty liver, was found to have a 12cm diameter tumour in a cirrhotic liver, during an abdominal Computed Tomography (CT) scan. Patient was asymptomatic with negative tumour markers, yet tumour liver biopsy revealed a Liver Angiosarcoma with positive immunohistochemistry for neoplastic cells CD31 and CD34. Patient was deemed candidate for a partial hepatectomy of the affected liver segments which was done without complications and no evidence of other tumour lesions was found during surgery. Patient continued oncologic management with ongoing chemotherapy. Liver Angiosarcoma, although rare, persists with a high mortality due to its aggressive nature. Never the less liver transplantation, although proven to be an effective treatment for many pathologies that culminate in liver failure, fails to improve patients' survival and prognosis, when compared to partial hepatectomy as surgical management to for liver Angiosarcoma, CONCLUSION: Partial hepatectomy as surgical management, followed by adjuvant therapy, for Liver Angiosarcoma continues to prove favourable results and prognosis compared to Liver Transplantation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. High Nuclear Expression of HDGF Correlates with Disease Progression and Poor Prognosis in Human Endometrial Carcinoma

    Directory of Open Access Journals (Sweden)

    Lijing Wang

    2014-01-01

    Full Text Available Aims. This study examined the correlation between high nuclear expression of hepatoma-derived growth factor (HDGF and clinicopathologic data in endometrial carcinoma (EC, including patient survival. Methods. One hundred and twenty-two endometrial carcinoma (EC patients from 2002 to 2008 were reviewed in the study. HDGF expression in tumor tissues was examined using immunohistochemistry (IHC, and its association with clinicopathological parameters was evaluated. Tumors with 80% or more nuclei staining were regarded as high expression and tumors with less than 80% nuclei staining considered as low expression. Results and Conclusions. Immunohistochemical analysis revealed that HDGF was expressed in both the nucleus and cytoplasm. High nuclear expression of HDGF was positively correlated with FIGO stage (P=0.032, but not associated with other clinical features, such as histological grading or lymph node status. Patients with high expression of HDGF had poorer overall survival rates than those with low expression of HDGF (P=0.001. However, multivariate analyses showed that high nuclear expression of HDGF protein was not an independent predictor of prognosis for EC patients (P=0.111. Our results suggest that high nuclear expression of HDGF is a potential unfavorable factor for the progression and prognosis of EC.

  16. Poor prognosis after surgery for intertrochanteric fracture in elderly patients with clopidogrel treatment: A cohort study.

    Science.gov (United States)

    Zhang, Jianzheng; Chen, Xiaobin; Wang, Juan; Liu, Zhi; Wang, Xiaowei; Ren, Jixin; Sun, Tiansheng

    2017-09-01

    Choice of surgical approach in patients under clopidogrel treatment is controversial. Intertrochanteric fractures are common in the elderly, who also suffer from a number of comorbidities.The aim of this study is to assess the prognosis of elderly patients with clopidogrel treatment after surgery for intertrochanteric fracture.This was a cohort study of 238 elderly patients who underwent proximal femur intramedullary nailing for intertrochanteric fracture between January 2012 and December 2013 at the Geriatric Trauma Center of the Beijing Army General Hospital. The patients were divided into the clopidogrel (n = 32) and control (n = 206) groups according to their history of long-term clopidogrel treatment before surgery. Demographic and clinical characteristics, intraoperative parameters, postoperative complications, and 1-year survival were compared between the 2 groups.Preoperative American Society of Anesthesiologists (ASA) grade and the frequency of arterial stenting were different between the 2 groups (P = .002 and P clopidogrel group compared with the control group (all P clopidogrel group compared with the control group (37.5% vs 20.3%, P = .030).Prognosis after surgery for intertrochanteric fracture was poorer in elderly patients with clopidogrel treatment; these patients had lower 1-year survival, more intraoperative blood transfusion, longer ICU stay, and longer hospital stay. ASA grade, arterial stenting, and anesthesia mode were prognostic factors.

  17. Usefulness of immunohistochemical indicators for diagnosis and prognosis of poorly differentiated tumours

    OpenAIRE

    Kandefer-Gola Małgorzata; Nowak Marcin; Ciaputa Rafał; Madej Janusz A.

    2016-01-01

    Immunohistochemical studies have become an indispensable element of establishing the correct histopathological diagnosis of poorly differentiated lesions, proving particularly suitable, and occasionally indispensable, for diagnosis of poorly differentiated neoplastic tumours. Knowledge of the mechanism of action and normal reaction of individual proteins is required in selection of the antibody pattern for a given tissue and in evaluation of the obtained results. This paper aims to promote th...

  18. Aurora-A identifies early recurrence and poor prognosis and promises a potential therapeutic target in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Jie Xu

    Full Text Available Triple negative breast cancer (TNBC acquires an unfavorable prognosis, emerging as a major challenge for the treatment of breast cancer. In the present study, 122 TNBC patients were subjected to analysis of Aurora-A (Aur-A expression and survival prognosis. We found that Aur-A high expression was positively associated with initial clinical stage (P = 0.025, the proliferation marker Ki-67 (P = 0.001, and the recurrence rate of TNBC patients (P<0.001. In TNBC patients with Aur-A high expression, the risk of distant recurrence peaked at the first 3 years and declined rapidly thereafter, whereas patients with Aur-A low expression showed a relatively constant risk of recurrence during the entire follow-up period. Univariate and multivariate analysis showed that overexpression of Aur-A predicted poor overall survival (P = 0.002 and progression-free survival (P = 0.012 in TNBC. Furthermore, overexpression of Aur-A, associated with high Ki-67, predicted an inferior prognosis compared with low expression of both Aur-A and Ki-67. Importantly, we further found that Aur-A was overexpressed in TNBC cells, and inhibition of this kinase inhibited cell proliferation and prevented cell migration in TNBC. Our findings demonstrated that Aur-A was a potential therapeutic target for TNBC and inhibition of Aur-A kinase was a promising regimen for TNBC cancer therapy.

  19. Quantitative Multiplex Immunohistochemistry Reveals Myeloid-Inflamed Tumor-Immune Complexity Associated with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Takahiro Tsujikawa

    2017-04-01

    Full Text Available Here, we describe a multiplexed immunohistochemical platform with computational image processing workflows, including image cytometry, enabling simultaneous evaluation of 12 biomarkers in one formalin-fixed paraffin-embedded tissue section. To validate this platform, we used tissue microarrays containing 38 archival head and neck squamous cell carcinomas and revealed differential immune profiles based on lymphoid and myeloid cell densities, correlating with human papilloma virus status and prognosis. Based on these results, we investigated 24 pancreatic ductal adenocarcinomas from patients who received neoadjuvant GVAX vaccination and revealed that response to therapy correlated with degree of mono-myelocytic cell density and percentages of CD8+ T cells expressing T cell exhaustion markers. These data highlight the utility of in situ immune monitoring for patient stratification and provide digital image processing pipelines to the community for examining immune complexity in precious tissue sections, where phenotype and tissue architecture are preserved to improve biomarker discovery and assessment.

  20. Overexpression of long noncoding RNA HOTTIP promotes tumor invasion and predicts poor prognosis in gastric cancer

    Directory of Open Access Journals (Sweden)

    Ye H

    2016-04-01

    Full Text Available Heng Ye,1 Kun Liu,2 Keqing Qian1 1Department of Oncology, 2Department of General Surgery, The Affiliated Hospital of Nanjing Medical University, Changzhou No 2 People’s Hospital, Changzhou, Jiangsu, People’s Republic of China Purpose: Long noncoding RNAs have been proved to play important roles in the tumorigenesis and development of human gastric cancer (GC. Our study aims to investigate the expression and function of Homeobox A transcript at the distal tip (HOTTIP in GC.Methods: HOTTIP expression was detected in GC tissues and cell lines by using quantitative reverse transcription polymerase chain reaction. Association between HOTTIP levels and clinicopathological factors and patient prognosis was also analyzed. MTT, flow cytometry, and transwell invasion and migration assays were used to investigate the role of HOTTIP in the regulation of biological behaviors of GC cells.Results: HOTTIP expression was remarkably increased in GC tissues and cell lines compared with that in the normal control. Clinicopathologic analysis revealed that high HOTTIP expression correlated with larger tumor size, deeper invasion depth, positive lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis identified HOTTIP overexpression as an independent unfavorable prognostic factor in GC patients. Moreover, HOTTIP downregulation by si-HOTTIP transfection impaired GC cell proliferation, promoted cell apoptosis, and reduced cell invasion and migration.Conclusion: These findings suggested that HOTTIP may contribute to GC initiation and progression, and would be not only a novel prognostic marker but also a potential therapeutic target for this disease. Keywords: long noncoding RNA, HOTTIP, gastric cancer, prognosis

  1. Upregulation of KLHDC4 Predicts a Poor Prognosis in Human Nasopharyngeal Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yi-Fan Lian

    Full Text Available Kelch proteins are implicated in the pathogenesis of many human diseases, including cancer. Nasopharyngeal carcinoma (NPC is a rare malignancy in most countries, but prevalent in southern China and certain areas of Southeast Asia. In this study, we identified Kelch Domain Containing 4 (KLHDC4, an orphan member of the kelch repeat superfamily, as a prognosis marker for NPC. We examined the expression of KLHDC4 in 168 NPC cases by immunohistochemical staining and found a substantially higher level of KLHDC4 in NPC biopsies compared to adjacent normal nasopharyngeal mucosa. KLHDC4 expression was significantly related to the T classification (P <0.05, N classification (P <0.05 and total staging (P <0.01 in NPC, and patients with higher KLHDC4 expression had poorer overall (P <0.01 and metastasis-free survival (P <0.05 rates. Knockout (KO of KLHDC4 via CRISPR/Cas9-mediated gene editing in NPC cell line dramatically inhibited cell proliferation, colony formation in soft agar and tumor formation in nude mice. In addition, cell migration and invasion were also impaired by KLHDC4 depletion as revealed by wound healing and Transwell assay. Mechanically, loss of KLHDC4 markedly induced spontaneous apoptosis in NPC cells, as evidenced by increased levels of cleaved caspase-3 and cleaved PARP. Consistently, KLHDC4 knockout cell-derived xenografts also showed elevated cleaved caspase-3 and PARP but reduced Ki-67 staining. In conclusion, our results suggest that KLHDC4 promotes NPC oncogenesis by suppressing cellular apoptosis. Thus, KLHDC4 may serve as a prognosis biomarker and a potential therapeutic target for NPC.

  2. Tako-tsubo Syndrome in Men: Rare, but With Poor Prognosis.

    Science.gov (United States)

    Pérez-Castellanos, Alberto; Martínez-Sellés, Manuel; Mejía-Rentería, Hernán; Andrés, Mireia; Sionis, Alessandro; Almendro-Delia, Manuel; Martín-García, Ana; Aguilera, María Cruz; Pereyra, Eduardo; Linares Vicente, José A; García de la Villa, Bernardo; Núñez-Gil, Iván J

    2017-11-06

    Tako-tsubo syndrome is a potentially serious disease during the acute phase. It mimics myocardial infarction, but with no potentially causative coronary lesions. The aim of this study was to analyze the clinical course and outcome of patients with tako-tsubo syndrome by sex. We analyzed the characteristics of patients included in the RETAKO registry from 2003 to 2015, a multicenter registry with participation of 32 Spanish hospitals. Of 562 patients included, 493 (87.7%) were women. Chest pain was less frequent as an initial symptom in men than in women (43 [66.2%] vs 390 [82.8%]; P < .01). The prognosis was worse in men, with higher in-hospital mortality (3 [4.4%] vs 1 [0.2%]; P < .01), longer intensive care stay (4.2 ± 3.7 vs 3.2 ± 3.2 days; P = .03) and a higher frequency of severe heart failure (22 [33.3%] vs 95 [20.3%]; P = .02). However, dynamic obstruction at the left-ventricular outflow tract occurred exclusively in women (39 [7.9%] vs 0 [0.0%]; P = .02). The incidence of functional mitral regurgitation was also higher in women (52 [10.6%] vs 2 [2.9%]; P = .04). Tako-tsubo syndrome shows wide differences by sex in terms of its incidence, presentation, and outcomes. Prognosis is worse in men. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  3. Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma.

    Science.gov (United States)

    Komatsu, Hisateru; Iguchi, Tomohiro; Masuda, Takaaki; Hirata, Hidenari; Ueda, Masami; Kidogami, Shinya; Ogawa, Yushi; Sato, Kuniaki; Hu, Qingjiang; Nambara, Sho; Saito, Tomoko; Sakimura, Shotaro; Uchi, Ryutaro; Ito, Shuhei; Eguchi, Hidetoshi; Sugimachi, Keishi; Eguchi, Hidetoshi; Doki, Yuichiro; Mori, Masaki; Mimori, Koshi

    2017-03-01

    The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520. Gene set enrichment analysis (GSEA) was also conducted. Finally, knockdown experiments were performed using small interfering RNA (siRNA) in vitro. In all cohorts, RND1 expression was decreased as cancer progressed, and was affected by promoter methylation. In our HCC cases, the 5-year overall survival (OS) and recurrence-free survival of patients with low RND1 expression was significantly poorer than those of patients with high RND1 expression. TCGA and GSE14520 analyses provided similar results for OS. Multivariate analysis indicated that RND1 expression was an independent prognostic factor for OS in all three cohorts. Additionally, GSEA showed an inverse correlation between RND1 expression and the Ras signaling activity. In vitro, knockdown of RND1 expression resulted in significant increases in proliferation, invasion, and chemoresistance to cisplatin in HCC cells. Reduced RND1 expression in HCC was associated with cancer progression, likely through regulation of the Ras signaling pathway, and may serve as a novel clinical biomarker for predicting prognosis in patients with HCC.

  4. Identification of novel molecular markers for prognosis estimation of acute myeloid leukemia: over-expression of PDCD7, FIS1 and Ang2 may indicate poor prognosis in pretreatment patients with acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Yiming Tian

    Full Text Available Numerous factors impact on the prognosis of acute myeloid leukemia (AML, among which molecular genetic abnormalities are developed increasingly, however, accurate prediction for newly diagnosed AML patients remains unsatisfied. For further improving the prognosis evaluation system, we investigated the transcripts levels of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 in 97 AML patients and 30 non-malignant controls, and validated using the published microarray data from 225 cytogenetically normal AML (CN-AML patients treated according to the German AMLCG-1999 protocol. Real-time quantitative polymerase chain reaction and western blot were carried out, and clinical data were collected and analyzed. High Ang2 and FIS1 expression discriminated the CR rate of AML patients (62.5% versus 82.9% for Ang2, P = 0.011; 61.4% versus 82.2% for FIS1, P = 0.029. In CN-AML, patients with high FIS1 expression were more likely to be resistant to two courses of induction (P = 0.035. Overall survival (OS and relapse-free survival (RFS were shorter in CN-AML patients with high PDCD7 expression (P<0.001; P = 0.006, and PDCD7 was revealed to be an independent risk factor for OS in CN-AML (P = 0.004. In the analysis of published data from 225 CN-AML patients, PDCD7 remained independently predicting OS in CN-AML (P = 0.039. As a conclusion, Ang2 and FIS1 seem related to decreased CR rate of AML patients, and PDCD7 is associated with shorter OS and RFS in CN-AML. Hence, PDCD7, Ang2 and FIS1 may indicate a more aggressive form and poor prognosis of AML.

  5. PROLONG: a cluster controlled trial to examine identification of patients with COPD with poor prognosis and implementation of proactive palliative care

    OpenAIRE

    Duenk, R.G.; Heijdra, Y.F.; Verhagen, C.A.H.H.V.M.; Dekhuijzen, P. N. R.; Vissers, K C P; Engels, Y.M.

    2014-01-01

    BACKGROUND: Proactive palliative care is not yet common practice for patients with COPD. Important barriers are the identification of patients with a poor prognosis and the organization of proactive palliative care dedicated to the COPD patient. Recently a set of indicators has been developed to identify those patients with COPD hospitalized for an acute exacerbation who are at risk for post-discharge mortality. Only after identification of these patients with poor prognosis a multi disciplin...

  6. Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma.

    Science.gov (United States)

    Piao, Songlin; Zhao, Shu; Guo, Fulin; Xue, Jie; Yao, Guodong; Wei, Zhili; Huang, Qi; Sun, Yao; Zhang, Bin

    2012-04-01

    The aim of this study was to investigate expression of CD147 and MMP-9 in salivary duct carcinoma (SDC) so as to determine whether these two genes may be correlated with poor prognosis of SDC. We examined the significance of the CD147 and MMP-9 expression in SDC (n = 35), non-cancerous salivary tissue (n = 20) in previously untreated patients using immunohistochemical staining. Furthermore, we analyzed the correlation between the expression of these two genes and various clinicopathologic factors including survival status of patients with SDC. Positive stain of CD147 and MMP-9 was seen in all 35 cases of tumor samples. A statistical correlation was observed between CD147 and MMP-9 expression in SDC tissues. The incidences of high expression were 45.71% for CD147 and 51.43% for MMP-9 in 35 SDC tissues, respectively. High expression of CD147 and MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P (CD147) = 0.031; P (MMP-9) = 0.020) and overall survival (OS) (P (CD147) = 0.044; P (MMP-9) = 0.013). CD147 and MMP-9 expression is correlated with invasion, metastasis and shorter PFS/OS of SDC. Patients with high expression of CD147 and MMP-9 had poor prognosis than SDC patients with low expression.

  7. Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4 breast cancer

    Directory of Open Access Journals (Sweden)

    F. Piras

    2011-11-01

    Full Text Available Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients’ outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02 and with borderline significance at 10-years of survival (P=0.05 in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.

  8. Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT

    Directory of Open Access Journals (Sweden)

    Zhen-Yu He

    2017-02-01

    Full Text Available Triple-negative breast cancer (TNBC was regarded as the most aggressive and mortal subtype of breast cancer (BC since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3 significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway. In TNBC cells, knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate epithelial markers, significantly attenuated cell proliferation, migration and invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor volume, weight and relieve lung metastasis in vivo. Furthermore, we also demonstrated that overexpression of RFC3 in TNBC showed increased metastasis, progression and poor prognosis. We confirmed all of these results by immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3 expression was significantly associated with poor prognosis in TNBC. Taken all these findings into consideration, we can conclude that up-regulation of RFC3 promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an independent prognostic factor and therapeutic target for TNBC.

  9. Factors associated with poor prognosis in very-lowbirth- weight infants

    African Journals Online (AJOL)

    Outcome measures: Death or impainnent (namely oxygen therapy> 28 days, grade 3 or 4 intraventricular haemorrhage, or ventricular enlargement). Results: Poor outcome was predicted by birth weight, lowest oxygen requirement in the first 12 hours (which are two components of the CRIB score), and maximum partial ...

  10. Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER

    NARCIS (Netherlands)

    van den Beucken, Twan; Koch, Elizabeth; Chu, Kenneth; Rupaimoole, Rajesha; Prickaerts, Peggy; Adriaens, Michiel; Voncken, Jan Willem; Harris, Adrian L.; Buffa, Francesca M.; Haider, Syed; Starmans, Maud H. W.; Yao, Cindy Q.; Ivan, Mircea; Ivan, Cristina; Pecot, Chad V.; Boutros, Paul C.; Sood, Anil K.; Koritzinsky, Marianne; Wouters, Bradly G.

    2014-01-01

    MicroRNAs are small regulatory RNAs that post transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microRNA processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet, the underlying mechanisms are

  11. Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

    Science.gov (United States)

    He, F-Y; Liu, H-J; Guo, Q; Sheng, J-L

    2017-02-01

    miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p 300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p 300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.

  12. Association between poor clinical prognosis and sleep duration among breast cancer patients

    Directory of Open Access Journals (Sweden)

    Thalyta Cristina Mansano-Schlosser

    Full Text Available ABSTRACT Objective: to investigate the association between clinical progression and the quality and duration of sleep in women with breast cancer. Method: longitudinal study, with 114 participants, conducted in a hospital in Brazil. The instruments used were: questionnaire for sociodemographic and clinical characterization, Pittsburgh Sleep Quality Index; Beck Depression Inventory and Herth Hope Scale. Data were analyzed through descriptive statistics and survival analyses (outcome: poor clinical progression, using the Kaplan-Meier curve, Log-rank test and Cox proportional model. Results: a higher probability of poor clinical progression was verified in women with sleep durations of less than six hours or nine hours and over (p=.0173. Conclusion: the results suggest the importance of further studies that seek to verify whether the quantitative management of sleep disorders would have an impact on the progression of breast cancer. Women should be encouraged to report sleep problems to nurses.

  13. Overexpression of Fli-1 in astrocytoma is associated with poor prognosis

    OpenAIRE

    Tsai, Hung-Pei; Tsai, Tai-Hsin; Hsieh, Ya-Ju; Chen, Yi-Ting; Lee, Chih-Ling; Tsai, Yi-Cheng; She, Ting-Chang; Lin, Chih-Lung; Chai, Chee-Yin; Kwan, Aij-Lie

    2017-01-01

    Background Astrocytoma, a common and highly malignant type of brain tumor, is associated with poor overall survival despite advances in surgical treatment, radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been shown to increase cellular proliferation and tumorigenesis in many types of cancer; however, previous reports have not described a correlation between clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to elucidate the clinical role of...

  14. Increased vasohibin-1 expression is associated with metastasis and poor prognosis of renal cell carcinoma patients.

    Science.gov (United States)

    Mikami, Shuji; Oya, Mototsugu; Kosaka, Takeo; Mizuno, Ryuichi; Miyazaki, Yasumasa; Sato, Yasufumi; Okada, Yasunori

    2017-07-01

    The microvascular density detected by markers of endothelial cells (ECs), such as CD31 and CD34, is considered to be a biomarker for angiogenesis, and it is generally associated with the malignant potential of solid tumors. However, there is a conflicting relationship between the microvascular density and prognosis in clear-cell renal cell carcinoma (ccRCC) patients. It may be explained by the suggestion that the microvascular density cannot fully reflect the angiogenic activity in ccRCC, as the markers of ECs are expressed by both quiescent and activated ECs. To investigate the real angiogenic activity, we examined vasohibin-1 (VASH1), a recently identified regulator of angiogenesis, which was demonstrated to be specifically expressed by ECs of newly formed blood vessels. Expression of VASH1 and CD34 were immunohistochemically examined in 116 primary untreated ccRCCs, 10 metastatic untreated ccRCCs, and 9 metastatic ccRCCs treated with sunitinib. ECs in the tumor microvessels were sporadically immunostained for VASH1, although no VASH1 staining was observed in the non-neoplastic renal tissues. CD34 was ubiquitously expressed by all ECs in both ccRCC and non-neoplastic renal tissues. Multivariate Cox analysis indicated that an elevated VASH1 density, but not microvascular density, was a significant and independent predictor of overall survival (odds ratio, 7.71; P=0.003). The microvascular density was significantly decreased in the sunitinib-treated metastases compared with untreated tumors (P=0.001). On the other hand, the VASH1 density was significantly higher in the metastatic ccRCCs treated with sunitinib compared with non-treated ones (P=0.010), indicating that VASH1 may be associated with the resistance of ECs to sunitinib treatment. Thus, VASH1 expression may reflect the actual activity of angiogenesis, and VASH1 can serve as a new prognostic and predictive biomarker in patients with ccRCC.

  15. Phosphoglycerate dehydrogenase is a novel predictor for poor prognosis in gastric cancer

    Directory of Open Access Journals (Sweden)

    Xian Y

    2016-09-01

    Full Text Available Yun Xian,1,* Shu Zhang,2,* Xudong Wang,3 Jin Qin,2 Wei Wang,2 Han Wu4 1School of Public Health, Nantong University, 2Department of Pathology, 3Department of Laboratory Medicine, 4Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China *These authors contributed equally to this work Purpose: Phosphoglycerate dehydrogenase (PHGDH acts as a key metabolic enzyme in the rate-limiting step in serine biosynthesis and plays an important role in metastasis of several cancers. The aim of this study was to investigate the prognostic value of PHGDH in gastric cancer (GC. Methods: The messenger RNA expression of PHGDH was determined in 20 pairs of cancerous and adjacent nontumor tissues by real-time polymerase chain reaction. Immunohistochemistry of PHGDH was performed on tissue microarray, composed of 482 GC and 64 matched adjacent nontumor tissues acquired from surgery, 20 chronic gastritis, 18 intestinal metaplasia, and 31 low-grade and 66 high-grade intraepithelial neoplasias acquired through gastric endoscopic biopsy. Univariate and multivariate Cox proportional hazard models were used to perform survival analyses. Results: Both PHGDH messenger RNA and protein product exhibited GC tissue-preferred expression, when compared with benign tissues. The high PHGDH expression was significantly correlated with histological type (P=0.011, tumor stage (P=0.014, and preoperative carcinoembryonic antigen (P<0.001. A negative correlation was found between PHGDH expression and the 5-year survival rate of patients with GC. Furthermore, multivariate analysis indicated that PHGDH was an independent prognostic factor for outcome in GC. Conclusion: PHGDH is important in predicting patient outcomes and is a potential target for the development of therapeutic approaches to GC. Keywords: metabolism, gastric cancer, prognosis, serine biosynthesis

  16. Upregulation of CENP-H in tongue cancer correlates with poor prognosis and progression

    Directory of Open Access Journals (Sweden)

    Weng Gui-Xiang

    2009-06-01

    Full Text Available Abstract Background Centromere protein H (CENP-H is one of the fundamental components of the human active kinetochore. Recently, CENP-H was identified to be associated with tumorigenesis. This study was aimed to investigate the clinicopathologic significance of CENP-H in tongue cancer. Methods RT-PCR, real time RT-PCR and Western blot were used to examine the expression of CENP-H in tongue cancer cell lines and biopsies. CENP-H protein level in paraffin-embedded tongue cancer tissues were tested by immunohistochemical staining and undergone statistical analysis. CENP-H-knockdown stable cell line was established by infecting cells with a retroviral vector pSuper-retro-CENP-H-siRNA. The biological function of CENP-H was tested by MTT assay, colony formation assay, and Bromodeoxyuridine (BrdU incorporation assay. Results CENP-H expression was higher in tongue cancer cell lines and cancer tissues (T than that in normal cell and adjacent noncancerous tongue tissues (N, respectively. It was overexpressed in 55.95% (94/168 of the paraffin-embedded tongue cancer tissues, and there was a strong correlation between CENP-H expression and clinical stage, as well as T classification. CENP-H can predict the prognosis of tongue cancer patients especially those in early stage. Depletion of CENP-H can inhibit the proliferation of tongue cancer cells (Tca8113 and downregulate the expression of Survivin. Conclusion These findings suggested that CENP-H involves in the development and progression of tongue cancer. CENP-H might be a valuable prognostic indicator for tongue cancer patients within early stage.

  17. High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhang L

    2016-10-01

    Full Text Available Lingfu Zhang,1 Dianrong Xiu,1 Jun Zhan,2,3 Xiaokun He,3 Limei Guo,4,5 Jilian Wang,1 Ming Tao,1 Wei Fu,1 Hongquan Zhang2,3 1Department of General Surgery, Peking University Third Hospital, 2Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, State Key Laboratory of Natural and Biomimetic Drugs, 3Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, 4Department of Pathology, Peking University Health Science Center, 5Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China Aims: Recent studies showed that muscarinic acetylcholine receptor 3 (M3, as a muscarinic acetylcholine receptor family member that plays an important role in normal physiological function, is engaged in cancer progression. However, the role of M3 in pancreatic ductal adenocarcinoma (PDAC is not known. The aim of this study is to investigate the expression and prognostic value of M3 in patients with PDAC.Materials and methods: The localization and expression of M3 in PDAC were examined by immunohistochemistry. VAChT was employed to detect parasympathetic nerve fibers in the corresponding M3 PDAC tissues. The correlation between M3 expression and patients’ survival was assessed by Kaplan–Meier analysis.Results: M3 was discovered predominantly localized in the cell cytoplasm and expressed in all specimens of PDAC patients. Significant correlation was noted between increased M3 intensity and high grade of PDAC (P<0.01, more lymph node metastasis (P<0.01 as well as shorter patient overall survival (P<0.01. Morphologically, cells with high M3 expression were more frequently located at the invasive tumor front/tumor budding cells, metastatic lymph nodes and parasympathetic nerve fibers.Conclusion: High expression of M3 is a prognostic marker for PDAC. Keywords: PDAC, muscarinic acetylcholine receptor 3, M3, tumor budding, parasympathetic nerve fiber, prognosis

  18. High Expression of PHGDH Predicts Poor Prognosis in Non–Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jinhong Zhu

    2016-12-01

    Full Text Available Tumors have exceptionally high demands for energy and anabolism because of their rapid growth. The de novo serine synthesis pathway initiated by phosphoglycerate dehydrogenase (PHGDH has been recognized as a hallmark of metabolic adaption in carcinogenesis. The oncogenic role and prognostic value of PHGDH have been investigated in multiple cancer types, including breast cancer, melanoma, cervical cancer, and colon cancer. Due to the importance of PHGDH in cancer, we attempted to determine the clinical significance of PHGDH in 319 patients with non–small cell lung cancer (NSCLC. We evaluated the mRNA and protein expression levels of PHGDH gene, using quantitative reverse transcriptase polymerase chain reaction and tissue array–based immunohistochemistry, respectively. Significantly increased PHGDH expression in mRNA and protein levels was identified in tumor tissues versus matched adjacent nontumor tissues. More interestingly, immunohistochemical expression of PHGDH was significantly associated with lymph node metastasis (P = .021 and TNM stage (P = .016. Kaplan-Meier survival analysis indicated that NSCLC patients with low levels of PHGDH outperformed patients with high levels of PHGDH regarding 5-year overall survival. Significantly longer survival in the former suggested the prognostic implication of PHGDH in NSCLC. Multivariate survival analysis using Cox regression model demonstrated that high PHGDH levels and advanced TNM stage (III + IV were independent predictors of prognosis in NSCLC. Moreover, bioinformatics analysis confirmed the increase in PHGDH transcripts (data from The Cancer Genome Atlas and its prognostic value (Kaplan-Meier plotter in NSCLC. In conclusion, this study suggested the clinical implication of PHGDH in NSCLC. PHGDH may be a promising therapeutic target in NSCLC.

  19. High Expression of Yes-activated Protein-1 in Papillary Thyroid Carcinoma Correlates With Poor Prognosis.

    Science.gov (United States)

    Liu, Zeming; Zeng, Wen; Maimaiti, Yusufu; Ming, Jie; Guo, Yawen; Liu, Yan; Liu, Chunping; Huang, Tao

    2017-07-04

    The Hippo signal transduction pathway is highly conserved in mammals. It plays a critical role in tissue and organ size by regulating the balance between cell proliferation and apoptosis. However, there have been few reports concerning Yes-activated protein-1 (YAP-1) elevation in papillary thyroid cancer (PTC). The objective of this study was to determine whether YAP-1 expression is a biomarker and high-risk clinicopathologic prognosticator in PTC. A large series of patients of PTC with a long follow-up were investigated for YAP-1 expression. Our study was carried out in the laboratory of breast and thyroid and Department of pathology. Immunohistochemical staining was performed on 240 patient-derived PTC specimens to analyze the correlation of YAP-1 expression with clinicopathologic features and prognosis in patients with PTC. The 240 PTC patients were immunohistochemically assessed for YAP-1 expression. Kaplan-Meier analysis was conducted to assess recurrence-free survival (RFS). Univariate and multivariate analyses were conducted to determine prognosticators of RFS. YAP-1 expression was observed in 62.1% of PTC tumors. There were significant positive correlations between YAP-1 expression and tumor size, lymph node metastases, extrathyroidal extension, and tissue infiltration. YAP-1 expression was significantly associated with RFS. Univariate analysis revealed that YAP-1 expression significantly affects RFS. YAP-1 and extrathyroidal extension were significant independent prognosticators for RFS. YAP-1 expression was significantly correlated with high-risk clinicopathologic features and inferior RFS in patients with PTC.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http

  20. Downregulation of ALDOB is associated with poor prognosis of patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    He J

    2016-10-01

    Full Text Available Jun He,1 Yi Jin,1 Yuan Chen,2 Hai-Bo Yao,1 Ying-Jie Xia,3 Ying-Yu Ma,4 Wei Wang,2 Qin-Shu Shao1 1Department of Gastroenterology and Pancreatic Surgery, 2Department of Pathology, 3Key Laboratory of Gastroenterology of Zhejiang Province, 4Clinic Research Institute, Zhejiang Provincial People’s Hospital, Hangzhou, People’s Republic of China Objectives: To examine the expression of ALDOB in gastric cancer (GC tissue and to reveal its potential clinicopathological and prognostic significance.Materials and methods: We screened for genes that were differentially expressed between GC and nontumor tissues using a microarray, specifically the Affymetrix U133 Plus 2.0 Array platform. We then verified the transcriptional and translational levels of ALDOB by performing quantitative real-time polymerase chain reaction (qRT-PCR and immunohistochemistry (IHC. In addition, a merged data set based on the Gene Expression Omnibus was generated and a survival analysis performed.Results: The microarray analysis revealed that ALDOB was downregulated (more than sevenfold in GC compared with nontumor tissue. Both qRT-PCR and IHC validated the decrease of ALDOB in GC tissue. Moreover, we found that the expression of ALDOB was significantly related to tumor-invasion depth, lymph-node metastasis, distant metastasis, and TNM stage. The survival analysis, based on the IHC and merged data set, indicated that the overall survival was better in patients with high ALDOB expression. The Cox regression analysis showed that ALDOB expression was an independent prognostic factor for GC.Conclusion: The expression of ALDOB in GC tissue was significantly related to the clinicopathological features and prognosis of the disease, thus suggesting that ALDOB could act as a novel molecular marker for GC. Keywords: ALDOB, gastric cancer, microarray analysis, molecular marker

  1. Overexpression of glucose transporter-1 (GLUT-1) predicts poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Cho, Hanbyoul; Lee, You Sun; Kim, Julie; Chung, Joon-Yong; Kim, Jae-Hoon

    2013-11-01

    Illumina microarray was used to identify differentially expressed genes in three epithelial ovarian cancer (EOC) cells. To validate the microarray data, mRNA and protein level of glucose transporter-1 (GLUT-1) was examined. GLUT-1 had an EOC/normal cells ratio of 5.51 based on microarray. Real-time PCR and immunohistochemistry demonstrated that GLUT-1 expression was significantly increased in EOC (p = .029 and p GLUT-1 overexpression (HR = 4.80, p = .027) and lymph node metastases (HR = 8.35, p = .016) conferred a significantly worse overall survival. In conclusion, GLUT-1 expression is remarkably upregulated in EOC and predicts a poor overall survival.

  2. ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas

    DEFF Research Database (Denmark)

    Bueno, R C; Canevari, R A; Villacis, R A R

    2014-01-01

    BACKGROUND: Ataxia telangiectasia-mutated (ATM) gene downexpression has been reported in sporadic breast carcinomas (BC); however, the prognostic value and mechanisms of ATM deregulation remain unclear. PATIENTS AND METHODS: ATM and miRNAs (miR-26a, miR-26b, miR-203, miR-421, miR-664, miR-576-5p...

  3. High Expression of HULC Is Associated with Poor Prognosis in Osteosarcoma Patients.

    Science.gov (United States)

    Uzan, Vanessa Regina Maciel; Lengert, André van Helvoort; Boldrini, Érica; Penna, Valter; Scapulatempo-Neto, Cristovam; Scrideli, Carlos Alberto; Filho, Alberto Paiva de Moraes; Cavalcante, Carlos Eduardo Bezerra; de Oliveira, Cleyton Zanardo; Lopes, Luiz Fernando; Vidal, Daniel Onofre

    2016-01-01

    Osteosarcoma (OS) is the most common primary bone cancer in childhood. OS is an aggressive disease, and metastatic patients evolve with very poor clinical outcomes. Genetically, OSs are extremely complex tumors, and the related metastatic process is not well understood in terms of the biology of the disease. In this context, long non-coding RNAs (lncRNAs) have emerged as an important class of gene expression regulators that play key roles in the invasion and metastasis of several human tumors. Here, we evaluated the expression of HULC, which is an lncRNA that is associated with the tumor metastatic process, and assessed its potential role as a prognostic marker in OS. HULC expression was evaluated in primary OS samples using real-time RT-PCR. HULC expression status was determined by receiver operating characteristic (ROC) analysis, and its association with survival was assessed using the Kaplan-Meier method. The HULC expression level was not significantly associated with the clinicopathological characteristics of the OS patients. However, our data demonstrated that higher levels of expression of HULC were associated with lower survival rates in OS patients, both in terms of overall and event-free survival. Elevated HULC expression was associated with poor clinical outcomes among the OS patients, which suggests that HULC could be a potential prognostic biomarker in OS.

  4. High Expression of HULC Is Associated with Poor Prognosis in Osteosarcoma Patients.

    Directory of Open Access Journals (Sweden)

    Vanessa Regina Maciel Uzan

    Full Text Available Osteosarcoma (OS is the most common primary bone cancer in childhood. OS is an aggressive disease, and metastatic patients evolve with very poor clinical outcomes. Genetically, OSs are extremely complex tumors, and the related metastatic process is not well understood in terms of the biology of the disease. In this context, long non-coding RNAs (lncRNAs have emerged as an important class of gene expression regulators that play key roles in the invasion and metastasis of several human tumors. Here, we evaluated the expression of HULC, which is an lncRNA that is associated with the tumor metastatic process, and assessed its potential role as a prognostic marker in OS. HULC expression was evaluated in primary OS samples using real-time RT-PCR. HULC expression status was determined by receiver operating characteristic (ROC analysis, and its association with survival was assessed using the Kaplan-Meier method. The HULC expression level was not significantly associated with the clinicopathological characteristics of the OS patients. However, our data demonstrated that higher levels of expression of HULC were associated with lower survival rates in OS patients, both in terms of overall and event-free survival. Elevated HULC expression was associated with poor clinical outcomes among the OS patients, which suggests that HULC could be a potential prognostic biomarker in OS.

  5. Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor Prognosis in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Tao Jiang

    2017-01-01

    Full Text Available Deregulation of G protein-coupled receptor kinase 3 (GRK3, which belongs to a subfamily of kinases called GRKs, acts as a promoter mechanism in some cancer types. Our study found that GRK3 was significantly overexpressed in 162 pairs of colon cancer tissues than in the matched noncancerous mucosa (P<0.01. Based on immunohistochemistry staining of TMAs, GRK3 was dramatically stained positive in primary colon cancer (130/180, 72.22%, whereas it was detected minimally or negative in paired normal mucosa specimens (50/180, 27.78%. Overexpression of GRK3 was closely correlated with AJCC stage (P=0.001, depth of tumor invasion (P<0.001, lymph node involvement (P=0.004, distant metastasis (P=0.016, and histologic differentiation (P=0.004. Overexpression of GRK3 is an independent prognostic indicator that correlates with poor survival in colon cancer patients. Consistent with this, downregulation of GRK3 exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate, and impaired colon tumorigenicity in a xenograft model. Hence, a specific overexpression of GRK3 was observed in colon cancer, GRK3 potentially contributing to progression by mediating cancer cell proliferation and functions as a poor prognostic indicator in colon cancer and potentially represent a novel therapeutic target for the disease.

  6. EZH2 overexpression is associated with poor prognosis in patients with glioma.

    Science.gov (United States)

    Zhang, Yanyang; Yu, Xinguang; Chen, Ling; Zhang, Zhibin; Feng, Shiyu

    2017-01-03

    Previous studies have investigated the prognostic value of enhancer of zeste homolog 2 (EZH2) expression in patients with glioma but conclude contradictory results. We aimed to comprehensively evaluate the prognostic role of EZH2 in glioma by meta-analysis. The databases of PubMed, Embase and Web of Science were searched. Hazard ratio (HR) and 95% confidence interval (CI) were combined to assess the association between EZH2 and overall survival (OS) as well as progression-free survival (PFS). Odd ratio (OR) and 95% CI were calculated to investigate the relevance of EZH2 on clinical factors. Six studies with 575 patients were included for meta-analysis. The results showed that EZH2 overexpression was correlated with poor OS (n = 6, HR = 2.23, 95% CI: 1.56-3.19, p EZH2 had enhanced prognostic value in Asian patients, for WHO grade I-IV and when using immunohistochemistry (IHC) method. In addition, EZH2 was associated with KPS score EZH2 was a potential prognostic marker for poor OS, PFS and lower KPS score in glioma patients.

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

    Science.gov (United States)

    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

    2012-12-28

    To elucidate high mobility group-box 3 (HMGB3) protein expression in gastric adenocarcinoma, its potential prognostic relevance, and possible mechanism of action. 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. 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 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

  8. CHKA mediates the poor prognosis of lung adenocarcinoma and acts as a prognostic indicator

    OpenAIRE

    Zhang, Li; Chen, Ping; Yang, Shen; Li, Guodong; Bao, Wentao; Wu, Peng; Jiang, Shujuan

    2016-01-01

    Choline kinase ? (CHKA), the enzyme that converts choline to phosphocholine, has been studied in human carcinogenesis widely. However, the expression and underlying clinicopathological characteristics of CHKA in lung adenocarcinoma remains elusive. In the present study, a tissue microarray of 119 pairs of lung adenocarcinoma samples and corresponding adjacent normal mucosae was used to analysis CHKA expression by immunohistochemistry, and CHKA was observed to exhibit enhanced expression in lu...

  9. High expression of TRIM11 correlates with poor prognosis in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Chen, Yue; Li, Liang; Qian, Xiaoxing; Ge, Yongsheng; Xu, Geliang

    2017-03-01

    Tripartite Motif Containing 11 (TRIM11), a member of TRIM proteins is overexpressed in gliomas and lung cancer. However, the role of TRIM11 in hepatocellular carcinoma (HCC) is unknown. Herein, we aimed to investigate the expression and clinical significance role of TRIM11 in HCC. In this study, our data showed significant higher TRIM11 in HCC tissues (n=117) than in the matched non-tumor liver (NTL) tissues (Pprotein expression was significantly increased compared with the matched NTL (Pprotein expression in HCC tissues was significantly associated with pathological grade (Pprotein expression. Furthermore, we found that TRIM11 protein was an independent prognostic factor for disease-free (Pexpression was significantly elevated in HCC tissues. The overexpression of TRIM11 is closely associated with HCC progression and poor survival of the patients, indicating TRIM11 is a potential therapeutic target for HCC patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Hu, Liren; Wu, Fenping; Zou, Lei; He, Taiping

    2017-05-09

    Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CI) were calculated to estimate the effect size. Positive HK2 expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P digestive system cancers.

  11. Oncogene mutation profiling reveals poor prognosis associated with FGFR1/3 mutation in liposarcoma.

    Science.gov (United States)

    Li, Chengfang; Shen, Yaoyuan; Ren, Yan; Liu, Wei; Li, Man; Liang, Weihua; Liu, Chunxia; Li, Feng

    2016-09-01

    Liposarcoma (LPS) is one of the most prevalent soft tissue sarcomas. LPS shows a poor response to radiation and chemotherapy. The causes of death in patients with LPS include locally recurrent and metastatic disease. We sought to examine novel gene mutations and pathways in primary and matched recurrent LPSs to identify potential therapeutic targets. We conducted a high-throughput analysis of 238 known mutations in 19 oncogenes using Sequenom MassARRAY technology. Nucleic acids were extracted from 19 primary and recurrent LPS samples, encompassing 9 dedifferentiated LPSs (DDLPS), 9 myxoid/round cell LPSs, and 1 pleomorphic LPS. Mutation screening revealed missense mutations in 21.1% (4/19) of the LPS specimens, including 4 different genes (FGFR1, FGFR3, PIK3CA, and KIT). Based on histologic subtypes, 22.2% DDLPS (2/9) and 22.2% myxoid cell LPS (2/9) contained gene mutations. Specifically, 3 (23.1%) of 13 primary tumors harbored mutations. Furthermore, although gene mutations were identified in 1 (11.1%) of 9 recurrent LPS samples, the difference between the primary and the recurrence was not statistically significant. Analysis of patient survival data indicated that patients harboring FGFR1/3 mutations experienced reduced overall survival (P<.05). Despite the limited number of samples, our findings provide the first evidence of FGFR1/3 mutations in DDLPS, which were associated with poor clinical outcomes. The FGFR pathway may play an important role in the development and progression of DDLPS and warrants further investigation; moreover, PIK3CA mutation is a common event (11.1%) in myxoid cell LPS. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Upregulation of PP2Ac predicts poor prognosis and contributes to aggressiveness in hepatocellular carcinoma

    Science.gov (United States)

    Gong, Shao-Juan; Feng, Xiao-Jun; Song, Wei-Hua; Chen, Jian-Ming; Wang, Shou-Mei; Xing, Dong-Juan; Zhu, Ming-Hua; Zhang, Shu-Hui; Xu, Ai-Min

    2016-01-01

    ABSTRACT Protein phosphatase 2A (PP2A) is a heterotrimeric protein phosphatase consisting of a 36-kD catalytic C subunit (PP2Ac). This study aimed to explore the prognostic and biological significance of PP2Ac in human hepatocellular carcinoma (HCC). High PP2Ac expression was significantly (P < 0.01) associated with serum hepatitis B surface antigen positivity, serum hepatitis B e antigen positivity, liver cirrhosis, moderate to poor differentiation grade, advanced disease stage, intrahepatic metastasis, and early recurrence in HCC. Multivariate analysis revealed PP2Ac as an independent prognostic factor for overall survival. Enforced expression of hepatitis B virus X protein (HBx) and its carboxyl-terminal truncated isoform induced PP2Ac expression in HCC cells. Co-immunoprecipitation assay revealed a direct interaction between PP2Ac and HBx. Small interfering RNA-mediated knockdown of PP2Ac significantly inhibited in vitro cell proliferation, colony formation, migration, and invasion and reduced tumor growth in an xenograft mouse model. In contrast, overexpression of PP2Ac promoted HCC cell proliferation, colony formation, and tumorigenesis. Additionally, silencing of PP2Ac impaired the growth-promoting effects on HepG2 HCC cells elicited by overexpression of carboxyl-terminal truncated HBx. Gene expression profiling analysis showed that PP2Ac downregulation modulated the expression of numerous genes involved in cell cycle and apoptosis regulation. Collectively, PP2Ac upregulation has a poor prognostic impact on the overall survival of HCC patients and contributes to the aggressiveness of HCC. PP2Ac may represent a potential therapeutic target for HCC. PMID:26618405

  13. Integrative genomics reveals hypoxia inducible genes that are associated with a poor prognosis in neuroblastoma patients

    Science.gov (United States)

    Kao, Clara; Hernandez, Kyle M.; DeWane, Gillian; Salwen, Helen R.; Chlenski, Alexandre; Dobratic, Marija; Mariani, Christopher J.; Godley, Lucy A.; Prabhakar, Nanduri; White, Kevin; Stranger, Barbara E.; Cohn, Susan L.

    2016-01-01

    Neuroblastoma is notable for its broad spectrum of clinical behavior ranging from spontaneous regression to rapidly progressive disease. Hypoxia is well known to confer a more aggressive phenotype in neuroblastoma. We analyzed transcriptome data from diagnostic neuroblastoma tumors and hypoxic neuroblastoma cell lines to identify genes whose expression levels correlate with poor patient outcome and are involved in the hypoxia response. By integrating a diverse set of transcriptome datasets, including those from neuroblastoma patients and neuroblastoma derived cell lines, we identified nine genes (SLCO4A1, ENO1, HK2, PGK1, MTFP1, HILPDA, VKORC1, TPI1, and HIST1H1C) that are up-regulated in hypoxia and whose expression levels are correlated with poor patient outcome in three independent neuroblastoma cohorts. Analysis of 5-hydroxymethylcytosine and ENCODE data indicate that at least five of these nine genes have an increase in 5-hydroxymethylcytosine and a more open chromatin structure in hypoxia versus normoxia and are putative targets of hypoxia inducible factor (HIF) as they contain HIF binding sites in their regulatory regions. Four of these genes are key components of the glycolytic pathway and another three are directly involved in cellular metabolism. We experimentally validated our computational findings demonstrating that seven of the nine genes are significantly up-regulated in response to hypoxia in the four neuroblastoma cell lines tested. This compact and robustly validated group of genes, is associated with the hypoxia response in aggressive neuroblastoma and may represent a novel target for biomarker and therapeutic development. PMID:27765905

  14. Predictive implications of albumin and C-reactive protein for progression to pneumonia and poor prognosis in Stenotrophomonas maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Harada, Kaito; Sekiya, Noritaka; Konishi, Tatsuya; Nagata, Akihito; Yamada, Yuta; Takezaki, Toshiaki; Kaito, Satoshi; Kurosawa, Shuhei; Sakaguchi, Masahiro; Yasuda, Shunichiro; Sasaki, Shugo; Yoshioka, Kosuke; Watakabe-Inamoto, Kyoko; Igarashi, Aiko; Najima, Yuho; Hagino, Takeshi; Muto, Hideharu; Kobayashi, Takeshi; Doki, Noriko; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2017-09-22

    Stenotrophomonas maltophilia (S. maltophilia) bacteremia causes significant morbidity and mortality in immunocompromised hosts. However, incidence and risk factors for mortality in S. maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain controversial. The primary aim of this study is to clarify factors associated with poor prognosis of allo-HSCT recipients with S. maltophilia bacteremia. From January 2005 to December 2014, patients with hematological diseases and S. maltophilia bacteremia at a single transplantation center in Japan were examined for incidence and 90-day mortality. Prognostic factors associated with 90-day mortality among allo-HSCT recipients were analyzed by log-rank test, and significant variables in the univariate analysis were included in the multivariate Cox proportional-hazards regression model. A total of 65 patients, including 47 patients undergoing allo-HSCT, developed S. maltophilia bacteremia. The incidence of S. maltophilia bacteremia was significantly higher in allo-HSCT recipients compared to patients not receiving allo-HSCT (6.53 vs. 0.36 per 100 admissions, respectively; p pneumonia at the onset of bacteremia and the remaining 4 patients developed pneumonia in a median of 3 days (range, 1 to 8 days) even under effective treatment. All 9 patients eventually died in a median of 2 days (range, 2 to 32 days). The probabilities of developing pneumonia in patients with or without high CRP and low albumin levels were 100% (9/9) and 10.5% (4/38), respectively (p pneumonia and poor prognosis.

  15. End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

    Science.gov (United States)

    Kumar, Manish; Mehra, Siddharth; Thakar, Alok; Shukla, Nootan Kumar; Roychoudhary, Ajoy; Sharma, Mehar Chand; Ralhan, Ranju; Chauhan, Shyam Singh

    2016-08-01

    Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and despite the improvement in treatment strategy, 5-year survival rates are about 50%. Identification of patients at high risk of recurrence may enable rigorous personalized post-treatment management. In an earlier proteomics study we observed overexpression of End Binding Protein (EB1) in OSCC. In the present study we investigated the diagnostic and prognostic significance of alterations in expression of EB1 in oral cancer. In this retrospective study, the expression of EB1 protein was evaluated in 259 OSCCs, 41 dysplasia, 166 hyperplasia and 126 normal tissues using immunohistochemistry and correlated with clinical-pathological parameters and prognosis of OSCC patients over a follow-up period of up to 91months. Significantly higher expression of cytoplasmic EB1 was observed in hyperplasia [ppatients showing cytoplasmic EB1 overexpression demonstrated significantly reduced DFS (p=0.004, HR=2.1). EB1 overexpression is an early event in oral tumorigenesis and cytoplasmic EB1 accumulation is associated with poor prognosis and tumor recurrence in OSCC patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. APACHE II score, rather than cardiac function, may predict poor prognosis in patients with stress-induced cardiomyopathy.

    Science.gov (United States)

    Joe, Byung-Hyun; Jo, Uk; Kim, Hyun-Soo; Park, Chang-Bum; Hwang, Hui-Jeong; Sohn, Il-Suk; Jin, Eun-Sun; Cho, Jin-Man; Park, Jeong-Hwan; Kim, Chong-Jin

    2012-01-01

    While the disease course of stress-induced cardiomyopathy (SIC) is usually benign, it can be fatal. The prognostic factors to predict poorer outcome are not well established, however. We analyzed the Acute Physiology And Chronic Health Evaluation (APACHE) II score to assess its value for predicting poor prognosis in patients with SIC. Thirty-seven consecutive patients with SIC were followed prospectively during their hospitalization. Clinical factors, including APACHE II score, coronary angiogram, echocardiography and cardiac enzymes at presentation were analyzed. Of the 37 patients, 27 patients (73%) were women. The mean age was 66.1 ± 15.6 yr, and the most common presentation was chest pain (38%). Initial echocardiographic left ventricular ejection fraction (EF) was 42.5% ± 9.3%, and the wall motion score index (WMSI) was 1.9 ± 0.3. Six patients (16%) expired during the follow-up period of hospitalization. Based on the analysis of characteristics and clinical factors, the only predictable variable in prognosis was APACHE II score. The patients with APACHE II score greater than 20 had tendency to expire than the others (P = 0.001). Based on present study, APACHE II score more than 20, rather than cardiac function, is associated with mortality in patients with SIC.

  17. Overexpression of CD47 predicts poor prognosis and promotes cancer cell invasion in high-grade serous ovarian carcinoma

    Science.gov (United States)

    Li, Yinuo; Lu, Shuhua; Xu, Ying; Qiu, Chunping; Jin, Chengjuan; Wang, Yuqiong; Liu, Zhaojian; Kong, Beihua

    2017-01-01

    CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. CD47 is overexpressed in various human malignancies. However, the expression and functional significance of CD47 in high-grade serous ovarian carcinoma (HGSOC) has not been completely understood. In this study, we reported that CD47 was commonly overexpressed in HGSOC. Higher CD47 expression was significantly correlated with poor prognosis of HGSOC patients. Functional investigations revealed that CD47 overexpression in ovarian cancer cells significantly promoted migration and invasion. Moreover, CD47 induced epithelial-mesenchymal transition (EMT) through modulating E-cadherin and N-cadherin. Our findings suggest that up-regulation of CD47 is correlated with ovarian cancer progression and it might be a potential biomarker for predicting clinical outcomes. PMID:28670378

  18. Alphav integrin expression is a novel marker of poor prognosis in advanced-stage ovarian carcinoma.

    Science.gov (United States)

    Goldberg, I; Davidson, B; Reich, R; Gotlieb, W H; Ben-Baruch, G; Bryne, M; Berner, A; Nesland, J M; Kopolovic, J

    2001-12-01

    To analyze the possible correlation between expression of the alphav and beta1 integrin chains and survival in advanced-stage ovarian carcinomas, studying two patient groups with extremely different disease outcome. Sections from 56 primary ovarian carcinomas and metastatic lesions from 34 patients diagnosed with advanced-stage ovarian carcinoma (Fédération Internationale des Gynaecologistes et Obstetristes stages III-IV), divided into long-term (16) and short-term (18) survivors, were evaluated for expression of alphav and beta1 integrin chains using mRNA in situ hybridization. Protein expression was additionally studied in 52 specimens using immunohistochemistry. The mean values for disease-free survival and overall survival were 115 and 132 months for long-term survivors, as compared with 4 and 23 months for short-term survivors, respectively. Expression of alphav integrin mRNA was observed in carcinoma (18 of 56; 32%) and stromal (17 of 56; 30%) cells. beta1 integrin mRNA was similarly detected in carcinoma (25 of 56; 47%) and stromal (19 of 56; 34%) cells. No significant differences were observed when primary and metastatic lesions were compared (P > 0.05). Alphav integrin mRNA was present more often in carcinoma cells in tumors of short-term survivors (P = 0.017 for carcinoma cells). In univariate survival analysis for all cases, alphav integrin mRNA expression in tumor cells correlated with poor survival (P = 0.012). This finding retained its predictive power in a multivariate survival analysis, in which all of the molecules studied previously in this patient cohort were included (P = 0.031). Immunohistochemistry confirmed the differences in alphav integrin expression in tumor cells of short-term as compared with long-term survivors, whereas beta1 integrin protein expression was comparable in the two groups. To our best knowledge, this is the first evidence associating integrin expression with poor survival in ovarian carcinoma. Alphav integrin is, thus, a

  19. Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Chen

    Full Text Available To investigate the role of SET domain containing 7 (SETD7 in hepatocellular carcinoma (HCC and determine whether SETD7 can be used as a predictor of overall survival in HCC patients.mRNAs and proteins of SETD7 and related genes in HCC tumor samples and paired adjacent non-tumorous liver tissues (ANLTs (n = 20 or culture cells were determined by quantitative real-time PCR and Western blot. Cell proliferation and apoptosis with SETD7 knockdown SMMC-7721 cells or SETD7 overexpressed HepG2 cells were analyzed by CCK8 assay or flow cytometry. Gene expression alterations in SETD7 knockdown of SMMC-7721 cells were determined by digital gene expression (DGE profiling. Defined data on patients (n = 225 with HCC were retrieved for the further study. Tissue microarrays (TMAs were performed using paraffin tissues with tumor and ANLTs. SETD7 and related proteins were determined by TMAs immunohistochemistry. Statistical analyses were conducted to associate SETD7 expression with tumor features and patient outcomes, as well as related proteins expression.SETD7 expression was significantly higher in HCC tumor tissues than in ANLTs. SETD7 overexpression in vitro can promote HepG2 cell proliferation, whereas SETD7 knockdown can inhibit SMMC-7721 cell proliferation by regulating the cell cycle. SETD7 expression was significantly correlated with five genes expression. Increased SETD7 is associated with metastasis, recurrence, large tumor size, and poor tumor differentiation, and indicates poor prognosis in HCC patients.SETD7 plays a critical role in HCC, and its immunohistochemistry signature provides potential clinical significance for personalized prediction of HCC prognosis.

  20. Increased Expression of SETD7 Promotes Cell Proliferation by Regulating Cell Cycle and Indicates Poor Prognosis in Hepatocellular Carcinoma.

    Science.gov (United States)

    Chen, Yuanyuan; Yang, Shengsheng; Hu, Jiewei; Yu, Chaoqin; He, Miaoxia; Cai, Zailong

    2016-01-01

    To investigate the role of SET domain containing 7 (SETD7) in hepatocellular carcinoma (HCC) and determine whether SETD7 can be used as a predictor of overall survival in HCC patients. mRNAs and proteins of SETD7 and related genes in HCC tumor samples and paired adjacent non-tumorous liver tissues (ANLTs) (n = 20) or culture cells were determined by quantitative real-time PCR and Western blot. Cell proliferation and apoptosis with SETD7 knockdown SMMC-7721 cells or SETD7 overexpressed HepG2 cells were analyzed by CCK8 assay or flow cytometry. Gene expression alterations in SETD7 knockdown of SMMC-7721 cells were determined by digital gene expression (DGE) profiling. Defined data on patients (n = 225) with HCC were retrieved for the further study. Tissue microarrays (TMAs) were performed using paraffin tissues with tumor and ANLTs. SETD7 and related proteins were determined by TMAs immunohistochemistry. Statistical analyses were conducted to associate SETD7 expression with tumor features and patient outcomes, as well as related proteins expression. SETD7 expression was significantly higher in HCC tumor tissues than in ANLTs. SETD7 overexpression in vitro can promote HepG2 cell proliferation, whereas SETD7 knockdown can inhibit SMMC-7721 cell proliferation by regulating the cell cycle. SETD7 expression was significantly correlated with five genes expression. Increased SETD7 is associated with metastasis, recurrence, large tumor size, and poor tumor differentiation, and indicates poor prognosis in HCC patients. SETD7 plays a critical role in HCC, and its immunohistochemistry signature provides potential clinical significance for personalized prediction of HCC prognosis.

  1. Over expression of galectin-3 associates with short-term poor prognosis in stage II colon cancer.

    Science.gov (United States)

    Huang, Zhiliang; Ai, Zenan; Li, Nan; Xi, Haofeng; Gao, Xucan; Wang, Feng; Tan, Xiaojun; Liu, Haiying

    2016-01-01

    Over expression of galectin-3 (gal-3) has been associated with tumor invasion and distant metastases, but few reports investigated the relation between gal-3 expression and prognosis in stage II colon cancer. We studied the expressions of gal-3, E-cadherin, and vimentin in stage II colon cancer to identify predictive factors of clinical outcome. Clinical and laboratory data from 117 consecutive patients of stage II colon cancer during 2008-2010 were collected and analyzed retrospectively. Expressions of gal-3, E-cadherin, and vimentin in tumor tissue were investigated by immunohistochemistry. Potential correlations between these markers and various clinicopathological parameters as well as clinical outcomes were studied. Human colon cancer cell line SW480 was used to test the epithelial-mesenchymal transition (EMT) inducing effects of gal-3 in vitro. High expression of tumoral gal-3 was associated with tumor size, poor differentiation and negatively related to low E-cadherin expression. Compare with adjacent normal colon tissue, most tumor tissues strongly expressed gal-3 and vimentin, but had lower E-cadherin expression. Univariate analysis showed that expressions of gal-3 and vimentin in tumor were predictors of tumor recurrence and overall survival. Multivariate analysis revealed that tumoral gal-3 expression was the only independent predictor of both tumor recurrence and overall survival after resection. Cell experiments and western blotting showed exogenous gal-3 could induce SW480 cells become more aggressive and express more hallmarks of EMT. Galectin-3 may be a useful marker for identification of poor prognosis in stage II colon cancer. Cell experiments and western blotting showed exogenous gal-3 could induce SW480 cells become more aggressive and express more hallmarks of EMT.

  2. CCR6 overexpression predicted advanced biological behaviors and poor prognosis in patients with gastric cancer.

    Science.gov (United States)

    Zhang, X G; Song, B T; Liu, F J; Sun, D; Wang, K X; Qu, H

    2016-07-01

    CCR6 expression is deregulated in some human malignancies and may be involved in the tumor progression. The aim of the present study was to determine the CCR6 expression in gastric cancer (GC) and to clarify its clinical significance. We used western blotting to examine CCR6 protein expression in GC tissues and matched adjacent non-tumor tissues. Immunohistochemistry was performed on a large cohort of 372 postoperative GC samples. Chi-square test, Kaplan-Meier analysis and Cox regression model were used to analyze the data. Upregulated CCR6 protein expression was observed in the GC tissues by western blotting compared with the adjacent non-cancerous gastric tissues. High CCR6 expression was detected in 56.5 % (210/372) samples and significantly associated with the extracapsular extension of the tumor, tumor relapse and poor overall survival in GC (P Cox regression analysis showed that high expression of CCR6 was an independent prognostic factor for GC patients. CCR6 expression may be a novel biomarker for predicting clinical outcomes for GC patients.

  3. Low thrombin generation predicts poor prognosis in ischemic stroke patients after thrombolysis.

    Science.gov (United States)

    Hudák, Renáta; Székely, Edina G; Kovács, Katalin R; Nagy, Attila; Hofgárt, Gergely; Berényi, Ervin; Csiba, László; Kappelmayer, János; Bagoly, Zsuzsa

    2017-01-01

    Thrombolysis by intravenous recombinant tissue plasminogen activator (rt-PA) is an effective therapy in acute ischemic stroke (AIS). Thrombin generation test (TGT) is a global hemostasis test providing information about the speed and amount of generated thrombin in plasma. Here we aimed to find out whether results of this test before the initiation of thrombolysis might predict outcomes. Study population included 120 consecutive AIS patients, all within 4.5 hours of their symptom onset, who underwent thrombolysis by rt-PA. Blood samples were collected from all patients upon admission and TGT was performed using platelet poor plasma. Clinical data of patients including the NIHSS were registered at admission, day 1 and 7 after therapy. The ASPECT score was assessed using CT images taken before and 24 hours after thrombolysis. Long-term functional outcome was defined 3 months after the event by the modified Rankin Scale. Endogenous Thrombin Potential (ETP) and Peak Thrombin were significantly lower in patients with cardioembolic IS. Symptomatic intracranial hemorrhage (SICH) was found in 6 patients and was significantly associated with low ETP and Peak Thrombin levels. A multiple logistic regression model revealed that an ETP result in the lower quartile is an independent predictor of mortality within the first two weeks (OR: 6.03; 95%CI: 1.2-30.16, pThrombin parameters increase the risk of therapy associated SICH. A low ETP result is an independent predictor of short- and long-term mortality following thrombolysis.

  4. ZNF217 is associated with poor prognosis and enhances proliferation and metastasis in ovarian cancer.

    Science.gov (United States)

    Li, Jing; Song, Lanlin; Qiu, Yuwen; Yin, Ailan; Zhong, Mei

    2014-01-01

    ZNF217 is an alternatively spliced Kruppel-like transcription factor that has recently been implicated to play a role in human carcinogenesis. Here, we used immunohistochemistry (IHC) to show that ZNF217 protein is overexpressed in nearly 60% of ovarian tumor samples. The disease-free survival time was shorter in patients with positive ZNF217 expression than in ZNF217-negative patients (P=0.042). Fluorescence in situ hybridization (FISH) analysis showed ZNF217 genomic amplification in the poorly differentiated tumors, suggesting that ZNF217 is associated with the progression of ovarian cancer. Invasion was enhanced in HO-8910 cells stably transfected with constructs carrying full-length ZNF217 relative to cells transfected with the empty vector. To confirm our findings in vivo, we performed a tumorigenicity assay in nude mice inoculated with the HO-8910 overexpressing ZNF217 cells. As expected, tumors grown in the ZNF217 group were more invasive and prone to metastasis than those formed control groups. Based on these clinical and laboratory observations, we conclude that ZNF217 may contribute to ovarian cancer invasion and metastasis, and associated with worse clinical outcomes.

  5. MCT4 Defines a Glycolytic Subtype of Pancreatic Cancer with Poor Prognosis and Unique Metabolic Dependencies

    Directory of Open Access Journals (Sweden)

    GuemHee Baek

    2014-12-01

    Full Text Available KRAS mutation, which occurs in ∼95% of pancreatic ductal adenocarcinoma (PDA, has been shown to program tumor metabolism. MCT4 is highly upregulated in a subset of PDA with a glycolytic gene expression program and poor survival. Models with high levels of MCT4 preferentially employ glycolytic metabolism. Selectively in such “addicted” models, MCT4 attenuation compromised glycolytic flux with compensatory induction of oxidative phosphorylation and scavenging of metabolites by macropinocytosis and autophagy. In spite of these adaptations, MCT4 depletion induced cell death characterized by elevated reactive oxygen species and metabolic crisis. Cell death induced by MCT4-depletion was augmented by inhibition of compensatory pathways. In xenograft models, MCT4 had a significant impact on tumor metabolism and was required for rapid tumor growth. Together, these findings illustrate the metabolic diversity of PDA described by MCT4, delineate pathways through which this lactate transporter supports cancer growth, and demonstrate that PDA can be rationally targeted based on metabolic addictions.

  6. High programmed cell death 1 ligand-1 expression: association with CD8+ T-cell infiltration and poor prognosis in human medulloblastoma.

    Science.gov (United States)

    Murata, Daiki; Mineharu, Yohei; Arakawa, Yoshiki; Liu, Bin; Tanji, Masahiro; Yamaguchi, Makoto; Fujimoto, Ko-Ichi; Fukui, Nobuyuki; Terada, Yukinori; Yokogawa, Ryuta; Yamaguchi, Maki; Minamiguchi, Sachiko; Miyamoto, Susumu

    2017-05-05

    OBJECTIVE Medulloblastoma is a type of malignant tumor arising in the cerebellum. The clinical importance of programmed cell death 1 ligand-1 (PD-L1) expression in medulloblastoma remains unknown. The aim of the present study was to examine the expression of PD-L1 and tumor-infiltrating T cells, and to evaluate their relationships to the prognosis of patients with medulloblastoma. METHODS The authors immunohistochemically analyzed PD-L1 expression and CD3+ and CD8+ lymphocyte infiltrations in tumor specimens from 16 patients with medulloblastoma. RESULTS High expression of PD-L1 was observed in 9 (56.3%) of 16 samples studied. High expression of PD-L1 was associated with low infiltrations of CD3+ or CD8+ lymphocytes. Patients with high expression of PD-L1 had shorter progression-free survival and overall survival times than those with low expression (p = 0.076 and p = 0.099, respectively). In addition, patients with high expression of PD-L1 and with low infiltration of CD8+ lymphocytes had a significantly worse outcome, with a 5-year survival rate of 15%, as compared with the other patients, who had a 5-year survival rate of nearly 90% (p = 0.0048 for progression-free survival and p = 0.010 for overall survival). CONCLUSIONS These findings indicate that PD-L1 expression was associated with a reduced infiltration of CD8+ T cells and poor prognosis in human medulloblastoma.

  7. Association between poor clinical prognosis and sleep duration among breast cancer patients.

    Science.gov (United States)

    Mansano-Schlosser, Thalyta Cristina; Ceolim, Maria Filomena

    2017-06-05

    to investigate the association between clinical progression and the quality and duration of sleep in women with breast cancer. longitudinal study, with 114 participants, conducted in a hospital in Brazil. The instruments used were: questionnaire for sociodemographic and clinical characterization, Pittsburgh Sleep Quality Index; Beck Depression Inventory and Herth Hope Scale. Data were analyzed through descriptive statistics and survival analyses (outcome: poor clinical progression), using the Kaplan-Meier curve, Log-rank test and Cox proportional model. a higher probability of poor clinical progression was verified in women with sleep durations of less than six hours or nine hours and over (p=.0173). the results suggest the importance of further studies that seek to verify whether the quantitative management of sleep disorders would have an impact on the progression of breast cancer. Women should be encouraged to report sleep problems to nurses. mensurar a associação entre evolução clínica e qualidade e duração do sono em mulheres com câncer de mama. estudo longitudinal, com 114 participantes, realizado em um hospital do Brasil. Os instrumentos utilizados foram: questionário para caracterização sociodemográfica e clínica, Índice de Qualidade do Sono de Pittsburgh; Inventário de Depressão de Beck e Escala de Esperança de Herth. Os dados foram analisados via análises descritivas e de sobrevivência (resultado: evolução clínica desfavorável), utilizando-se a curva de Kaplan-Meier, o teste log-rank e o modelo proporcional de Cox. verificou-se maior probabilidade de evolução clínica desfavorável em mulheres com duração de sono inferior a seis ou mais de nove horas (p = 0,0173). os resultados sugerem a importância de mais estudos que buscam verificar se a gestão quantitativa dos distúrbios do sono teria um impacto sobre a evolução do câncer de mama. As mulheres devem ser encorajadas a relatar isso espontaneamente aos enfermeiros. medir

  8. Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Maruse, Y; Kawano, S; Jinno, T; Matsubara, R; Goto, Y; Kaneko, N; Sakamoto, T; Hashiguchi, Y; Moriyama, M; Toyoshima, T; Kitamura, R; Tanaka, H; Oobu, K; Kiyoshima, T; Nakamura, S

    2018-01-26

    Programmed cell death ligand 1 (PD-L1) and its receptor PD-1 are immune checkpoint molecules that attenuate the immune response. Blockade of PD-L1 enhances the immune response in a variety of tumours and thus serves as an effective anti-cancer treatment. However, the biological and prognostic roles of PD-L1/PD-1 signalling in oral squamous cell carcinoma (OSCC) remain to be elucidated. The purpose of this study was to examine the correlation of PD-L1/PD-1 signalling with the prognosis of OSCC patients to assess its potential therapeutic relevance. The expression of PD-L1 and of PD-1 was determined immunohistochemically in 97 patients with OSCC and the association of this expression with clinicopathological characteristics was examined. Increased expression of PD-L1 was found in 64.9% of OSCC cases and increased expression of PD-1 was found in 61.9%. Univariate and multivariate analysis revealed that increased expression of PD-L1 and PD-1 positively correlated with cervical lymph node metastasis. The expression of CD25, an activated T-cell marker, was negatively correlated with the labelling index of PD-L1 and PD-1. Moreover, the patient group with PD-L1-positive and PD-1-positive expression showed a more unfavourable prognosis than the group with PD-L1-negative and PD-1-negative expression. These data suggest that increased PD-L1 and PD-1 expression is predictive of nodal metastasis and a poor prognosis and is possibly involved in cancer progression via attenuating the immune response. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma.

    Science.gov (United States)

    Wu, Lei; Deng, Wei-Wei; Yu, Guang-Tao; Mao, Liang; Bu, Lin-Lin; Ma, Si-Rui; Liu, Bing; Zhang, Wen-Feng; Sun, Zhi-Jun

    2016-09-01

    Checkpoint blockade therapy utilizing monoclonal antibodies to reactivate T cells and recover their antitumor activity makes an epoch in cancer immunotherapy. The role of B7-H4, a novel negative immune checkpoint, in oral squamous cell carcinoma (OSCC) has still not been elucidated. In this study, tissue samples from human OSCC, which contains 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa specimens, and Tgfbr1/Pten 2cKO mice OSCC model were stained with B7-H4 antibody to analyze the correlations between B7-H4 expression and clinicopathological characteristics. Kaplan-Meier analysis was used to compare the survival of patients with high B7-H4 expression and patients with low B7-H4 expression. We found B7-H4 is highly expressed in human OSCC tissue, and the B7-H4 expression level was associated with the clinicopathological parameters containing pathological grade and lymph node status. Moreover, we confirmed that B7-H4 was overexpressed in Tgfbr1/Pten 2cKO mice OSCC model. Our data also indicated that patients with high B7-H4 expression had poor overall survival compared with those with low B7-H4 expression. Furthermore, this study demonstrated that B7-H4 was positively associated with PD-L1, CD11b, CD33, PI3Kα p110, and p-S6 (S235/236). Taken together, these findings suggest B7-H4 is a potential target in the treatment of OSCC.

  10. Association of increased DNA methyltransferase expression with carcinogenesis and poor prognosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Zhang, Jing-Jing; Zhu, Yi; Zhu, Yan; Wu, Jun-Li; Liang, Wen-Biao; Zhu, Rong; Xu, Ze-Kuan; Du, Qing; Miao, Yi

    2012-02-01

    Epigenetic modifications play an important role in multistage carcinogenesis. The role of the three functional DNA methyltransferases (DNMTs) in pancreatic carcinogenesis has not been fully understood. The main goal of this study was to examine DNMT expression in different stages of pancreatic ductal adenocarcinoma (PDAC), and evaluate their prognostic significance in PDAC. A large number of premalignant and malignant pancreatic lesions were obtained by manual microdissection. Quantitative real-time RT-PCR was used to detect DNMTs mRNA expression. Nonparametric test, logrank test and Cox regression analysis were used to evaluate the clinical significance of DNMT expression. The mRNA expression of the three DNMTs increased with the development of pancreatic cancer from normal duct to pancreatic intraductal neoplasia and further to PDAC, and were statistically correlated with each other. Expression of the three DNMTs was statistically correlated with TNM staging and history of chronic pancreatitis. DNMT3A and DNMT3B, but not DNMT1 expression, was statistically correlated with tumour size. Patients with higher levels of DNMT1, DNMT3A and/or DNMT3B expression had an overall lower survival than those with lower levels of expression. Univariate analysis showed that high expression levels of DNMTs, alcohol consumption, tumour differentiation and TNM staging were statistically significant risk factors. Multivariate analysis showed that high level of DNMT3B expression and tumour differentiation were statistically significant independent poor prognostic factors. These results suggested that pancreatic carcinogenesis involves an increased mRNA expression of three DNMTs, and they may become valuable diagnostic and prognostic markers as well as potential therapeutic targets for pancreatic cancer.

  11. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

    Directory of Open Access Journals (Sweden)

    Jakubowski Ann A

    2009-12-01

    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  12. Interleukin 10 expression is related to aggressiveness and poor prognosis of patients with thyroid cancer.

    Science.gov (United States)

    Cunha, Lucas Leite; Morari, Elaine Cristina; Nonogaki, Sueli; Marcello, Marjory Alana; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian

    2017-02-01

    Most patients with thyroid cancer will evolve very well with current therapies. However, 10-30% of these patients will present recurrent disease and some of them will eventually die. IL-10 is an anti-inflammatory and immunosuppressive cytokine that can contribute to the immune escape of neoplastic cells. We aimed to investigate IL-10 as a molecular marker to improve the clinical management of patients with thyroid cancer. We retrospectively studied 162 patients with follicular cell-derived thyroid cancer who attended to our institution, including 63 classic papillary thyroid carcinomas, 46 follicular variant of papillary thyroid carcinomas, 11 poorly differentiated thyroid carcinomas and 42 follicular thyroid carcinomas. Patients were treated according to current guidelines and followed-up for 1-150 months. Additionally, we studied 96 samples of non-malignant tissues. We investigated the expression of IL-10 in tumor cells by semiquantitative and quantitative methods. Malignant tissues presented higher positivity (0.773 ± 0.140) than non-malignant samples (0.623 ± 0.190; p IL-10 (0.802 ± 0.125) than tumors without extrathyroidal invasion (0.731 ± 0.147; p = 0.004). We observed a positive correlation between tumor size and IL-10 positivity (correlation coefficient = 0.407; p IL-10 positivity above the median presented lower relapse-free survival rate compared to those patients whose tumors presented IL-10 positivity below the median. We suggest that a simple IL-10 IHC analysis could help selecting patients who would benefit from a more intensive approach.

  13. Autonomic nervous system dysfunction predicts poor prognosis in patients with mild to moderate tetanus

    Directory of Open Access Journals (Sweden)

    Shamsi Rohmah

    2005-01-01

    , irrespective of the need of mechanical ventilation or severity of tetanus, predicted poor outcome.

  14. High expression of WISP-1 correlates with poor prognosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Yang, Jian-Yu; Yang, Min-Wei; Huo, Yan-Miao; Liu, Wei; Liu, De-Jun; Li, Jiao; Zhang, Jun-Feng; Hua, Rong; Sun, Yong-Wei

    2015-01-01

    WNT1 inducible signaling pathway protein 1 (WISP-1) is a member of the CCN family of growth factors and reported to possess an important role in tumorigenesis by triggering downstream events via integrin signaling. However, the exact role of WISP-1 in cancer remains unclear. In this study, we examined the expression pattern of WISP-1 at both mRNA and protein levels and evaluated the prognostic value of WISP-1 in pancreatic ductal adenocarcinoma (PDA). Expression of WISP-1 at mRNA level was upregulated in 17/24 tumor tissues compared to the matched adjacent non-tumor tissues and the result was confirmed by western blotting at protein level. Immunohistochemical staining of 194 pairs of PDA specimens suggested that high expression of WISP-1 is strongly correlated with clinical stage (P=0.003), T classification (P=0.008) and liver metastasis (P=0.012). Consistently, Kaplan-Meier survival curves indicated that patients with high expression of WISP-1 had a shorter survival time independent of clinical stage and lymphatic metastasis status. Moreover, univariate and multivariate analysis confirmed WISP-1 expression, age, classification and liver metastasis as independent prognostic factors for overall survival of PDA patients. Taken together, these results suggest that WISP-1 may serve as a potential prognostic biomarker for PDA.

  15. Decreased expression of zinc-alpha2-glycoprotein in hepatocellular carcinoma associates with poor prognosis

    Directory of Open Access Journals (Sweden)

    Huang Yan

    2012-05-01

    Full Text Available Abstract Background Zinc-alpha2-glycoprotein (AZGP1, ZAG was recently demonstrated to be an important factor in tumor carcinogenesis. However, AZGP1 expression in hepatocellular carcinoma (HCC and its significance remain largely unknown. Methods Quantitative real-time polymerase chain reaction (qRT-PCR was applied to determine mRNA level of AZGP1 in 20 paired fresh HCC tissues. Clinical and pathological data of 246 HCC patients were collected. Tissue-microarray-based immunohistochemistry (IHC was performed to examine AZGP1 expression in HCC samples. Relationship between AZGP1 expression and clinicopathological features was analyzed by Chi-square test, Kaplan-Meier analysis and Cox proportional hazards regression model. Results AZGP1 expression was significantly lower in 80.0% (16/20 of tumorous tissues than that in the corresponding adjacent nontumorous liver tissues (P P P = 0.013, liver cirrhosis (P = 0.002 and tumor differentiation (P = 0.025. Moreover, HCC patients with high AZGP1 expression survived longer, with better overall survival (P = 0.006 and disease-free survival (P = 0.025. In addition, low AZGP1 expression associated with worse relapse-free survival (P = 0.046 and distant metastatic progression-free survival (P = 0.036. Conclusion AZGP1 was downregulated in HCC and could be served as a promising prognostic marker for HCC patients.

  16. High expression of HEF1 is associated with poor prognosis in urinary bladder carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Q

    2014-07-01

    Full Text Available Qi Zhang,1 Hui-Ju Wang,2 Da-Hong Zhang,1 Guo-Qing Ru,3 Xu-Jun He,2 Ying-Yu Ma2 1Department of Urology, 2Key Laboratory of Gastroenterology of Zhejiang Province, 3Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China Abstract: Human enhancer of filamentation 1 (HEF1 is a multidomain scaffolding protein that has been thought to play an important role in the tumor progression of various cancers. HEF1 expression has not previously been reported in urinary bladder carcinoma, and little is known about its prognostic significance. The aim of this study was to evaluate the expression patterns of HEF1 in urinary bladder carcinoma and to investigate its prognostic significance. HEF1 expression was analyzed by immunohistochemistry using tissue microarray. A significant relationship between HEF1 expression and sex, tumor size, number of tumors, invasion depth, lymph node metastasis, and distant metastasis was found, and high expression of HEF1 was associated with worse overall survival when compared to low expression of HEF1. Multivariate analysis showed that HEF1 expression was an independent prognostic factor for overall survival in urinary bladder carcinoma. We investigated HEF1 expression in urinary bladder carcinoma and found that high HEF1 expression was associated with advanced stage, large tumor size, and shortened progression-free survival. Although the biologic function of HEF1 in urinary bladder carcinoma remains unknown, the expression of HEF1 can provide new prognostic information for disease progression. Keywords: human enhancer of filamentation 1, progression-free survival, immunohistochemistry, metastasis, bladder cancer

  17. High co-expression of Sp1 and HER-2 is correlated with poor prognosis of gastric cancer patients.

    Science.gov (United States)

    Jiang, Weihua; Jin, Ziliang; Zhou, Fei; Cui, Jiujie; Wang, Lei; Wang, Liwei

    2015-09-01

    The aim of this study was to investigate co-expression of HER-2 and Sp1 in gastric cancer (GC) so as to determine whether these two proteins may be correlated with poor prognosis of GC patients. We examined the HER-2 overexpression and amplification and expression levels of Sp1 in 227 GC patients using immune-histochemical staining and fluorescence in situ hybridization. Data on clinicopathological features and relevant prognostic factors in these patients were analyzed. Of the 227 gastric cancer samples, 11.89% were positive for HER-2 overexpression/amplification under the new scoring system, and the frequency of negative, weak positive and strong positive expression of Sp1 was 14.98%, 48.01% and 37.0% respectively. No statistically positive correlation was observed between the expression levels of HER-2 and Sp1 in GC tissues. HER-2 overexpression was closely correlated to the Lauren type, degree of differentiation, tumor size and lymph node metastasis, and Sp1 as well (P HER-2 and Sp1 predicted poor survival in univariate analysis as well as in a Cox proportional hazards model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Decreased expression of PBLD correlates with poor prognosis and functions as a tumor suppressor in human hepatocellular carcinoma.

    Science.gov (United States)

    Li, Aimin; Yan, Qun; Zhao, Xinmei; Zhong, Jietao; Yang, Haiyun; Feng, Zhiqiang; Du, Yanlei; Wang, Yadong; Wang, Zenan; Wang, Hong; Zhou, Yongjian; Liu, Side; Nie, Yuqiang

    2016-01-05

    Recent accumulating genomic and proteomic data suggested that decreased expression of phenazine biosynthesis-like domain-containing protein (PBLD) was frequently involved in hepatocellular carcinoma (HCC). However, there is lack of systematical investigation focusing on its expression pattern, clinical relevance, and biological function. Here, we found that PBLD was frequently decreased in HCC tissues relative to adjacent non-tumorigenic liver tissues. This decreased expression was significantly associated with poor tumor differentiation and advanced tumor stage. Kaplan-Meier analysis further showed that recurrence-free survival and overall survival were significantly worse among patients with low PBLD expression. Moreover, multivariate analyses revealed that PBLD was an independent predictor of OS and RFS. This prognostic value of PBLD was further validated in another independent cohort. We also found PBLD inhibited HCC cell growth and invasion in vitro and tumor growth in vivo. Furthermore, forced expression of PBLD influenced multiple downstream genes related to MAPK, NF-κB, EMT, and angiogenesis signaling pathways. PBLD deletion was an independent predictor of poor prognosis in patients with HCC. Elevated PBLD expression may reduce HCC cell growth and invasion via inactivation of several tumorigenesis-related signaling pathways.

  19. Cancer‐testis antigens PRAME and NY‐ESO‐1 correlate with tumour grade and poor prognosis in myxoid liposarcoma

    Science.gov (United States)

    Iura, Kunio; Kohashi, Kenichi; Hotokebuchi, Yuka; Ishii, Takeaki; Maekawa, Akira; Yamada, Yuichi; Yamamoto, Hidetaka; Iwamoto, Yukihide

    2015-01-01

    Abstract Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer‐testis antigen PRAME was up‐regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real‐time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer‐testis antigen, NY‐ESO‐1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well‐differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY‐ESO‐1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well‐differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY‐ESO‐1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round‐cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY‐ESO‐1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY‐ESO‐1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY‐ESO‐1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high‐level expression correlated with tumour grade and poor prognosis. Our

  20. Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.

    Science.gov (United States)

    Iura, Kunio; Kohashi, Kenichi; Hotokebuchi, Yuka; Ishii, Takeaki; Maekawa, Akira; Yamada, Yuichi; Yamamoto, Hidetaka; Iwamoto, Yukihide; Oda, Yoshinao

    2015-07-01

    Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer-testis antigen PRAME was up-regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real-time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer-testis antigen, NY-ESO-1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well-differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY-ESO-1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well-differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY-ESO-1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round-cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY-ESO-1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY-ESO-1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY-ESO-1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high-level expression correlated with tumour grade and poor prognosis. Our results support the potential use of PRAME and NY

  1. High expression of PI3K core complex genes is associated with poor prognosis in chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Kristensen, Louise; Kielsgaard Kristensen, Thomas; Abildgaard, Niels

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in the Western world. Autophagy is a highly conserved process in eukaryotic cells. In CLL autophagy is involved in mediating the effect of chemotherapy but the role of autophagy in CLL pathogenesis remains unknown....... In the present study, we used real-time RT-PCR to analyze expression of the PIK3C3, PIK3R4, and BECN1 genes. These genes encode the components of the PI3K core complex, which is central to initiation of autophagy. A consecutive series of 149 well-characterized CLL cases from Region of Southern Denmark were...... included in the study. All three genes were observed to be independent markers of prognosis in CLL with high expression being associated with more aggressive disease. With this clear association with outcome in CLL, these genes thereby represent promising candidates for future functional studies...

  2. β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases.

    Science.gov (United States)

    Bleckmann, Annalen; Conradi, Lena-Christin; Menck, Kerstin; Schmick, Nadine Annette; Schubert, Antonia; Rietkötter, Eva; Arackal, Jetcy; Middel, Peter; Schambony, Alexandra; Liersch, Torsten; Homayounfar, Kia; Beißbarth, Tim; Klemm, Florian; Binder, Claudia; Pukrop, Tobias

    2016-04-01

    Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, β-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12-12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the β-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed β-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis.

  3. NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Chunhao Niu

    2016-10-01

    Full Text Available Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6 in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC. NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO stage (p = 0.006, squamous cell carcinoma antigen (p = 0.006, vital status (p < 0.001, tumor recurrence (p = 0.001, chemotherapy (p = 0.039, and lymph node metastasis (p < 0.001. Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

  4. Elevated Levels of Dickkopf-1 Are Associated with β-Catenin Accumulation and Poor Prognosis in Patients with Chondrosarcoma

    Science.gov (United States)

    Chen, Changbao; Zhou, Hua; Zhang, Xiaolin; Ma, Xinlong; Liu, Zhongjun; Liu, Xiaoguang

    2014-01-01

    Background Dickkopf-1 (DKK1) is an antagonist of Wnt/β-catenin signaling implicated in tumorigenesis. However, the biological role of DKK1 and β-catenin involved in chondrosarcoma has not been sufficiently investigated. This study was designed to investigate the expression profiles of DKK1 and β-catenin, and to clarify their clinical values in chondrosarcoma. Methods The mRNA and protein levels of DKK1 and β-catenin in fresh chondrosarcoma and the corresponding non-tumor tissues were analyzed by Real-time PCR and Western blot, respectively. The protein expression patterns of DKK1 and β-catenin were investigated by immunohistochemistry. The associations among DKK1 level, β-catenin accumulation, clinicopathological factors and the overall survival were separately evaluated. Results Both DKK1 and β-catenin levels were remarkably elevated in chondrosarcoma compared with the corresponding non-tumor tissues. High DKK1 level and positive β-catenin accumulation in chondrosarcoma specimens were 58.7% and 53.9%, respectively. Elevated DKK1 level significantly correlated with positive β-catenin accumulation, and they were remarkably associated with histological grade and Musculoskeletal Tumor Society stage. Furthermore, DKK1 level and β-catenin accumulation had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that DKK1 level was an independent prognostic factor for overall survival. Conclusions Elevated DKK1 levels associated with β-catenin accumulation play a crucial role in chondrosarcoma. DKK1 can serve as a novel predictor of poor prognosis in patients with chondrosarcoma. PMID:25144498

  5. Upregulation of the proto-oncogene Bmi-1 predicts a poor prognosis in pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Peng, Hong-Xia; Liu, Xiao-Dan; Luo, Zi-Yan; Zhang, Xiao-Hong; Luo, Xue-Qun; Chen, Xiao; Jiang, Hua; Xu, Ling

    2017-01-25

    Bmi-1, the B cell-specific moloney murine leukemia virus insertion site 1, is a member of the Polycomb-group (PcG) family and acts as an oncogene in various tumors; however, its expression related to the prognosis of pediatric patients with acute lymphoblastic leukemia (ALL) has not been well studied. The Bmi-1 expression levels in the bone marrow of 104 pediatric ALL patients and 18 normal control subjects were determined by using qRT-PCR. The association between the Bmi-1 expression and the clinicopathological characteristics of pediatric ALL patients was analyzed, and the correlation between Bmi-1 and the prognosis of pediatric ALL was calculated according to the Kaplan-Meier method. Furthermore, the association between Bmi-1 expression and its transcriptional regulator Sall4 was investigated. Compared to normal control subjects, patients with primary pediatric ALL exhibited upregulated levels of Bmi-1. However, these levels were sharply decreased in patients who achieved complete remission. A significant positive association between elevated Bmi-1 levels and a poor response to prednisone as well as an increased clinical risk was observed. Patients who overexpressed Bmi-1 at the time of diagnosis had a lower relapse-free survival (RFS) rate (75.8%), whereas patients with lower Bmi-1 expression had an RFS of 94.1%. Furthermore, in ALL patients, the mRNA expression of Bmi-1 was positively correlated to the mRNA expression of Sall4a. Taken together, these data suggest that Bmi-1 could serve as a novel prognostic biomarker in pediatric primary ALL and may be partially regulated by Sall4a. Our study also showed that Bmi-1 could serve as a new therapeutic target for the treatment of pediatric ALL.

  6. Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guo-Liang Huang

    Full Text Available OBJECTIVES: The role of heparanase (HPSE gene in cancers including hepatocellular carcinoma (HCC is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC. METHODS: The HPSE gene was studied in three different aspects: (1 loss of heterozygosity (LOH by a custom SNP microarray and DNA copy number by real-time PCR; (2 mRNA level by qRT-PCR; and (3 protein expression by immunohistochemistry. The clinical significances of allele loss and expression change of HPSE were analyzed. RESULTS: Microarray analysis showed that the average LOH frequency for 10 SNPs located within HPSE gene was 31.6%, three of which were significantly correlated with tumor grade, serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA copy number loss of HPSE was observed in 38.74% (43/111 of HCC cases. HPSE mRNA level was notably reduced in 74.1% (83/112 of tumor tissues compared with non-tumor liver tissues, which was significantly associated with DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was also remarkably reduced in 66.3% (53/80 of tumor tissues, which was correlated with tumor grade. Patients with lower expression level of HPSE mRNA or protein had a significantly lower survival rate than those with higher expression. Cox regression analysis suggested that HPSE protein was an independent predictor of overall survival in HCC patients. CONCLUSIONS: The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of HCCs, suggesting that HPSE behaves like a tumor suppressor gene and is a potential prognostic marker for HCC patients.

  7. High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential.

    Science.gov (United States)

    Uranbileg, Baasanjav; Enooku, Kenichiro; Soroida, Yoko; Ohkawa, Ryunosuke; Kudo, Yotaro; Nakagawa, Hayato; Tateishi, Ryosuke; Yoshida, Haruhiko; Shinzawa, Seiko; Moriya, Kyoji; Ohtomo, Natsuko; Nishikawa, Takako; Inoue, Yukiko; Tomiya, Tomoaki; Kojima, Soichi; Matsuura, Tomokazu; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

    2014-05-01

    We previously reported the increased serum mitochondrial creatine kinase (MtCK) activity in patients with hepatocellular carcinoma (HCC), mostly due to the increase in ubiquitous MtCK (uMtCK), and high uMtCK mRNA expression in HCC cell lines. We explored the mechanism(s) and the relevance of high uMtCK expression in HCC. In hepatitis C virus core gene transgenic mice, known to lose mitochondrial integrity in liver and subsequently develop HCC, uMtCK mRNA and protein levels were increased in HCC tissues but not in non-tumorous liver tissues. Transient overexpression of ankyrin repeat and suppressor of cytokine signaling box protein 9 (ASB9) reduced uMtCK protein levels in HCC cells, suggesting that increased uMtCK levels in HCC cells may be caused by increased gene expression and decreased protein degradation due to reduced ASB9 expression. The reduction of uMtCK expression by siRNA led to increased cell death, and reduced proliferation, migration and invasion in HCC cell lines. Then, consecutive 105 HCC patients, who underwent radiofrequency ablation with curative intent, were enrolled to analyze their prognosis. The patients with serum MtCK activity >19.4 U/L prior to the treatment had significantly shorter survival time than those with serum MtCK activity ≤ 19.4 U/L, where higher serum MtCK activity was retained as an independent risk for HCC-related death on multivariate analysis. In conclusion, high uMtCK expression in HCC may be caused by hepatocarcinogenesis per se but not by loss of mitochondrial integrity, of which ASB9 could be a negative regulator, and associated with highly malignant potential to suggest a poor prognosis. © 2013 UICC.

  8. Prognostic Nutritional Index Predicts Severe Complications, Recurrence, and Poor Prognosis in Patients With Colorectal Cancer Undergoing Primary Tumor Resection.

    Science.gov (United States)

    Tokunaga, Ryuma; Sakamoto, Yasuo; Nakagawa, Shigeki; Miyamoto, Yuji; Yoshida, Naoya; Oki, Eiji; Watanabe, Masayuki; Baba, Hideo

    2015-11-01

    The prognostic nutritional index is reportedly related to postoperative outcomes. The aim of this study was to elucidate the clinical importance of the prognostic nutritional index in patients with colorectal cancer who were undergoing primary tumor resection. This is a retrospective study from a single institution. This study was conducted at a colorectal surgery service in an academic teaching hospital. The 556 patients with colorectal cancer who were undergoing surgery between March 2005 and August 2014 were eligible for this study. The preoperative prognostic nutritional index was calculated. Classification and regression tree analysis was performed to determine the prognostic nutritional index cutoff value. The associations of the prognostic nutritional index status with clinicopathological factors and postoperative outcomes were examined using univariate and multivariate analyses. Classification and regression tree analysis demonstrated that 45.5 was the optimal cutoff value. The low status (≤45.5) was correlated with older age, low BMI, low estimated glomerular filtration rate, CEA positivity, carbohydrate antigen 19-9 positivity, preoperative chemotherapy, tumors invading muscular or deeper layers, distant metastasis, poor differentiation, severe postoperative complications, tumor recurrence, and poor survival. In multivariate analysis, the low status was an independent risk factor for severe postoperative complications (OR = 2.06 [95% CI, 1.22-3.50]; p = 0.007) and low overall survival (HR =3.98 [95% CI, 2.38-6.89]; p nutritional index status, not considering the postoperative host status. The preoperative prognostic nutritional index predicts severe complications, recurrence, and poor prognosis in patients with colorectal cancer who are undergoing primary tumor resection. Investigation of the nutritional and immunologic statuses using the prognostic nutritional index could be a useful clinical approach.

  9. An Ep-ICD based index is a marker of aggressiveness and poor prognosis in thyroid carcinoma.

    Directory of Open Access Journals (Sweden)

    Helen C-H He

    Full Text Available Nuclear accumulation of the intracellular domain of epithelial cell adhesion molecule (Ep-ICD in tumor cells was demonstrated to predict poor prognosis in thyroid carcinoma patients in our earlier study. Here, we investigated the clinical significance of Ep-ICD subcellular localization index (ESLI in distinguishing aggressive papillary thyroid carcinoma (PTC from non-aggressive cases.Using domain specific antibodies against the intracellular (Ep-ICD and extracellular (EpEx domains of epithelial cell adhesion molecule, 200 archived tissues from a new cohort of patients with benign thyroid disease as well as malignant aggressive and non aggressive PTC were analyzed by immunohistochemistry (IHC. ESLI was defined as sum of the IHC scores for accumulation of nuclear and cytoplasmic Ep-ICD and loss of membranous EpEx; ESLI = [Ep-ICD(nuc + Ep-ICD(cyt + loss of membranous EpEx].For the benign thyroid tissues, non-aggressive PTC and aggressive PTC, the mean ESLI scores were 4.5, 6.7 and 11 respectively. Immunofluorescence double staining confirmed increased nuclear Ep-ICD accumulation and decreased membrane EpEx expression in aggressive PTC. Receiver-operating characteristic (ROC curve analysis showed an area under the curve (AUC of 0.841, 70.2% sensitivity and 83.9% specificity for nuclear Ep-ICD for differentiating aggressive PTC from non-aggressive PTC. ESLI distinguished aggressive PTC from non-aggressive cases with improved AUC of 0.924, 88.4% sensitivity and 85.5% specificity. Our study confirms nuclear accumulation of Ep-ICD and loss of membranous EpEx occurs in aggressive PTC underscoring the potential of Ep-ICD and ESLI to serve as diagnostic markers for aggressive PTC. Kaplan Meier survival analysis revealed significantly reduced disease free survival (DFS for ESLI positive (cutoff >10 PTC (p<0.05, mean DFS=133 months as compared to 210 months for patients who did not show positive ESLI.ESLI scoring improves the identification of aggressive

  10. A Functional Polymorphism (rs10817938 in the XPA Promoter Region Is Associated with Poor Prognosis of Oral Squamous Cell Carcinoma in a Chinese Han Population.

    Directory of Open Access Journals (Sweden)

    Chunhai Gao

    Full Text Available Single nucleotide polymorphisms of XPA gene have been studied in several cancers such as rs10817938, rs2808668. However, the role of XPA polymorphisms in patients with oral squamous cell carcinoma (OSCC remains unclear. Thus, we analyzed the association of XPA polymorphisms with OSCC risk, clinicopathological characteristics and prognosis in the present study. TaqMan genotyping was used to evaluate the frequency of rs10817938, rs2808668 polymorphisms in OSCC patients. The prognostic significance of these polymorphisms was evaluated using Kaplan-Meier curves, Log-Rank analyses, and the Cox proportional hazard model. Luciferase reporter assay, RT-PCR and western blot were used to determine whether rs10817938 could influence transcription activity and XPA expression. The results showed that individuals carrying TC and CC genotypes had significantly greater risk of developing OSCC (OR = 1.42, 95% CI 1.04-1.93; OR = 2.75, 95% CI 1.32-5.71, respectively when compared with wild-type TT genotype at rs10817938. OSCC patients with C allele at rs10817938 were more susceptible to lymph metastases, poor pathological differentiation and late TNM stage (OR = 1.67, 95% CI 1.17-2.37; OR = 1.64, 95% CI 1.18-2.28; OR = 1.54, 95% CI 1.11-2.14; respectively. A significant gene-environment interaction between smoking and CC genotype at rs10817938 was observed (COR = 3.60, 95% CI 1.20-10.9 and data also showed that OSCC patients with CC genotype and C allele had worse survival (p<0.001 for both. The T to C substitution at rs10817938 significantly decreased transcription activity of XPA gene, XPA mRNA and protein were also decreased in individuals with C allele at rs10817938. In addition, no significant association of rs2808668 polymorphism with OSCC risk, prognosis could be observed. In conclusion, the present study showed that XPA rs10817938 polymorphism is a functional SNP in vitro and in vivo and a biomarker for poor prognosis in OSCC patients.

  11. Higher Tissue Levels of Thymidylate Synthase Determined by ELISA Are Associated with Poor Prognosis of Patients with Lung Cancer.

    Science.gov (United States)

    Shiina, Takayuki; Saito, Gaku; Sakaizawa, Takao; Agatsuma, Hiroyuki; Tominaga, Yoshiaki; Hyogotani, Akira; Hamanaka, Kazutoshi; Toishi, Masayuki; Takasuna, Keiichiro; Kondo, Ryoichi; Yoshida, Kazuo; Ito, Ken-Ichi

    2017-08-01

    Thymidylate synthase (TS) is essential in thymidylate biosynthesis and DNA replication. Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in pyrimidine catabolism and is important in catabolism of 5-fluorouracil (5-FU). The significance of TS and DPD expressed in lung cancer remains controversial. Here we analyzed the relationship between TS and DPD expression and clinicopathological features of lung cancer. Enzyme-linked immunosorbent assays (ELISAs) were used to measure TS and DPD levels in paired tumor and non-tumor lung tissues obtained from 168 patients (107 adenocarcinomas, 39 squamous cell carcinomas, and 22 others), who had operations at the Shinshu University Hospital from 2004 to 2007 and were followed up for a median of 57.0 months. TS and DPD expression levels were higher in tumor tissues, and TS expression levels were significantly lower in adenocarcinomas than those in other subtypes. In addition, patients with low TS levels survived longer compared with patents with high TS levels. By contrast, DPD expression levels were not correlated with overall patient survival. Importantly, patients with low TS and DPD levels exhibited significantly prolonged survival than those with high TS and DPD. Among the 168 patients, 59 patients were treated with tegafur-uracil (UFT), a DPD-inhibitory fluoropyrimidine, and the UFT-treated patients with high TS and high DPD levels showed worst prognosis. Our study demonstrates a significant correlation between low TS expression levels and long-term prognosis of patients with lung cancer. Thus, ELISA is a clinically useful method to measure TS and DPD expression in lung cancer tissues.

  12. Overexpression of EZH2 is associated with the poor prognosis in osteosarcoma and function analysis indicates a therapeutic potential

    Science.gov (United States)

    Sun, Ranran; Shen, Jacson; Gao, Yan; Zhou, Yubing; Yu, Zujiang; Hornicek, Francis; Kan, Quancheng; Duan, Zhenfeng

    2016-01-01

    Osteosarcoma is a primary malignant bone tumor that has a poor prognosis due to local recurrence, metastasis, and chemotherapy resistance. Therefore, there is an urgent need to develop novel potential therapeutic targets for osteosarcoma. Enhancer of zeste homologue 2 (EZH2) is a member of the polycomb group of proteins, which has important functions in epigenetic silencing and cell cycle regulation. Overexpression of EZH2 has been found in several malignancies, however, its expression and the role of EZH2 in osteosarcoma is largely unknown. In this study, we examined EZH2 expression by immunohistochemistry in a large series of osteosarcoma tissues in association with tumor characteristics and patient outcomes. EZH2 expression was also analyzed in a microarray dataset of osteosarcoma. Results showed that higher expression of EZH2 was significantly associated with more aggressive tumor behavior and poor patient outcomes of osteosarcoma. We subsequently investigated the functional and therapeutic relevance of EZH2 as a target in osteosarcoma. Immunohistochemical analysis indicated that EZH2 expression was significantly associated with more aggressive tumor behavior and poorer patient outcomes of osteosarcoma. EZH2 silencing by siRNA inhibited osteosarcoma cell growth, proliferation, migration, and invasion. Moreover, suppression of EZH2 attenuated cancer stem cell functions. Similar results were observed in osteosarcoma cells treated with EZH2 specific inhibitor 3-deazaneplanocin A (DZNep), which exhausted cellular levels of EZH2. These results suggest that EZH2 is critical for the growth and metastasis of osteosarcoma, and an epigenetic therapy that pharmacologically targets EZH2 via specific inhibitors may constitute a novel approach to the treatment of osteosarcoma. PMID:27223261

  13. Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Jing Liu

    Full Text Available BACKGROUND: S-phase kinase protein 2 (Skp2, an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined. METHODS: To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models. RESULTS: Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7% patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94 of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157 of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS, and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas. CONCLUSION: Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a

  14. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Keck Bastian

    2013-02-01

    Full Text Available Abstract Background Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. Methods We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC and 9 micropapillary (MPC carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox’s proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Results Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis. Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters showed a hazard ratio of 3.2 (p=0.045 for PUC in contrast to patients suffering from MPC. Conclusions Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.

  15. Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Jiang Zhu

    Full Text Available Monocarboxylate transporter 4 (MCT4 is a cell membrane transporter of lactate. Recent studies have shown that MCT4 is over-expressed in various cancers; however, its role in cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the role of MCT4 in oral squamous cell carcinoma (OSCC, and found that it is highly expressed in OSCC patients by using immunohistochemistry. Moreover, this over-expression of MCT4 was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis and tumor recurrence, and also poor prognosis. To further study mechanisms of MCT4 in vitro, we used small-interfering RNA to silence its expression in OSCC cell lines. The results showed that knock-down of MCT4 decreased cell proliferation, migration, and invasion. The inhibition of proliferation was associated with down-regulation of p-AKT and p-ERK1/2, while decreased cell migration and invasion may be caused by down-regulation of integrin β4-SRC-FAK and MEK-ERK signaling. Together, these findings provide new insight into the critical role of MCT4 in cell proliferation and metastasis in OSCC.

  16. Protocadherin-17 promoter methylation in serum-derived DNA is associated with poor prognosis of bladder cancer.

    Science.gov (United States)

    Luo, Zhen-Guo; Li, Zhi-Gang; Gui, Shi-Liang; Chi, Bao-Jin; Ma, Jian-Guo

    2014-02-01

    To investigate the prognostic value of protocadherin 17 (PCDH17) promoter methylation in serum-derived DNA of patients with bladder cancer. DNA was isolated from serum of patients with bladder cancer and from age- and sex-matched controls. Methylation-specific polymerase chain reaction was used to examine the methylation status of the PCDH17 promoter. The correlations between methylation status and clinicopathological characteristics and overall survival were examined. PCDH17 promoter methylation was detected in 79/151 (52.3%) of patients with bladder cancer, and none of the 43 control subjects. Methylation was significantly associated with larger tumour diameter (>3 cm), high grade (G3) and advanced stage (T2-T4). Patients with PCDH17 promoter methylation had significantly shorter overall survival than those with unmethylated PCDH17 promoter. Methylation was an independent predictor of overall survival. PCDH17 promoter methylation was significantly associated with malignant behaviour and poor prognosis of bladder cancer. The detection of PCDH17 promoter methylation in serum-derived DNA may be a convenient and noninvasive predictive biomarker in routine clinical practice.

  17. Overexpression of Transforming Acidic Coiled Coil‑Containing Protein 3 Reflects Malignant Characteristics and Poor Prognosis of Glioma

    Directory of Open Access Journals (Sweden)

    Ying Sun

    2017-03-01

    Full Text Available Gliomas are malignant primary brain tumors with poor prognosis. Recently, research was indicative of a tight connection between tumor malignancy and genetic alterations. Here, we propose an oncogenic implication of transforming acidic coiled-coil-containing protein 3 (TACC3 in gliomas. By comprehensively analyzing the Chinese glioma genome atlas (CGGA and publicly available data, we demonstrated that TACC3 were overexpressed along with glioma grade and served as an independent negative prognostic biomarker for glioma patients. Functions’ annotations and gene sets’ enrichment analysis suggested that TACC3 may participate in cell cycle, DNA repair, epithelium-mesenchymal transition and other tumor-related biological processes and molecular pathways. Patients with high TACC3 expression showed CD133+ stem cell properties, glioma plasticity and shorter overall survival time under chemo-/radio-therapy. Additionally, a TACC3 associated the miRNA-mRNA network was constructed based on in silico prediction and expression pattern, which provide a foundation for further detection of TACC3-miRNA-mRNA axis function. Collectively, our observations identify TACC3 as an oncogene of tumor malignancy, as well as a prognostic and motoring biomarker for glioma patients.

  18. Deletion and low expression of NFKBIA are associated with poor prognosis in lower-grade glioma patients

    Science.gov (United States)

    Kinker, Gabriela Sarti; Thomas, Andrew Maltez; Carvalho, Vinicius Jardim; Lima, Felipe Prata; Fujita, André

    2016-01-01

    Lower-grade gliomas (LGGs), which are uniformly fatal in young adults, are classified as grades II-III tumors according to their histological features. The NFκB transcription factor, a crucial player in cancer initiation and progression, is inactivated in the cytoplasm by inhibitory proteins (IκBs) that have been shown to exert tumor-suppressor activity. Therefore, using The Cancer Genome Atlas copy number alteration and RNA-Seq data from 398 patients, we evaluated the association between the expression and dosage of NFKBIA, which encodes IκBα, and the overall malignancy of LGGs. Deletion and low expression of NFKBIA were associated with enhanced tumor aggressiveness and poor prognosis in LGGs. Accordingly, the dosage and expression of NFKBIA were independent prognostic factors for 5-year survival (dosage: P = 0.016; expression: P = 0.002) and 5-year recurrence-free survival (dosage: P = 0.009; expression: P = 0.005). Moreover, gene set enrichment analyses and co-expression network analyses indicated a role for NFKBIA in the negative regulation of cell proliferation, possibly through the modulation of downstream NFκB activation. Overall, the present findings reveal the prognostic value of NFKBIA in LGGs, reinforcing the relevance of NFκB signaling in the development and progression of gliomas. PMID:27052952

  19. Over-Expression of POU Class 1 Homeobox 1 Transcription Factor (Pit-1) Predicts Poor Prognosis for Breast Cancer Patients.

    Science.gov (United States)

    Gao, Zhongcheng; Xue, Kecheng; Zhang, Lianfang; Wei, Meng

    2016-10-31

    The POU class 1 homeobox 1 transcription factor (POU1F1, also known as Pit-1) was reported to be associated with tumor progression and metastasis. The purpose of this study was to evaluate the prognostic value of Pit-1 in breast cancer patients. The relative expression levels of Pit-1 in breast cancer patients were detected by quantitative real-time PCR (qRT-PCR). Chi-square analysis was used to analyze the association between Pit-1 expression and clinical features. The Kaplan-Meier method was used to estimate the overall survival of the patients and Cox regression analysis was used to analyze the prognostic value of Pit-1. Increased expression of Pit-1 was detected in the tumor tissues compared with the normal tissues (1.086 vs. 0.541) and the abnormal expression was associated with tumor size, clinical stage, tumor grade, and lymph node metastasis (PPit-1 was significantly associated with poor overall survival of the patients (P=0.001) and Cox regression analysis indicated that Pit-1 might be a prognostic factor for breast cancer prognosis (HR=1.955, 95% CI=1.295-3.035, P=0.003). Pit-1 may be a potential prognostic biomarker for breast cancer patients and it is associated with tumor progression.

  20. Plasmacytoid variant of bladder cancer defines patients with poor prognosis if treated with cystectomy and adjuvant cisplatin-based chemotherapy.

    Science.gov (United States)

    Keck, Bastian; Wach, Sven; Stoehr, Robert; Kunath, Frank; Bertz, Simone; Lehmann, Jan; Stöckle, Michael; Taubert, Helge; Wullich, Bernd; Hartmann, Arndt

    2013-02-08

    Since the definition of different histologic subtypes of urothelial carcinomas by the World Health Organization (WHO) 2004 classification, description of molecular features and clinical behavior of these variants has gained more attention. We reviewed 205 tumor samples of patients with locally advanced bladder cancer mainly treated within the randomized AUO-AB05/95 trial with radical cystectomy and adjuvant cisplatin-based chemotherapy for histologic subtypes. 178 UC, 18 plasmacytoid (PUC) and 9 micropapillary (MPC) carcinomas of the bladder were identified. Kaplan Meier analysis and backward multivariate Cox's proportional hazards regression analysis were performed to compare overall survival between the three histologic subtypes. Patients suffering from PUC have the worst clinical outcome regarding overall survival compared to conventional UC and MPC of the bladder that in turn seem have to best clinical outcome (27.4 months, 62.6 months, and 64.2 months, respectively; p=0.013 by Kaplan Meier analysis). Backward multivariate Cox´s proportional hazards regression analysis (adjusted to relevant clinicopathological parameters) showed a hazard ratio of 3.2 (p=0.045) for PUC in contrast to patients suffering from MPC. Histopathological diagnosis of rare variants of urothelial carcinoma can identify patients with poor prognosis.

  1. Lewis Y antigen modified CD47 is an independent risk factor for poor prognosis and promotes early ovarian cancer metastasis

    Science.gov (United States)

    Tan, Mingzi; Zhu, Liancheng; Zhuang, Huiyu; Hao, Yingying; Gao, Song; Liu, Shuice; Liu, Qing; Liu, Dawo; Liu, Juanjuan; Lin, Bei

    2015-01-01

    CD47 is a membrane receptor that belongs to the immunoglobulin superfamily and plays an important role in the mechanisms of tumor immune escape. CD47 participates in tumor immune escape by combining with SIRPα to reduce the phagocytic activity of macrophages. There are six potential N-glycosylation sites on CD47, and glycosylation is known to be necessary for its membrane localization. However, it is still unknown to what extent glycosylation influences CD47 ligand binding properties and subsequent signaling. By using immunoprecipitation and confocal laser scanning microscopy, we showed that CD47 contains Lewis y antigen. Immunohistochemical analysis demonstrated that both the positive expression and the overexpression of CD47 and Lewis y antigen in cancer tissues and borderline tumors were significantly higher than those in benign ovarian tumors and normal ovarian tissues (P CD47 and Lewis y antigen was evident (r = 0.47, P CD47 and Lewis y antigen showed significant correlations with the clinical pathological parameters of ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) standards, lymph node metastasis, and degree of differentiation] (P CD47 was an independent adverse risk factor for the prognosis of ovarian cancer. Cases with both high CD47 and Lewis y antigen expression had poor prognoses. Our study demonstrates that Lewis y antigens of CD47 may play a crucial role in the development of ovarian cancer, and could be new targets for immunotherapy for ovarian cancer. PMID:26609483

  2. miR-21 Expression in Pregnancy-Associated Breast Cancer: A Possible Marker of Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Beatriz A. Walter, Gabriela Gómez-Macias, Vladimir A. Valera, Mark Sobel, Maria J. Merino

    2011-01-01

    Full Text Available Aims: microRNAs (miRNAs are a class of small noncoding RNAs that can act as key modulators in tumorigenesis-related genes. Specifically, it has been suggested that miR-21 overexpression plays a role in the development and progression of breast cancer. So far, the role of miRNAs in pregnancy-associated breast cancer (PABC has not been investigated.Methods and Results: We evaluated miR-21 expression by quantitative RT-PCR in 35 patients, 25 with PABC and 10 control breast cancer cases not pregnancy-associated with similar clinicopathological features. We then analyzed protein expression for PTEN, BCL2 and PDCD4 as miR-21 target genes by IHC, and finally correlated the results with patients' clinicopathological features.Significant overexpression of miR-21 in PABC tumors compared to normal adjacent tissue was found. Overexpression of miR-21 was frequently found in high grade tumors with loss of hormone receptor expression and was significantly associated with positive lymph nodes (p=0.025. In PABC patients, PTEN, BCL2 and PDCD4 target protein expression was decreased in 80%, 76% and 40% respectively.Conclusion: Our study supports the involvement of miR-21 in breast cancer progression and metastasis formation in PABC implying a role of this miRNA as a marker for poor prognosis in PABC patients.

  3. Poor prognosis with in vitro fertilization in Indian women compared to Caucasian women despite similar embryo quality.

    Directory of Open Access Journals (Sweden)

    Lora K Shahine

    Full Text Available BACKGROUND: Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared live birth rates (LBR between Indian and Caucasian women after blastocyst transfer to investigate whether differences in IVF outcomes between these ethnicities would persist in patients who transferred similar quality embryos. METHODOLOGY/PRINCIPAL FINDINGS: In this retrospective cohort analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a blastocyst transfer between January 1, 2005 and June 31, 2007 in our university center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P = 0.03, were more likely to have an agonist down regulation protocol (68% vs. 43%, P<0.01, and were more likely to have polycystic ovarian syndrome (PCOS, although not significant, (24% vs. 14%, P = 0.06. Sixty eight percent of Indian patients had the highest quality embryos (4AB blastocyst or better transferred compared to 71% of the Caucasians (P = 0.2. LBR was significantly lower in the Indians compared to the Caucasians (24% vs. 41%, P<0.01 with an odds ratio of 0.63, (95%CI 0.46-0.86. Controlling for age, stimulation protocol and PCOS showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40-0.79 in the multivariate analysis. CONCLUSIONS/SIGNIFICANCE: Despite younger age and similar embryo quality, Indians had a significantly lower LBR than Caucasians. In this preliminary study, poor prognosis after IVF for Indian ethnicity persisted despite limiting analysis to patients with high quality embryos transferred

  4. High levels of D-dimer correlated with disease status and poor prognosis of inoperable metastatic colorectal cancer patients treated with bevacizumab

    Directory of Open Access Journals (Sweden)

    Liming Zhu

    2014-01-01

    Conclusion: High levels of plasma baseline D-dimer correlated with high tumor load, advanced disease status and poor prognosis of inoperable mCRC patients treated with bevacizumab. However, clinical research on a much larger cohort of patients will be required to verify these findings.

  5. Overexpression of NIMA-related kinase 2 is associated with progression and poor prognosis of prostate cancer.

    Science.gov (United States)

    Zeng, Yan-Ru; Han, Zhao-Dong; Wang, Cong; Cai, Chao; Huang, Ya-Qiang; Luo, Hong-Wei; Liu, Ze-Zhen; Zhuo, Yang-Jia; Dai, Qi-Shan; Zhao, Hai-Bo; Liang, Yu-Xiang; Zhong, Wei-De

    2015-08-29

    The NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that is involved in regulation of centrosome duplication and spindle assembly during mitosis. Dysregulation of these processes causes chromosome instability and aneuploidy, which are hallmark changes of many solid tumors. However, whether aberrant expression of NEK2 is associated with outcome of prostate cancer (PCa) patients remains to be determined. Expression of NEK2 in human PCa cells and primary PCa tissues was assessed by quantitative RT-PCR. Expression of NEK2 in human PCa cells was depleted with siRNA. Effects of the depletion on cell proliferation, survival, and tumorigenicity were assessed both in vitro with cell cultures and in vivo with subcutaneous implantation of xenografts. In silico analyses of the online Taylor dataset were carried out to determine whether the expression level of NEK2 correlated with the clinicopathological characteristics of prostate cancer. Compared with benign human prostatic epithelial cells and tissues, the expression of NEK2 was elevated in human PCa cells and primary PCa tissues. Depleting NEK2 expression inhibited human PCa cell proliferation in vitro and xenograft growth in vivo. Expression level of NEK2 in PCa positively correlated with the Gleason score and pathologic stage of the patient. The results suggest that overexpression of NEK2 has the potential to serve as a biomarker for PCa prognosis. Further validation with large sample pool is warrant.

  6. Association of PITX2 mRNA down-regulation in prostate cancer with promoter hypermethylation and poor prognosis.

    Science.gov (United States)

    Vinarskaja, Anna; Schulz, Wolfgang A; Ingenwerth, Marc; Hader, Christiane; Arsov, Christian

    2013-07-01

    Hypermethylation of the PITX2 (paired-like homeodomain transcription factor 2) gene promoter is strongly associated with recurrence after radical prostatectomy. We hypothesized that PITX2 hypermethylation leads to PITX2 silencing and that decreased PITX2 expression is likewise associated with poor prognosis in prostate cancers. Moreover, it is unknown so far how PITX2 hypermethylation relates to other molecular changes in prostate cancer, such as ERG oncogenic activation in about half of all cases. To investigate how PITX2 expression and methylation are related, whether biochemical recurrence after radical prostatectomy can be predicted by PITX2 mRNA levels, and how changes in PITX2 relate to ERG overexpression. We measured PITX2 and ERG expression in 45 cancerous and 13 benign tissues from patients undergoing radical prostatectomy (age range: 59-74 years). Methylation of the PITX2 gene was analyzed in an extended series of 93 cancers. Follow-up was performed for all patients for a 98-month median period. Additionally, expression and methylation changes of PITX2 were investigated in prostate carcinoma cell lines. Gene expression and methylation were determined by quantitative RT-PCR and methylation-specific PCR, respectively. Biochemical recurrence defined as a total PSA of >0.2 ng/ml on 2 consecutive tests was considered as the surrogate endpoint for survival analysis. PITX2 expression was significantly and strongly decreased in prostate cancer compared to benign tissues. Cases with decreased PITX2 experienced significantly earlier biochemical recurrences. PITX2 down-regulation was associated with PITX2 promoter hypermethylation in tumor samples and cell lines. PITX2 hypermethylation was more pronounced in cases with ERG overexpression. PITX2 down-regulation is associated with promoter hypermethylation and is a good predictor of clinical outcomes after radical prostatectomy. PITX2 methylation might be influenced by oncogenic ERG. Copyright © 2013 Elsevier Inc

  7. Expression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Ivana Grbesa

    Full Text Available Sirtuin 1 (SIRT1 and sirtuin 2 (SIRT2 are NAD+-dependent protein deacetylases involved in the regulation of key cancer-associated genes. In this study we evaluated the relevance of these deacetylases in lung cancer biology.Protein levels of SIRT1 and SIRT2 were determined in non-small cell lung cancer (NSCLC cell lines and primary tumors from 105 patients. Changes in proliferation were assessed after SIRT1 and SIRT2 downregulation in lung cancer cell lines using siRNA-mediated technology or tenovin-1, a SIRT1 and SIRT2 inhibitor.High SIRT1 and SIRT2 protein levels were found in NSCLC cell lines compared with non-tumor lung epithelial cells. The expression of SIRT1 and SIRT2 proteins was also significantly higher in lung primary tumors than in normal tissue (P<0.001 for both sirtuins. Stronger nuclear SIRT1 staining was observed in adenocarcinomas than in squamous cell carcinomas (P=0.033. Interestingly, in NSCLC patients, high SIRT1 and SIRT2 expression levels were associated with shorter recurrence-free survival (P=0.04 and P=0.007, respectively. Moreover, the combination of high SIRT1 and SIRT2 expression was an independent prognostic factor for shorter recurrence-free survival (P=0.002 and overall survival (P=0.022. In vitro studies showed that SIRT1 and/or SIRT2 downregulation significantly decreased proliferation of NSCLC.Our results support the hypothesis that SIRT1 and SIRT2 have a protumorigenic role in lung cancer, promoting cell proliferation. Moreover, the expression of these proteins is associated with poor prognosis in NSCLC patients and may help to identify those NSCLC patients with high risk of recurrence that could benefit from adjuvant therapy after resection.

  8. Single-centre retrospective analysis of growth hormone supplementation in IVF patients classified as poor-prognosis.

    Science.gov (United States)

    Keane, Kevin N; Yovich, John L; Hamidi, Anahita; Hinchliffe, Peter M; Dhaliwal, Satvinder S

    2017-10-08

    Patients undergoing in vitro fertilisation (IVF) receive various adjuvant therapies in order to enhance success rates, but the true benefit is actively debated. Growth hormone (GH) supplementation was assessed in poor-prognosis women undergoing fresh IVF transfer cycles. Data were retrospectively analysed from 400 IVF cycles, where 161 women received GH and 239 did not. Clinical pregnancy, live birth rates and corresponding ORs and CIs were significantly greater with GH, despite patients being significantly older with lower ovarian reserve. Patient's age, quality of transferred embryo and GH were the only significant independent predictors of clinical pregnancy (OR: 0.90, 5.00 and 2.49, p<0.002, respectively) and live birth chance (OR: 0.91, 3.90 and 4.75, p<0.014, respectively). GH increased clinical pregnancy chance by 3.42-fold (95% CI 1.82 to 6.44, p<0.0005) and live birth chance by 6.16-fold (95% CI 2.83 to 13.39, p<0.0005) after adjustment for maternal age, antral follicle count and transferred embryo quality. These data provided further evidence to indicate that GH may support more live births, particularly in younger women. It also appears that embryos generated under GH have a better implantation potential, but whether the biological mechanism is embryo-mediated or endometrium-mediated is unclear. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. An increase in long non-coding RNA PANDAR is associated with poor prognosis in clear cell renal cell carcinoma.

    Science.gov (United States)

    Xu, Yi; Tong, Yanyue; Zhu, Jianyong; Lei, Zhangming; Wan, Lijun; Zhu, Xiuwen; Ye, Feng; Xie, Liping

    2017-05-25

    Nearly 30% of clear cell renal cell carcinoma (ccRCC) patients present with metastasis at the time of diagnosis, and the prognosis for these patients is poor. Therefore, novel potential prognostic biomarkers and therapeutic targets for ccRCC could be helpful. Emerging evidence indicates that lncRNAs play important roles in cancer tumorigenesis and could be used as potential biomarkers or therapeutic targets. PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) is a relatively novel lncRNA that plays an important role in the development of multiple cancers. However, the clinical significance and molecular mechanism of PANDAR in ccRCC are still elusive. In the present study, we attempted to elucidate the role of PANDAR in ccRCC. The relative expression level of lncRNA PANDAR was quantified by real-time qPCR in 62 paired ccRCC tissues and in renal cancer cell lines, and its association with overall survival was assessed by statistical analysis. The biological functions of lncRNA PANDAR on ccRCC cells were determined both in vitro and in vivo. PANDAR expression was significantly upregulated in tumor tissues and cell lines compared with normal counterparts. Moreover, PANDAR served as an independent predictor of overall survival, and increased PANDAR expression was positively correlated with an advanced TNM stage. Further experiments demonstrated that PANDAR silencing can significantly inhibit cell proliferation and invasion, induce cell cycle arrest in the G1 phase and significantly promote apoptosis in 7860 and Caki-1 cell lines. In addition, in vivo experiments confirmed that downregulation of PANDAR inhibited the tumorigenic ability of 7860 cells in nude mice. Silencing of PANDAR also inhibited the expression of Bcl-2 and Mcl-1 and upregulated the expression of Bax in vivo. Our results suggest that PANDAR is involved in ccRCC progression and may serve as a potential prognostic biomarker and therapeutic target.

  10. Overexpression of RBBP6, alone or combined with mutant TP53, is predictive of poor prognosis in colon cancer.

    Directory of Open Access Journals (Sweden)

    Jian Chen

    Full Text Available Retinoblastoma binding protein 6 (RBBP6 plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of RBBP6 expression in colon cancer is unknown; in particular, the prognostic value of RBBP6 combined with TP53 expression has not been explored. Therefore, quantitative real-time PCR and western blot analyses were performed to detect RBBP6 expression in colon cancer tissues. RBBP6 and TP53 expression were assessed by immunohistochemistry in a tissue microarray format, in which the primary colon cancer tissue was paired with noncancerous tissue. Tissue specimens were obtained from 203 patients. We found that RBBP6 was overexpressed in colon tumorous tissues and was significantly associated with clinical stage, depth of tumor invasion, lymph node metastasis (LNM, distant metastasis, and histologic grade. Further studies revealed that a corresponding correlation between RBBP6 overexpression and mutant TP53 was evident in colon cancer (r = 0.450; P<0.001. RBBP6 expression was an independent prognostic factor for overall survival (OS and disease free survival (DFS. Interestingly, patients with tumors that had both RBBP6 overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P<0.001. Multivariate analysis showed that patients with LNM and patients with both RBBP6- and TP53-positive tumors had extremely poor OS (HR 6.75; 95% CI 2.63-17.35; P<0.001 and DFS (HR 8.08; 95% CI 2.80-23.30; P<0.001. These clinical findings indicate that the assessment of both RBBP6 and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

  11. High expression of Y-box-binding protein 1 correlates with poor prognosis and early recurrence in patients with small invasive lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhao S

    2016-05-01

    Full Text Available Shilei Zhao,1,* Wei Guo,1,* Jinxiu Li,1 Wendan Yu,1 Tao Guo,1 Wuguo Deng,2,3 Chundong Gu1 1The First Affiliated Hospital, Institute of Cancer Stem Cell, Lung Cancer Diagnosis and Treatment Center, Dalian Medical University, Dalian, 2Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University, Guangzhou, 3State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Prognosis of small (≤2 cm invasive lung adenocarcinoma remains poor, and identification of high-risk individuals from the patients after complete surgical resection of lung adenocarcinoma has become an urgent problem. YBX1 has been reported to be able to predict prognosis in many cancers (except lung adenocarcinoma that are independent of TNM (tumor, nodes, metastases staging, especially small invasive lung adenocarcinoma. Therefore, we examined the significance of YBX1 expression on prognosis and recurrence in patients with small invasive lung adenocarcinoma. Material and methods: A total of 75 patients with small invasive lung adenocarcinoma after complete resection were enrolled from January 2008 to December 2010. Immunohistochemical staining was used to detect the expression of YBX1, and receiver operating characteristic curve analysis was performed to precisely assess the overall expression of YBX1. Meanwhile, primary lesions were identified based on the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society’s classification of lung adenocarcinoma. The effect of different clinicopathological factors on patients’ survival was examined. Furthermore, Western blot analysis was used to show the expression of YBX1 in vitro. Results: Sensitivity and specificity of YBX1 for detecting small

  12. High expression of transcriptional coactivator p300 correlates with aggressive features and poor prognosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cao Yun

    2011-01-01

    an aggressive phenotype, suggesting that p300 overexpression, as examined by IHC, is an independent biomarker for poor prognosis of patients with HCC. The combined clinicopathologic prognostic model may become a useful tool for identifying HCC patients with different clinical outcomes.

  13. Alpha B-crystallin - a validated prognostic factor for poor prognosis in squamous cell carcinoma of the oral cavity.

    Science.gov (United States)

    Annertz, Karin; Enoksson, Jens; Williams, Rebecca; Jacobsson, Helene; Coman, William B; Wennerberg, Johan

    2014-05-01

    Alpha B-crystallin was found to be an independent prognostic marker for poor prognosis in oral cavity tumours. For oropharyngeal cancer, alpha B-crystallin had no prognostic value. The aim of this study was to see if earlier findings of alpha B-crystallin as an independent prognostic marker, and SPARC/osteonectin, PAI-1 and uPA as a prognostic combination for poor outcome in squamous cell carcinoma (SCC) of the head and neck could be confirmed in a new set of tumours. In a consecutive series of patients, assessed and primarily treated at a tertiary referral centre, histological sections from 55 patients with oral and SCC (OOPHSSC) with complete clinical data and follow-up were obtained. Oral and oropharyngeal tumours were studied separately. Immunohistochemical detection of alpha B-crystallin, SPARC/osteonectin, PAI-1 and uPA expression was performed. Thirty-five patients had an oral tumour and 20 patients an oropharyngeal tumour. Twenty-five oral tumours stained negatively and 10 positively for alpha B-crystallin. For oropharyngeal tumours the figures were 15 negatively and 5 positively. Median disease-specific survival (DSS) for both sites was 33.8 and 11.9 months, for negative and positive alpha B-crystallin staining, respectively (p = 0.046). For the oral cavity, median DSS was 27.3 months for negative tumours and 7.5 months for positive tumours (p = 0.012). Corresponding figures for oropharyngeal tumours were 33.8 and 34.1 months (p = 0.95). Thus, significance in survival was only found in oral cavity tumours. In multivariate analyses there were no significant differences in DSS in the oropharyngeal group when adjusted for tumour size (T status) and presence of neck node metastasis (N status). In the oral cavity group, the significantly better DSS for negative tumours became even stronger when adjusted for T and N status. No statistical difference was found in DSS between positive and negative staining for SPARC/osteonectin, PAI-1 or uPA.

  14. Family history of cancer other than breast or ovarian cancer in first-degree relatives is associated with poor breast cancer prognosis.

    Science.gov (United States)

    Song, Jun-Long; Chen, Chuang; Yuan, Jing-Ping; Li, Juan-Juan; Sun, Sheng-Rong

    2017-04-01

    Whether a first-degree family history of others cancers (FHOC) than breast or ovarian cancer (BOC) is associated with breast cancer prognosis remains unknown. Thus, the aim of the present study was to clarify this issue. Women who were diagnosed with invasive breast cancer at the Renmin Hospital of Wuhan University from 2010 to 2013 were included in the study. The demographic and clinicopathological characteristics of these patients were extracted. FHOC was considered positive for any patient who had a relative who had been diagnosed with cancer other than BOC. Disease-free survival (DFS) was calculated based on the date of diagnosis. DFS was analyzed using the Cox proportional hazards model. A total of 434 breast cancer patients were included in this study. Among these patients, 61 (14.06%) had a positive FHOC in first-degree relatives. Patients with a positive FHOC tended to have HER2-positive breast cancer (p = 0.03). In the survival analysis, FHOC was associated with poor DFS in both univariate (HR = 2.21 (1.28-3.83), 95% CI: 1.28-3.83, p breast cancer patients with FHOC, especially in patients with luminal A subtype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB

    Directory of Open Access Journals (Sweden)

    Zhang Xin

    2009-07-01

    Full Text Available Abstract Background Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors. Patients and methods Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed. Results The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5% were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%. Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth. Conclusion The fact that a higher percentage CD133+ cells were strongly associated

  16. Decreased expression of the ARID1A gene is associated with poor prognosis in primary gastric cancer.

    Directory of Open Access Journals (Sweden)

    Dan-dan Wang

    Full Text Available BACKGROUND: The ARID1A gene encodes adenine-thymine (AT-rich interactive domain-containing protein 1A, which participates in chromatin remodeling. ARID1A has been showed to function as a tumor suppressor in various cancer types. In the current study, we investigated the expression and prognosis value of ARID1A in primary gastric cancer. Meanwhile, the biological role of ARID1A was further investigated using cell model in vitro. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of ARID1A gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were used to examine the ARID1A expression in paired cancerous and noncancerous tissues. Results revealed decreased ARID1A mRNA (P = 0.0029 and protein (P = 0.0015 expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues, and in gastric cancer cell lines. To further investigate the clinicopathological and prognostic roles of ARID1A expression, we performed immunohistochemical analyses of the 224 paraffin-embedded gastric cancer tissue blocks. Data revealed that the loss of ARID1A expression was significantly correlated with T stage (P = 0.001 and grade (P = 0.006. Consistent with these results, we found that loss of ARID1A expression was significantly correlated with poor survival in gastric cancer patients (P = 0.003. Cox regression analyses showed that ARID1A expression was an independent predictor of overall survival (P = 0.029. Furthermore, the functions of ARID1A in the proliferation and colony formation of gastric cell lines were analyzed by transfecting cells with full-length ARID1A expression vector or siRNA targeting ARID1A. Restoring ARID1A expression in gastric cancer cells significantly inhibited cell proliferation and colony formation. Silencing ARID1A expression in gastric epithelial cell line significantly enhanced cell growth rate. CONCLUSIONS/SIGNIFICANCE: Our data suggest that ARID1A may play an important role

  17. High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zijian; Huang, Shanzhou [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Wang, Huanyu [Department of Thyroid and Breast Surgery, Nanshan District People’s Hospital, Shenzhen, 518000 (China); Wu, Jian [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Chen, Dong [Department of Biliopancreatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Peng, Baogang [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China); Zhou, Qi, E-mail: hnzhouqi@163.com [Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 (China)

    2016-06-10

    Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines. The Oncomine™ Cancer Microarray Database was applied to analysis the correlations between HKDC1 expression and HCC clinical characteristics. MTT and Transwell migration assays were performed to determine the functions of HKDC1 in HCC cells. The effect of HKDC1 on Wnt/β-catenin signaling pathway was assessed using Western blotting assay. In this study, we found that HKDC1 expression levels were elevated in HCC tissues compared with the adjacent tissues. HCC patients with high expression levels of HKDC1 had poor overall survival (OS). Furthermore, higher HKDC1 levels also predicted a worse OS of patients within solitary, elevated pre-operated serum alpha fetoprotein (AFP) level and higher tumor diameter. Moreover, silencing HKDC1 suppressed HCC cells proliferation and migration in vitro. Downregulated HKDC1 expression repressed β-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/β-catenin signaling pathway in HCC. In summary, HKDC1 provides further insight into HCC tumor progression and may provide a novel prognostic biomarker and therapeutic target for HCC treatment. -- Highlights: •HKDC1 is upregulated in HCC. •Patients with high HKDC1 expressions perform worse OS. •Silencing HKDC1 suppresses proliferation and migration. •Silencing HKDC1 represses Wnt/β-catenin signaling pathway.

  18. CYP19 Genetic Polymorphism Haplotype AASA Is Associated with a Poor Prognosis in Premenopausal Women with Lymph Node-Negative, Hormone Receptor-Positive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sung-Hsin Kuo

    2013-01-01

    Full Text Available Given the critical role of CYP19 in estrogen synthesis, we investigated the influence of CYP19 gene polymorphisms on the clinical outcome of lymph node- (LN- negative, hormone receptor- (HR- positive early breast cancers. Genotyping for the CYP19 polymorphisms rs4646 (A/C, rs1065779 (A/C, CYP19 (TTTAn (short allele/long (S/L allele using the 7 TTTA repeat polymorphism as the cut-off, and rs1870050 (A/C was performed on 296 patients with LN-negative, HR-positive breast cancers. All patients received adjuvant hormonal therapy. Associations were examined between these 4 genotypes and 6 common haplotypes of CYP19 and distant disease-free survival (DDFS, disease-free survival (DFS, and overall survival (OS. Patients were divided into the 6 subhaplotypes of CCLA (41.1%, AASA (17.1%, CASA (11.9%, CCLC (8.9%, CCSA (7.5%, AASC (8.9%, and others (4.6%. In premenopausal patients, haplotype AASA was significantly associated with a poor DDFS (adjusted hazard ratio (aHR, 3.3; P=0.001, DFS (aHR, 2.5; P=0.0008, and OS (aHR, 2.9; P=0.0004 after adjusting for age, tumor size, tumor grade, estrogen receptor status, progesterone receptor status, chemotherapy, pathology, adjuvant hormone therapy, menopausal status, and radiotherapy. Furthermore, haplotype AASA remained a negative prognostic factor for premenopausal patients receiving adjuvant chemotherapy in terms of DDFS (aHR, 4.5; P=0.0005, DFS (HR, 3.2; P=0.003, and OS (HR, 6.4; P=0.0009. However, in postmenopausal patients, haplotype AASA was not associated with a poor prognosis, whereas the AASC haplotype was significantly associated with a poor DFS (aHR, 3.1; P=0.03 and OS (aHR, 4.4; P=0.01. Our results indicate that, in patients with LN-negative, HR-positive breast cancers, genetic polymorphism haplotype AASA is associated with poor survival of premenopausal women but does not affect survival of postmenopausal women.

  19. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients

    OpenAIRE

    Fengxia Qin; Huikun Zhang; Li Ma; Xiaoli Liu; Kun Dai; Wenliang Li; Feng Gu; Li Fu; Yongjie Ma

    2015-01-01

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast canc...

  20. Decreased expression of the ATM gene linked to poor prognosis for gastric cancer of different nationalities in Xinjiang.

    Science.gov (United States)

    Han, Mei; Ma, Lanying; Qu, Yanli; Tang, Yong

    2017-08-01

    To explore the clinicopathological significance of ATM gene in the occurrence and prognosis of gastric cancer (GC) from different nationalities in Xinjiang. The expression of ATM in 385 patients with GC (including 98 Uygurs, 231 Hans and 56 Kazaks) and its corresponding adjacent tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry assay to, analyze its correlations with clinicopathological features and prognosis of GC. The ATM expression in GC tissues was significantly decreased when compared to that in adjacent normal tissues of Uygur, Han and Kazak patients in Xinjiang, while Uygurs and Kazaks were much lower than Hans in the ATM expression of GC tissues (all PATM-negative tumors had a markedly lower survival rate than patients in Hans (P=0.028), and GC patients with ATM negative expression presented more unfavorable overall survival rate than those with positive expression among the three different nationalities (all PATM expression, TNM staging, depth of invasion, and lymph node metastasis were independent factors affecting the prognosis of GC patients in Xinjiang (all PATM was downregulated in GC patients in Xinjiang, especially for Uygurs and Kazaks, which suggested ATM to be an independent indicator of prognosis for GC therapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study.

    Science.gov (United States)

    Tiede, Andreas; Hofbauer, Christoph J; Werwitzke, Sonja; Knöbl, Paul; Gottstein, Saskia; Scharf, Rüdiger E; Heinz, Jürgen; Groß, Jürgen; Holstein, Katharina; Dobbelstein, Christiane; Scheiflinger, Fritz; Koch, Armin; Reipert, Birgit M

    2016-05-12

    Neutralizing autoantibodies against factor VIII (FVIII), also called FVIII inhibitors, are the cause of acquired hemophilia A (AHA). They are quantified in the Bethesda assay or Nijmegen-modified Bethesda assay by their ability to neutralize FVIII in normal human plasma. However, FVIII inhibitors do not represent the whole spectrum of anti-FVIII autoantibodies. Here, we studied isotypes, immunoglobulin G subclasses, and apparent affinities of anti-FVIII autoantibodies to assess their prognostic value for the outcome in AHA. We analyzed baseline samples from patients enrolled in the prospective GTH-AH 01/2010 study. Our data suggest that anti-FVIII immunoglobulin A (IgA) autoantibodies are predictors of poor outcome in AHA. Anti-FVIII IgA-positive patients achieved partial remission similar to anti-FVIII IgA-negative patients but had a higher risk of subsequent recurrence. Consequently, IgA-positive patients achieved complete remission less frequently (adjusted hazard ratio [aHR], 0.35; 95% confidence interval [CI], 0.18-0.68; P < .01) and had a higher risk of death (aHR, 2.62; 95% CI, 1.11-6.22; P < .05). Anti-FVIII IgA was the strongest negative predictor of recurrence-free survival after achieving partial remission and remained significant after adjustment for baseline demographic and clinical characteristics. In conclusion, anti-FVIII IgA represents a potential novel biomarker that could be useful to predict prognosis and tailor immunosuppressive treatment of AHA. © 2016 by The American Society of Hematology.

  2. Decreased mRNA expression of transcription factor forkhead box F2 is an indicator of poor prognosis in patients with resected esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zheng, Yu-Zhen; Wen, Jing; Cao, Xun; Yang, Hong; Luo, Kong-Jia; Liu, Qian-Wen; Huang, Qing-Yuan; Chen, Jun-Ying; Fu, Jian-Hua

    2015-05-01

    The transcription factor forkhead box F2 (FOXF2) is an evolutionarily conserved DNA-binding protein involved in embryogenesis and metabolism. Although recent studies prove that FOXF2 is a tumor suppressor in various human cancers, the role of FOXF2 in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, samples were collected from 188 ESCC patients, including 33 pairs of tumor and non-tumor tissues, and FOXF2 mRNA expression was investigated by quantitative polymerase chain reaction. The results demonstrated that FOXF2 mRNA is downregulated in tumor tissues compared to paired non-tumor tissues (P=0.048). The receiver operating characteristic curve analysis indicated 1.2 as a cut-off point and, thus, 125 and 63 tumors were classified as low- and high-level FOXF2 mRNA expression, respectively. We observed that low-level FOXF2 mRNA expression in the tumors was associated with a higher frequency of lymph node metastasis (P=0.044), an effect further suggested by the multivariate logistic regression analysis (P=0.060). According to the univariate Cox analysis, patients harboring tumors with low-level FOXF2 mRNA expression had a significantly increased mortality risk compared to those with high-level expression (hazard ratio=1.700, 95% confidence interval, 1.077-2.681), with 5-year survival rates of 41.1 and 61.9%, respectively. This negative prognostic effect of low-level FOXF2 mRNA expression was further validated in the multivariate Cox analysis (P=0.021). The subgroup analysis demonstrated that the effect of FOX2 mRNA expression was limited to male patients and those with advanced-stage disease. Taken together, these findings suggest that FOXF2 may be an anti-oncogene for ESCC and decreased FOXF2 mRNA expression is associated with a poor prognosis in patients with ESCC.

  3. Strengthening the case that elevated levels of programmed death ligand 1 predict poor prognosis in hepatocellular carcinoma patients

    Directory of Open Access Journals (Sweden)

    Zhong J

    2016-12-01

    Full Text Available Jian-Hong Zhong,1,* Cheng-Piao Luo,2,* Chun-Yan Zhang,2 Le-Qun Li1 1Hepatobiliary Surgery Department, 2Experimental Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Abstract: Immunotherapy targeting programmed death receptor 1 and programmed death ligand 1 (PD-L1 has shown impressive antitumor efficacy in several solid cancers, including advanced hepatocellular carcinoma (HCC. Since response rates of various cancers to such immunotherapy appear to correlate with PD-L1 expression levels, several studies have examined whether PD-L1 expression correlates with HCC pathology and patient prognosis. In this paper, we analyzed the strength and limitations of a recent meta-analysis of associations of PD-L1 with HCC characteristics and patient prognosis. Keywords: hepatocellular carcinoma, programmed death ligand 1, hepatic resection, prognoses

  4. Elevated Preoperative Neutrophil-Lymphocyte Ratio Is Associated with Poor Prognosis in Hepatocellular Carcinoma Patients Treated with Liver Transplantation: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Sun

    2016-01-01

    Full Text Available This study aims to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR in hepatocellular carcinoma (HCC patients treated with liver transplantation (LT through meta-analysis. Relevant articles were sought in PubMed, Embase, and Wangfang databases up to July 2015. A total of 1687 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that elevated NLR was significantly associated with poorer overall survival (OS (HR = 2.71, 95% CI: 1.91–3.83 and poorer disease-free survival (DFS (HR = 3.61, 95% CI: 2.23–5.84 in HCC patients treated with LT. Moreover, subgroup analysis showed the significant association between elevated preoperative NLR and poor prognosis was not altered by cutoff values of NLR or types of LT. Therefore, elevated preoperative NLR is associated with poor prognosis in HCC patients treated with LT. Preoperative NLR should be used to predict the prognosis of HCC after LT in our clinical work.

  5. Factors associated with a poor prognosis for the IVF-ICSI live birth rate in women with rAFS stage III and IV endometriosis.

    Science.gov (United States)

    Roux, Pauline; Perrin, Jeanne; Mancini, Julien; Agostini, Aubert; Boubli, Léon; Courbiere, Blandine

    2017-07-01

    To assess the factors associated with a poor prognosis for a cumulative IVF live birth rate (LBR) in women with stage III and IV endometriosis according to the revised classification of the American Fertility Society (rAFS). A retrospective cohort study was conducted between January 1, 2010, and December 31, 2014, in our Reproductive Medicine Center. We analyzed different factors associated with a poor prognosis for a cumulative IVF LBR in women with rAFS stage III and IV endometriosis. A total of 101 patients were included, representing 232 IVF-ICSI cycles and 212 embryo transfers. The primary endpoint was the cumulative LBR per cycle and per patient. The cumulative LBR per cycle was 14.7% (n = 34) and that per patient was 31.7% (n = 32). The cumulative LBR was significantly decreased by active smoking [adjOR = 3.4, 95% CI (1.12-10.60), p = 0.031], poor ovarian response (POR) according to the Bologna criteria [adjOR = 11.5, 95% CI (1.37-96.83), p = 0.024], and rAFS stage IV [adjOR = 3.2, 95% CI (1.13-8.95), p = 0.024]. The cumulative LBR per women was 59.4% without factors associated with a poor prognosis and 25.6% in the case of one factor, and it decreased to 7.7% in the case of two or three factors (p IVF-ICSI cumulative LBR for women with rAFS stage III and IV endometriosis. Because smoking dramatically decreases the LBR with endometriosis, stopping smoking before IVF-ICSI should be strongly advised.

  6. A decision-analytic approach to define poor prognosis patients: a case study for non-seminomatous germ cell cancer patients

    Directory of Open Access Journals (Sweden)

    Steyerberg Ewout W

    2008-01-01

    Full Text Available Abstract Background Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to define the treatment threshold for more aggressive treatment. This approach is illustrated by a case study in advanced testicular cancer, where patients with a high risk of mortality under standard treatment may be eligible for high-dose chemotherapy with stem cell support, which is currently defined by the IGCC classification. Methods We used published literature to estimate the benefit and harm of high-dose chemotherapy (HD-CT versus standard-dose chemotherapy (SD-CT for patients with advanced non-seminomatous germ cell cancer. Benefit and harm were defined as the reduction and increase in absolute risk of mortality due to HD-CT respectively. Harm included early and late treatment related death, and treatment related morbidity (weighted by 'utility'. Results We considered a conservative and an optimistic benefit of 30 and 40% risk reduction respectively. We estimated the excess treatment related mortality at 2%. When treatment related morbidity was taken into account, the harm of HD-CT increased to 5%. With a relative benefit of 30% and harm of 2 or 5%, HD-CT might be beneficial for patients with over 7 or 17% risk of cancer specific mortality with SD chemotherapy, while with a relative benefit of 40% HD-CT was beneficial over 5 and 12.5% risk respectively. Compared to the IGCC classification 14% of the patients would receive more aggressive treatment, and 2% less intensive treatment. Conclusion Benefit and harm can be used to define 'poor prognosis' explicitly for non-seminomatous germ cell cancer patients who are considered for high-dose chemotherapy. This approach can readily be adapted to new results and extended to other cancers to define candidates for

  7. Poor Prognosis with In Vitro Fertilization in Indian Women Compared to Caucasian Women Despite Similar Embryo Quality

    OpenAIRE

    Shahine, Lora K.; Lamb, Julie D.; Lathi, Ruth B.; Milki, Amin A.; Langen, Elizabeth; Westphal, Lynn M.

    2009-01-01

    BACKGROUND: Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF) treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared...

  8. LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations

    DEFF Research Database (Denmark)

    Kristensen, Louise; Kielsgaard Kristensen, Thomas; Abildgaard, Niels

    2016-01-01

    Chronic lymphocytic leukemia is a heterogeneous yet incurable disease. Whole genome and - exome sequencing studies have revealed recurrently occurring somatic mutations in some genes. Several other prognostic markers have previously been tested for their prognostic value in CLL. LPL is among...... these markers. AIM: To evaluate LPL gene expression together with the well-established prognostic markers of CLL and investigate correlations with more recently identified prognostic markers, NOTCH1 and TP53 mutations. METHODS: On 149 patients LPL gene expression was analyzed by real-time RT-PCR. Exon 34...... and new prognostic markers, 3 out of 4 patients, who received treatment within 24 months after diagnosis, were LPL+ (p=0.03). There was a strong correlation between NOTCH1 mutation and LPL+ (p=0.005). The unfavorable prognosis of LPL+ was maintained in CLL with wild-type NOTCH1. CONCLUSIONS: NOTCH1...

  9. Low Merlin expression and high Survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma.

    Science.gov (United States)

    Meerang, Mayura; Bérard, Karima; Friess, Martina; Bitanihirwe, Byron K Y; Soltermann, Alex; Vrugt, Bart; Felley-Bosco, Emanuela; Bueno, Raphael; Richards, William G; Seifert, Burkhardt; Stahel, Rolf; Weder, Walter; Opitz, Isabelle

    2016-10-01

    Alterations of the tumor suppressor Neurofibromatosis type II (NF2) have been reported in about 40% of Malignant pleural mesothelioma (MPM) patients. NF2 (Merlin) deficiency leads to alterations of the Hippo pathway; resulting in activation of the oncogenic Yes Associated Protein-1 (YAP1). Our aim was to investigate the association between these alterations and clinical outcomes. Tissue microarrays composed of MPM tumors derived from 2 independent MPM cohorts were employed for this study. Immunohistochemical expression of Merlin, YAP1 and its target genes, Survivin and connective tissue growth factor (CTGF) were assessed in nuclear and cytoplasmic fractions. Cohort 1 was comprised of 145 patients intended to be treated with chemotherapy (CTX) followed by extrapleural pneumonectomy (EPP), thus both pre- and post-CTX tissues were available. Cohort 2 was comprised of 59 patients treated with EPP followed by intraoperative hyperthermic cisplatin and/or adjuvant CTX and/or radiotherapy. Marker expression was quantified by means of labeling index (%) for nuclear Survivin and by H-score for the other markers. The dichotomized marker expression was tested for the association with overall survival (OS) and freedom from recurrence (FFR). Kaplan-Meier survival curves revealed a significant association between low cytoplasmic Merlin expression in pre-induction CTX tissues of cohort 1 with shorter FFR (p = 0.02) and OS (p = 0.03). The same tendency was observed in the chemotherapy naïve tissues obtained during EPP of cohort 2. Low nuclear Merlin expression in post-CTX tissues (available from cohort 1 only) was associated with shorter FFR (p = 0.04) and OS (p = 0.05). High nuclear Survivin labeling indices in both pre- and post-CTX tissues of cohort 1 was associated with shorter FFR (p = 0.02). In cohort 2, this was associated with both FFR and OS (p = 0.046 and p = 0.002, respectively). In multivariate analysis, low expression of cytoplasmic Merlin remained an

  10. Poor-prognosis disclosure preference in cancer patient-caregiver dyads and its association with their quality of life and perceived stress: a cross-sectional survey in mainland China.

    Science.gov (United States)

    Nie, Xin; Ye, Dawei; Wang, Qiming; Manyande, Anne; Yang, Lin; Qiu, Hong; Chao, Tengfei; Zhang, Peng; Gong, Chen; Zhuang, Liang; Yu, Shiying; Xiong, Huihua

    2016-09-01

    This study attempted to examine the discordance between family caregivers and cancer patients in their poor-prognosis disclosure preferences in mainland China and then ascertained the associations between quality of life (QoL), perceived stress, and poor-prognosis disclosure preferences. Six hundred fifty-one pairs of inpatients and their matched caregivers (participation rate = 92.2%) were recruited in this cross-sectional survey. A set of paired self-administered questionnaires were completed independently by patient-caregiver dyads. Fewer family caregivers than cancer patients felt that poor prognosis should be disclosed to patients (61.2% vs. 90.0%, p perceived stress levels (p = 0.013). However, caregivers' poor-prognosis disclosure preference correlated only with their own physical state (p = 0.028). Moreover, the caregivers who concurred with patients in positive poor-prognosis disclosure preference were more likely to experience a better QoL (p perceived stress levels (p = 0.048) in the III-IV stage subgroup. There was a significant discrepancy in poor-prognosis disclosure preference between cancer patients and caregivers in China. The caregivers' preference of concealing poor prognosis from patients was not related to cancer patients' QoL or perceived stress. In addition, caregivers had better QoL and lower stress levels when they held the same positive poor-prognosis disclosure preference as the patients. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Increased circulating CD14(+)HLA-DR-/low myeloid-derived suppressor cells are associated with poor prognosis in patients with small-cell lung cancer.

    Science.gov (United States)

    Tian, Tian; Gu, Xiaobin; Zhang, Bo; Liu, Yang; Yuan, Chao; Shao, Lijuan; Guo, Yajun; Fan, Kexing

    2015-01-01

    High expression of CD14(+)HLA-DR-/low myeloid-derived suppressor cells (MDSCs) is correlated with immunosuppressive activity in various cancers, however, no studies have shown a correlation of these immunosuppressive cells with clinical outcomes in small-cell lung cancer (SCLC) patients. The purpose of the study was to investigate the number, frequency and clinical significance of CD14(+)HLA-DR-/low MDSCs in SCLC patients. The peripheral blood of 42 patients with SCLC and 37 healthy controls was analyzed by using flow cytometry. The relationships between the number and frequency of MDSCs, clinicopathological features and overall survival(OS) were analyzed. The prognostic value of MDSCs was tested by using univariate and multivariate analysis. Our results demonstrated that number and frequency of peripheral CD14(+)HLA-DR-/low MDSCs were significantly increased in SCLC patients than in controls (pDR-/low MDSCs as an independent biomarker for poor prognosis in SCLC patients during follow-up. Our study provides the first evidence that the frequency of CD14(+)HLA-DR-/low MDSCs negatively correlates with clinical outcomes in SCLC patients. The frequency of CD14(+)HLA-DR-/low MDSCs could be considered as a poor prognostic predictor in SCLC and the elimination of MDSCs during medical interventions may improve the prognosis of SCLC patients.

  12. [Cerebral and extracerebral insufficiency in patients with poor prognosis of surgical treatment of cerebrovascular circulation disorders of hemorrhagic type].

    Science.gov (United States)

    Chepkiĭ, L P; Kamenskaia, O I; Tsimeĭko, O A; Moroz, V V

    2013-01-01

    Objective of the study was to investigate cerebral and extracerebral insufficiency in survived and died patients after surgical treatment of hemorrhagic stroke for outcome prognosis and decision making on postoperative intensive care. The study included 224 patients after transcranial surgery for hemorrhagic stroke. 119 patients survived and 105 patients died SOFA scale and SIRS criteria were used to assess severity of the patients state. Hemorrhagic stroke before the operation was accompanied with cerebral insufficiency (Glasgow Coma Scale Lungs and kidneys dysfunction (SOFA = 1-2) were common. In the early postoperative period 54% of patients had cerebral insufficiency and 36%--organ dysfunction. Acute cerebral insufficiency was closely associated with systemic inflammatory response. Severity of organs (heart, lungs, kidneys) failure and SIRS correlated with GCS score in early postoperative period. There was close correlation between MODS and SIRS scores in survived patients and there wasn't such phenomenon in died patients. This indicates leading role of CNS in homeostasis regulation. SOFA scale using for express diagnosis of perioperative complications is useful for providing adequate intensive therapy.

  13. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors.

    Directory of Open Access Journals (Sweden)

    Cristina Balbás-Martínez

    Full Text Available Urothelial bladder cancer (UBC is heterogeneous at the clinical, pathological, genetic, and epigenetic levels. Exome sequencing has identified ARID1A as a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in UBC. Here, we assess ARID1A alterations in two series of patients with UBC. In the first tumor series, we analyze exons 2-20 in 52 primary UBC and find that all mutant tumors belong to the aggressive UBC phenotype (high grade non-muscle invasive and muscle invasive tumors (P = 0.05. In a second series (n = 84, we assess ARID1A expression using immunohistochemistry, a surrogate for mutation analysis, and find that loss of expression increases with higher stage/grade, it is inversely associated with FGFR3 overexpression (P = 0.03 but it is not correlated with p53 overexpression (P = 0.30. We also analyzed the expression of cytokeratins in the same set of tumor and find, using unsupervised clustering, that tumors with ARID1A loss of expression are generally KRT5/6-low. In this patient series, loss of ARID1A expression is also associated with worse prognosis, likely reflecting the higher prevalence of losses found in tumors of higher stage and grade. The independent findings in these two sets of patients strongly support the notion that ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors.

  14. Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.

    Directory of Open Access Journals (Sweden)

    Qinchuan Liang

    Full Text Available Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3 expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM cell lines (U251 and U87, and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705 correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705 is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705 is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705could be an important biomarker for astrocytoma prognosis.

  15. Increased interleukin-35 expression in tumor-infiltrating lymphocytes correlates with poor prognosis in patients with breast cancer.

    Science.gov (United States)

    Zhao, Zhonghua; Chen, Xi; Hao, Shengnan; Jia, Rui; Wang, Nana; Chen, Shaoshui; Li, Mianli; Wang, Chuanxin; Mao, Haiting

    2017-01-01

    Interleukin-35 (IL-35) is a recently discovered inhibitory cytokine, which is firstly discovered to be produced by regulatory T cells (Tregs) and proposed as a key effector molecule of Treg function. This study aims to analyze the correlation between IL-35 expression in tumor-infiltrating lymphocytes (TILs) of breast cancer tissue and patients' clinical characteristics. Plasma IL-35 was also determined in 60 patients with breast invasive ductal carcinoma (IDC) and 30 healthy women by enzyme-linked immunosorbent assay. IL-35 expression in the tissue specimens was analyzed by immunohistochemistry. It was shown that 39.1%, 43.6% and 17.3% of the 110 patients were absent, weak, and strong IL-35 expression in the TILs, respectively. Strong IL-35 expression in TILs was significantly associated with age >50years, tumor size >2cm, TNM stage III, and negative ER (All P35 expression in TILs had significantly worse progression-free survival (PFS) and overall survival (OS) than patients with weak or no IL-35 expression (All P35 levels were significantly associated with TNM stage III and lymph node metastasis (All P35 level and IL-35 expression in the TILs of breast cancer tissues may be a valuable biomarker in the development and prognosis of IDC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors.

    Science.gov (United States)

    Balbás-Martínez, Cristina; Rodríguez-Pinilla, María; Casanova, Ariel; Domínguez, Orlando; Pisano, David G; Gómez, Gonzalo; Lloreta, Josep; Lorente, José A; Malats, Núria; Real, Francisco X

    2013-01-01

    Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological, genetic, and epigenetic levels. Exome sequencing has identified ARID1A as a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in UBC. Here, we assess ARID1A alterations in two series of patients with UBC. In the first tumor series, we analyze exons 2-20 in 52 primary UBC and find that all mutant tumors belong to the aggressive UBC phenotype (high grade non-muscle invasive and muscle invasive tumors) (P = 0.05). In a second series (n = 84), we assess ARID1A expression using immunohistochemistry, a surrogate for mutation analysis, and find that loss of expression increases with higher stage/grade, it is inversely associated with FGFR3 overexpression (P = 0.03) but it is not correlated with p53 overexpression (P = 0.30). We also analyzed the expression of cytokeratins in the same set of tumor and find, using unsupervised clustering, that tumors with ARID1A loss of expression are generally KRT5/6-low. In this patient series, loss of ARID1A expression is also associated with worse prognosis, likely reflecting the higher prevalence of losses found in tumors of higher stage and grade. The independent findings in these two sets of patients strongly support the notion that ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors.

  17. Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer

    Directory of Open Access Journals (Sweden)

    Zhaoxia Liu

    2016-01-01

    Full Text Available Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p0.05 but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p<0.05 or p<0.01. A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p<0.01, in which the clinical stage (p<0.05 and Notch3 expression (p<0.01 played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis.

  18. Association of decreased expression of the macrophage scavenger receptor MARCO with tumor progression and poor prognosis in human hepatocellular carcinoma.

    Science.gov (United States)

    Sun, Haoyu; Song, Jiaxi; Weng, Chenchun; Xu, Jing; Huang, Mei; Huang, Qiang; Sun, Rui; Xiao, Weihua; Sun, Cheng

    2017-05-01

    The macrophage receptor with collagenous structure (MARCO) belongs to the scavenger receptor family; however, few studies have assessed their potentials in modulating inflammatory signaling other than the typical function of pattern recognition and phagocytic clearance. Interestingly, RNA-Seq analyses of hepatocellular carcinoma (HCC) have identified MARCO as one of the top 30 differentially expressed genes between cancerous and adjacent noncancerous tissues. However, no research has been performed to study MARCO in liver cancer. MARCO protein expression was evaluated by immunostaining liver tissue specimens collected from 88 HCC patients, 10 liver cirrhosis patients, 6 metastatic patients, and 5 healthy controls. All sections were reviewed by blinded observers followed by the interpretation of integral optical density per area as a measure of protein intensity. We observed significantly decreased expression of MARCO in intratumoral tissues of HCC compared with expression in peritumoral tissues. The expression of MARCO declined progressively as the disease condition was aggravated, with the highest expression found in healthy controls and the lowest found in patients with HCC metastasis. Furthermore, MARCO expression decreased along with tumor progression. MARCO + cells co-localized with CD68 + cells, indicating predominant expression on macrophages. The overall survival rate was significantly increased in patients with high intratumoral MARCO expression compared with that of patients with low intratumoral MARCO expression. Our study is the first to demonstrate an association between MARCO expression and the progression and prognosis of HCC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  19. Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients.

    Science.gov (United States)

    Chen, Luguang; Ma, Chao; Bian, Yun; Shao, Chengwei; Wang, Tiegong; Li, Jing; Chong, Xiaodan; Su, Li; Lu, Jianping

    2017-12-19

    Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with normal pancreas tissues. STYK1 level was positively correlated with lymph node metastasis and clinical stage in pancreatic cancer patients. E-cadherin expression was inversely correlated with STYK1 expression in pancreatic cancer tissue samples. Patients with high STYK1 and low E-cadherin expression had the worst prognosis. In addition, STYK1 knockdown in pancreatic cancer cell lines inhibited cell proliferation, enhanced cell apoptosis, induced cell cycle arrest, and prohibited cell migration, while STYK1 over-expression showed the opposite effects. Silencing STYK1 also increased E-cadherin expression and inhibited epithelial-to-mesenchymal transition (EMT) and p-p38 expression in vitro. Over-expression had showed the opposite trends, and treatment with p38 inhibitor, SB203580, could reverse the trends. Thus, STYK1 repressed E-cadherin expression and promoted EMT, mediated by p38 MAPK signaling pathway, which was the possible mechanism for STYK1-mediated pancreatic cancer cell proliferation and migration. In summary, our results showed that STYK1 might be a prognostic marker for pancreatic cancer patients and might be a novel strategy for the treatment of pancreatic cancer.

  20. Poor long-term prognosis in mixed bipolar patients: 10-year outcomes in the Vitoria prospective naturalistic study in Spain.

    Science.gov (United States)

    González-Pinto, Ana; Barbeito, Sara; Alonso, Marta; Alberich, Susana; Haidar, Mahmoud Karim; Vieta, Eduard; Tabarés-Seisdedos, Rafael; Zorrilla, Iñaki; González-Pinto, Maria Asun; López, Purificación

    2011-05-01

    There have been few prospective long-term naturalistic studies of patients with mixed episodes of bipolar disorder. The aim of this study was to examine 10-year outcomes in patients with at least 1 mixed episode. A naturalistic sample of bipolar I disorder patients (n = 120), representative of bipolar patients treated in a catchment area of Spain, was followed prospectively for up to 10 years. Outcomes including number (primary study outcome) and severity of episodes, hospitalizations, and suicide attempts were recorded at bimonthly visits. Bivariate and logistic regression models identified factors significantly associated with mixed episodes. The study was conducted from 1994 through 2004. 37% of patients had mixed episodes. Mixed-episode patients had younger mean age at onset compared with the nonmixed group (25.3 vs 30.8 years; P = .025). After adjusting for age at onset, mixed-episode patients had an increased risk of hospitalization compared with the nonmixed group (OR = 2.86; 95% CI, 1.09-7.52; P = .033) and more episodes (OR = 1.21; 95% CI, 1.10-1.31; P < .001). Other differences between mixed and nonmixed patients, such as alcohol abuse, psychotic symptoms, and suicidality, were partially mediated by age at onset and were not significantly different after controlling for this variable. Mixed-episode patients with previous suicide attempts had a significantly shorter time to first suicide attempt during follow-up than those without history of suicide attempts (P = .014). Although some factors associated with mixed episodes are mediated by a younger age at onset, the long-term prognosis of mixed-episode patients is worse than patients with nonmixed episodes. © Copyright 2011 Physicians Postgraduate Press, Inc.

  1. Aberrant GSTP1 promoter methylation predicts poor prognosis of acute-on-chronic hepatitis B pre-liver failure.

    Science.gov (United States)

    Qiao, Chen-Yang; Li, Feng; Teng, Yue; Zhao, Jing; Hu, Na; Fan, Yu-Chen; Wang, Kai

    2017-07-04

    It has been demonstrated that glutathione-S-transferase P1 (GSTP1) could protect cells from DNA damage mediated by oxidizing agents or electrophiles in hepatic inflammatory response. Our study evaluated the methylation status and the predictive value for prognosis of GSTP1 promoter region in patients with acute-on-chronic hepatitis B pre-liver failure (pre-ACHBLF). Methylation status of GSTP1 promoter in peripheral blood mononuclear cells (PBMCs) and plasma was measured in 103 patients with pre-ACHBLF, 80 patients with chronic hepatitis B (CHB) and 30 healthy controls (HCs) by methylation-specific polymerase chain reaction. The mRNA level of GSTP1 was detected by quantitative real-time polymerase chain reaction. The methylation frequency of GSTP1 promoter region in patients with pre-ACHBLF (35/103 in PBMCs and 33/103 in plasma) was significantly higher than CHB (2/80) and HCs (0/30), respectively. The mRNA level of GSTP1 in patients with pre-ACHBLF was significantly lower than CHB and HCs. Additionally, pre-ACHBLF patients with methylated GSTP1 presented strikingly higher incidence of ACHBLF than those without. Of note, GSTP1 methylation presented distinctly better performance than model for end-stage liver disease score [area under the receiver operating characteristic curves (AUCs) 0.825 in PBMCs and 0.798 in plasma VS 0.589; AUC 0.804 in PBMCs and 0.779 in plasma VS 0.622; AUC 0.767 in PBMCs and 0.744 in plasma VS 0.602, respectively] when used to predict the 1-, 2- or 3-month incidence of ACHBLF in patients with pre-ACHBLF. Aberrant methylation of GSTP1 has potential to be a prognostic biomarker for pre-ACHBLF.

  2. Low Expression of Circulating MicroRNA-34c is Associated with Poor Prognosis in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Zeng, Zhihao; Chen, Xiaowu; Zhu, Dajian; Luo, Zhongran; Yang, Min

    2017-07-01

    The microRNA-34 (miR-34) family is important in tumor regulation. This study aimed to investigate the association of circulating miR-34 family proteins with clinicopathological features and their prognostic value in triple-negative breast cancer (TNBC) patients. In this cohort study, 173 TNBC patients admitted to First People's Hospital of Shunde from May 1, 2009 to April 30, 2013 were enrolled. Meanwhile, 75 age-matched healthy women volunteers were identified as healthy controls (HCs). We examined the expression of miR-34 family (miR-34a/b/c) proteins in plasma collected from TNBC patients before any treatment was performed and from age-matched HCs using qPCR methods. The expressions of miR-34a/34b/34c were significantly lower in TNBC patients than in HC (pp=0.027, pp=0.038), lymph node positive (p=0.027), distant metastasis (p=0.004), and surgery (p=0.023); miR-34b was correlated with lymph node positivity (p=0.027); and miR-34c was correlated with tumor grade (p=0.017) and distant metastasis (pp=0.011), as well as miR-34c low expression (p=0.002). In addition, univariate and multivariate Cox proportional hazards regression was performed, and low expression of miR-34c (p=0.011) was found to be an independent risk factor for OS, as well as tumor grade (p=0.013), lymph node positive (p=0.050), and distant metastasis (p=0.021). In conclusion, this study demonstrated reduced miR-34a/c expression is highly associated with tumor progression and indicated worse prognosis. Also, miR-34c was an independent risk factor for OS in TNBC patients.

  3. Secreted protein acidic and rich in cysteine (SPARC is associated with nasopharyngeal carcinoma metastasis and poor prognosis

    Directory of Open Access Journals (Sweden)

    Wang Hai-Yun

    2012-02-01

    Full Text Available Abstract Background The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC in nasopharyngeal carcinoma (NPC specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC Methods NPC tissue microarrays (TMAs were constructed from Sun Yat-sen University Cancer Center (SYSUCC, another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs induced by Bmi-1 (NPEC2 Bmi-1. The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Results The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001. SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium. In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001 and WHO histological classification (P = 0.023. NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P P P Conclusions SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.

  4. TP53-induced glycolysis and apoptosis regulator protects from spontaneous apoptosis and predicts poor prognosis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Hong, Ming; Xia, Yi; Zhu, Yu; Zhao, Hui-Hui; Zhu, Han; Xie, Yue; Fan, Lei; Wang, Li; Miao, Kou-Rong; Yu, Hui; Miao, Yu-Qing; Wu, Wei; Zhu, Hua-Yuan; Chen, Yao-Yu; Xu, Wei; Qian, Si-Xuan; Li, Jian-Yong

    2016-11-01

    Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis. TIGAR mRNA expression was investigated by quantitative PCR in 102 newly diagnosed CLL patients. Furthermore, the relationship between the expression of TIGAR and its clinical characteristics and prognosis were investigated. Moreover, we also investigated the correlation between TIGAR expression and apoptosis in primary CLL cells. Our data revealed that TIGAR overexpression was correlated with the protection from spontaneous apoptosis in CLL cells, and is strongly associated with advanced Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 positivity, β2-microglobulin and p53 aberrations. Higher expression of TIGAR was associated with shorter treatment-free survival (median: three months vs. 51 months, P=0.0108), worse overall survival (median: 74 months vs. not reached, P=0.0242), and the diverse responses to fludarabine-based chemotherapy. TIGAR expression in patients resistant to chemotherapy was significantly higher than in patients sensitive to chemotherapy (mean: 0.3859±0.1710 vs. 0.0974±0.0291, P=0.0290). Taken together, our findings revealed that high TIGAR expression is closely correlated with worse clinical outcome in CLL patients, and depicted how bioenergetic characteristics could be therapeutically exploited in CLL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Enhanced expression of ANO1 in head and neck squamous cell carcinoma causes cell migration and correlates with poor prognosis.

    Science.gov (United States)

    Ruiz, Christian; Martins, Joana Raquel; Rudin, Florian; Schneider, Sandra; Dietsche, Tanja; Fischer, Claude A; Tornillo, Luigi; Terracciano, Luigi M; Schreiber, Rainer; Bubendorf, Lukas; Kunzelmann, Karl

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) has the potential for early metastasis and is associated with poor survival. Ano1 (Dog1) is an established and sensitive marker for the diagnosis of gastrointestinal stromal tumors (GIST) and has recently been identified as a Ca(2+) activated Cl(-) channel. Although the ANO1 gene is located on the 11q13 locus, a region which is known to be amplified in different types of human carcinomas, a detailed analysis of Ano1 amplification and expression in HNSCC has not been performed. It is thus still unclear how Ano1 contributes to malignancy in HNSCC. We analyzed genomic amplification of the 11q13 locus and Ano1 together with Ano1-protein expression in a large collection of HNSCC samples. We detected a highly significant correlation between amplification and expression of Ano1 and showed that HNSCC patients with Ano1 protein expression have a poor overall survival. We further analyzed the expression of the Ano1 protein in more than 4'000 human samples from 80 different tumor types and 76 normal tissue types and detected that besides HNSCC and GISTs, Ano1 was rarely expressed in other tumor samples or healthy human tissues. In HNSCC cell lines, expression of Ano1 caused Ca(2+) activated Cl(-) currents, which induced cell motility and cell migration in wound healing and in real time migration assays, respectively. In contrast, knockdown of Ano1 did not affect intracellular Ca(2+) signaling and surprisingly did not reduce cell proliferation in BHY cells. Further, expression and activity of Ano1 strongly correlated with the ability of HNSCC cells to regulate their volume. Thus, poor survival in HNSCC patients is correlated with the presence of Ano1. Our results further suggest that Ano1 facilitates regulation of the cell volume and causes cell migration, which both can contribute to metastatic progression in HNSCC.

  6. Nuclear localization of the CK2α-subunit correlates with poor prognosis in Clear Cell Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Rabjerg, Maj; Guerra, Barbara; Oliván-Viguera, Aida

    2017-01-01

    Protein kinase CK2a, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell...... renal cortex. Nuclear protein expression of CK2a correlated in univariate analysis with poor Progression Free Survival (HR = 8.11, p = 0.016). Functional analyses (cell proliferation assay) revealed an inhibitory effect of Caki-2 cell growth following CK2 inhibition with CX-4945. Our results suggest...

  7. Decreased ex vivo production of interferon-gamma is associated with severity and poor prognosis in patients with lupus.

    Science.gov (United States)

    Ahn, Sung Soo; Park, Eun Seong; Shim, Joo Sung; Ha, Sang-Jun; Kim, Beom Seok; Jung, Seung Min; Lee, Sang-Won; Park, Yong-Beom; Song, Jason Jungsik

    2017-08-25

    Lupus pathogenesis is closely associated with interferon gamma (IFN-γ), which plays a central role in innate and adaptive immunity. The aim of this study was to evaluate the ex vivo production of IFN-γ after stimulation of peripheral blood mononuclear cells with phytohemagglutinin (PHA) in patients with lupus, according to disease activity. This study included 118 patients with lupus who had undergone IFN-γ-releasing assays (IGRAs) to screen for tuberculosis. Data on IFN-γ production in negative (nil) and positive (mitogen with PHA) controls were collected and analysed. The difference (mitogen minus nil) was used to calculate ex vivo IFN-γ production. Disease activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K). Poor hospitalisation outcome was defined as in-hospital mortality or intensive care unit admission. Associations among disease activity, poor hospitalisation outcome, and ex vivo IFN-γ production were assessed. The level of ex vivo IFN-γ production was significantly lower in patients with active systemic lupus erythematosus (SLE) (n = 64) than in those with inactive SLE (n = 54) (median 0.92 vs. 11.06 IU/mL, p vivo IFN-γ production was correlated with the SLEDAI-2 K (r = - 0.587, p vivo IFN-γ production ≤ 7.19 IU/mL was an independent predictor for discriminating active and inactive lupus. In addition, patients with ex vivo IFN-γ production ≤ 0.40 IU/mL had more frequent poor hospitalisation outcomes than those with ex vivo IFN-γ production > 0.40 (40.0% vs. 9.3%, p = 0.001). The proportion of indeterminate IGRA results was higher in patients with active lupus than in those with inactive lupus (45.3% vs. 0.0%, p vivo IFN-γ production. Ex vivo IFN-γ production is a useful biomarker for assessing disease activity and predicting poor clinical outcomes of SLE.

  8. Reduced expression of EphA5 is associated with lymph node metastasis, advanced TNM stage, and poor prognosis in colorectal carcinoma.

    Science.gov (United States)

    Gu, Shudong; Feng, Jia; Jin, Qin; Wang, Wei; Zhang, Shu

    2017-05-01

    Colorectal carcinoma (CRC) is the third most common cancer and a major cause of morbidity and mortality throughout the world. The prognosis of patients has improved markedly over the last 15 years because of the introduction of new therapy including molecular target drugs. To comprehensively understand the molecular process of carcinogenesis of colorectal carcinoma is essential for the diagnosis, prognosis and treatment. EphA5 is a member of the Eph family and plays a critical role in carcinogenesis of lung cancer, prostate cancer, and breast cancer. The expression profile and the role of EphA5 in colorectal carcinoma have not been well investigated till now. In this study, a set of colorectal carcinoma specimens was subjected to immunohistochemical assay using an EphA5 specific antibody. The relationship between the expression of EphA5 and clinicopathological parameters was statistically analyzed. EphA5 was positively expressed in all tested normal mucosa specimens (120/120, 100%) and partly in colorectal carcinoma specimens (70/120, 58.3%). The loss of EphA5 protein was associated with depth of wall invasion (P=0.002), poor tumor differentiation (Pcarcinoma and it may be a new therapeutic target for colorectal carcinoma.

  9. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.

    Science.gov (United States)

    Qin, Fengxia; Zhang, Huikun; Ma, Li; Liu, Xiaoli; Dai, Kun; Li, Wenliang; Gu, Feng; Fu, Li; Ma, Yongjie

    2015-09-24

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.

  10. Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients

    Science.gov (United States)

    Luo, Minna; Zhang, Xin; Wei, Xiaofei; Gao, Jiyue; Zhao, Zuowei; Liu, Caigang

    2014-01-01

    Oct-4 and Nanog in regulating the epithelial-mesenchymal transition (EMT) and metastasis of breast cancer has not been clarified. We found that both Oct-4 and Nanog expression were significantly associated with tumor pathology and poor prognosis in 126 breast cancer patients. Characterization of CD44+CD24-Cancer stem cell(CSC) derived from breast cancer cells indicated that CSC rapidly formed mammospheres and had potent tumorigenicity in vivo. Furthermore, TGF-β up-regulated the expression of Oct-4, Nanog, N-cadherin, vimentin, Slug, and Snail, but down-regulated E-cadherin and cytokeratin 18 expression, demonstrating that CSC underwent EMT. Knockdown of both Oct-4 and Nanog expression inhibited spontaneous changes in the expression of EMT-related genes, while induction of both Oct-4 and Nanog over-expression enhanced spontaneous changes in the expression of EMT-related genes in CSC. However, perturbing alternation of Oct-4 and Nanog expression also modulated TGF-β-induced EMT-related gene expression in CSC. Induction of Oct-4 and Nanog over-expression enhanced the invasiveness of CSC, but knockdown of both Oct-4 and Nanog inhibited the migration of CSC in vitro. Our data suggest that both Oct-4 and Nanog may serve as biomarkers for evaluating breast cancer prognosis. Our findings indicate that Oct-4 and Nanog positively regulate the EMT process, contributing to breast cancer metastasis. PMID:25301732

  11. Myelodysplastic Syndrome, Unclassifiable (MDS-U) With 1% Blasts Is a Distinct Subgroup of MDS-U With a Poor Prognosis.

    Science.gov (United States)

    Margolskee, Elizabeth; Hasserjian, Robert P; Hassane, Duane; Tam, Wayne; Mathew, Susan; Ok, Chi Young; Wang, Sa A; Oak, Jean; Arber, Daniel A; Orazi, Attilio

    2017-07-01

    Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. MDS-U cases were reviewed at four major academic institutions. Targeted next-generation sequencing for genes implicated in myeloid neoplasms was performed in a subset of cases. Twenty-seven patients were identified (six MDS-U BL, 13 MDS-U Pan, and eight MDS-U CG). Clonal cytogenetic abnormalities were found in six of six, seven of 13, and eight of eight cases in MDS-U BL, Pan, and CG, respectively (P > .05). Overall, four of six patients with MDS-U BL progressed to acute myeloid leukemia; no MDS-U Pan or CG patients did. The rates of progression-free survival and mortality (overall survival) were significantly higher in MDS-U BL compared with Pan and CG (P MDS-U BL is a distinct subset of MDS-U with a poor prognosis, while MDS-U Pan and CG are relatively indolent. Evaluation of peripheral blood smears in patients with MDS is essential for accurate classification and prognosis.

  12. Overexpression of cannabinoid receptor 1 in esophageal squamous cell carcinoma is correlated with metastasis to lymph nodes and distant organs, and poor prognosis.

    Science.gov (United States)

    Hijiya, Naoki; Shibata, Tomotaka; Daa, Tsutomu; Hamanaka, Ryoji; Uchida, Tomohisa; Matsuura, Keiko; Tsukamoto, Yoshiyuki; Nakada, Chisato; Iha, Hidekatsu; Inomata, Masafumi; Moriyama, Masatsugu

    2017-02-01

    In patients with esophageal squamous cell carcinoma (ESCC), the status of metastasis to lymph nodes is strongly associated with prognosis. Consequently, development of a biomarker to detect the presence of metastasis would be clinically valuable. In this study, we found that overexpression of cannabinoid receptor 1 (CB1R) was applicable as a marker for prediction of metastasis in ESCC. CB1R overexpression was detected immunohistochemically in 54 of 88 cases (61.4%). The intensity of CB1R expression was uniform in both intraepithelial and invasive regions in each case, and was significantly correlated with the status of metastasis to lymph nodes (P = 0.046) and distant organs (P = 0.047). Furthermore, multivariate analysis revealed that CB1R overexpression was independently associated with poor prognosis (P = 0.019). Biological analysis of CB1R overexpression using ESCC cell lines revealed that CB1R activation appeared to promote cell proliferation and invasion. On the basis of these findings, we propose that evaluation of CB1R expression status in biopsy specimens of ESCC using immunohistochemistry might be clinically useful for prediction of metastasis to lymph nodes and distant organs. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  13. Hypermethylation of secreted frizzled-related proteins predicts poor prognosis in non-M3 acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Guo H

    2017-07-01

    .023 patients. In leukemic cell line HL60 treated with 5-aza-2'-deoxycytidine, the alteration of SFRP1/2 expression inversely correlated with change in SFRP1/2 methylation (r=-0.975, P=0.005 and r=-0.975, P=0.005, respectively. A tendency of negative correlation was observed between SFRP1 expression and its promoter methylation in AML patients (r=-0.334, P=0.038.Conclusion: These findings suggested that hypermethylation of SFRP1/2 was a frequent event and silenced SFRP1/2 expression in AML. Moreover, hypermethylation of SFRPs promoter was an adverse risk factor for OS in Chinese non-M3 AML patients. Keywords: SFRPs, methylation, RQ-MSP, non-M3 AML, prognosis 

  14. A poor long-term neurological prognosis is associated with abnormal cord insertion in severe growth-restricted fetuses.

    Science.gov (United States)

    Nakamura, Masamitsu; Umehara, Nagayoshi; Ishii, Keisuke; Sasahara, Jun; Kiyoshi, Kenji; Ozawa, Katsusuke; Tanaka, Kei; Tanemoto, Tomohiro; Ichizuka, Kiyotake; Hasegawa, Junichi; Ishikawa, Hiroshi; Murakoshi, Takeshi; Sago, Haruhiko

    2017-12-21

    To clarify and compare if the neurological outcomes of fetal growth restriction (FGR) cases with abnormal cord insertion (CI) are associated with a higher risk of a poor neurological outcome in subjects aged 3 years or less versus those with normal CI. A multicenter retrospective cohort study was conducted among patients with a birth weight lower than the 3rd percentile, based on the standard reference values for Japanese subjects after 22 weeks' gestation, who were treated at a consortium of nine perinatal centers in Japan between June 2005 and March 2011. Patients whose birth weights were less than the 3rd percentile and whose neurological outcomes from birth to 3 years of age could be checked from their medical records were analyzed. The relationship between abnormal CI and neurological outcomes was analyzed. Univariate and multivariate models of multivariate logistic regression were employed to estimate the raw and odds ratio (OR) with 95% confidence intervals comparing marginal (MCI) and velamentous cord insertion (VCI) to normal CI. Among 365 neonates, 63 cases of MCI and 14 cases of VCI were observed. After excluding 24 cases with neonatal or infant death from the total FGR population, the assessment of the outcomes of the infants aged 3 years or younger showed the following rates of neurological complications: 7.3% (n=25) for cerebral palsy, 8.8% (n=30) for developmental disorders, 16.7% (n=57) for small-for-gestational-age short stature (SGA), 0.6% (n=2) for impaired hearing, 0.9% (n=3) for epilepsy, 1.2% (n=4). The ORs (95% confidence intervals) based on multivariate analysis were as follows: cerebral palsy=10.1 (2.4-41.5) in the VCI group and 4.3 (1.6-11.9) in the MCI group, developmental disorders=6.7 (1.7-26) in the VCI group and 3.9 (1.1-14.2) in the single umbilical artery (SUA) group, 5.1 (1.4-18.7) for birth weight <1000 g and 2.8 (1.2-6.7) for placental weight <200 g. The present results indicate that growth-restricted fetuses diagnosed with a

  15. Aberrant expression of PHLPP1 and PHLPP2 correlates with poor prognosis in patients with hypopharyngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Jieyu Zhou

    Full Text Available The PHLPP (pleckstrin homology [PH] domain leucine rich repeat protein phosphatase family, which represents a family of novel Ser/Thr protein phosphatases, is composed of 2 members: PHLPP1 and PHLPP2. PHLPPs partake in diverse cellular activities to exhibit their antitumor and metastasis suppressor functions. It is necessary to investigate the expression patterns of PHLPP1 and PHLPP2 in hypopharyngeal squamous cell carcinomas (HSCCs and clarify their clinical significance. A total of 138 patients with primary HSCC who underwent curative surgical treatment as an initial treatment were enrolled in this study. A total of 138 HSCC specimens and 64 adjacent noncancerous mucosal epithelial tissues were collected. The expression levels of PHLPP1 and PHLPP2 were examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry assays. Correlations between clinicopathological parameters of the patients were further evaluated. PHLPP1 and PHLPP2 mRNA transcript levels were significantly lower in tumor samples than in paired adjacent nontumor mucosae (P<0.0001, both. Positive correlations were observed between the mRNA levels of PHLPP1 and PHLPP2 in HSCC tissues (correlation coefficient r = 0.678, P<0.001 and in adjacent nontumor mucosae (r = 0.460, P<0.001. The majority of the noncancerous tissues showed high expression levels of PHLPP1 (87.5%, 56/64 and PHLPP2 (85.9%, 55/64. However, the expressions of PHLPP1 and PHLPP2 were significantly decreased in 83.3% (115/138 and 82.6% (114/138 of tumor tissues, respectively (P<0.0001, both. The expressions of both PHLPP isoforms were significantly related to the tumor clinical stage, differentiation, and cervical lymph node metastasis (P<0.05, all. It was PHLPP1 but not PHLPP2 that was significantly related to the tumor T stage. Low PHLPP1 and PHLPP2 expressions were associated with poor overall survival (OS in HSCC patients (P = 0.004, P = 0.008, respectively. Multivariate analysis

  16. Failure of CRP decline within three days of hospitalization is associated with poor prognosis of Community-acquired Pneumonia

    DEFF Research Database (Denmark)

    Andersen, Stine Bang; Baunbæk Egelund, Gertrud Louise; Jensen, Andreas Vestergaard

    2017-01-01

    BACKGROUND: C-reactive protein (CRP) is a well-known acute phase protein used to monitor the patient's response during treatment in infectious diseases. Mortality from Community-acquired Pneumonia (CAP) remains high, particularly in hospitalized patients. Better risk prediction during hospitaliza......BACKGROUND: C-reactive protein (CRP) is a well-known acute phase protein used to monitor the patient's response during treatment in infectious diseases. Mortality from Community-acquired Pneumonia (CAP) remains high, particularly in hospitalized patients. Better risk prediction during....... Predictive associations of CRP3 (absolute levels and relative decline) and 30 days mortality were analysed using receiver operating characteristics and logistic regression. RESULTS: Eight hundred and fourteen patients were included and 90 (11%) died within 30 days. The area under the curve for CRP3 level...... and decline for predicting 30 days mortality were 0.64 (0.57-0.70) and 0.71 (0.65-0.76). Risk of death was increased in patients with CRP3 level >75 mg/l (OR 2.44; 95%CI 1.36-4.37) and in patients with a CRP3 decline

  17. Mutations of codon 918 in the RET proto-oncogene correlate to poor prognosis in sporadic medullary thyroid carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Zedenius, J.; Svensson, A.; Baeckdahl, M.; Wallin, G. [Karolinska Hospital, Stockholm (Sweden)] [and others

    1995-10-01

    The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and has in a previous study been correlated with a less favorable clinical outcome. In the present study, 46 MTCs were selected for investigation of the codon 918 mutation. The mutation was found in 29 tumors (63%), and was significantly correlated with a poor outcome, with regard to distant metastasis or tumor recurrence (p<10{sup 4}). Two tumors showed multifocal growth and C-cell hyperplasia, and these patients were therefore also investigated for germline mutations in exons 10, 11 and 16. The codon 918 mutation was found only in the tumors, thus of somatic origin. The RET codon 918 mutation may have prognostic impact, and therefore preoperative assessment may influence decision-making in the treatment of patients suffering from MTC. 13 refs., 1 fig., 1 tab.

  18. Downregulated ECRG4 is associated with poor prognosis in renal cell cancer and is regulated by promoter DNA methylation.

    Science.gov (United States)

    Luo, Liya; Wu, Jianting; Xie, Jun; Xia, Lingling; Qian, Xuemin; Cai, Zhiming; Li, Zesong

    2016-01-01

    Esophageal cancer-related gene 4 (ECRG4) has been proposed as a putative tumor suppressor gene in several tumors. However, the role and regulation of ECRG4 in the pathogenesis of human renal cancer remain largely unknown. Our current study revealed that expression of ECRG4 is downregulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of tumors (p renal cancer patients. Silencing of ECRG4 expression in renal cell lines was associated with its promoter methylation. Moreover, ectopic expression of ECRG4 markedly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicated that ECRG4 is frequently silenced by the methylation of promoter in renal cell cancers. ECRG4 may be a tumor suppressor in renal cancer and serve as a prognostic marker.

  19. High expression of CIP2A protein is associated with tumor aggressiveness in stage I–III NSCLC and correlates with poor prognosis

    Directory of Open Access Journals (Sweden)

    Cha GQ

    2017-12-01

    Full Text Available Geqi Cha,1 Jianyu Xu,1 Xiangying Xu,1 Bin Li,2 Shan Lu,1 Abiyasi Nanding,3 Songliu Hu,1 Shilong Liu1 1Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 2Department of Plastic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, 3Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China Abstract: The aim of this work was to examine the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A in non-small cell lung cancer (NSCLC and analyze its correlation with clinical outcomes. CIP2A protein levels were detected by immunohistochemistry (IHC. One hundred and eighty-four of 209 (88.3% primary stage I–III NSCLC specimens and 4 of 38 (10.5% adjacent normal lung tissue specimens expressed CIP2A protein. High expression of CIP2A was detected in 38.8% (81/209 of the NSCLC specimens. Patients diagnosed histologically with late-stage NSCLC (p<0.001 and malignant nodes (p=0.001 exhibited high CIP2A expression. Univariate analysis using the log-rank test identified CIP2A expression as a prognostic predictor for overall survival (p=0.005. In multivariate analyses using the Cox regression test, CIP2A expression, T stage, N stage, histological type, and chemotherapy were identified as independent prognostic factors (p=0.007, 0.001, 0.003, <0.001, and <0.001, respectively. Furthermore, Kaplan–Meier survival curves demonstrated that high CIP2A expression indicated poor prognosis in the subgroup of patients with squamous cell carcinoma (p=0.008. Similar results were noted in the subgroup of patients with adenocarcinoma, but the results did not reach statistical significance (p=0.084. We also used univariate analysis and multivariate analysis to assess the prognostic factors for overall survival in the subgroup of patients who received postoperative chemotherapy. CIP2A expression was also an independent prognostic factor in NSCLC

  20. Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Qingguo Li

    2017-05-01

    Full Text Available Background: Glycolysis is considered to be the root of cancer development and progression, which involved a multi-step enzymatic reaction. Our study aimed at figuring out which glycolysis enzyme participates in the development of colorectal cancer and its possible mechanisms. Methods: We firstly screened out Aldolase B (ALDOB by performing qRT-PCR arrays of glycolysis-related genes in five paired liver metastasis and primary colorectal tissues, and further detected ALDOB protein with immunohistochemistry in tissue microarray (TMA consisting of 229 samples from stage I-III colorectal cancer patients. CRISPR-Cas9 method was adopted to create knock out colon cancer cell lines (LoVo and SW480 of ALDOB. The effect of ALDOB on cell proliferation and metastasis was examined in vitro using colony formation assay as well as transwell migration and invasion assay, respectively. Results: In TMA, there was 64.6% of samples demonstrated strong intensity of ALDOB. High ALDOB expression were associated with poor overall survival and disease-free survival in both univariate and multivariate regression analyses (P<0.05. In vitro functional studies of CCK-8 demonstrated that silencing ALDOB expression significantly (P<0.05 inhibited proliferation, migration and invasion of colon cancer cells. Mechanically, silencing ALDOB activated epithelial markers and repressed mesenchymal markers, indicating inactivation of ALDOB may lead to inhibition of epithelial-mesenchymal transition (EMT. Conclusion: Upregulation of ALDOB promotes colorectal cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colorectal cancer.

  1. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

    Science.gov (United States)

    Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

    2014-01-01

    The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

  2. High Immunoreactivity of DUOX2 Is Associated With Poor Response to Preoperative Chemoradiation Therapy and Worse Prognosis in Rectal Cancers.

    Science.gov (United States)

    Lin, Shih-Chun; Chang, I-Wei; Hsieh, Pei-Ling; Lin, Ching-Yih; Sun, Ding-Ping; Sheu, Ming-Jen; Yang, Ching-Chieh; Lin, Li-Ching; He, Hong-Lin; Tian, Yu-Feng

    2017-01-01

    Purpose: Colorectal cancer is the third most common cancer and also the fourth most common cause of cancer mortality worldwide. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that DUOX2 was the most significantly up-regulated transcript among those related to cytokine and chemokine mediated signaling pathway (GO:0019221). Hence, the aim of this study was to assess the DUOX2 expression level and its clinicopathological correlation and prognostic significance in patients of rectal cancer. Materials and Methods: DUOX2 immunostain was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by radical proctectomy, which were divided into high- and low-expression subgroups. Furthermore, statistical analyses were examined to correlate the relationship between DUOX2 immunoreactivity and important clinical and pathological characteristics, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: DUOX2 overexpression was linked to post-CCRT tumor advancement, pre- and post-CCRT nodal metastasis and poor response to CCRT (all P ≤ 0.021). Furthermore, DUOX2 high expression was significantly associated with inferior DSS, LRFS and MeFS in univariate analysis ( P ≤ 0.0097) and also served as an independent prognosticator indicating shorter DSS and LRFS interval in multivariate analysis (hazard ratio (HR) = 3.413, 95% confidence interval (CI): 1.349-8.633; HR = 4.533, 95% CI: 1.499-13.708, respectively). Conclusion: DUOX2 may play a pivotal role in carcinogenesis, tumor progression and response to neoadjuvant CCRT in rectal cancers, and serve as a novel prognostic

  3. High ΔNp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia.

    Science.gov (United States)

    Lucena-Araujo, Antonio R; Kim, Haesook T; Thomé, Carolina; Jacomo, Rafael H; Melo, Raul A; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Glória, Ana Beatriz F; Chauffaille, Maria de Lourdes; Athayde, Melina; Chiattone, Carlos S; Mito, Ingrid; Bendlin, Rodrigo; Souza, Carmino; Bortolheiro, Cristina; Coelho-Silva, Juan L; Schrier, Stanley L; Tallman, Martin S; Grimwade, David; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C; Lo-Coco, Francesco; Löwenberg, Bob; Sanz, Miguel A; Rego, Eduardo M

    2015-11-12

    The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (ΔNp73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between ΔNp73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher ΔNp73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high ΔNp73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data support the hypothesis that the ΔNp73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells. © 2015 by The American Society of Hematology.

  4. The tenacity and tenuousness of hope: parental experiences of hope when their child has a poor cancer prognosis.

    Science.gov (United States)

    Barrera, Maru; Granek, Leeat; Shaheed, Jenny; Nicholas, David; Beaune, Laura; D'Agostino, Norma M; Bouffet, Eric; Antle, Beverly

    2013-01-01

    The meaning and role of hope in parents of children with life-threatening illnesses remain relatively unstudied. The objectives of this study were to explore parental hope when a child is being treated for a malignancy resistant to treatment and to identify facilitators and barriers to maintaining hope in this context. Thirty-five parents of children with difficult-to-treat cancer were interviewed 3 months after diagnosis. Line-by-line coding of transcripts was used to establish categories and themes. Constant comparison was used to examine relationships within and across codes and categories. Parental hope was related to the child's cure and future. The concept, however, oscillated between being tenacious and robust, and tenuous and elusive, depending on how the child was responding to treatment and the psychosocial context. Focusing on positive outcomes and experiences, spirituality, and social support facilitated being hopeful. Awareness of negative outcomes, information overload, physical and emotional depletion, and fear and uncertainty challenged parental hope. Developing a model that identifies the nature of parental hope as well as barriers and facilitators to maintaining hope shortly after childhood cancer diagnosis may assist healthcare professionals in supporting parents. Understanding parental hope may assist healthcare professionals to avoid overloading parents with too much information at once. Healthcare professionals can also ensure that social support from family, community, and the medical center is available for parents and that their physical and emotional needs are being met to ensure that they maintain hope to best care for their child with cancer.

  5. Comparison of The Effectiveness of Clomiphene Citrate versus Letrozole in Mild IVF in Poor Prognosis Subfertile Women with Failed IVF Cycles

    Directory of Open Access Journals (Sweden)

    Mesut Oktem

    2015-10-01

    Full Text Available Background: Our objective was to evaluate the effectiveness of clomiphene citrate (CC vs. letrozole (L plus human menopausal gonadotropin (hMG in gonadotropin releasing hormone (GnRH antagonist protocol in poor prognosis women with previous failed ovarian stimulation undergoing intracytoplasmic sperm injection (ICSI. Materials and Methods: This retrospective cohort study included cycles with CC and L plus hMG/GnRH antagonist protocols of 32 poor responders who had failed to have ideal follicles to be retrieved during oocyte pick-up (OPU or embryo transfer (ET at least for 2 previous in vitro fertilization (IVF cycles with microdose flare protocol or GnRH antagonist protocol from January 2006 to December 2009. Main outcome measures were implantation, clinical pregnancy and live birth rates per cycle. Duration of stimulation, mean gonadotropin dose used, endometrial thickness, number of mature follicles, serum estradiol (E2 and progesterone (P levels on the day of human chorionic gonadotropin (hCG administration, number of retrieved oocytes and fertilization rates were also evaluated. Results: A total number of 42 cycles of 32 severe poor responders were evaluated. Total gonadotropin consumption was significantly lower (1491 ± 873 vs. 2808 ± 1581 IU, P=0.005 and mean E2 level on the day of hCG injection were significantly higher in CC group than L group (443.3 ± 255.2 vs. 255.4 ± 285.2 pg/mL, P=0.03. ET, overall pregnancy and live birth rates per cycle were significantly higher in CC than L protocol (27.2 vs. 15%, 13.6 vs. 0% and 4.5 vs. 0%, respectively, P<0.05. Conclusion: Severe poor responders who had previously failed to respond to microdose or GnRH antagonist protocols may benefit from CC plus hMG/GnRH antagonist protocol despite high cancellation rate.

  6. Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma.

    Science.gov (United States)

    Xia, Y; Xu-Monette, Z Y; Tzankov, A; Li, X; Manyam, G C; Murty, V; Bhagat, G; Zhang, S; Pasqualucci, L; Visco, C; Dybkaer, K; Chiu, A; Orazi, A; Zu, Y; Richards, K L; Hsi, E D; Choi, W W L; van Krieken, J H; Huh, J; Ponzoni, M; Ferreri, A J M; Møller, M B; Parsons, B M; Winter, J N; Piris, M A; Westin, J; Fowler, N; Miranda, R N; Ok, C Y; Li, Y; Li, J; Medeiros, L J; Young, K H

    2017-03-01

    PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBCL was effectively evaluated for PRDM1/BLIMP-1 deletion, mutation, and protein expression. BLIMP-1 expression was frequently associated with the ABC phenotype and plasmablastic morphologic subtype of DLBCL, yet 63% of the ABC-DLBCL patients were negative for BLIMP-1 protein expression. In these patients, loss of BLIMP-1 was associated with Myc overexpression and decreased expression of p53 pathway molecules. In addition, homozygous PRDM1 deletions and PRDM1 mutations within exons 1 and 2, which encode for domains crucial for transcriptional repression, were found to show a poor prognostic impact in patients with ABC-DLBCL but not in those with germinal center B-cell-like DLBCL (GCB-DLBCL). Gene expression profiling revealed that loss of PRDM1/BLIMP-1 expression correlated with a decreased plasma-cell differentiation signature and upregulation of genes involved in B-cell receptor signaling and tumor-cell proliferation. In conclusion, these results provide novel clinical and biological insight into the tumor-suppressive role of PRDM1/BLIMP-1 in ABC-DLBCL patients and suggest that loss of PRDM1/BLIMP-1 function contributes to the overall poor prognosis of ABC-DLBCL patients.

  7. Illness Progression as a Function of Independent and Accumulating Poor Prognosis Factors in Outpatients With Bipolar Disorder in the United States

    Science.gov (United States)

    Altshuler, Lori L.; Leverich, Gabriele S.; Nolen, Willem A.; Kupka, Ralph; Grunze, Heinz; Frye, Mark A.; Suppes, Trisha; McElroy, Susan L.; Keck, Paul E.; Rowe, Mike

    2014-01-01

    Objective: Many patients with bipolar disorder in the United States experience a deteriorating course of illness despite naturalistic treatment in the community. We examined a variety of factors associated with this pattern of illness progression. Method: From 1995 to 2002, we studied 634 adult outpatients with bipolar disorder (mean age of 40 years) emanating from 4 sites in the United States. Patients gave informed consent and completed a detailed questionnaire about demographic, vulnerability, and course-of-illness factors and indicated whether their illness had shown a pattern of increasing frequency or severity of manic or depressive episodes. Fifteen factors previously linked in the literature to a poor outcome were examined for their relationship to illness progression using Kruskal-Wallis test, followed by a 2-sample Wilcoxon rank sum (Mann-Whitney) test, χ2, and logistical regression. Results: All of the putative poor prognosis factors occurred with a high incidence, and, with the exception of obesity, were significantly (P bipolar disorder from onset to study entry in adulthood. The identification of these factors provides important targets for earlier and more effective therapeutic intervention in the hope of achieving a more benign course of bipolar disorder. PMID:25834764

  8. The elevated preoperative fasting blood glucose predicts a poor prognosis in patients with esophageal squamous cell carcinoma: The Fujian prospective investigation of cancer (FIESTA) study.

    Science.gov (United States)

    Hu, Dan; Peng, Feng; Lin, Xiandong; Chen, Gang; Liang, Binying; Li, Chao; Zhang, Hejun; Liao, Xuehong; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

    2016-10-04

    Diabetes as a latent risk factor for cancer has been extensively investigated, while its postoperative prognosis for esophageal cancer is rarely reported. We therefore sought to assess whether the elevated fasting blood glucose before surgery was associated with poor survival in esophageal cancer patients by eliciting a subset of data from the ongoing Fujian prospective investigation of cancer (FIESTA) study. Over 15-year follow-up, 2535 patients receiving three-field lymphadenectomy were assessable. Only patients with esophageal squamous cell carcinoma (ESCC) (n=2396) were analyzed due to the lower prevalence of the other histological types. In ESCC patients, the follow-up duration ranged from 0.5 to 180 months (median 38.2 months). The median survival time (MST) was remarkably shorter in males than in females (80.7 vs. 180+ months, Log-rank test: Pfasting blood glucose was 1.11 (95% confidence interval or CI: 1.09-1.14, Pfasting blood glucose for the survival of ESCC patients. Taken together, our findings convincingly demonstrated that the elevated preoperative fasting blood glucose can predict poor survival of ESCC patients, especially in males.

  9. Circulating CD14(+)HLA-DR(-/low) myeloid-derived suppressor cell is an indicator of poor prognosis in patients with ESCC.

    Science.gov (United States)

    Huang, Haitao; Zhang, Guangbo; Li, Guangbin; Ma, Haitao; Zhang, Xueguang

    2015-09-01

    Accumulating evidences demonstrate that a population of suppressive cells known as myeloid-derived suppressor cells (MDSCs) is key immune modulators which suppress antitumor immunity. In this study, we found that the level of circulating CD14(+)HLA-DR(-/low) cells in patients was significantly higher than that of healthy donors and was correlated with tumor burden, lymph node metastasis, and tumor, node, and metastasis (TNM) clinical stage. More importantly, we for the first time find the level of CD14(+)HLA-DR(-/low) is a biological indicator of poor prognosis through the analysis of 3-year overall survival. Furthermore, we evidenced that the proportion of CD14(+)HLA-DR(-/low) cells in the tumor metastatic tumor-draining lymph nodes (TDLNs) was notably higher compared to tumor-free TDLNs. Additionally, CD14(+)HLA-DR(-/low) cells from esophageal squamous cell carcinoma (ESCC) patients expressed dramatically increased programmed death ligand 1 (PD-L1) comparing to that from healthy control. Subsequently, blocking PD-L1 pathway by antibody could effectively reverse the suppressive effect on autologous T cell proliferation mediated by CD14(+)HLA-DR(-/low) cells in vitro. In conclusion, our data revealed CD14(+)HLA-DR(-/low) MDSCs which increase in ESCC patients is a novel poor prognostic indicator and may exert immunosuppressive properties through PD-L1/PD-1 pathway.

  10. High-dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

    Science.gov (United States)

    Farquhar, Cindy; Marjoribanks, Jane; Lethaby, Anne; Azhar, Maimoona

    2016-05-20

    Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the woman is both donor and recipient) has been considered a promising technique because it permits use of much higher doses of chemotherapy. To compare the effectiveness and safety of high-dose chemotherapy and autograft (either autologous bone marrow or stem cell transplantation) with conventional chemotherapy for women with early poor prognosis breast cancer. We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE (1966 to October 2015), EMBASE (1980 to October 2015), the World Health Organization's International Clinical Trials Registry Search Platform, and ClinicalTrials.gov on the 21 October 2015. Randomised controlled trials (RCTs) comparing high-dose chemotherapy and autograft (bone marrow transplant or stem cell rescue) versus chemotherapy without autograft for women with early poor prognosis breast cancer. Two review authors selected RCTs, independently extracted data and assessed risks of bias. We combined data using a Mantel-Haenszel fixed-effect model to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed the quality of the evidence using GRADE methods. Outcomes were survival rates, toxicity and quality of life. We included 14 RCTs of 5600 women randomised to receive high-dose chemotherapy and autograft (bone marrow transplant or stem cell rescue) versus chemotherapy without autograft for women with early poor prognosis breast cancer. The studies were at low risk of bias in most areas.There is high-quality evidence that high-dose chemotherapy does not increase the likelihood of overall survival at any stage of follow-up (at three years: RR 1.02, 95% CI 0.95 to 1.10, 3 RCTs, 795 women, I² = 56%; at five years: RR 1.00, 95% CI 0.96 to 1.04, 9 RCTs, 3948 women, I² = 0%; at six years: RR 0.94, 95% CI 0.81 to 1.08, 1 RCT, 511 women; at

  11. PROLONG: a cluster controlled trial to examine identification of patients with COPD with poor prognosis and implementation of proactive palliative care

    Science.gov (United States)

    2014-01-01

    Background Proactive palliative care is not yet common practice for patients with COPD. Important barriers are the identification of patients with a poor prognosis and the organization of proactive palliative care dedicated to the COPD patient. Recently a set of indicators has been developed to identify those patients with COPD hospitalized for an acute exacerbation who are at risk for post-discharge mortality. Only after identification of these patients with poor prognosis a multi disciplinary approach to proactive palliative care with support of a specialized palliative care team can be initiated. Methods/Design The PROLONG study is a prospective cluster controlled trial in which 6 hospitals will participate. Three hospitals are selected for the intervention condition based on the presence of a specialized palliative care team. The study population consists of patients with COPD and their main informal caregivers. Patients will be included during hospitalization for an acute exacerbation. All patients in the study receive standard care (usual care). Besides, patients in the intervention condition who meet two or more criteria of the set of indicators for proactive palliative care will have additionally regular consultations with a specialized palliative care team. The objectives of the PROLONG study are: 1) to assess the discriminating power of the proposed set of indicators (indicator study) and 2) to assess the effects of proactive palliative care for qualifying patients with COPD on the wellbeing of these patients and their informal caregivers (intervention study). The primary outcome measure of the indicator study is time to death for any cause. The primary outcome measure of the intervention study is the change in quality of life measured by the St George Respiratory Questionnaire (SGRQ) three months after inclusion. Discussion The PROLONG study may lead to better understanding of the conditions to start and the effectiveness of proactive palliative care for

  12. PROLONG: a cluster controlled trial to examine identification of patients with COPD with poor prognosis and implementation of proactive palliative care.

    Science.gov (United States)

    Duenk, Ria G; Heijdra, Yvonne; Verhagen, Stans C; Dekhuijzen, Richard P N R; Vissers, Kris C P; Engels, Yvonne

    2014-04-02

    Proactive palliative care is not yet common practice for patients with COPD. Important barriers are the identification of patients with a poor prognosis and the organization of proactive palliative care dedicated to the COPD patient. Recently a set of indicators has been developed to identify those patients with COPD hospitalized for an acute exacerbation who are at risk for post-discharge mortality. Only after identification of these patients with poor prognosis a multi disciplinary approach to proactive palliative care with support of a specialized palliative care team can be initiated. The PROLONG study is a prospective cluster controlled trial in which 6 hospitals will participate. Three hospitals are selected for the intervention condition based on the presence of a specialized palliative care team. The study population consists of patients with COPD and their main informal caregivers. Patients will be included during hospitalization for an acute exacerbation. All patients in the study receive standard care (usual care). Besides, patients in the intervention condition who meet two or more criteria of the set of indicators for proactive palliative care will have additionally regular consultations with a specialized palliative care team. The objectives of the PROLONG study are: 1) to assess the discriminating power of the proposed set of indicators (indicator study) and 2) to assess the effects of proactive palliative care for qualifying patients with COPD on the wellbeing of these patients and their informal caregivers (intervention study). The primary outcome measure of the indicator study is time to death for any cause. The primary outcome measure of the intervention study is the change in quality of life measured by the St George Respiratory Questionnaire (SGRQ) three months after inclusion. The PROLONG study may lead to better understanding of the conditions to start and the effectiveness of proactive palliative care for patients with COPD. Innovative

  13. Ureteral Involvement Is Associated with Poor Prognosis in Upper Urinary Tract Urothelial Carcinoma Patients Treated by Nephroureterectomy: A Multicenter Database Study.

    Science.gov (United States)

    Waseda, Yuma; Saito, Kazutaka; Ishioka, Junichiro; Matsuoka, Yoh; Numao, Noboru; Fujii, Yasuhisa; Sakai, Yasuyuki; Koga, Fumitaka; Okuno, Tetsuo; Arisawa, Chizuru; Kamata, Shigeyoshi; Nagahama, Katsuji; Masuda, Hitoshi; Yonese, Junji; Kageyama, Yukio; Noro, Akira; Tsujii, Toshihiko; Morimoto, Shinji; Gotoh, Shuichi; Kihara, Kazunori

    2016-08-01

    The prognostic significance of tumor location for patients with upper urinary tract urothelial carcinoma (UUT-UC) has been disputed. Several papers have reported that ureteral cancer is associated with worse prognosis. To investigate the prognostic significance of the presence of ureteral tumors in UUT-UC patients who underwent radical nephroureterectomy (RNU). In this multicenter retrospective study, 1068 eligible patients (median follow-up: 40 mo [interquartile range: 17-77 mo]) were divided into three groups based on tumor location: renal pelvic, ureteral, and both-regional (having both renal pelvic and ureteral tumors). The ureteral and both-regional groups were subsequently integrated into the ureteral involvement group to evaluate its prognostic impact. All patients underwent RNU. The prognostic impact of tumor location on survival was analyzed. The renal pelvic, ureteral, and both-regional groups consisted of 507 (47.5%), 430 (40.3%), and 131 (12.3%) patients, respectively. The ureteral and both-regional groups had a higher rate of lymphovascular invasion and lymph node metastasis compared with the renal pelvic group. The renal pelvic and both-regional tumors presented more frequently with locally advanced stages (pT3/T4) compared with the ureteral tumors. The 5-yr cancer-specific survival (CSS) and progression-free survival (PFS) rates of patients in the ureteral (70.5% and 66.7%, respectively) and both-regional groups (64.8% and 57.8%, respectively) were significantly worse than those in the renal pelvic group (81.9% and 78.1%, respectively). In a multivariate analysis, the presence of ureteral involvement was a significant prognostic factor for CSS (hazard ratio [HR]: 1.50; p=0.006) and PFS (HR: 1.35; p=0.023). This study is inherently limited by the biases associated with its retrospective and multicenter design. The presence of ureteral involvement had a significant impact on the survival of surgically treated UUT-UC patients associated with a poor

  14. IS THERE ANY DIFFERENCE IN THE PROGNOSIS FOR PATIENTS WITH PRIMARY OSTEOSARCOMA WITH A POOR RESPONSE TO NEOADJUVANT CHEMOTHERAPY BETWEEN HUVOS GRADES I AND II?

    Science.gov (United States)

    Bispo Júnior, Rosalvo Zósimo; Camargo, Olavo Pires de

    2011-01-01

    Would there be any difference in the prognosis for patients who presented, for example, 8% or 88% tumor necrosis induced by chemotherapy, even though both individuals were considered to be poor responders? The aim of this study was to compare the prognoses for different histological grades (Huvos grade I versus grade II), consequent to chemotherapy, among patients with primary osteosarcoma that was not metastatic at diagnosis. Twenty-four patients admitted to a referral center between 2000 and 2004 were selected for the study. The accumulated chances of survival were calculated using the Kaplan-Meier technique. Huvos grades I and II for necrosis consequent to chemotherapy were evaluated as variables in order to determine their prognostic value, in relation to local recurrence-free survival, metastasis-free survival and overall survival, using the log-rank test. Comparing Huvos grades I and II, the following P values for survival were attained: local recurrence-free survival (P = 0.731), metastasis-free survival (P = 0.596) and overall survival (P = 0.669). In this series, Huvos grades I and II did not have any comparative prognostic value and had similar behavior.

  15. Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Grossi

    2015-01-01

    Full Text Available Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1, breast cancer 1 (BRCA1, ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2, subunit p53R2, thymidylate synthase (TS, and class III beta-tubulin (TUBB3. Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS. Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients.

  16. Proteinuria is a simple sign of systemic inflammation that leads to a poor prognosis in individuals affected with non-Hodgkin lymphoma.

    Science.gov (United States)

    Hara, Masaki; Ando, Minoru; Maeda, Yoshiharu; Tsuchiya, Ken; Nitta, Kosaku

    2014-07-01

    The clinical significance of proteinuria has not been fully understood among patients who are affected with non-Hodgkin lymphoma (NHL). A 1-year prospective cohort study was conducted to ascertain the association between proteinuria and mortality in 46 hospitalized NHL patients. Proteinuria was defined as persistent dipstick test >= 1+, and the urinary protein creatinine ratio (UPCR),as a quantitative index of protein excretion, was measured simultaneously. A multivariable linear regression model was constructed to determine factors associated with UPCR. Statistical associations between proteinuria and time to mortality were analyzed using the Kaplan-Meier method and multivariable proportional hazards regression analysis, adjusted for covariates including disease severity, renal function, and serum interleukin-6(IL-6) concentration. The prevalence of proteinuria was 15.2% in the NHL patients. UPCR was significantly associated with the serum IL-6 level (standardized beta = 0.360, p = 0.0440). The cumulative mortality was significantly higher in proteinuric patients than in non-proteinuric patients, with a graded relationship between the severity of UPCR and mortality. The mortality risk increased with increasing UPCR grade: the hazard ratio (95% confidence interval) was 4.90 (1.29 - 32.3) for UPCR 30 - 300 mg/gand 17.8 (2.84 - 150) for UPCR > 300 mg/g, respectively, when UPCR Proteinuria is a simple sign of coexisting systemic inflammation due to NHL and a harbinger of a poor prognosis.

  17. DHEA Supplementation Confers No Additional Benefit to that of Growth Hormone on Pregnancy and Live Birth Rates in IVF Patients Categorized as Poor Prognosis.

    Science.gov (United States)

    Keane, Kevin N; Hinchliffe, Peter M; Rowlands, Philip K; Borude, Gayatri; Srinivasan, Shanti; Dhaliwal, Satvinder S; Yovich, John L

    2018-01-01

    In vitro fertilization (IVF) patients receive various adjuvant therapies to enhance success rates, but the true benefit is actively debated. Growth hormone (GH) and dehydroepiandrosterone (DHEA) supplementation were assessed in women undergoing fresh IVF transfer cycles and categorized as poor prognosis from five criteria. Data were retrospectively analyzed from 626 women undergoing 626 IVF cycles, where they received no adjuvant, GH alone, or GH-DHEA in combination. A small group received DHEA alone. The utilization of adjuvants was decided between the attending clinician and the patient depending on various factors including cost. Despite patients being significantly older with lower ovarian reserve, live birth rates were significantly greater with GH alone (18.6%) and with GH-DHEA (13.0%) in comparison to those with no adjuvant ( p  birth chance. Following adjustment for patient age, antral follicle count, and quality of transferred embryo, GH alone and GH-DHEA led to a 7.1-fold and 5.6-fold increase in live birth chance, respectively ( p  births, particularly in younger women, and importantly, the positive effects of GH treatment were still observed even if DHEA was also used in combination. However, supplementation with DHEA did not indicate any potentiating benefit or modify the effects of GH treatment. Due to the retrospective design, and the risk of a selection bias, caution is advised in the interpretation of the data.

  18. Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia.

    Science.gov (United States)

    Jabbour, Elias; Takahashi, Koichi; Wang, Xuemei; Cornelison, A Megan; Abruzzo, Lynne; Kadia, Tapan; Borthakur, Gautam; Estrov, Zeev; O'Brien, Susan; Mallo, Mar; Wierda, William; Pierce, Sherry; Wei, Yue; Sole, Francisco; Chen, Rui; Kantarjian, Hagop; Garcia-Manero, Guillermo

    2013-10-01

    We hypothesized that the dynamic acquisition of cytogenetic abnormalities (ACA) during the follow up of myelodysplastic syndromes (MDS) could be associated with poor prognosis. We conducted a retrospective analysis of 365 patients with IPSS low or intermediate-1 risk MDS who had at least two consecutive cytogenetic analyses during the follow up. Acquisition of cytogenetic abnormalities was detected in 107 patients (29%). The most frequent alteration involved chromosome 7 in 21% of ACA cases. Median transformation-free and overall survival for patients with and without ACA were 13 vs. 52 months (P = 0.01) and 17 vs. 62 months (P = 0.01), respectively. By fitting ACA as a time-dependent covariate, multivariate Cox regression analysis showed that patients with ACA had increased risk of transformation (HR = 1.40; P = 0.03) or death (HR = 1.45; P = 0.02). Notably, female patients with therapy-related MDS (t-MDS) had an increased risk of developing ACA (OR = 5.26; P < 0.0001), although subgroup analysis showed that prognostic impact of ACA was not evident in t-MDS. In conclusion, ACA occurs in close to one third of patients with IPSS defined lower risk MDS, more common among patients with t-MDS, but has a significant prognostic impact on de novo MDS. Copyright © 2013 Wiley Periodicals, Inc.

  19. Poor prognosis of colorectal cancer in patients over 80 years old is associated with down-regulation of tumor suppressor genes.

    Science.gov (United States)

    Nagaoka, Sakae; Shiraishi, Junichi; Utsuyama, Masanori; Seki, Sachiko; Takemura, Tamiko; Kitagawa, Masanobu; Sawabe, Motoji; Takubo, Kaiyo; Hirokawa, Katsuiku

    2003-07-01

    GOALS, BACKGROUND: The elderly population has been increasing during the last half a century and it would be important to know how aging influences the occurrence and biologic behavior of cancers. We investigated clinicopathologic characteristics of colorectal cancer in 1354 patients who underwent colorectal cancer resection and compared the results between extremely elderly patients (over 80 years old) and middle-aged/elderly patients (40 to less than 80 years old). Furthermore, we also examined expression of tumor suppressor genes and Cox-2 using frozen samples of colorectal cancer obtained from 62 patients ranging in age from 45 to 87 years. The results obtained in the extremely aged patients were: (1) higher ratio of women, (2) higher incidence at the proximal site, (3) higher incidence of cases with deeper invasion, (4) higher incidence of cases with lymph node metastasis (5) poorer survival rate as compared with middle-aged/elderly patients, and (6) lower mRNA expression levels of p27 and p53. These findings taken together suggest that poor prognosis of colorectal cancer in patients over 80 years is associated with down-regulation of mRNA expression of some tumor suppressor genes.

  20. Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Hao Tang

    2015-03-01

    Full Text Available Both BRCA1 and Beclin 1 (BECN1 are tumor suppressor genes, which are in close proximity on the human chromosome 17q21 breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human breast cancer is not known. To interrogate the effects of BECN1 and BRCA1 in breast cancer, we studied their mRNA expression patterns in breast cancer patients from two large datasets: The Cancer Genome Atlas (TCGA (n = 1067 and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC (n = 1992. In both datasets, low expression of BECN1 was more common in HER2-enriched and basal-like (mostly triple-negative breast cancers compared to luminal A/B intrinsic tumor subtypes, and was also strongly associated with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1 was associated with poor prognosis, and BECN1 (but not BRCA1 expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers.

  1. Loss of the cell polarity determinant human Discs-large is a novel molecular marker of nodal involvement and poor prognosis in endometrial cancer.

    Science.gov (United States)

    Sugihara, Takeru; Nakagawa, Shunsuke; Sasajima, Yuko; Ichinose, Takayuki; Hiraike, Haruko; Kondo, Fukuo; Uozaki, Hiroshi; Fukusato, Toshio; Ayabe, Takuya

    2016-04-26

    Recent Drosophila studies showed that Discs-large (Dlg) is critical for regulation of cell polarity and tissue architecture. We investigated the possibility that loss of the human homologue of Drosophila Dlg (DLG1) is involved in endometrial carcinogenesis. We analysed DLG1 expression in 160 endometrial cancers by immunohistochemical staining. Its expression was confirmed by quantitative real-time PCR (RT-PCR). We investigated the roles of DLG1 in growth and invasion by knockdown experiment in endometrial cancer cell lines. Human DLG1 localises at cellular membrane in normal endometrial tissues. Loss of DLG1 was observed in 37 cases (23.1%). Loss of DLG1 was observed in patients with advanced stage and high-grade histology. It was also observed in patients with nodal metastasis, deep myometrial invasion, and negative oestrogen and progesterone receptors. Patients with loss of DLG1 showed poorer overall survival (P=0.0019). Immunohistochemistry data correlated with RT-PCR data. Knockdown of Dlg1 in endometrial cancer cells resulted in accelerated tumour migration and invasion in vitro. Tissue polarity disturbance because of loss of DLG1 was shown to confer more aggressive characteristics to endometrial cancer cells. Our study revealed that DLG1 expression is a novel molecular biomarker of nodal metastasis, high-grade histology, and poor prognosis in endometrial cancer.

  2. Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix.

    Directory of Open Access Journals (Sweden)

    Long Huang

    Full Text Available BACKGROUND: Small cell carcinoma of the cervix (SCCC is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC. METHODOLOGY/PRINCIPAL FINDINGS: Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One™ Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly down-regulated in advanced stage SCCC patients (FIGO IB2-IV compared to early stage SCCC patients (FIGOIB1. Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan-Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019 and has-miR-125b (P = 0.020 projected a significant tendency towards poorer prognosis. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy.

  3. Hybrid Stochastic Models for Remaining Lifetime Prognosis

    Science.gov (United States)

    2004-08-01

    literature for techniques and comparisons. Os- ogami and Harchol-Balter [70], Perros [73], Johnson [36], and Altiok [5] provide excellent summaries of...and type of PH-distribution approximation for c2 > 0.5 is not as obvious. In order to use the minimum distance estimation, Perros [73] indicated that...moment-matching techniques. Perros [73] indicated that the maximum likelihood and minimum distance techniques require nonlinear optimization. Johnson

  4. The correlation between poor prognosis and increased yes-associated protein 1 expression in keratin 19 expressing hepatocellular carcinomas and cholangiocarcinomas.

    Science.gov (United States)

    Lee, KyuHo; Lee, Kyoung-Bun; Jung, Hae Yoen; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk; Jang, Ja-June

    2017-06-23

    The Hippo pathway plays a vital role in liver regeneration and development by determining cellular lineage and regulating cell proliferation and apoptosis. In this study, we aimed to assess the role of the Hippo pathway in hepatic carcinogenesis and morphogenesis by examining Yes-associated protein 1 (YAP1) expression in the spectrum of hepatic carcinomas based on cellular lineage. We examined 913 primary hepatic carcinomas, including hepatocellular carcinomas (HCCs), combined hepatocellular and cholangiocarcinomas (cHC-CCAs), intrahepatic cholangiocarcinomas (IHCCAs) and perihilar extrahepatic bile duct carcinomas (EHBCAs). Our study group was categorized into 8 disease groups, based on histological diagnosis and cytokeratin 19 (CK19) expression, and immunohistochemistry was used to detect and compare YAP1 expression levels between the groups. The eight disease groups we identified were: 1) CK19(-) HCC, 2) CK19(-) scirrhous HCC, 3) CK19(+) HCC, 4) stem cell feature of cHC-CCA, 5) classical cHC-CCA, 6) cholangiolocellular IHCCA, 7) non-cholangiolocellular IHCCA, and 8) EHBCA. Positive rates of YAP1 were the highest in the EHBCA group (21%). CK19(+) HCC and non-cholangiolocellular IHCCA groups also showed high expression levels (10% -11%), while the CK19 (-) HCC, CK19 (-) scirrhous HCC, cHC-CCA, and cholangiolocellular IHCCA groups showed low expression levels, ranging between 0% and 5%. Survival analysis, restricted to pT1 stage HCCs and IHCCAs, showed poor overall survival for YAP1(+) IHCCA patients (39 ± 17 vs. 109 ± 10 months, mean ± SD, log rank p-value 0.005). For HCCs, a trend of poor progression-free survival for YAP1(+) HCCs was observed (39 ± 18 vs. 81 ± 5 months, mean ± SD, log rank p-value 0.205) CONCLUSIONS: YAP1 activation was more commonly found in CCAs than in pure HCCs. However, a differing pattern of YAP1 expression between cHC-CCAs and CK19(+) HCCs and the poor prognosis of YAP1 positive hepatic carcinomas suggests that YAP1

  5. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

    Science.gov (United States)

    Lichtman, Judith H; Froelicher, Erika S; Blumenthal, James A; Carney, Robert M; Doering, Lynn V; Frasure-Smith, Nancy; Freedland, Kenneth E; Jaffe, Allan S; Leifheit-Limson, Erica C; Sheps, David S; Vaccarino, Viola; Wulsin, Lawson

    2014-03-25

    Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

  6. DHEA Supplementation Confers No Additional Benefit to that of Growth Hormone on Pregnancy and Live Birth Rates in IVF Patients Categorized as Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Kevin N. Keane

    2018-01-01

    Full Text Available BackgroundIn vitro fertilization (IVF patients receive various adjuvant therapies to enhance success rates, but the true benefit is actively debated. Growth hormone (GH and dehydroepiandrosterone (DHEA supplementation were assessed in women undergoing fresh IVF transfer cycles and categorized as poor prognosis from five criteria.MethodsData were retrospectively analyzed from 626 women undergoing 626 IVF cycles, where they received no adjuvant, GH alone, or GH–DHEA in combination. A small group received DHEA alone. The utilization of adjuvants was decided between the attending clinician and the patient depending on various factors including cost.ResultsDespite patients being significantly older with lower ovarian reserve, live birth rates were significantly greater with GH alone (18.6% and with GH-DHEA (13.0% in comparison to those with no adjuvant (p < 0.003. No significant difference was observed between the GH groups (p = 0.181. Overall, patient age, quality of the transferred embryo, and GH treatment were the only significant independent predictors of live birth chance. Following adjustment for patient age, antral follicle count, and quality of transferred embryo, GH alone and GH–DHEA led to a 7.1-fold and 5.6-fold increase in live birth chance, respectively (p < 0.000.ConclusionThese data indicated that GH adjuvant may support more live births, particularly in younger women, and importantly, the positive effects of GH treatment were still observed even if DHEA was also used in combination. However, supplementation with DHEA did not indicate any potentiating benefit or modify the effects of GH treatment. Due to the retrospective design, and the risk of a selection bias, caution is advised in the interpretation of the data.

  7. The self-care practices of family caregivers of persons with poor prognosis cancer: differences by varying levels of caregiver well-being and preparedness.

    Science.gov (United States)

    Dionne-Odom, J Nicholas; Demark-Wahnefried, Wendy; Taylor, Richard A; Rocque, Gabrielle B; Azuero, Andres; Acemgil, Aras; Martin, Michelle Y; Astin, Meka; Ejem, Deborah; Kvale, Elizabeth; Heaton, Karen; Pisu, Maria; Partridge, Edward E; Bakitas, Marie A

    2017-08-01

    Little is known about the impact of family caregiving for adults with poor prognosis cancer on caregivers' own individual self-care practices. We explored differences in caregivers' discrete self-care practices associated with varying levels of caregiver well-being, preparedness, and decision-making self-efficacy. Cross-sectional survey within eight community-based southeastern U.S. cancer centers was conducted. Family caregivers of Medicare beneficiaries ≥65 years with pancreatic, lung, brain, ovarian, head and neck, hematologic, or stage IV cancer completed measures of individual self-care practices (health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, stress management, and sleep), well-being (anxiety, depression, and health-related quality of life [HRQoL]), preparedness, and decision-making self-efficacy. Caregivers (n = 294) averaged 66 years, were mostly female (72.8%), white (91.2%), Protestant (76.2%), retired (54.4%), and patients' spouse/partner (60.2%). Approximately, half were rural-dwellers (46.9%) with incomes 1 year (68%). Nearly a quarter (23%) reported high depression and 34% reported borderline or high anxiety. Low engagement in all self-care practices was associated with worse caregiver anxiety, depression, and mental HRQoL (all p values care practices, high depression and anxiety, and low HRQoL mental health scores. Caregiver well-being, preparedness, and decision-making self-efficacy might be optimized through interventions targeted at enhancing health responsibility, stress management, interpersonal relationships, and spiritual growth self-care practices.

  8. Tumor budding correlates with occult cervical lymph node metastasis and poor prognosis in clinical early-stage tongue squamous cell carcinoma.

    Science.gov (United States)

    Xie, Nan; Wang, Cheng; Liu, Xiqiang; Li, Ruyao; Hou, Jinsong; Chen, Xiaohua; Huang, Hongzhang

    2015-04-01

    Tumor budding has been suggested to be a prognostic factor in various human cancers. However, the prognostic value of tumor budding for early-stage (cT1/2N0) tongue squamous cell carcinoma remains inconclusive. This study analyzed the correlation of tumor budding with the clinicopathologic features, and its prognostic significance for cT1/2N0 stage tongue squamous cell carcinoma. One hundred and ninety-five patients with T1/2 stage tongue squamous cell carcinoma enrolled in the retrospective study. Tumor invasive depth, the intensity of tumor budding, and other clinicopathological features were reviewed. Overall survivals were evaluated by the Kaplan-Meier method. For multivariable analysis, Cox's proportional hazards regression models were performed. The frequency of tumor buds in tongue squamous cell carcinoma is about 85.6% in this study. The intensity of tumor budding showed strong correlations with occult lymph node metastasis (P tumor budding and deeper invasive depth correlated with reduced overall survival. Cox's regression models proved tumor budding to be an independent prognostic factor in clinical early-stage tongue squamous cell carcinoma. Tumor local relapses were also a predictor of tongue squamous cell carcinoma progression. Tumor budding is a frequent event in tongue squamous cell carcinoma. It independently predicted prognosis of patients with T1/2 stage tongue squamous cell carcinoma and may be used for routing pathological diagnosis and the decision of elective lymph node dissection. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. An array CGH based genomic instability index (G2I is predictive of clinical outcome in breast cancer and reveals a subset of tumors without lymph node involvement but with poor prognosis

    Directory of Open Access Journals (Sweden)

    Bonnet Françoise

    2012-11-01

    Full Text Available Abstract Background Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established. Methods To explore the prognostic value of genomic alterations present in primary tumors, we performed a comparative genomic hybridization study on BAC arrays with a panel of breast carcinomas from 45 patients with metastatic relapse and 95 others, matched for age and axillary node involvement, without any recurrence after at least 11 years of follow-up. Array-CGH data was used to establish a two-parameter index representative of the global level of aneusomy by chromosomal arm, and of the number of breakpoints throughout the genome. Results Application of appropriate thresholds allowed us to distinguish three classes of tumors highly associated with metastatic relapse. This index used with the same thresholds on a published set of tumors confirms its prognostic significance with a hazard ratio of 3.24 [95CI: 1.76-5.96] p = 6.7x10-5 for the bad prognostic group with respect to the intermediate group. The high prognostic value of this genomic index is related to its ability to individualize a specific group of breast cancers, mainly luminal type and axillary node negative, showing very high genetic instability and poor outcome. Indirect transcriptomic validation was obtained on independent data sets. Conclusion Accurate evaluation of genetic instability in breast cancers by a genomic instability index (G2I helps individualizing specific tumors with previously unexpected very poor prognosis.

  10. Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zang JL

    2017-01-01

    : In conclusion, the serum VEGF levels were found to be a poor prognostic biomarker for the efficacy of platinum-based chemotherapy in terms of PFS, but it was not shown to be a suitable predictive marker for clinical response to platinum-based chemotherapy. Keywords: non-small cell lung cancer, VEGF, progression-free survival, platinum, chemotherapy, Luminex multiplex, prognosis

  11. Long noncoding nature brain-derived neurotrophic factor antisense is associated with poor prognosis and functional regulation in non-small cell lung caner.

    Science.gov (United States)

    Shen, MingJing; Xu, Zhonghua; Jiang, Kanqiu; Xu, Weihua; Chen, Yongbin; Xu, ZhongHeng

    2017-05-01

    In this study, we evaluated the prognostic potential and functional regulation of human nature antisense, brain-derived neurotrophic factor antisense, in non-small cell lung cancer. Non-small cell lung cancer carcinoma and adjacent non-carcinoma lung tissues were extracted from 151 patients. Their endogenous brain-derived neurotrophic factor antisense expression levels were compared by quantitative reverse transcription polymerase chain reaction. Clinical relevance between endogenous brain-derived neurotrophic factor antisense expression level and patients' clinicopathological variances or overall survival was analyzed. The potential of brain-derived neurotrophic factor antisense being an independent prognostic factor in non-small cell lung cancer was also evaluated. In in vitro non-small cell lung cancer cell lines, brain-derived neurotrophic factor antisense was upregulated through forced overexpression. The effects of brain-derived neurotrophic factor antisense upregulation on non-small cell lung cancer in vitro survival, proliferation, and migration were evaluated by viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and transwell assays. Brain-derived neurotrophic factor antisense is lowly expressed in non-small cell lung cancer carcinoma tissues and further downregulated in late-stage carcinomas. Brain-derived neurotrophic factor antisense downregulation was closely associated with non-small cell lung cancer patients' advanced tumor, lymph node, metastasis stage, and positive status of lymph node metastasis, and confirmed to be an independent prognostic factor for patients' poor overall survival. In non-small cell lung cancer A549 and H226 cell lines, forced overexpression of brain-derived neurotrophic factor antisense did not alter cancer cell viability but had significantly tumor suppressive effect in inhibiting in vitro non-small cell lung cancer proliferation and migration. Endogenous brain-derived neurotrophic factor antisense in

  12. Altered expression of different GalNAc‑transferases is associated with disease progression and poor prognosis in women with high-grade serous ovarian cancer.

    Science.gov (United States)

    Sheta, Razan; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Popa, Ion; Bachvarov, Dimcho

    2017-10-09

    Protein glycosylation perturbations are implicated in a variety of diseases, including cancer. Aberrant glycosylation in cancer is frequently attributed to altered expression of polypeptide GalNAc transferases (GalNAc‑Ts) - enzymes initiating mucin-type O-glycosylation. A previous study from our group demonstrated that one member of this family (GALNT3) is overexpressed in epithelial ovarian cancer (EOC), and GALNT3 expression correlated with shorter progression-free survival (PFS) in EOC patients with advanced disease. As considerable degree of redundancy between members of the GalNAc‑Ts gene family has been frequently observed, we decided to investigate whether other members of this family are essential in EOC progression. In silico analysis based on publically available data was indicative for altered expression of five GalNAc‑Ts (GALNT2, T4, T6, T9 and T14) in ovarian high-grade serous carcinoma (HGSC) samples compared to non-tumoral (control) ovarian tissue. We analyzed protein expression of these GalNAc‑Ts in EOC cells and tumors by western blotting, followed by immunohistochemical (IHC) evaluation of their expression in EOC tumor and control samples using tissue microarrays (TMAs). Western blot analyses were indicative for low expression of GALNT2 and strong expression of GALNT6, T9 and T14 in both EOC cells and tumors. These observations were confirmed by IHC. GALNT2 displayed significantly lower expression, while GALNT6, GALNT9 and GALNT14 showed significantly higher expression in HGSC tumors compared to control tissue. Importantly, GALNT6 and GALNT14 expression correlated with poor prognosis of serous EOC patients. Moreover, our results suggest for overlapping functions of some GalNAc‑Ts, more specifically GALNT3 and GALNT6, in directing EOC progression. Our results are indicative for a possible implication of different members of the GalNAc‑T gene family in modulating EOC progression, and the potential use of GALNT6 and GALNT14 as novel

  13. Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb-mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients.

    Science.gov (United States)

    Bandino, Andrea; Geerts, Dirk; Koster, Jan; Bachmann, André S

    2014-12-01

    Neuroblastoma (NB) is an aggressive pediatric malignancy that typically occurs in infants and children under the age of 5 years. High-stage tumors relapse frequently even after aggressive multimodal treatment, resulting in therapy resistance and eventually in patient death. Clearly, new biologically-targeted drugs are needed that more efficiently suppress tumor growth and prevent relapse. We and others previously showed that polyamines such as spermidine play an essential role in NB tumorigenesis and that DFMO, an inhibitor of the central polyamine synthesis gene ODC, is effective in vitro and in vivo, prompting its evaluation in NB clinical trials. However, the specific molecular actions of polyamines remain poorly defined. Spermidine and deoxyhypusine synthase (DHPS) are essential components in the hypusination-driven post-translational activation of eukaryotic initiation factor 5A (eIF5A). We assessed the role of DHPS in NB and the impact of its inhibition by N(1)-guanyl-1,7-diaminoheptane (GC7) on tumor cell growth using cell proliferation assays, Western blot, immunofluorescence microscopy, and Affymetrix micro-array mRNA expression analyses in NB tumor samples. We found that GC7 inhibits NB cell proliferation in a dose-dependent manner, through induction of the cell cycle inhibitor p21 and reduction of total and phosphorylated Rb proteins. Strikingly, high DHPS mRNA expression correlated significantly with unfavorable clinical parameters, including poor patient survival, in a cohort of 88 NB tumors (all P DHPS are key contributing factors in NB tumor proliferation through regulation of the p21/Rb signaling axis.

  14. TIGAR cooperated with glycolysis to inhibit the apoptosis of leukemia cells and associated with poor prognosis in patients with cytogenetically normal acute myeloid leukemia.

    Science.gov (United States)

    Qian, Sixuan; Li, Jianyong; Hong, Ming; Zhu, Yu; Zhao, Huihui; Xie, Yue; Huang, Jiayu; Lian, Yun; Li, Yanru; Wang, Shuai; Mao, Jianping; Chen, Yaoyu

    2016-11-25

    Cancer cells show increased glycolysis and take advantage of this metabolic pathway to generate ATP. The TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits aerobic glycolysis and protects tumor cells from intracellular reactive oxygen species (ROS)-associated apoptosis. However, the function of TIGAR in glycolysis and survival of acute myeloid leukemia cells remains unclear. We analyzed TIGAR expression in cytogenetically normal (CN-) AML patients and the correlations with clinical and biological parameters. In vivo and in vitro, we tested whether glycolysis may induce TIGAR expression and evaluated the combination effect of glycolysis inhibitor and TIGAR knockdown on human leukemia cell proliferation. High TIGAR expression was an independent predictor of poor survival and high incidence of relapse in adult patients with CN-AML. TIGAR also showed high expression in multiple human leukemia cell lines and knockdown of TIGAR activated glycolysis through PFKFB3 upregulation in human leukemia cells. Knockdown of TIGAR inhibited the proliferation of human leukemia cells and sensitized leukemia cells to glycolysis inhibitor both in vitro and in vivo. Furthermore, TIGAR knockdown in combination with glycolysis inhibitor 2-DG led leukemia cells to apoptosis. In addition, the p53 activator Nutlin-3α showed a significant combinational effect with TIGAR knockdown in leukemia cells. However, TIGAR expression and its anti-apoptotic effects were uncoupled from overexpression of exogenous p53 in leukemia cells. TIGAR might be a predictor of poor survival and high incidence of relapse in AML patients, and the combination of TIGAR inhibitors with anti-glycolytic agents may be novel therapies for the future clinical use in AML patients.

  15. Loneliness is associated with poor prognosis in late-life depression : Longitudinal analysis of the Netherlands study of depression in older persons

    NARCIS (Netherlands)

    Holvast, Floor; Burger, Huibert; de Waal, Margot M. W.; van Marwijk, Harm W. J.; Comijs, Hannie C.; Verhaak, Peter F. M.

    2015-01-01

    Background: Although depression and loneliness are common among older adults, the role of loneliness on the prognosis of late life depression has not yet been determined. Therefore, we examined the association between loneliness and the course of depression. Methods: We conducted a 2-year follow-up

  16. Loneliness is associated with poor prognosis in late-life depression: Longitudinal analysis of the Netherlands study of depression in older persons

    NARCIS (Netherlands)

    Holvast, F.; Burger, H.; de Waal, M.M.; van Marwijk, H.W.J.; Comijs, H.C.; Verhaak, P.F.

    2015-01-01

    Background Although depression and loneliness are common among older adults, the role of loneliness on the prognosis of late-life depression has not yet been determined. Therefore, we examined the association between loneliness and the course of depression. Methods We conducted a 2-year follow-up

  17. Time resolved amplified FRET identifies protein kinase B activation state as a marker for poor prognosis in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    James Miles

    2017-12-01

    General significance: The quantitative imaging technology based on Amplified-FRET can rapidly analyse protein activation states and molecular interactions. It could be used for prognosis and assess drug function during the early cycles of chemotherapy. It enables evaluation of clinical efficiency of personalised cancer treatment.

  18. Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Gerdes, A M; Skjødt, K

    1999-01-01

    (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of delta p53 was highly significant in the low-intermediate-risk group (P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 delta p53 patients died within 1 year...

  19. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... medical records. Relative survival This statistic is another method used to estimate cancer-specific survival that does ... poor prognosis if the cancer is harder to control. Whatever your doctor tells you, keep in mind ...

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... suggest that your cancer is likely to respond well to treatment. Or, he may tell you that you have a poor prognosis if the cancer is harder to control. Whatever your doctor tells you, keep in mind ...

  1. The new truncated somatostatin receptor variant sst5TMD4 is associated to poor prognosis in breast cancer and increases malignancy in MCF-7 cells.

    Science.gov (United States)

    Durán-Prado, M; Gahete, M D; Hergueta-Redondo, M; Martínez-Fuentes, A J; Córdoba-Chacón, J; Palacios, J; Gracia-Navarro, F; Moreno-Bueno, G; Malagón, M M; Luque, R M; Castaño, J P

    2012-04-19

    Somatostatin receptors (sst1-5) are present in different types of tumors, where they inhibit key cellular processes such as proliferation and invasion. Although ssts are densely expressed in breast cancer, especially sst2, their role and therapeutic potential remain uncertain. Recently, we identified a new truncated sst5 variant, sst5TMD4, which is related to the abnormal response of certain pituitary tumors to treatment with somatostatin analogs. Here, we investigated the possible role of sst5TMD4 in breast cancer. This study revealed that sst5TMD4 is absent in normal mammary gland, but is abundant in a subset of poorly differentiated human breast tumors, where its expression correlated to that of sst2. Moreover, in the MCF-7 breast cancer model cell, sst5TMD4 expression increased malignancy features such as invasion and proliferation abilities (both in cell cultures and nude mice). This was likely mediated by sst5TMD4-induced increase in phosphorylated extracellular signal-regulated kinases 1 and 2 and p-Akt levels, and cyclin D3 and Arp2/3 complex expression, which also led to mesenchymal-like phenotype. Interestingly, sst5TMD4 interacts physically with sst2 and thereby alters its signaling, enabling disruption of sst2 inhibitory feedback and providing a plausible basis for our findings. These results suggest that sst5TMD4 could be involved in the pathophysiology of certain types of breast tumors.

  2. High expressions of BCL6 and Lewis y antigen are correlated with high tumor burden and poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Zhu, Liancheng; Feng, Huilin; Jin, Shan; Tan, Mingzi; Gao, Song; Zhuang, Huiyu; Hu, Zhenhua; Wang, Huimin; Song, Zuofei; Lin, Bei

    2017-07-01

    Aberrant regulation of BCL6 plays crucial oncogenic roles in various malignant tumors; howbeit, the function of BCL6 in tumorigenesis of ovarian cancer remains unclear. The aim of this study is to investigate the role of BCL6 in ovarian cancer. The methods of immunohistochemical staining, quantitative real-time polymerase chain reaction, immunocytochemical staining, and gene expression profile enrichment analysis were performed to identify the possible role of BCL6 in ovarian cancer. We observed that the expression of BCL6 was significantly higher in ovarian cancer tissues and correlated with higher tumor burden including advanced International Federation of Gynecology and Obstetrics stages, poor differentiation, Type II ovarian cancer, the presence of >1 cm residual tumor size, and appearance of recurrence or death (all p 1 cm, as well as high expressions of BCL6 and Lewis y antigen were independent factors of worse progression-free survival and overall survival (all p ovarian cancer and targeting BCL6 could be a novel therapeutic strategy for ovarian cancer treatment.

  3. Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma.

    Science.gov (United States)

    Lu, Ning; Lin, Tao; Wang, Lin; Qi, Mei; Liu, Zhiyan; Dong, Hongyan; Zhang, Xiying; Zhai, Chunyan; Wang, Yan; Liu, Long; Xiang, Lei; Qi, Lei; Han, Bo; Li, Jinsong

    2015-05-01

    The sex-determining region Y-box 4 (SOX4), a transcription factor, is involved in various developmental processes. It has been reported in multiple human cancers. However, the prognostic value and its exact role in chondrosarcoma remain poorly understood. In the current study, SOX4 was overexpressed in 28 of 92 (30.4 %) interpretable chondrosarcoma patients compared with 3 of 43 (6.9 %) interpretable chondroma cases (P = 0.003). Its overexpression in chondrosarcoma was significantly associated with histological grade (P chondrosarcoma patients with low histological grade. Functionally, SOX4 silencing significantly suppressed the proliferation, migratory, and invasive capacity of SW1353 cells, suggesting an oncogenic role of SOX4 in chondrosarcoma in vitro. In an attempt of characterizing SOX4 overexpression mechanism, we identified miR-30a as a tumor suppressor that directly targets SOX4 in chondrosarcoma cells. Clinically, miR-30a expression was negatively correlated with SOX4 expression in chondrosarcoma cases. In all, we identified that SOX4 was oncogenic in chondrosarcoma and negatively regulated by miR-30a in vitro. Importantly, SOX4 overexpression may serve as a prognostic marker for patients with low-histological-grade chondrosarcoma.

  4. Tumour cell expression of C4.4A, a structural homologue of the urokinase receptor, correlates with poor prognosis in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Hansen, Line V.; Skov, Birgit G; Ploug, Michael

    2007-01-01

    expression. In the present study, we therefore explored the possible association between C4.4A expression and prognosis in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tissue sections from 108 NSCLC patients were subjected to immunohistochemical staining using a polyclonal antibody......PURPOSE: C4.4A expression has been implicated in human cancer progression. This protein is a structural homologue of the urokinase receptor, uPAR, which constitutes a well-established prognostic marker in various human cancers. Nonetheless, little is known about the prognostic significance of C4.4A...... that specifically recognises human C4.4A. Staining frequency and intensity was scored semiquantitatively and grouped into cancers with high and low expression of C4.4A. Kaplan-Meier survival curves were generated to evaluate the significance of C4.4A expression in prognosis of NSCLC patients. RESULTS: High C4.4A...

  5. Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease

    DEFF Research Database (Denmark)

    Brauner, S; Zhou, W; Backlin, C

    2015-01-01

    between TRIM21 expression and proliferation of leucocytes in vitro. CONCLUSIONS: We show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our...... findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival....

  6. ELMO1 is upregulated in AML CD34+ stem/progenitor cells, mediates chemotaxis and predicts poor prognosis in normal karyotype AML.

    Directory of Open Access Journals (Sweden)

    Marta E Capala

    Full Text Available Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML cells (n = 46, their more differentiated CD34- leukemic progeny, and normal CD34+ bone marrow cells (n = 31 and focused on differentially expressed genes involved in adhesion and migration. Thus, Engulfment and Motility protein 1 (ELMO1 was identified amongst the top 50 most differentially expressed genes. ELMO1 is a crucial link in the signaling cascade that leads to activation of RAC GTPases and cytoskeleton rearrangements. We confirmed increased ELMO1 expression at the mRNA and protein level in a panel of AML samples and showed that high ELMO1 expression is an independent negative prognostic factor in normal karyotype (NK AML in three large independent patient cohorts. Downmodulation of ELMO1 in human CB CD34+ cells did not significantly alter expansion, progenitor frequency or differentiation in stromal co-cultures, but did result in a decreased frequency of stem cells in LTC-IC assays. In BCR-ABL-transduced human CB CD34+ cells depletion of ELMO1 resulted in a mild decrease in proliferation, but replating capacity of progenitors was severely impaired. Downregulation of ELMO1 in a panel of primary CD34+ AML cells also resulted in reduced long-term growth in stromal co-cultures in two out of three cases. Pharmacological inhibition of the ELMO1 downstream target RAC resulted in a severely impaired proliferation and survival of leukemic cells. Finally, ELMO1 depletion caused a marked decrease in SDF1-induced chemotaxis of leukemic cells. Taken together, these data show that inhibiting the ELMO1-RAC axis might be an alternative way to target leukemic cells.

  7. DHX15 is associated with poor prognosis in acute myeloid leukemia (AML) and regulates cell apoptosis via the NF-kB signaling pathway.

    Science.gov (United States)

    Pan, Lili; Li, Yang; Zhang, Hai-Ying; Zheng, Yi; Liu, Xiao-Li; Hu, Zheng; Wang, Yi; Wang, Jing; Cai, Yuan-Hua; Liu, Qiao; Chen, Wan-Ling; Guo, Ying; Huang, Yuan-Mao; Qian, Feng; Jin, Li; Wang, Jiucun; Wang, Shao-Yuan

    2017-10-27

    The role of DHX15, a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15. DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells. DHX15 was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate. DHX15 silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of DHX15 expression rescued cell viability and reduced cell apoptosis. In addition, we found that DHX15 was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of DHX15 caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for DHX15 in cell apoptosis. We further explored the mechanism of DHX15 in apoptosis and found that overexpression of DHX15 activated NF-kB transcription. Knockdown of DHX15 inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes CASP3 and PARP were activated. In conclusion, this study represents the first demonstration that DHX15 plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.

  8. Loneliness is associated with poor prognosis in late-life depression: Longitudinal analysis of the Netherlands study of depression in older persons.

    Science.gov (United States)

    Holvast, Floor; Burger, Huibert; de Waal, Margot M W; van Marwijk, Harm W J; Comijs, Hannie C; Verhaak, Peter F M

    2015-10-01

    Although depression and loneliness are common among older adults, the role of loneliness on the prognosis of late-life depression has not yet been determined. Therefore, we examined the association between loneliness and the course of depression. We conducted a 2-year follow-up study of a cohort from the Netherlands Study of Depression in Older Persons (NESDO). This included Dutch adults aged 60-90 years with a diagnosis of major depression, dysthymia, or minor depression according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We performed regression analyses to determine associations between loneliness at baseline and both severity and remission of depression at follow-up. We controlled for potential confounders and performed multiple imputations to account for missing data. Of the 285 respondents, 48% were still depressed after 2 years. Loneliness was independently associated with more severe depressive symptoms at follow-up (beta 0.61; 95% CI 0.12-1.11). Very severe loneliness was negatively associated with remission after 2 years compared with no loneliness (OR 0.25; 95% CI 0.08-0.80). Despite using multiple imputation, the large proportion of missing values probably reduces the study's precision. Generalizability to the general population may be limited by the overrepresentation of ambulatory patients with possibly more persistent forms of depression. In this cohort, the prognosis of late-life depression was adversely affected by loneliness. Health care providers should seek to evaluate the degree of loneliness to obtain a more reliable assessment of the prognosis of late-life depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients

    Science.gov (United States)

    Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B. Paul; Ito, Yasuhiko

    2017-01-01

    Background We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. Methods We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. Results When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Conclusion Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis. PMID:28046064

  10. High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients.

    Science.gov (United States)

    Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B Paul; Ito, Yasuhiko

    2017-01-01

    We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

  11. Abstract 20854: A Tale of Self-Fulfilling Prophecies in Out-of-Hospital Cardiac Arrest: Emergency Medical Technicians Deliberately Perform Substandard CPR When Anticipating Poor Prognosis

    DEFF Research Database (Denmark)

    Bødtker, Henrik; Klausen, Troels M; Lauridsen, Kasper G

    2017-01-01

    Background: Emergency medical technicians (EMTs) play a crucial role in resuscitating patients with out-of-hospital cardiac arrest. Perception of prognosis may affect level and quality of treatment. The aim of this study was to investigate if EMTs delay start of cardiopulmonary resuscitation (CPR......) if they believe resuscitation to be futile. Furthermore, to investigate if different patient and resuscitation attempt characteristics result in EMTs deliberately performing substandard CPR.Methods: This was a cross-sectional questionnaire survey study conducted in 2016 through 2017 including EMTs from a Danish...... and compressions). Overall, 22% and 51% would perform substandard CPR if the patient were 80 or 90 years old respectively, 46% if the patient was living in a nursing home and up to 31% due to comorbidity such as cancer. EMTs (51%) would deliberately perform substandard CPR in case of on-going bystander CPR >20...

  12. Low Mast Cell Density Predicts Poor Prognosis in Oral Squamous Cell Carcinoma and Reduces Survival in Head and Neck Squamous Cell Carcinoma.

    Science.gov (United States)

    Attramadal, Cecilie Gjøvaag; Kumar, Sheeba; Gao, Jian; Boysen, Morten Ebbe; Halstensen, Trond Sundby; Bryne, Magne

    2016-10-01

    The cellular composition of the tumor microenvironment (TME) at the invading front of oral squamous cell carcinomas (OSCCs) may reflect biologically important cancer features and host responses, and thus be related to disease progression. The TME density of mast cells (MCs), macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells were quantified at the invasive front and analyzed regarding their relation to disease recurrence in patients with small T1/2N0M0 OSCCs. mRNA for MC-specific proteins were analyzed in a second patient cohort with head and neck squamous cell carcinoma (HNSCC). Samples from 62 patients with T1/2N0M0 OSCC were immunohistochemically stained and scored for the cellular expression of mast/stem cell growth factor receptor (c-KIT) (MCs), CD68 (macrophages), α-smooth muscle actin (α-SMA) (CAFs) and CD31 (endothelial cells) and this was analyzed according to disease recurrence. Data from The Cancer Genome Atlas database were used to examine mRNA expression profiles and clinical data of patients with 399 HNSCC. Increased MC density at the invasive front was significantly associated with reduced disease recurrence, as none of the patients with high MC density experienced relapse. Moreover, increased expression of mRNA for MC specific markers as c-KIT, and α-, β-, and δ-tryptases and the MC-stimulating factor, stem cell factor (SCF), was significantly associated with good prognosis in patients with HNSCC. Decreased MC density at the invasive front may reflect tumor biology related to disease progression and prognosis. Counting MCs seems to be an easy and practical tool, that could be utilized for prognostic evaluation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. A low percentage of HER-2 amplification whereas indicates poor prognosis in salivary carcinoma ex pleomorphic adenoma: a study of 140 cases.

    Science.gov (United States)

    Xia, Liang; Hu, Yuhua; Li, Jiang; Gu, Ting; Zhang, Chunye; Wang, Lizhen; Tian, Zhen

    2017-03-01

    Human epidermal growth factor receptor 2 (HER-2) has been found in many malignant tumours including salivary malignancy. HER-2-targeted therapy has been applied in the treatment of HER-2-overexpressing carcinoma. The aim of this study was to determine the status of HER-2 in salivary invasive carcinoma ex pleomorphic adenoma (ICXPA) in a relatively large Chinese sample, which may provide HER-2-targeted therapy with profound support in the future. We collected 140 ICXPAs and their related clinicopathological and follow-up data. All cases were examined for HER-2 expression by immunohistochemistry and gene amplification by fluorescence in situ hybridization, if necessary. The study showed that the ratio of HER-2 positivity was only 25% (35/140) in all cases, but the positive ratio in ICXPAs with luminal differentiation for malignant component (32/79, 40.5%) was much higher than that in cases with non-luminal differentiation (3/61, 4.9%). The overexpression of HER-2 was closely associated with gender, histological grade and N stage. HER-2-positive tumours conferred short overall survival time (P = 0.036) and short disease-specific survival time (P = 0.042) in patients, but HER-2 status was not an independent predictor of prognosis. Human epidermal growth factor receptor 2 amplification is significantly associated with cell differentiation of the malignant component in ICXPA and it implies an unfavourable prognosis. Although HER-2 positivity is not common in the tumour, HER-2-targeted therapy for those HER-2-positive patients is still worth expecting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers.

    Science.gov (United States)

    Watanabe, Takahiro; Hida, Akira I; Inoue, Natsuko; Imamura, Michiko; Fujimoto, Yukie; Akazawa, Kouhei; Hirota, Seiichi; Miyoshi, Yasuo

    2017-11-22

    The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2-) BC is still controversial. We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2- BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2- BCs. A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2- BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2- cases with a high TIL score also tended to achieve pCR (p = 0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2- BC (p = 0.034). Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2- BC.

  15. Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScope(TM)) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study.

    Science.gov (United States)

    Wu, Yan-Guang; Lazzaroni-Tealdi, Emanuela; Wang, Qi; Zhang, Lin; Barad, David H; Kushnir, Vitaly A; Darmon, Sarah K; Albertini, David F; Gleicher, Norbert

    2016-08-24

    Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope™) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope™ and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope™ and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo. Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope™ and standard embryology. The EmbryoScope™, however, more than doubled embryology staff time (P embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well-defined patient populations before the uncontrolled utilization of these instruments further expands. NCT02246309 Registered September 18, 2014.

  16. LncRNA SNHG6 is Associated with Poor Prognosis of Gastric Cancer and Promotes Cell Proliferation and EMT through Epigenetically Silencing p27 and Sponging miR-101-3p

    Directory of Open Access Journals (Sweden)

    Kai Yan

    2017-06-01

    Full Text Available Background/Amis: Long non-coding RNAs (lncRNAs, a novel class of transcripts, have been shown to play critical roles in diverse cellular biological processes, including tumorigenesis. Small nucleolar RNA host gene 6 (SNHG6 regulates various biological processes in cancer cells. However, the biological role of SNHG6 in gastric cancer still remains to be explored. The aim of this study is to investigate the characteristic of the SNHG6 in gastric cancer. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR was used to measure the expression of SNHG6 in gastric cancer tissues and cell lines. MTT assays, colony formation assays were used to determine the impact of SNHG6 on tumorigenesis . Flow cytometric analysis of cell cycle and apoptosis was performed to measure the effect of SNHG6 on cell cycle and apoptosis rate. Transwell assay was performed to measure the effect of SNHG6 on cell migration. Western blotting and immunofuorescence were utilized to examine the effect of SNHG6 on epithelial-mesenchymal transition (EMT of GC cells. Chromatin immunoprecipitation (ChIP, RNA immunoprecipitation (RIP, RNA-pulldown and luciferase reporter assays were employed to dissect molecular mechanisms. Results: In this study, we revealed that SNHG6 was overexpressed in gastric cancer tissues and cell lines. High expression levels of SNHG6 wereassociated with invasion depth, lymph node metastasis, distant metastasis and tumor/node/metastasis (TNM stage, and predicted poor prognosis. Loss-of-function assays revealed that silenced SNHG6 obviously inhibited gastric cancer cell growth, weakened cell migration capacity and suppressed the EMT processes of gastric cancer cells. Additionally, ChIP, RIP, RNA-pulldown and luciferase reporter assays evidenced that SNHG6 could epigenetically silenced p27 and could competitively sponging miR-101-3p thereby regulating zinc finger E-box-binding homeobox 1 (ZEB1. Conclusion: In summary, our findings demonstrated that

  17. Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xia, Yi; Xu-Monette, Z Y; Tzankov, A

    2017-01-01

    of BLIMP-1 was associated with Myc overexpression and decreased expression of p53 pathway molecules. In addition, homozygous PRDM1 deletions and PRDM1 mutations within exons 1 and 2, which encode for domains crucial for transcriptional repression, were found to show a poor prognostic impact in patients...

  18. Programmed death-ligand 1 expression correlates with diminished CD8+ T cell infiltration and predicts poor prognosis in anal squamous cell carcinoma patients

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2017-12-01

    Full Text Available Yu-Jie Zhao,1 Wei-Peng Sun,2 Jian-Hong Peng,1 Yu-Xiang Deng,1 Yu-Jing Fang,1 Jun Huang,2 Hui-Zhong Zhang,3 De-Sen Wan,1 Jun-Zhong Lin,1,* Zhi-Zhong Pan,1,* 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 2Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, 3Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Increased expression of programmed death-ligand 1 (PD-L1 on tumor cells can be found in various malignancies; however, very limited information is known about its role in anal squamous cell carcinoma (ASCC. This study explored PD-L1 expression in ASCC patients and its association with patients’ clinicopathological features, CD8+ T cell infiltration, and prognosis.Methods: Formalin-fixed paraffin-embedded tumor samples from 26 patients with ASCC were retrieved. The levels of PD-L1 expression on the membrane of both tumor cells and tumor-infiltrating mononuclear cells (TIMCs were evaluated by immunohistochemistry. CD8+ T cell densities, both within tumors and at the tumor–stromal interface, were also analyzed. Baseline clinicopathological characteristics, human papilloma virus (HPV status, and outcome data correlated with PD-L1-positive staining.Results: PD-L1 expression on tumor cells and TIMCs was observed in 46% and 50% of patients, respectively. Nineteen patients (73% were HPV positive, with 7 showing PD-L1-positive staining on tumor cells and 9 showing PD-L1-positive staining on TIMCs. Increasing CD8+ density within tumors, but not immune stroma, was significantly associated with decreased PD-L1 expression by both tumor cells and TIMCs (P=0.0043 and P=0.0007. Patients with negative PD-L1 expression had significantly better progression-free survival (P=0.038 and P

  19. Alteration of Human Papillomavirus Type 16 Genetic and Epigenetic Profiles in Cervical Cancer Patients Is Indicative of Poor Disease Prognosis: A Cohort Analysis.

    Science.gov (United States)

    Dutta, Sankhadeep; Singh, Ratnesh Kumar; Mandal, Ranajit Kumar; Roychoudhury, Susanta; Basu, Partha; Panda, Chinmay Kumar

    2016-05-01

    Aim of this study was to assess the changes in genetic and epigenetic profiles of human papillomavirus type 16 (HPV16), if any, in primary cervical cancer (CaCx) and corresponding plasma before and after therapy for possible prognostic evaluation. The genetic (integration status) and epigenetic (methylation of enhancer, early promoter, and late promoter sequences) profiles of HPV16 were analyzed in pretherapy CaCx (n = 46), corresponding plasma, posttherapy cervical swabs (n = 39), and corresponding plasma from a single patient cohort. Quantitative viral load was also measured in these HPV16-positive primary CaCx and posttherapy cervical swabs. Presence of HPV16 in the patients' plasma before/after therapy was significantly (P = 0.03) associated with higher viral load in the primary tumor site. Human papillomavirus type 16 integration and hypomethylation of the early (14 of 29, Z = 4.47, P disease recurrence with distant metastases. The genetic-epigenetic profile of HPV16 in pretherapy/posttherapy CaCx samples showed significant association with disease prognosis.

  20. Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis

    Directory of Open Access Journals (Sweden)

    Rocha Gislene FS

    2008-02-01

    Full Text Available Abstract Background Immunohistochemical studies of lymphatic vessels have been limited by a lack of specific markers. Recently, the novel D2-40 antibody, which selectively marks endothelium of lymphatic vessels, was released. The aim of our study is to compare lymphatic and blood vessel invasion detected by hematoxylin and eosin (H&E versus that detected by immunohistochemistry, relating them with morphologic and molecular prognostic factors. Methods We selected 123 cases of invasive mammary carcinomas stratified into three subgroups according to axillary lymph node status: macrometastases, micrometastases, and lymph node negative. Lymphatic (LVI and blood (BVI vessel invasion were evaluated by H&E and immunohistochemistry using the D2-40 and CD31 antibodies, and related to histologic tumor type and grade, estrogen and progesterone receptors, E-cadherin, Ki67, p53, and Her2/neu expression. Results LVI was detected in H&E-stained sections in 17/123 cases (13.8%, and in D2-40 sections in 35/123 cases (28.5% (Kappa = 0.433. BVI was detected in H&E-stained sections in 5/123 cases (4.1%, and in CD31 stained sections in 19/123 cases (15.4% (Kappa = 0.198. LVI is positively related to higher histologic grade (p = 0.013, higher Ki67 expression (p = 0.00013, and to the presence of macrometastases (p = 0.002, and inversely related to estrogen (p = 0.0016 and progesterone (p = 0.00017 receptors expression. Conclusion D2-40 is a reliable marker of lymphatic vessels and is a useful tool for lymphatic emboli identification in immunostained sections of breast carcinomas with higher identification rates than H&E. Lymphatic vessel invasion was related to other features (high combined histologic grade, high Ki67 score, negative hormone receptors expression associated with worse prognosis, probable reflecting a potential for lymphatic metastatic spread and aggressive behavior.

  1. HMGA1 Expression in Human Hepatocellular Carcinoma Correlates with Poor Prognosis and Promotes Tumor Growth and Migration in in vitro Models.

    Science.gov (United States)

    Andreozzi, Mariacarla; Quintavalle, Cristina; Benz, David; Quagliata, Luca; Matter, Matthias; Calabrese, Diego; Tosti, Nadia; Ruiz, Christian; Trapani, Francesca; Tornillo, Luigi; Fusco, Alfredo; Heim, Markus H; Ng, Charlotte Ky; Pallante, Pierlorenzo; Terracciano, Luigi M; Piscuoglio, Salvatore

    2016-12-01

    HMGA1 is a non-histone nuclear protein that regulates cellular proliferation, invasion and apoptosis and is overexpressed in many carcinomas. In this study we sought to explore the expression of HMGA1 in HCCs and cirrhotic tissues, and its effect in in vitro models. We evaluated HMGA1 expression using gene expression microarrays (59 HCCs, of which 37 were matched with their corresponding cirrhotic tissue and 5 normal liver donors) and tissue microarray (192 HCCs, 108 cirrhotic tissues and 79 normal liver samples). HMGA1 expression was correlated with clinicopathologic features and patient outcome. Four liver cancer cell lines with stable induced or knockdown expression of HMGA1 were characterized using in vitro assays, including proliferation, migration and anchorage-independent growth. HMGA1 expression increased monotonically from normal liver tissues to cirrhotic tissue to HCC (Pexpressed HMGA1, respectively. Patients with HMGA1-positive HCCs had earlier disease progression and worse overall survival. Forced expression of HMGA1 in liver cancer models resulted in increased cell growth and migration, and vice versa. Soft agar assay showed that forced expression of HMGA1 led to increased foci formation, suggesting an oncogenic role of HMGA1 in hepatocarcinogenesis. HMGA1 is frequently expressed in cirrhotic tissues and HCCs and its expression is associated with high Edmondson grade and worse prognosis in HCC. Our results suggest that HMGA1 may act as oncogenic driver of progression, implicating it in tumor growth and migration potential in liver carcinogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. A Decreased Ratio of Laminin-332 β3 to γ2 Subunit mRNA is Associated with Poor Prognosis in Colon Cancer

    Science.gov (United States)

    Guess, Cherise M.; LaFleur, Bonnie J.; Weidow, Brandy L.; Quaranta, Vito

    2010-01-01

    Laminin-332 (Ln-332) is a heterotrimeric glycoprotein (α3β3γ2) unique to epithelial cells with crucial roles in signaling, adhesion, and migration. Altered localization or expression levels of Ln-332, particularly its γ2 subunit, are of prognostic value in a variety of cancers. However, the lack of standardized methodology and the limited quantification of previous study results have left unanswered questions, including the role of γ2 transcript variants and whether differential expression of this chain represents dysregulation of the whole heterotrimer. Herein, we test the hypothesis that mRNA changes in one or more Ln-332 encoding genes can be used to distinguish between early- and advanced-stage cancer specimens and shed light on mechanistic questions raised by previous studies. Statistical analyses of human microarray data from the publicly available expression project in Oncology (expO) dataset, including examination of the distributions of Ln-332 subunit mRNA levels, identified a significant decrease in the Ln-332 β3:γ2 mRNA ratio between normal (n = 10) and early-stage colon cancer (n = 29) specimens. The β3:γ2 ratio was further decreased in metastatic colon cancer (n = 41) compared with early-stage samples. Our findings raise the possibility that Ln-332 γ2 may be a therapeutic target against metastatic colon cancer because a lowered β3:γ2 ratio would reduce expression of heterotrimeric Ln-332 and increase monomeric γ2 secretion. Further, standardized, quantitative methods for patient prognosis and therapeutic choice could be developed based upon the Ln-332 mRNA changes we uncovered. PMID:19383890

  3. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li Xin

    2010-04-01

    Full Text Available Abstract Background The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1 in nasopharyngeal carcinoma (NPC and its correlation with clinicopathologic features, including patients' survival time. Methods Using real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated. Results The expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (P EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues (P EIF4G1 protein in tumors were positively correlated with tumor T classification (P = 0.039, lymph node involvement (N classification, P = 0.008, and the clinical stages (P = 0.003 of NPC patients. Patients with higher EIF4G1 expression had shorter overall survival time (P = 0.019. Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth. Conclusion Our data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.

  4. Angels and demons: Th17 cells represent a beneficial response, while neutrophil IL-17 is associated with poor prognosis in squamous cervical cancer

    NARCIS (Netherlands)

    S. Punt (Simone); G.J. Fleuren (G.); E. Kritikou (Eva); E.W. Lubberts (Erik); J.B. Trimbos; E.S. Jordanova (Ekaterina S.); A. Gorter (Arko)

    2015-01-01

    textabstractThe role of interleukin (IL)-17 in cancer remains controversial. In view of the growing interest in the targeting of IL-17, knowing its cellular sources and clinical implications is crucial. In the present study, we unraveled the phenotype of IL-17 expressing cells in cervical cancer

  5. In patients with metastatic breast cancer the identification of circulating tumor cells in epithelial-to-mesenchymal transition is associated with a poor prognosis.

    Science.gov (United States)

    Bulfoni, Michela; Gerratana, Lorenzo; Del Ben, Fabio; Marzinotto, Stefania; Sorrentino, Marisa; Turetta, Matteo; Scoles, Giacinto; Toffoletto, Barbara; Isola, Miriam; Beltrami, Carlo Alberto; Di Loreto, Carla; Beltrami, Antonio Paolo; Puglisi, Fabio; Cesselli, Daniela

    2016-03-09

    Although recent models suggest that the detection of Circulating Tumor Cells (CTC) in epithelial-to-mesenchymal transition (EM CTC) might be related to disease progression in metastatic breast cancer (MBC) patients, current detection methods are not efficient in identifying this subpopulation of cells. Furthermore, the possible association of EM CTC with both clinicopathological features and prognosis of MBC patients has still to be demonstrated. Aims of this study were: first, to optimize a DEPArray-based protocol meant to identify, quantify and sort single, viable EM CTC and, subsequently, to test the association of EM CTC frequency with clinical data. This prospective observational study enrolled 56 MBC patients regardless of the line of treatment. Blood samples, depleted of CD45(pos) leukocytes, were stained with an antibody cocktail recognizing both epithelial and mesenchymal markers. Four CD45(neg) cell subpopulations were identified: cells expressing only epithelial markers (E CTC), cells co-expressing epithelial and mesenchymal markers (EM CTC), cells expressing only mesenchymal markers (MES) and cells negative for every tested marker (NEG). CTC subpopulations were quantified as both absolute cell count and relative frequency. The association of CTC subpopulations with clinicopathological features, progression free survival (PFS), and overall survival (OS) was explored by Wilcoxon-Mann-Whitney test and Univariate Cox Regression Analysis, respectively. By employing the DEPArray-based strategy, we were able to assess the presence of cells pertaining to the above-described classes in every MBC patient. We observed a significant association between specific CD45(neg) subpopulations and tumor subtypes (e.g. NEG and triple negative), proliferation (NEG and Ki67 expression) and sites of metastatic spread (e.g. E CTC and bone; NEG and brain). Importantly, the fraction of CD45(neg) cells co-expressing epithelial and mesenchymal markers (EM CTC) was significantly

  6. Membranous expressions of Lewis y and CAM-DR-related markers are independent factors of chemotherapy resistance and poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Zhu, Lian-Cheng; Gao, Jian; Hu, Zhen-Hua; Schwab, Carlton L; Zhuang, Hui-Yu; Tan, Ming-Zi; Yan, Li-Mei; Liu, Juan-Juan; Zhang, Dan-Ye; Lin, Bei

    2015-01-01

    Chemotherapy resistance is a common problem faced by patients diagnosed with epithelial ovarian cancer (EOC). Currently there are no specific or sensitive clinical biomarkers that maybe implemented to identify chemotherapy resistance and give insight to prognosis. The aim of this study is to investigate the roles of Lewis y antigen and the markers associated with cell-adhesion-mediated drug resistance (CAM-DR) in patients with EOC. 92 EOC patients who were treated with systemic chemotherapy after cytoreductive surgery were included in this analysis. Patients were divided into two groups, chemotherapy sensitive (n = 56) and resistant (n = 36). Immunohistochemical (IHC) staining for Lewis y and CAM-DR-related cell surface proteins including CD44, CD147, HE4 (Human epididymis protein 4), integrin α5, β1, αv and β3 were conducted on tissues collected during primary debulking surgery. Using multivariate logistic regressions, IHC results were compared to clinical variables and chemotherapy resistance to determine possible correlations. The relationships between IHC expression and progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox regression analysis. Membranous expression of Lewis y and all these CAM-DR-related markers were significantly higher in the resistant group than that of the sensitive group (all P < 0.01). Multivariate regression analysis revealed that high expression of Lewis y, CD44, HE4, integrin α5 and β1 as well as advanced FIGO stage were independent risk factors for chemotherapy resistance (all P < 0.05). Advanced FIGO stage, lymph node metastasis and high expression of Lewis y, CD44, CD147, HE4, integrin α5, β1 were associated with a shorter PFS and OS (all P < 0.05). Moreover, multivariate COX analysis demonstrated that the following variates were independent predictors of worse PFS and OS survival: late FIGO stage (P = 0.013, 0.049), high expressions of Lewis y (P = 0.010, 0.036), HE4 (P

  7. Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral Squamous Cell Carcinomas, Which Contributes to Poor Prognosis.

    Directory of Open Access Journals (Sweden)

    Andreia Bufalino

    Full Text Available Deregulated expression of activin A is reported in several tumors, but its biological functions in oral squamous cell carcinoma (OSCC are unknown. Here, we investigate whether activin A can play a causal role in OSCCs. Activin A expression was assessed by qPCR and immunohistochemistry in OSCC tissues. Low activin A-expressing cells were treated with recombinant activin A and assessed for apoptosis, proliferation, adhesion, migration, invasion and epithelial-mesenchymal transition (EMT. Those phenotypes were also evaluated in high activin A-expressing cells treated with follistatin (an activin A antagonist or stably expressing shRNA targeting activin A. Transfections of microRNA mimics were performed to determine whether the overexpression of activin A is regulated by miR-143/miR-145 cluster. Activin A was overexpressed in OSCCs in comparison with normal oral mucosa, and high activin A levels were significantly associated with lymph node metastasis, tumor differentiation and poor survival. High activin A levels promoted multiple properties associated with malignant transformation, including decreased apoptosis and increased proliferation, migration, invasion and EMT. Both miR-143 and miR-145 were markedly downregulated in OSCC cell lines and in clinical specimens, and inversely correlated to activin A levels. Forced expression of miR-143 and miR-145 in OSCC cells significantly decreased the expression of activin A. Overexpression of activin A in OSCCs, which is controlled by downregulation of miR-143/miR-145 cluster, regulates apoptosis, proliferation and invasiveness, and it is clinically correlated with lymph node metastasis and poor survival.

  8. Overexpression of the secretory small GTPase Rab27B in human breast cancer correlates closely with lymph node metastasis and predicts poor prognosis

    Directory of Open Access Journals (Sweden)

    Zhang Jia-Xing

    2012-12-01

    Full Text Available Abstract Background The secretory small GTPase Rab27b was recently identified as an oncogene in breast cancer (BC in vivo and in vitro studies. This research was designed to further explore the clinical and prognostic significance of Rab27B in BC patients. Methods The mRNA/protein expression level of Rab27B was examined by performing Real-time PCR, western blot, and immunohistochemistry (IHC assays in 12 paired BC tissues and matched adjacent noncancerous tissues (NAT. Then we carried out IHC assay in a large cohort of 221 invasive BC tissues, 22 normal breast tissues, 40 fibroadenoma (FA, 30 ductual carcinoma in situ (DCIS and 40 metastatic lymph nodes (LNs. The receiver operating characteristic curve method was applied to obtain the optimal cutoff value for high Rab27B expression. Epithelial-mesenchymal transition (EMT marker expression levels were detected in relation to Rab27B expression. Results We observed that the increased expression of Rab27B was dependent upon the magnitude of cancer progression (P P  Conclusion Our findings suggest that overexpression of Rab27B in BC coincides with lymph node metastasis and acquisition of a poor prognostic phenotype.

  9. Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma

    Directory of Open Access Journals (Sweden)

    Piotr Czapiewski

    2016-11-01

    Full Text Available Colorectal carcinoma (CRC is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7, are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases and the second one free of LN metastases (LN–, 85 cases. Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4% of primary tumours (PT and lymph node metastases (LNM; concordance between them was 94% ( 0.396. Keratin 7 was expressed in 8/85 cases (9.4% in the LN– group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS (p = 0.047 and presence of distant metastases at diagnosis (p = 0.005. Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.

  10. High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis.

    Science.gov (United States)

    Kao, Hsiao-Wen; Liang, D Cherng; Kuo, Ming-Chung; Wu, Jin-Hou; Dunn, Po; Wang, Po-Nan; Lin, Tung-Liang; Shih, Yu-Shu; Liang, Sung-Tzu; Lin, Tung-Huei; Lai, Chen-Yu; Lin, Chun-Hui; Shih, Lee-Yung

    2015-10-20

    The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML.

  11. CD47 overexpression is associated with decreased neutrophil apoptosis/phagocytosis and poor prognosis in non-small-cell lung cancer patients.

    Science.gov (United States)

    Barrera, Lourdes; Montes-Servín, Edgar; Hernandez-Martinez, Juan-Manuel; García-Vicente, María de Los Ángeles; Montes-Servín, Elizabeth; Herrera-Martínez, Marytere; Crispín, José C; Borbolla-Escoboza, José Rafael; Arrieta, Oscar

    2017-07-25

    Non-small-cell lung cancer (NSCLC) patients often exhibit neutrophilia, which has been associated with poor clinical outcomes. However, the mechanisms that lead to neutrophilia have not been fully established. CD47 is an antiphagocytic molecule that promotes neutrophil recruitment. Blood was collected from 50 treatment-naive patients with advanced NSCLC and from 25 healthy subjects. The frequency of CD66b+ cells and the expression of CD47 were determined by flow cytometry. Neutrophil apoptosis was determined by 7-amino-actinomycin D/Annexin V-APC staining. Phagocytosis was assessed by flow cytometry. Reactive oxygen species production after phorbol 12-myristate 13-acetate treatment was quantified by 2',7'-dichlorofluorescein fluorescence. Pro-inflammatory plasma cytokines were quantified using a cytometric bead array assay. The percentage of circulating neutrophils was significantly higher in patients than in controls (PCD47 expression in whole-blood samples and in the neutrophil fraction was higher in NSCLC patients than in controls (P=0.0408 and PCD47 expression in neutrophils negatively correlated with their ingestion by macrophages (P=0.0039). High CD47 expression was associated with a lower overall survival. Increased CD47 expression on the surface of neutrophils was associated with a delay in neutrophil apoptosis and with an impairment in their phagocytic clearance by macrophages, suggesting that CD47 overexpression may be one of the underlying mechanisms leading to neutrophilia in NSCLC patients.

  12. A CD21 low phenotype, with no evidence of autoantibodies to complement proteins, is consistent with a poor prognosis in CLL.

    Science.gov (United States)

    Nichols, Eva-Maria; Jones, Rachel; Watson, Rachael; Pepper, Chris J; Fegan, Chris; Marchbank, Kevin J

    2015-10-20

    B-cell chronic lymphocytic leukemia (CLL) is characterized by differential BCR signaling and autoimmune complications. Complement modulates B-cell function via C3d and CD21 cross-linked to the B-cell receptor (BCR). We hypothesized that CD21 contributes to BCR signaling and participates in the autoimmunity associated with CLL. We analyzed CD21 expression on 106 CLL patient samples and matched serum from 50 patients for the presence of soluble CD21 and autoantibodies to CR2, CR1, MCP and FH. CD21 expression on CLL B-cells was significantly lower than that expressed on B-cells from age-matched controls (P CLL patients, i.e. cases with unmutated IGHV genes (P = 0.0006), high CD38 (P = 0.02) and high ZAP70 expression (P = 0.0017). Low CD21 expression was inversely correlated to the levels of phosphotyrosine induced in CLL cells following BCR ligation with αIgM (r2 = -0.21). Importantly, lower CD21 expression was also predictive for reduced overall survival (P = 0.005; HR = 2.7). In conclusion, we showed that reduced expression of CD21 on CLL B-cells appears functionally relevant and was associated with poor clinical outcomes.

  13. High expression of C-X-C chemokine receptor 4 and Notch1 is predictive of lymphovascular invasion and poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Cong, Zhuangzhuang; Wu, Haiwei; Guo, Zhong; Qin, Tao; Xu, Yang; Jing, Hua; Wang, Yanqing; Shen, Yi

    2017-06-01

    C-X-C chemokine receptor 4 and Notch1 have been shown to play oncogenic role individually. This study aimed to determine the combinatorial role of C-X-C chemokine receptor 4 and Notch1 in lung adenocarcinoma. Expression of C-X-C chemokine receptor 4 and Notch1 was detected in resected tumor samples from 185 patients with lung adenocarcinoma at stage I-IIIa by immunohistochemistry. Correlations of their immunoscores with clinicopathological characteristics and disease-specific survival were retrospectively investigated. A three-dimensional capillary-like sprouting model was established to assess the effects of C-X-C chemokine receptor 4 and Notch1 on angiogenesis in vitro. The results revealed that expression of C-X-C chemokine receptor 4 and Notch1 was elevated in lung adenocarcinoma tissues. The high co-expression of C-X-C chemokine receptor 4 and Notch1 was significantly correlated with tumor size, tumor status, nodal status, tumor stage, and lymphovascular invasion, as well as decreased disease-specific survival. Multivariate analysis showed that lymphovascular invasion (hazard ratio: 0.205, 95% confidence interval: 0.086-0.491, p lung adenocarcinoma. Furthermore, Notch1 enhanced the effects of C-X-C chemokine receptor 4 to promote angiogenesis by regulating Flt1 and Flt4 in vitro. In conclusion, co-expression of C-X-C chemokine receptor 4 and Notch1 is associated with tumor progression and lymphovascular invasion and is an independent indicator of poor survival in lung adenocarcinoma. In lung adenocarcinoma patients with high C-X-C chemokine receptor 4 and Notch1 expression, simultaneous inhibition of both factors might be an effective treatment strategy.

  14. Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy

    Directory of Open Access Journals (Sweden)

    Xiubao Ren

    2017-04-01

    Full Text Available Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4 plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1 in non-small cell lung cancer (NSCLC tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled. All the patients had integrated clinicopathological records and follow-up data. TLR4 and PD-L1 expression on NSCLC samples were determined by immunohistochemistry, and serum soluble TLR4 (sTLR4 levels were measured by enzyme-linked immunosorbent assay. Results showed that TLR4 expression level in cancer tissue was significantly higher than that in para-cancer tissue. Elevated TLR4 expression was significantly associated with histological type (adenocarcinoma higher than squamous cell carcinoma, P = 0.041, increased clinical TNM stage (P < 0.001, and presence of lymphatic invasion (P < 0.001. Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC (r = −0.485, P = 0.003. TLR4 expression level was also positively correlated with the PD-L1 expression level (r = 0.545, P < 0.0001. Multivariate analysis showed that expression level of TLR4 was an independent prognostic factor and TLR4 overexpression indicated a poor overall survival and disease-free survival. Taken together, we conclude that expression of TLR4 in lung cancer is associated with PD-L1 and could predict the outcome of patients with NSCLC receiving pulmonary resection for cancer.

  15. Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor α-Chain (CD25 Expression Predicts a Poor Prognosis.

    Directory of Open Access Journals (Sweden)

    Kazunori Nakase

    Full Text Available A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML. We quantitatively examined the expression of interleukin-2 receptor α-chain (IL-2Rα, also known as CD25, IL-2Rβ, IL-3Rα, IL-4Rα, IL-5Rα, IL-6Rα, IL-7Rα, the common β-chain (βc, γc, granulocyte-macrophage colony-stimulating factor (GM-CSFRα, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3Rα, GM-CSFRα, IL-2Rα, γc, c-kit, and G-CSFR exhibited a wide spectrum of ≥10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFRα and c-fms were preferentially expressed in M4/M5 patients, G-CSF in M3 patients, and IL-2Rα in non-M3 patients. Elevated levels of IL-3Rα, GM-CSFRα, and IL-2Rα correlated with leukocytosis. In patients ≤60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2Rα was associated with a shorter overall survival. By incorporating IL-2Rα status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2Rα as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2Rα alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients ≤60 years old.

  16. Long Noncoding RNA RGMB-AS1 Indicates a Poor Prognosis and Modulates Cell Proliferation, Migration and Invasion in Lung Adenocarcinoma

    Science.gov (United States)

    Li, Ping; Zhang, Guojun; Li, Juan; Yang, Rui; Chen, Shanshan; Wu, Shujun; Zhang, Furui; Bai, Yong; Zhao, Huasi; Wang, Yuanyuan; Dun, Shaozhi; Chen, Xiaonan; Sun, Qianqian; Zhao, Guoqiang

    2016-01-01

    Lung cancer is the most common cause of cancer-related mortality worldwide. It is a complex disease involving multiple genetic and epigenetic alterations. The development of transcriptomics revealed the important role of long non-coding RNAs (lncRNAs) in lung cancer occurrence and development. Here, microarray analysis of lung adenocarcinoma tissues showed the abnormal expression of lncRNA RGMB-AS1. However, the role of lncRNA RGMB-AS1 in lung adenocarcinoma remains largely unknown. We showed that upregulation of lncRNA RGMB-AS1 was significantly correlated with differentiation, TNM stage, and lymph node metastasis. In lung adenocarcinoma cells, downregulation of lncRNA RGMB-AS1 inhibited cell proliferation, migration, invasion, and caused cell cycle arrest at the G1/G0 phase. In vivo experiments showed that lncRNA RGMB-AS1 downregulation significantly suppressed the growth of lung adenocarcinoma. The expression of lncRNA RGMB-AS1 was inversely correlated with that of repulsive guidance molecule b (RGMB) in lung adenocarcinoma tissues, and UCSC analysis and fluorescence detection assay indicated that lncRNA RGMB-AS1 may be involved in the development of human lung adenocarcinoma by regulating RGMB expression though exon2 of RGMB. In summary, our findings indicate that lncRNA RGMB-AS1 may play an important role in lung adenocarcinoma and may serve as a potential therapeutic target. PMID:26950071

  17. ROR functions as a ceRNA to regulate Nanog expression by sponging miR-145 and predicts poor prognosis in pancreatic cancer.

    Science.gov (United States)

    Gao, Song; Wang, Peng; Hua, Yongqiang; Xi, Hao; Meng, Zhiqiang; Liu, Te; Chen, Zhen; Liu, Luming

    2016-01-12

    lncRNAs have emerged as key regulators of tumor development and progression. ROR is a typical lncRNA that plays important regulatory roles in the pathogenesis and progression of tumors. Nevertheless, current understanding of the involvement of ROR in pancreatic adenocarcinoma tumorigenesis remains limited. In this study, we measured ROR in 61 paired cancerous and noncancerous tissue samples by qRT-PCR and investigated the biological role of ROR on the phenotypes of pancreatic cancer stem cells (PCSCs) in vitro and in vivo. The effects of ROR on PCSCs were studied by RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation. The positive ROR/Nanog interaction was identified and verified by immunohistochemistry assay. Compared with adjacent non-tumor tissues, ROR was up-regulated in most tumor tissues. Knockdown of ROR by RNA interference in PCSCs inhibited proliferation, induced apoptosis and decreased migration. Moreover, ROR silencing resulted in significantly decreased tumourigenicity of PCSCs in nude mice than controls. In particular, ROR may act as a ceRNA, effectively becoming a sink for miR-145, thereby activating the derepression of core transcription factors Nanog. In conclusions, we demonstrated that decreased ROR expression could inhibit cell proliferation, invasion, and tumourigenicity by modulating Nanog. Therefore, ROR is a potential novel prognostic marker to predict the clinical outcome of pancreatic cancer patients after surgery and may be a rational target for therapy.

  18. Overexpression of Forkhead Box M1 transcription factor and nuclear factor-κB in laryngeal squamous cell carcinoma: a potential indicator for poor prognosis.

    Science.gov (United States)

    Jiang, Li-Zhu; Wang, Peng; Deng, Bi; Huang, Chuang; Tang, Wei-Xue; Lu, Hong-Yi; Chen, Hong-Yan

    2011-08-01

    The Forkhead Box M1 transcription factor and nuclear factor-κB have been shown to play important roles in the development and progression of human cancers. However, the functional significance of Forkhead Box M1 transcription factor in laryngeal squamous cell carcinoma and the correlation between Forkhead Box M1 transcription factor and nuclear factor-κB remain unclear. In the current study, we have shown that Forkhead Box M1 transcription factor and nuclear factor-κB were significantly overexpressed in laryngeal squamous cell carcinoma tissues and precancerous lesions, compared with adjacent normal tissues (both P Box M1 transcription factor was significantly associated with histologic differentiation (rs = 0.321, P = .002), T stage (rs = 0.276, P = .009), lymph node metastasis (rs = 0.266, P = .012), and clinical stage (rs = 0.272, P = .010); overexpression of nuclear factor-κB was significantly associated with T stage (rs = 0.404, P Box M1 transcription factor and nuclear factor-κB were associated with worse overall survival (P = .041 and P Cox regression analysis showed that T stage, lymph node metastasis, and nuclear factor-κB were independent prognostic factors for laryngeal squamous cell carcinoma (P = .038, P = .014, and P = .005, respectively). Furthermore, a significant correlation was observed between Forkhead Box M1 transcription factor and nuclear factor-κB (rs = 0.683, P Box M1 transcription factor and nuclear factor-κB and the possible interaction between them may play important roles in the development and progression of laryngeal squamous cell carcinoma, and Forkhead Box M1 transcription factor and nuclear factor-κB may serve as useful prognostic markers for laryngeal squamous cell carcinoma. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  19. Many Terminal Cancer Patients Remain in Denial

    Science.gov (United States)

    ... professionals should appropriately assess patients' readiness for prognostic information," said study leader Siew-Tzuh Tang, a professor at Chang Gung University School of Nursing in Taiwan. Doctors should respect patients' reluctance to confront their poor prognosis if they ...

  20. ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Takafumi Kuroda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiating cells (CICs are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas by the ALDEFLUOR assay. ALDH1(high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high cells. ALDH1(high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

  1. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974)

    DEFF Research Database (Denmark)

    Daugaard, G; Skoneczna, I; Aass, N

    2011-01-01

    To compare the efficacy of one cycle of standard dose cisplatin, etoposide, and ifosfamide (VIP) plus three cycles of high-dose VIP followed by stem-cell infusion [high-dose chemotherapy (HD-CT arm)] to four cycles of standard cisplatin, etoposide, and bleomycin (BEP) in patients with poor......-prognosis germ-cell cancer (GCC). Patient and methods: Patients with poor-prognosis GCC were assigned to receive either BEP or VIP followed by HD-CT. To show a 15% improvement in a 1-year failure-free survival (FFS), the study aimed to recruit 222 patients but closed with 137, due to slow accrual....

  2. Isolated microalbuminuria indicates a poor medical prognosis

    NARCIS (Netherlands)

    Scheven, Lieneke; Van der Velde, Marije; Heerspink, Hiddo J. Lambers; De Jong, Paul E.; Gansevoort, Ron T.

    Background. Microalbuminuria is often regarded as a sign of end-organ damage due to diabetes and/or hypertension, and as such to be associated with an increased risk for cardiovascular events. It has been questioned whether isolated microalbuminuria, that is microalbuminuria in the absence of a

  3. Family with sequence similarity 83, member B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild-type epidermal growth factor receptor.

    Science.gov (United States)

    Yamaura, Takumi; Ezaki, Junji; Okabe, Naoyuki; Takagi, Hironori; Ozaki, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Muto, Satoshi; Matsumura, Yuki; Hasegawa, Takeo; Hoshino, Mika; Osugi, Jun; Shio, Yutaka; Waguri, Satoshi; Tamura, Hirosumi; Imai, Jun-Ichi; Ito, Emi; Yanagisawa, Yuka; Honma, Reiko; Watanabe, Shinya; Suzuki, Hiroyuki

    2018-02-01

    Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor ( EGFR ) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B ( FAM83B ) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated. Matched tumor and adjacent normal tissue samples were obtained from 216 patients who underwent complete lung resection for primary lung ADC and were examined for FAM83B expression using cDNA microarray analysis. The associations between FAM83B expression and clinicopathological parameters, including patient survival, were examined. FAM83B was highly expressed in tumors from males, smokers and in tumors with wild-type EGFR . Multivariate analyses further confirmed that wild-type EGFR tumors were significantly positively associated with FAM83B expression. In survival analysis, FAM83B expression was associated with poor outcomes in disease-free survival and overall survival, particularly when stratified against tumors with wild-type EGFR . Furthermore, FAM83B knockdown was performed to investigate its phenotypic effect on lung ADC cell lines. Gene silencing by FAM83B RNA interference induced growth suppression in the HLC-1 and H1975 lung ADC cell lines. FAM83B may be involved in lung ADC tumor proliferation and can be a predictor of poor survival. FAM83B is also a potential novel therapeutic target for ADC with wild-type EGFR .

  4. Factors of poor prognosis of visceral leishmaniasis among children under 12 years of age. A retrospective monocentric study in Belo Horizonte, State of Minas Gerais, Brazil, 2001-2005

    Directory of Open Access Journals (Sweden)

    Alexandre Sérgio da Costa Braga

    2013-01-01

    Full Text Available INTRODUTION: A major concern with the visceral leishmaniasis (VL is its high lethality rate, even with proper treatment. Low age, prior malnutrition, disease duration prior to diagnosis, severe anemia, fever for more than 60 days, diarrhea and jaundice are known poor prognostic factors. The goals of this study are to describe the clinical and laboratory characteristics of VL among children under 12 years of age and to identify the factors associated with VL poor outcome. METHODS: Two hundred and fifty children under 12 years of age with confirmed VL admitted to Hospital João Paulo II (FHEMIG, Belo Horizonte, Brazil, between January 2001 and December 2005 were evaluated retrospectively. The primary outcome was the poor clinical evolution: sepsis, and/or pneumonia, and/or urinary tract infection, and/or of bleeding (expect epistaxis, and/or severe neutropenia (neutrophil < 500 cells/mm3. Odds ratio (crude and adjusted and its 95% confidence interval for each variable were calculated. Values less than 0.05 were considered significant. RESULTS: Average age was 3.3 years (3.6 months-11.6 years, 71.2% were younger than 5 years and 47.2% lived in Metropolitan Area of Belo Horizonte. The mean fatality rate was 3.6%. Sixty-six (26.4% patients presented poor evolution. After a multivariate analysis, age <18 months, abnormal respiratory physical examination on hospital admission, and platelets <85,000/mm3 remained associated with increased chance of poor evolution. CONCLUSIONS: The results suggest that patients aged between 12 and 18 months, with platelet counts bellow 85,000/mm3, and respiratory abnormalities at admission should be considered potentially severe.

  5. Increased Levels of β-catenin, LEF-1, and HPA-1 Correlate with Poor Prognosis for Acral Melanoma with Negative BRAF and NRAS Mutation in BRAF Exons 11 and 15 and NRAS Exons 1 and 2

    Science.gov (United States)

    Xu, Sanxiong; Zhang, Jinyu; Jiang, Yongxin; Chen, Yongbin; Li, Hongjun; Liu, Xuefeng; Xu, Da; Chen, Yanjin; Yang, Yihao; Zhang, Ya; Li, Dongxu; Xia, Junfeng

    2015-01-01

    To determine the expression of β-catenin, lymphoid enhancer-binding protein-1 (LEF-1), and heparanase-1 (HPA-1) and to evaluate these proteins' potential prognostic values in malignant acral melanoma without mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2, specimens from 90 patients with wild-type BRAF and NRAS were assessed and analyzed by immunohistochemistry and western blotting. The positive expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was observed in 36 (72%), 31 (62%), and 32 (64%) of the detected acral melanomas, respectively. The expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was not correlated with gender, age, or diseased body parts (p>0.05), but was significantly positively correlated with the tumor node metastasis (TNM) stage and metastasis (correlation=0.406 and 0.716, 0.397 and 0.582, 0.353 and 0.579; p=0.040 and 0.0001, 0.0040 and 0.0001, 0.0120 and 0.0001, respectively). We also observed that the increased expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was significantly correlated with decreased survival and poor prognosis (p=0.001, 0.010, and 0.023, respectively). A multifactorial analysis using Cox's regression model revealed that β-catenin, lymphoid enhancer-binding protein-1, heparanase-1, and the TNM stage were all independent factors in malignant melanoma (risk ratios were 7.294, 5.550, 5.622, and 4.794; p-values were 0.007, 0.018, 0.018, and 0.029, respectively). This study may provide the basis for the use of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 as novel targets in the treatment of malignant invasion and metastasis in acral melanoma cancer. The expression of β-catenin, LEF-1, and HPA-1 was assessed and compared in malignant melanoma with that of peritumoral tissue and benign nevus in the patients with negative mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2. The study may provide the basis for

  6. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... your chances of survival. The estimate of how the disease will go for you is called prognosis. It ... to discuss cancer prognosis (the likely course of the disease). Learn key points about prognosis and how to ...

  7. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... disease will go for you is called prognosis. It can be hard to understand what prognosis means ... prognosis include: The type of cancer and where it is in your body The stage of the ...

  8. Care seeking for maternal health: challenges remain for poor women

    African Journals Online (AJOL)

    Bernt Lindtjorn

    and extend labor. Some women acknowledged that a young mother is physically unprepared for childbirth and therefore more susceptible to complications. The majority of all respondents identified breech presentation, prolonged labor, maternal exhaustion retained placenta, prolapsed uterus and excessive bleeding in the ...

  9. Care seeking for maternal health: challenges remain for poor women

    African Journals Online (AJOL)

    Objective: To explore the knowledge, attitudes and beliefs which influence maternal care seeking behaviour and practices in pregnancy and childbirth. Methods: Qualitative data - focus group discussions and in depth interviews with women, men and adolescents- were gathered from communities distributed across ...

  10. Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: the final results of a European Organization for Research in Cancer Therapy Genitourinary Group Trial

    NARCIS (Netherlands)

    de Reijke, T. M.; Keuppens, F. I.; Whelan, P.; Kliment, J.; Robinson, M. R.; Rea, L. A.; Sylvester, R. J.

    1999-01-01

    The outcome of patients with symptomatic metastatic prostate cancer is poor and improved treatment regimens are urgently needed. Theoretically, the combination of orchiectomy and chemotherapy could reduce androgen sensitive and insensitive cells in the prostate. This European Organization for

  11. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Overview Research Cancer Screening Cancer Screening Overview Screening Tests Research Diagnosis and Staging Symptoms Diagnosis Staging Prognosis ... Cancer Prevention Overview Screening Cancer Screening Overview Screening Tests Diagnosis & Staging Symptoms Diagnosis Staging Prognosis Treatment Types ...

  12. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Understanding Cancer Prognosis Oncologist Anthony L. Back, M.D., a national expert on doctor-patient communications, talks with one of his patients about what she'd like to know of her prognosis. Credit: National ...

  13. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... during a certain period of time after diagnosis. Disease-free survival This statistic is the percentage of ... discuss cancer prognosis (the likely course of the disease). Learn key points about prognosis and how to ...

  14. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... doctor may tell you that you have a good prognosis if statistics suggest that your cancer is ... about how to discuss prognosis with their patients. Good communication, he says, is part of providing good ...

  15. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Prognosis Questions to Ask about Your Diagnosis Research Understanding Cancer Prognosis Oncologist Anthony L. Back, M.D., a national expert on doctor-patient communications, talks with one of his patients about what ...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... doctor to give you an accurate prognosis. Understanding the Difference Between Cure and Remission Cure means that ... about her colorectal cancer prognosis. Diving Out of the Dark View this video on YouTube. Andrew wants ...

  17. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... chances of survival. The estimate of how the disease will go for you is called prognosis. It can be hard to understand what prognosis means and also hard to talk about, even for doctors. Many Factors Can Affect Your Prognosis Some of the factors that affect ...

  18. Factores que determinan el mal pronóstico y la exacerbación del asma en niños que asisten a consulta de alergología pediátrica Factors determining the poor prognosis and asthma exacerbation in children seen in the pediatric allergy service

    Directory of Open Access Journals (Sweden)

    Alain R. Rodríguez-Orozco

    2007-03-01

    Full Text Available El asma es una de las enfermedades de mayor impacto en la práctica pediátrica. Este es un estudio descriptivo, transversal que se realizó con el objetivo de identificar los factores que determinan la exacerbación y el mal pronóstico del asma bronquial en los niños. Se estudiaron 45 pacientes con diagnóstico de asma bronquial. Las crisis se presentaron en el hogar en el 76 % y en el 24 %, en la escuela. Los desencadenantes de las crisis agudas de asma bronquial fueron: el ejercicio (73 %, las infecciones respiratorias (57 % y la rinitis (55 %. Los factores de mal pronóstico más frecuentemente encontrados fueron: rinorrea sin catarro (60 %, sexo masculino (51 %, 3 o más episodios de sibilancias en los 6 meses previos (42 % y asma en los padres (37 %. La presencia de las exacerbaciones y los criterios de mal pronóstico repercuten en el control y en la calidad de vida del niño asmático y deben detectarse en la consulta de atención primaria.Asthma is one of the diseases with a greater impact on pediatric practice. This descriptive, cross-sectional study was undertaken to identify those factors determining the exacerbation and poor prognosis of bronchial asthma in children. Forty five patients with diagnosis of bronchial asthma were studied. The crises were developed at home in 76 % and at school in 24 % of the children. Triggering causes of acute crises of bronchial asthma were: exercise (73 %, respiratory infections (57 %, and rhinitis (55 %. The factors of poor prognosis most frequently found were: rhinorrhea without cold (60 %, male sex (51%, three or more episodes of wheezes in previous months (42 %, and asthma in parents (37 %. The presence of exacerbations and the criteria of poor prognosis influence on the control and quality of life of the asthmatic children, and they should be detected at the primary care level.

  19. Poor Sleep Habits = Poor Grades

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_166509.html Poor Sleep Habits = Poor Grades Study of college students finds ... socialize, college life seems geared toward an erratic sleep schedule. But new research suggests that an unpredictable ...

  20. Fish remains and humankind

    Directory of Open Access Journals (Sweden)

    Andrew K G Jones

    1997-08-01

    Full Text Available The four papers in this issue represent a trawl of the reports presented to the Fourth meeting of the International Council for Archaeozoology (ICAZ Fish Remains Working Group, which met at the University of York in 1987. The conference discussed material from many parts of the world - from Australasia to the north-west coast of America - and many eras, ranging in date from the early Pleistocene to the 1980s. It demonstrated both the variety of work being carried out and the growing interest in ancient fish remains. Internet Archaeology plans to publish other batches of papers from this conference. These reports will demonstrate the effort being made to distinguish between assemblages of fish remains which have been deposited by people and those which occur in ancient deposits as a result of the action of other agents. To investigate this area, experiments with modern material and observations of naturally occurring fish bone assemblages are supplemented with detailed analysis of ancient and modern fish remains. The papers published here illustrate the breadth of research into osteology, biogeography, documentary research, and the practicalities of recovering fish remains. Read, digest and enjoy them! Using the Internet for publishing research papers is not only ecologically sound (saving paper, etc. it disseminates scholarship to anyone anywhere on the planet with access to what is gradually becoming necessary technology in the late 20th century. Hopefully, future groups of papers will include video and audio material recorded at the conference, and so enable those who could not attend to gain further insights into the meeting and the scholarship underpinning this area of research.

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Diagnosis Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & ...

  3. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... our information on Coping With Cancer helpful. Understanding Statistics About Survival Doctors estimate prognosis by using statistics that researchers have collected over many years about ...

  4. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... and Prevention Risk Factors Genetics Cancer Prevention Overview Research Cancer Screening Cancer Screening Overview Screening Tests Research Diagnosis and Staging Symptoms Diagnosis Staging Prognosis Questions ...

  5. Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

    DEFF Research Database (Denmark)

    Jepsen, P; Schmidt, L E; Larsen, F S

    2010-01-01

    The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.......The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown....

  6. Differential Associations Between Specific Depressive Symptoms and Cardiovascular Prognosis in Patients With Stable Coronary Heart Disease

    NARCIS (Netherlands)

    Hoen, Petra W.; Whooley, Mary A.; Martens, Elisabeth J.; Na, Beeya; van Melle, Joost P.; de Jonge, Peter

    2010-01-01

    Objectives The purpose of this research was to evaluate the relationship between cognitive and somatic depressive symptoms and cardiovascular prognosis. Background Depression in patients with stable coronary heart disease (CHD) is associated with poor cardiac prognosis. Whether certain depressive

  7. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Questions to Ask about Your Diagnosis Research Understanding Cancer Prognosis Oncologist Anthony L. Back, M.D., a ... for provider care teams (PDF-210KB). Understanding Your Cancer Prognosis Video View this video on YouTube. Three ...

  8. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... with the same type of cancer. Several types of statistics may be used to estimate prognosis. The most ... see the benefit of new treatments and ways of finding cancer. So, the statistics your doctor uses to make a prognosis may ...

  9. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... hard to talk about, even for doctors. Many Factors Can Affect Your Prognosis Some of the factors that affect prognosis include: The type of cancer ... think they are too impersonal to be of value to you. It is up to you to ...

  10. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.

    Science.gov (United States)

    Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

    2015-01-01

    Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Our findings have major

  11. Clinical severity and prognosis of hand eczema

    DEFF Research Database (Denmark)

    Hald, M; Agner, T; Blands, J

    2009-01-01

    to identify factors associated with severe disease and a poor prognosis. METHODS: Study participants were 799 patients with HE from nine dermatological clinics in Denmark. Severity assessment of the HE was done at baseline and at the 6-month follow-up using the Hand Eczema Severity Index (HECSI...

  12. Allogeneic bone marrow transplantation for severe aplastic anemia patients with risk factors for poor prognosis: is fludarabine a requirement? Transplante alogênico de medula óssea em portadores de anemia aplásica severa com fatores de mau prognóstico: é necessário fludarabina?

    Directory of Open Access Journals (Sweden)

    Carlos R. de Medeiros

    2008-08-01

    Full Text Available Hematopoietic progenitor cell transplantation from HLA-identical sibling donors cures 70-90% of Severe Aplastic Anemia (sAA patients. Older age, heavy exposure to transfusions, immunosuppression treatment (IST with a long interval from diagnosis to transplant and infection at procedure are associated with poor outcomes. We transplanted 18 patients with sAA and at least one risk factor (RF for poor prognosis (age >35 years, >50 transfusions prior to transplant, unresponsiveness to previous IST and bacterial or fungal infection at transplant from 2001 to 2005, using cyclophosphamide (CY - 5 patients or busulfan plus CY (13 patients. Sixteen patients engrafted, two died with no engraftment, three patients had evidence of graft failure at days +67, +524 and +638 (two died and one was rescued with IST. Grade III/IV mucositis occurred in 39% but neither aGVHD nor cGVHD were observed. The Kaplan-Meier probability of survival was 75% at 2.14 years, with a trend favoring survival by number of RF (1 versus =2 RF (P = 0.06. These results are comparable to recent data reported with fludarabine-based conditioning in patients with poor prognosis sAA. Due to the small sample size, prospective clinical trials with larger cohorts of patients are needed to confirm the real benefits of fludarabine-based conditioning, and also to define the best agent(s to be associated with Fludarabine as preparative regimen for sAA patients with poor prognosis.Transplante de medula óssea de doador irmão HLA-idêntico pode curar 70%-90% dos portadores de anemia aplásica severa (AAs. Pacientes mais idosos, muito transfundidos, longamente tratados com imunossupressão (IS e com infecções ao tempo do transplante têm pior evolução. Nós transplantamos 18 pacientes com AAs e pelo menos um dos fatores associados a pior prognóstico (idade >35 anos, >50 transfusões antes do transplante, falta de resposta à imunossupressão prévia e infecção bacteriana ou fúngica ao

  13. Hand eczema - prognosis and consequences

    DEFF Research Database (Denmark)

    Petersen, A. H.; Johansen, J D; Hald, M

    2014-01-01

    BACKGROUND: Hand eczema is recognized as a long-lasting disease with personal and societal repercussions. Long-term studies are required to generate information on factors contributing to a poor outcome. OBJECTIVES: The aims of this 7-year follow-up study were to evaluate the clinical course...... of patients with hand eczema, the occupational consequences and to identify risk factors associated with a poor prognosis. MATERIALS AND METHODS: In all, 536 patients with hand eczema participated and were examined by a dermatologist. The clinical severity was assessed at baseline and 7 years later using...... a self-administrated photographic guide. Additional information was obtained from a questionnaire. RESULTS: Based on the photographic guide, 73% experienced a clinical improvement. Notably, 20% had moderate to very severe hand eczema at follow-up. Severe hand eczema or frequent eruptions at baseline...

  14. Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein.

    Science.gov (United States)

    Tan, Jintong; Kan, Juan; Qiu, Gang; Zhao, Dongying; Ren, Fang; Luo, Zhongcheng; Zhang, Yongjun

    2015-01-01

    Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1-4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis.

  15. Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein

    Science.gov (United States)

    Zhao, Dongying; Ren, Fang; Luo, Zhongcheng; Zhang, Yongjun

    2015-01-01

    Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1–4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis. PMID:26509880

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of Cancer Drugs ... Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer ...

  17. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View this ...

  18. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of Cancer ... Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & ...

  19. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Diagnosis Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to Cancer Self Image & Sexuality Day to Day Life Survivorship Support for Caregivers ...

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... help coping with your prognosis, you may find our information on Coping With Cancer helpful. Understanding Statistics ... comments on this post. All comments must follow our comment policy . National Cancer Institute at the National ...

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... to estimate cancer-specific survival that does not use information about the cause of death. It is ... of finding cancer. So, the statistics your doctor uses to make a prognosis may not be based ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... to talk about, even for doctors. Many Factors Can Affect Your Prognosis Some of the factors that ... Understanding your cancer and knowing what to expect can help you and your loved ones make decisions. ...

  3. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... of survival. The estimate of how the disease will go for you is called prognosis. It can ... they cannot be used to predict exactly what will happen to you. Everyone is different. Treatments and ...

  4. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... respond to treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you ... the decisions you may face include: Which treatment is best for you If you want treatment How ...

  5. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Research Diagnosis and Staging Symptoms Diagnosis Staging Prognosis Questions to Ask about Your Diagnosis Research Cancer Treatment ... List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping with ...

  6. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of Cancer Drugs ... Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer ...

  7. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... hard to talk about, even for doctors. Many Factors Can Affect Your Prognosis Some of the factors ... Services Website Linking U.S. Department of Health and Human Services National Institutes of Health National Cancer Institute ...

  8. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Research Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of ... Diagnosis Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping ...

  9. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... respond to treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you and ... certain how it will go for you. If You Decide Not to Have Treatment If you decide ...

  10. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... to treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you and ... will go for you. If You Decide Not to Have Treatment If you decide not to have ...

  11. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Research Tools, Specimens, and Data Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog ... before cancer How you respond to treatment Seeking Information About Your Prognosis Is a Personal Decision When ...

  12. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... to Ask about Your Diagnosis Research Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information ... Tests Diagnosis & Staging Symptoms Diagnosis Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs ...

  13. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View this ...

  14. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... on Coping With Cancer helpful. Understanding Statistics About Survival Doctors estimate prognosis by using statistics that researchers ... The most commonly used statistics include: Cancer-specific survival This is the percentage of patients with a ...

  15. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... side effects from the cancer treatments you received. Video Series This video series offers the perspectives of ... care teams (PDF-210KB). Understanding Your Cancer Prognosis Video View this video on YouTube. Three cancer patients ...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... to treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you and ... how long she has to live. For Doctors, a Patient-Centered Approach View this video on YouTube. ...

  17. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... spread. Certain traits of the cancer cells Your age and how healthy you were before cancer How ... Your Cancer Prognosis Video View this video on YouTube. Three cancer patients and their doctor share their ...

  18. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Diagnosis Staging Prognosis Questions to Ask about Your Diagnosis Research Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials ... Cancer Screening Overview Screening Tests Diagnosis & Staging ... Treatment Types of Treatment Side Effects Clinical Trials Cancer ...

  19. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... in a clear and supportive way. Two viewer guides are also available: for patients (PDF-210KB) and for provider care teams (PDF-210KB). Understanding Your Cancer Prognosis Video View this video on YouTube. ...

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... M.D., a national expert on doctor-patient communications, talks with one of his patients about what ... how to discuss prognosis with their patients. Good communication, he says, is part of providing good care. ...

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Unusual Cancers of Childhood Treatment Childhood Cancer Genomics Study Findings Metastatic Cancer Metastatic Cancer Research Common Cancer ... your prognosis. Survival statistics most often come from studies that compare treatments with each other, rather than ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you and your ... about it, and gain valuable insight from the personal ways each patient has approached questions about their ...

  3. The poor prognosis of childhood-onset bipolar disorder

    NARCIS (Netherlands)

    Leverich, Gabriele S.; Post, Robert M.; Keck, Paul E.; Altshuler, Lori L.; Frye, Mark A.; Kupka, Ralph W.; Nolen, Willem A.; Suppes, Trisha; McElroy, Susan L.; Grunze, Heinz; Denicoff, Kirk; Moravec, Maria K. M.; Luckenbaugh, David

    Objective We examined age of onset of bipolar disorder as a potential course-of-iflness modifier with the hypothesis that early onset will engender more severe illness. Study design A total of 480 carefully diagnosed adult outpatients with bipolar disorder (mean age, 42.5 +/- 11.6 years) were

  4. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Matthew H., E-mail: stenmark@med.umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); McHugh, Jonathan B. [Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Walline, Heather M.; Komarck, Christine [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Worden, Francis P. [Department of Medical Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Mukherji, Suresh K. [Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Carey, Thomas E. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2014-03-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.

  5. Visceral Obesity is Associated with Poor Prognosis in Pancreatic Adenocarcinoma.

    Science.gov (United States)

    Kim, Bun; Chung, Moon Jae; Park, Se Woo; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Chung, Jae Bock

    2016-01-01

    An association between obesity and unfavorable outcomes for various types of malignancy has been established. Nevertheless, the impact of visceral obesity (VO) on outcomes in pancreatic cancer is still unknown and controversial. The aim of this study was to uncover an association between VO and pancreatic cancer outcomes. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed and treated in Severance Hospital from January 2006 to December 2011. Compared to the low-VO group (n = 260), the high-VO group (n = 239) was mostly male (68.2% vs. 31.8%, P alcohol intake status (52.3% vs. 26.4%, P pancreatic cancer, VO at the time of diagnosis is associated with negative outcomes, such as shorter PFS and OS.

  6. Mild hyponatremia carries a poor prognosis in community subjects

    DEFF Research Database (Denmark)

    Sajadieh, Ahmad; Binici, Zeynep; Mouridsen, Mette Rauhe

    2009-01-01

    years with no history of cardiovascular disease, stroke, or cancer. Baseline evaluation included 48-hour ambulatory electrocardiogram monitoring, blood tests, and a questionnaire. Hyponatremia was defined as s-Na

  7. SULFs in human neoplasia: implication as progression and prognosis factors

    Directory of Open Access Journals (Sweden)

    Schved Jean-François

    2011-05-01

    Full Text Available Abstract Background The sulfation pattern of heparan sulfate chains influences signaling events mediated by heparan sulfate proteoglycans located on cell surface. SULF1 and SULF2 are two endosulfatases able to cleave specific 6-O sulfate groups within the heparan chains. Their action can modulate signaling processes, many of which with key relevance for cancer development and expansion. SULF1 has been associated with tumor suppressor effects in various models of cancer, whereas SULF2 dysregulation was in relation with protumorigenic actions. However, other observations argue for contradictory effects of these sulfatases in cancer, suggesting the complexity of their action in the tumor microenvironment. Methods We compared the expression of the genes encoding SULF1, SULF2 and heparan sulfate proteoglycans in a large panel of cancer samples to their normal tissue counterparts using publicly available gene expression data, including the data obtained from two cohorts of newly-diagnosed multiple myeloma patients, the Oncomine Cancer Microarray database, the Amazonia data base and the ITTACA database. We also analysed prognosis data in relation with these databases. Results We demonstrated that SULF2 expression in primary multiple myeloma cells was associated with a poor prognosis in two independent large cohorts of patients. It remained an independent predictor when considered together with conventional multiple myeloma prognosis factors. Besides, we observed an over-representation of SULF2 gene expression in skin cancer, colorectal carcinoma, testicular teratoma and liver cancer compared to their normal tissue counterpart. We found that SULF2 was significantly over-expressed in high grade uveal melanoma compared to low grade and in patients presenting colorectal carcinoma compared to benign colon adenoma. We observed that, in addition to previous observations, SULF1 gene expression was increased in T prolymphocytic leukemia, acute myeloid leukemia

  8. Number of tumor foci predicts prognosis in papillary thyroid cancer.

    Science.gov (United States)

    Qu, Ning; Zhang, Ling; Ji, Qing-hai; Zhu, Yong-xue; Wang, Zhuo-ying; Shen, Qiang; Wang, Yu; Li, Duan-shu

    2014-12-04

    Papillary thyroid cancer (PTC) often presents as multifocal. However, the association of multifocality with poor prognosis remains controversial. The aim of this retrospective study was to identify the characteristics of PTC with multiple foci and to evaluate the association between multifocality and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as G1 (1 tumor focus), G2 (2 foci), and G3 (3 or more foci). We analyzed the clinicopathological features and clinical outcomes in each classification. A Cox regression model was used to assess the relationship between multifocality and recurrence or cancer mortality. The G1, G2 and G3 groups included 287, 141 and 68 patients, respectively. The mean age was 47.1±16.1 yr in G1, 41.1±18.4 yr in G2, and 35.5±15.9 yr in G3 and differed significantly among the 3 groups (p=0.001). The proportion of extrathyroidal extension, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) in the G1 to G3 groups increased with increasing number of tumor foci. The Kaplan-Meier curves revealed that G3 had the shortest recurrence-free survival, and differences were significant among the 3 groups (p=0.001, Log Rank test). Furthermore, cancer-specific survival rates decreased significantly with increasing number of tumor foci (p=0.041). Independent predictors of recurrence by multivariate Cox analysis included >3 tumor foci [HR 2.60, 95% confidence interval (CI) 1.53-4.39, p=0.001] and extrathyroidal extension (HR 1.95, CI 1.12-3.38, p=0.018). An increase in the number of tumors is associated with a tendency toward more aggressive features and predicts poor prognosis in PTC.

  9. Poor title--poor manuscript?

    Science.gov (United States)

    Gjersvik, Petter; Gulbrandsen, Pål; Aasheim, Erlend T; Nylenna, Magne

    2013-12-10

    The title of a scientific article is important for several reasons. Does the title of a manuscript submitted for publication in a medical journal reflect the quality of the manuscript itself? We prepared criteria for poor, fair and good titles and tested them in pilot studies. All manuscripts submitted to the Journal of the Norwegian Medical Association during the period 1 September 2009-31 August 2011 as original articles (n = 211) or review articles (n = 110) were recorded. The quality of the titles was scored by two former editors. Primary outcome measures were rejection rates and odds ratio for rejection of manuscripts with a poor title compared to those with a good title. For original articles, the rejection rate for manuscripts with a poor, fair or good title amounted to 88%, 73% and 61% (p = 0.002) respectively, and for review articles 83%, 56% and 38% (p title compared to those with a good title was 4.6 (95% CI: 1.7-12.3) for original articles and 8.2 (95% CI: 2.6-26.4) for review articles. In a logistic regression model, the quality of the title explained 14% and 27% of the variance in outcome for original articles and review articles respectively. In this study, a poor manuscript title was significantly associated with manuscript rejection. This indicates that the quality of the title often reflects the quality of the manuscript itself.

  10. Novelties in COPD prognosis: evolution of survival indexes.

    Science.gov (United States)

    Sferrazza Papa, G F; Battaglia, S; Solidoro, P

    2015-04-01

    Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of the acute exacerbation, COPD remains affected by poor prognosis in the medium and long term. Moreover, the task of predicting prognosis remains a major challenge for respiratory physicians. In order to overcome this limitation, several indexes have been proposed to assess the COPD patient in his/her complexity. The rationale is that, by using numerical indexes physicians may improve their clinical judgment to tailor and share therapeutical choices, i.e. referring the patient for surgery or lung transplantation. On this ground, Almagro et al. recently proposed the CODEX index, as the latest evolution of the BODE through the BODEx (which takes into account exacerbations), by adding the evaluation of comorbidity to the severity of dyspnoea, airway obstruction and history of exacerbations. As afore mentioned, treatment of COPD with respiratory acidosis has been revolutionized by the use of NIV, by reducing the need for intubation and in-hospital mortality of patients with severe COPD exacerbations. Nowadays, new promising techniques, such as minimally invasive extracorporeal devices, may hasten the clearance of carbon dioxide and reduce the work of breathing and the need for ventilation of COPD patients. These techniques still lack of randomized controlled studies; however, the approach of extracorporeal CO2 removal has the potential to further improve the prognosis of severe exacerbation of COPD patients. In this paper we discuss the prognostic evaluation of patients affected by COPD through the evolution of dedicated indexes, which mirror the focus of current research on the disease.

  11. Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia.

    Science.gov (United States)

    Garcia-Manero, Guillermo; Almeida, Antonio; Giagounidis, Aristoteles; Platzbecker, Uwe; Garcia, Regina; Voso, Maria Teresa; Larsen, Stephen R; Valcarcel, David; Silverman, Lewis R; Skikne, Barry; Santini, Valeria

    2016-01-01

    on the efficacy and safety of CC-486 in the treatment of IPSS lower-risk MDS with poor prognosis due to the presence of both RBC transfusion-dependent anemia and thrombocytopenia. Positive results of the AZA-MDS-003 study may expand treatment options for patients with IPSS lower-risk MDS. ClinicalTrials.gov NCT01566695, registered March 27, 2012.

  12. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... medical records. Relative survival This statistic is another method used to estimate cancer-specific survival that does ... your prognosis. Survival statistics most often come from studies that compare ... by their creator. In such cases, it is necessary to contact the writer, artists, ...

  13. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung ... may have questions about how serious your cancer is and your chances of survival. The estimate of how the disease will go for you is called prognosis. It ...

  14. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Staging Prognosis Questions to Ask about Your Diagnosis Research Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information ... Cancer Genomics Study Findings Metastatic Cancer Metastatic Cancer Research ... Cancer Types Recurrent Cancer Midline Tract Carcinoma Childhood Midline Tract ...

  15. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) ... may have questions about how serious your cancer is and your chances of survival. The estimate of how the disease will go for you is called prognosis. It ...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... to you. Everyone is different. Treatments and how people respond to treatment can differ greatly. Also, it takes years to see the benefit of new treatments and ways of finding cancer. So, the statistics your doctor uses to make a prognosis may not be based on treatments ...

  17. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Your Cancer Prognosis Video View this video on YouTube. Three cancer patients and their doctor, Anthony L. ... One Couple's Creative Response View this video on YouTube. Vanessa, an artist, and her husband Roy discover ...

  18. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Your Diagnosis Research Understanding Cancer Prognosis Oncologist Anthony L. Back, M.D., a national expert on doctor- ... Centered Approach View this video on YouTube. Anthony L. Back, M.D., coaches other oncologists about how ...

  19. Prognosis of dementia

    NARCIS (Netherlands)

    van de Vorst, IE

    2016-01-01

    Background: In this thesis, we focused on the prognosis of patients with dementia who visited a hospital (inpatient or day clinic care) in the Netherlands. So far, absolute mortality risks for dementia were lacking in the Netherlands, whereas these risks have been available for years for cancer or

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... before cancer How you respond to treatment Seeking Information About Your Prognosis Is a Personal Decision When ... Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT INFORMATION Contact Us LiveHelp Online Chat MORE INFORMATION About ...

  1. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... it in a clear and supportive way. Two viewer guides are also available: for patients (PDF-210KB) and for provider care teams (PDF-210KB). Understanding Your Cancer Prognosis Video View this video on YouTube. Three cancer patients and their doctor, Anthony L. ...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... about what she'd like to know of her prognosis. Credit: National Cancer Institute If you have ... this video on YouTube. Vanessa, an artist, and her husband Roy discover how to support each other’s ...

  3. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Your Diagnosis Research Understanding Cancer Prognosis Oncologist Anthony L. Back, M.D., a national expert on doctor- ... YouTube. Three cancer patients and their doctor, Anthony L. Back, M.D. -- an oncologist who is also ...

  4. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) ... may have questions about how serious your cancer is and your chances of survival. The estimate of how the disease will go for you is called prognosis. It ...

  5. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... decisions you may face include: Which treatment is best for you If you want treatment How to best take care of yourself and manage treatment side ... the most about your situation is in the best position to discuss your prognosis and explain what ...

  6. Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoying Sun

    2017-07-01

    Full Text Available Stonin 2 (STON2, which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC. The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients.

  7. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge.

    Science.gov (United States)

    Pernot, Simon; Voron, Thibault; Perkins, Geraldine; Lagorce-Pages, Christine; Berger, Anne; Taieb, Julien

    2015-10-28

    While the incidence of gastric cancer has decreased worldwide in recent decades, the incidence of signet-ring cell carcinoma (SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer, which can be resected endoscopically in some cases and which has a better outcome than non-SRCC, and advanced gastric cancer, which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However, the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified, as the benefit of perioperative chemotherapy and the value of taxane-based chemotherapy are unclear. In this review we analyze recent data on the epidemiology, oncogenesis, prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.

  8. Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

    Directory of Open Access Journals (Sweden)

    Daniela Rizzo

    2015-01-01

    Full Text Available High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

  9. Prognosis in adult patients with idiopathic pulmonary hemosiderosis.

    Science.gov (United States)

    Miwa, Seiichi; Imokawa, Shiro; Kato, Masato; Ide, Kyotaro; Uchiyama, Hiroshi; Yokomura, Koushi; Suda, Takafumi; Shirai, Masahiro; Hayakawa, Hiroshi; Chida, Kingo

    2011-01-01

    Diffuse alveolar hemorrhage (DAH) of unknown cause has been characterized as idiopathic pulmonary hemosiderosis (IPH). IPH is a rare disease, which has a high prevalence in children and shows a poor prognosis. However, in adults, since there are few reports about collective cases, the details remain to be determined. Between January 2003 and June 2008, consecutive adult patients strictly defined as unknown cause DAH by chest images, fiberoptic bronchoscopy, autoantibody testing, and exclusion of systemic disease were enrolled. We investigated the clinical characterization and course of the enrolled patients. Nine patients were included. All patients were middle-aged men (56.1 ± 4.2 year-old) with sudden onset. They did not present with anemia (the hemoglobin level was 13.9 ± 0.5 g/dL) despite the quantity of bleeding. In bronchoalveolar-lavage fluid analysis, the cell count was increased (7.6 ± 1.6×10(5) cells/mL) with neutorophilia (33.3 ± 13.3%). The illness resolved within 2 weeks with or without corticosteroid therapy. All of the patients were alive without recurrence during the follow-up period (45.2 ± 6.2 months) after diagnosis. Adult IPH patients showed good prognosis. However, the present patients are clinically slightly different from the previously characterized IPH.

  10. IMP3 Predicts Invasion and Prognosis in Human Lung Adenocarcinoma.

    Science.gov (United States)

    Yan, Jinhai; Wei, Qingzhu; Jian, Wenjing; Qiu, Bo; Wen, Jing; Liu, Jianghuan; Fu, Bo; Zhou, Xinhua; Zhao, Tong

    2016-02-01

    Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with several aggressive and advanced cancers. Whether IMP3 can predict invasion, and prognosis in patients with human lung adenocarcinoma (LAC) remains unclear. Ninety-five LAC and 75 non-tumor lung tissue samples were included in a tissue microarray. IMP3 expression was assessed by immunohistochemical examination. Correlation between IMP3 expression levels, clinicopathological characteristics, and overall prognosis was evaluated. In a separate in vitro study, RNA interference method was applied for knockdown of IMP3 gene in human LAC cell lines. Invasive potential of LAC cells was then evaluated by transwell migration assay. IMP3 immunoreactivity was observed in 39 out of 95 (41.1 %) LAC patients, but not in non-tumor lung tissues. IMP3 expression levels were closely associated with histological grade (P = 0.037), TNM stage (P = 0.034), and lymph node metastasis (P = 0.011). Patients presenting with positive IMP3 expression (P = 0.000), an advanced TNM stage (P = 0.000), and lymph node metastasis (P = 0.001) had a worse overall survival, compared to those lacking these characteristics. Both IMP3 expression (hazard ratio [HR], 2.310; 95 % confidence interval [CI] 1.192-4.476; P = 0.013) and TNM stage (HR 2.338; 95 % CI 1.393-3.925; P = 0.001) were independent predictors of poor prognosis. The invasive potential of LAC cells was significantly inhibited by IMP3 knockdown. IMP3 appears to play an important role in tumor invasion in patients with LAC and may serve as a useful prognostic biomarker in these patients.

  11. Reproductive prognosis in endometriosis

    DEFF Research Database (Denmark)

    Hjordt Hansen, Maj V; Dalsgaard, Torur; Hartwell, Dorthe

    2014-01-01

    OBJECTIVE: To assess the reproductive long-term prognosis of women with and without endometriosis, to explore changes over time, and to quantify the contribution of artificial reproductive techniques. DESIGN: Cohort study. SETTING: Denmark 1977-2009. SAMPLE: Data retrieved from four national...... registries. Among 15-49-year-old women during the period 1977-82, 24 667 were diagnosed with endometriosis and 98 668 (1:4) women without endometriosis were age-matched. METHODS: To assess long-term reproductive prognosis, all pregnancy outcomes were identified among the women with and without endometriosis......, but this was restricted to pregnancies from assisted reproduction. CONCLUSION: Women with endometriosis have slightly fewer children, but this lessened over time due to artificially conceived pregnancies. The risk for miscarriages and ectopic pregnancies was increased compared with women without the disease....

  12. The natural history and prognosis of epilepsy.

    Science.gov (United States)

    Beghi, Ettore; Giussani, Giorgia; Sander, Josemir W

    2015-09-01

    Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Generally, prognosis refers to the probability of attaining seizure freedom on treatment and little is known about the natural history of the untreated condition. Here, we summarize aspects of the prognosis and prognostic predictors of treated and untreated epilepsy and of its different syndromes. Usually, epilepsy is a fairly benign condition. Most epilepsies have a good prognosis for full seizure control and eventual discontinuation of AEDs, but epilepsy syndromes have differing outcomes and responses to treatment. Prognostic factors include aetiology, EEG abnormalities, type of seizures and the number of seizures experienced before treatment onset, and poor early effects of drugs. Early response to treatment is an important positive predictor of long-term prognosis, while the history of a high number of seizures at the time of diagnosis, intellectual disability, and symptomatic aetiology are negative predictors. Different prognostic patterns can be identified, suggesting that the epileptogenic process is not static. Epilepsy carries a greater than expected risk of premature death. Aetiology is the single most important risk factor for premature death.

  13. magnitude, prognosis and markers

    African Journals Online (AJOL)

    Data developed by the massive Global Burden of Disease (GBD) revealed that neurobehavioural impairment ranks only second to cancer and coronary heart disease combined. These data may indeed be more gruesome owing to the poor regulation of exposure to environmental chemicals in resource poor countries.

  14. Prognosis for year 2013.

    Science.gov (United States)

    Silva, John S; Ball, Marion J

    2002-11-20

    New knowledge from biotechnology and new capabilities provided by the evolving global information infrastructure are already transforming health care. Three clusters of technologies hold particular promise: grid computing, intimate computing, and micro laboratory computing. The confluence of these technologies will change clinical laboratory equipment into portable devices, easing the administrative details involved in delivering care and ushering in a new age of monitoring clinical states. Two vignettes, an office visit and a clinical trial, are offered as prognosis for clinical care in 2013. New capabilities hold the power to transform health care, making it truly patient centered as the Institute of Medicine (IOM) has urged.

  15. Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer.

    Science.gov (United States)

    Qu, Ning; Zhang, Ling; Wu, Wei-Li; Ji, Qing-Hai; Lu, Zhong-Wu; Zhu, Yong-Xue; Lin, Dao-Zhe

    2016-07-01

    Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070-7.933), distant metastasis (HR = 3.860, 95 % CI 1.507-9.884), and cancer death (HR = 7.252, 95 % 2.189-24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185-4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300-19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.

  16. Parasite remains in archaeological sites

    Directory of Open Access Journals (Sweden)

    Françoise Bouchet

    2003-01-01

    Full Text Available Organic remains can be found in many different environments. They are the most significant source for paleoparasitological studies as well as for other paleoecological reconstruction. Preserved paleoparasitological remains are found from the driest to the moistest conditions. They help us to understand past and present diseases and therefore contribute to understanding the evolution of present human sociality, biology, and behavior. In this paper, the scope of the surviving evidence will be briefly surveyed, and the great variety of ways it has been preserved in different environments will be discussed. This is done to develop to the most appropriated techniques to recover remaining parasites. Different techniques applied to the study of paleoparasitological remains, preserved in different environments, are presented. The most common materials used to analyze prehistoric human groups are reviewed, and their potential for reconstructing ancient environment and disease are emphasized. This paper also urges increased cooperation among archaeologists, paleontologists, and paleoparasitologists.

  17. Vital prognosis after hospitalization for COPD

    DEFF Research Database (Denmark)

    Vestbo, J; Prescott, E; Lange, P

    1998-01-01

    STUDY AIM: To examine survival after admission due to chronic obstructive pulmonary disease (COPD) in a population sample over a time span of 15 years. DESIGN: Linkage between a prospective population cohort and register information on hospitalization and mortality. SETTING: The Copenhagen City...... Heart Study (CCHS). PARTICIPANTS: A total of 267 men and 220 women who had participated in the CCHS and who were hospitalized with a discharge diagnosis of COPD (ICD-8 491-2). MAIN RESULTS: The crude 5-yr survival rate after a COPD admission was 45% (37% for men and 52% for women). Mortality risk...... associated with prognosis. Survival after admission due to COPD did not change significantly over time. CONCLUSION: Compared to previous studies of COPD patients, the present study indicates that prognosis after hospital admission remains virtually unchanged over the last decades. FEV1 is still the strongest...

  18. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Still, some cancer cells can remain in your body for many years after treatment. These cells may cause the cancer to come ... Institutes of Health National Cancer Institute ...

  19. Melanoma prognosis in Europe: far from equal.

    Science.gov (United States)

    Forsea, A M; Del Marmol, V; Stratigos, A; Geller, A C

    2014-07-01

    Comprehensive, population-based analysis of melanoma survival throughout Europe is hindered by the uneven coverage and quality of European cancer registries, and by logistical and financial shortcomings. Mortality-to-incidence ratios (MIRs) have been used as a proxy for estimating survival for multiple cancers and to model melanoma prognosis, higher MIR values reflecting poorer prognosis. Updated and improved pan-European estimates of mortality and incidence rates for melanoma have become available through the International Agency for Research of Cancer project Globocan 2008, showing marked differences among European countries. To analyse MIRs for melanoma across Europe and their relationship with national health expenditures, aiming to identify countries and regions with disproportionately poor prognosis. Estimated age-standardized rates of melanoma incidence and mortality provided by Globocan 2008 were used to calculate the MIR for each European country and region. Total health expenditures per capita in European countries for 2008 were provided by the World Health Organization/Global Health Observatory. The potential correlation between MIR and total health expenditure per capita was analysed through Pearson's correlation. Mortality-to-incidence ratios for melanoma ranged between 0·09 in Switzerland and 0·44 in Latvia. The regional average MIR was the highest in Central and Eastern Europe at 0·35; the lowest was in Western Europe, at 0·13. We found a strong inverse correlation between the individual nation's total health expenditure per capita and the calculated melanoma MIR (r = -0·76, P < 0·05). While further improvement of melanoma registration is necessary, our findings reveal sharp disparities in the prognosis of melanoma across the Continent, correlated with significant differences in health care expenditures. © 2014 British Association of Dermatologists.

  20. Development and validation of a clinical score for prognosis ...

    African Journals Online (AJOL)

    Several independent risk factors at baseline are associated with a poor prognosis after ART initiation. These include: male sex, low body mass index, anemia, low CD4 count and stage-4 WHO disease. The aim of this research was evaluate prospectively a new scoring system composed by these factors. Methods: An open ...

  1. Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas.

    Directory of Open Access Journals (Sweden)

    Olga Martinho

    Full Text Available Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP, besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. Its role in the prognosis and tumourigenesis of gliomas remains unclear. In the present study, we found that RKIP protein is absent in a low frequency (10%, 20/193 of glioma tumors. Nevertheless, the absence of RKIP expression was an independent prognostic marker in glioma. Additionally, by in vitro downregulation of RKIP, we found that RKIP inhibition induces a higher viability and migration of the cells, having no effect on cellular proliferation and angiogenesis, as assessed by in vivo CAM assay. In conclusion, this is the largest series studied so far evaluating the expression levels of this important cancer suppressor protein in glioma tumors. Our results suggest that in a subset of tumors, the absence of RKIP associates with highly malignant behavior and poor survival of patients, which may be a useful biomarker for tailored treatment of glioma patients.

  2. Prognosis in Acute Cerebrovascular Accidents in Relation to Respiratory Pattern and Blood—gas Tensions

    Science.gov (United States)

    Rout, M. W.; Lane, D. J.; Wollner, L.

    1971-01-01

    Respiratory pattern and arterial blood gas tensions were assessed in patients with acute cerebrovascular accidents. Hyperventilation, low Pco2, and high arterial pH were associated with a poor prognosis, whereas patients with normal respiratory pattern and blood gas tensions survived. Periodic and Cheyne-Stokes breathing carried an intermediate prognosis. PMID:5091916

  3. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... of time may be 1 year, 2 years, 5 years, etc., with 5 years being the time period most often used. ... disappeared. If you remain in complete remission for 5 years or more, some doctors may say that ...

  4. New hominin remains from Uzbekistan.

    Science.gov (United States)

    Glantz, Michelle; Viola, Bence; Wrinn, Patrick; Chikisheva, Tatiana; Derevianko, Anatoly; Krivoshapkin, Andrei; Islamov, Uktur; Suleimanov, Rustam; Ritzman, Terrence

    2008-08-01

    Although the Paleolithic occupations of Uzbekistan and the neighboring foothill regions of Tajikistan and Kazakhstan are well-documented, almost no hominin fossil material has been discovered in the area since Teshik-Tash 1 in 1938. Here we describe and offer a preliminary comparative framework for hominin remains that were recovered in 2003 from two Middle Paleolithic sites in Uzbekistan, Obi-Rakhmat Grotto and Anghilak Cave. The description of Teshik-Tash as a Neandertal and the preponderance of lithic assemblages identified as Mousterian in character has supported the interpretation of the region as the eastern-most extent of the Neandertal range. The material from Obi-Rakhmat (OR-1), a subadult represented by part of a permanent maxillary dentition and a fragmentary cranium, expresses a relatively Neandertal-like dentition coupled with more ambiguous cranial anatomy. The remains from Anghilak Cave include a non-diagnostic, diminutive right fifth metatarsal (AH-1). These findings are important additions to the Central Asia hominin fossil record.

  5. Prognosis of Cyclic Vomiting Syndrome

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2016-03-01

    Full Text Available Investigators from Teikyo University School of Medicine, Tokyo, Japan, evaluated the clinical features, prognosis, and prophylaxis of cyclic vomiting syndrome and the relationship between the syndrome and levels of adrenocorticotropic/antidiuretic hormones (ACTH/ADH.

  6. Prognosis of critical limb ischemia: Major vs. minor amputation comparison.

    Science.gov (United States)

    Matsuzaki, Kyoichi; Hayashi, Ruka; Okabe, Keisuke; Aramaki-Hattori, Noriko; Kishi, Kazuo

    2015-09-01

    Healthcare providers treating wounds have difficulties assessing the prognosis of patients with critical limb ischemia who had been discharged after complete healing of major amputation wounds. The word "major" in "major amputation" gives the impression of "being more severe" than "minor amputation." Therefore, even if wounds are healed after major amputation, they imagine that prognosis after major amputation would be poorer than that after minor amputation. We investigated the prognosis of diabetic nephropathy patients 2 years after amputations. Those patients underwent dialysis as well as amputation following percutaneous transluminal angioplasty for their foot wounds. They were ambulatory prior to these surgeries. Among 56 cases of minor amputation, 45 were males and 11 were females, and mortality was 41.1%. The mortality of cases with and without a coronary intervention history was 53.1% and 25.0%, respectively (p = 0.034). Among 10 cases of major amputation, 9 were males and 1 was female, and mortality was 60%. The mortality of cases with and without a coronary intervention history was 75.0% and 0%, respectively. Although we predicted poor prognosis in cases with major amputation, there was no significant difference in mortality 2 years after amputations (p = 0.267). Thus far poor prognosis has been reported for major amputation. It might be due to inclusion of the following patients: patients with wounds proximal to ankle joints, patients with extensive gangrene spreading to the lower legs, patients with septicemia from wound infection and who died around the time of operation, and patients with malnutrition. The results of our present study showed that the outcomes at 2 years postoperatively were similar between patients with major amputations and those with minor amputations, if surgical wounds were able to heal. We should not estimate the prognosis by the level of amputation, rather we should consider the effect of coronary intervention history on

  7. Poorly Responsive Celiac Disease

    Science.gov (United States)

    ... Celiac Disease › Poorly Responsive Celiac Disease Poorly Responsive Celiac Disease It is estimated that up to 30% of ... continuing to ingest gluten. Causes of Poorly Responsive Celiac Disease Continuing Gluten Ingestion The most common reason for ...

  8. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Qiu-Li; Xu, Wang-Hong, E-mail: mtao@buffalo.edu [Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032 (China); Tao, Meng-Hua, E-mail: mtao@buffalo.edu [Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214 (United States)

    2010-04-28

    In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

  9. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Directory of Open Access Journals (Sweden)

    Meng-Hua Tao

    2010-04-01

    Full Text Available In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of the MS in the prognosis of breast cancer.

  10. The importance of genomic copy number changes in the prognosis of glioblastoma multiforme.

    Science.gov (United States)

    Arslantas, Ali; Artan, Sevilhan; Oner, Ulkü; Müslümanoğlu, Hamza; Durmaz, Ramazan; Cosan, Erhan; Atasoy, Metin Ant; Başaran, Nurettin; Tel, Eşref

    2004-01-01

    Glial tumors are the most common tumors of the nervous system, affecting individuals at any age. Since understanding of the molecular pathologies underlying human gliomas is still very poor, the treatment and therefore prognosis of this malignancy could not yet be improved. In order to determine whether different glioblastoma-associated genomic aberrations may serve as prognostic markers in combination with histopathological findings, 20 primary glioblastoma multiforme tumors were screened by comparative genomic hybridization, and the results were compared with histopathological and clinical features. All tumors showed genomic copy aberrations detected by comparative genomic hybridization. Regional and numerical increases in chromosome 7 copy number were the most frequently seen abnormality (10/20 tumors), followed by loss of chromosome 10 (8/20). Both of these aberrations were associated with shorter surveillance time. Chromosome 12q amplification was detected in seven tumors. Loss of 17p, 1p, and 19q in combination was seen in three cases. One of them was a giant cell GBM, whereas the remaining two cases were still alive. Combination of chromosome 1p and 19q deletions was also seen in a case with long surveillance. According to the preliminary findings of this study, in addition to the EGFR gene, amplification of other genes on chromosome 7 and the deletion of PTEN gene and other cancer-related genes on chromosome 10 appeared important to the development of glioblastoma multiforme and were associated with poor prognosis, whereas the combination of chromosome 1p and 19q deletions seems to be an informative molecular marker for better prognosis. The clinical features and genetic alterations of primary and secondary glioblastoma multiforme should be compared in large series to clarify the effective prognostic markers; and further molecular analyses focused on chromosomes 7 and 10 will be very helpful for understanding the molecular mechanisms underlying the

  11. Poor Americans: How the Poor White Live.

    Science.gov (United States)

    Pilisuk, Marc; Pilisuk, Phyllis

    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…

  12. Factors affecting epilepsy development and epilepsy prognosis in cerebral palsy.

    Science.gov (United States)

    Mert, Gulen Gul; Incecik, Faruk; Altunbasak, Sakir; Herguner, Ozlem; Mert, Mustafa Kurthan; Kiris, Nurcihan; Unal, Ilker

    2011-08-01

    A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Proteinuria can predict prognosis after liver transplantation.

    Science.gov (United States)

    Pan, Heng-Chih; Chen, Ying-Jen; Lin, Jhe-Ping; Tsai, Ming-Jung; Jenq, Chang-Chyi; Lee, Wei-Chen; Tsai, Ming-Hung; Fan, Pei-Chun; Chang, Chih-Hsiang; Chang, Ming-Yang; Tian, Ya-Chung; Hung, Cheng-Chieh; Fang, Ji-Tseng; Yang, Chih-Wei; Chen, Yung-Chang

    2016-09-15

    Proteinuria is a manifestation of renal dysfunction and it has been demonstrated to be a significant prognostic factor in various clinical situations. The study was designed to analyze prognosis of patients receiving liver transplantation as well as to determine predictive performance of perioperative proteinuria. We retrospectively reviewed data of patients who had received a liver transplant in a medical center between 2002 and 2010. Demographic information and clinical characteristic parameters were recorded on the day of intensive care unit admission before operation and on postoperative days 1, 7, and 14. Among a total of 323 patients, in-hospital mortality and 90-day mortality rates were 13.0 % (42/323) and 14.2 % (46/323), respectively. Patients with proteinuria on admission had higher rates of acute kidney injury (26.8 % vs. 8.8 %, p proteinuria on admission and Sequential Organ Failure Assessment (SOFA) score were independent predictors of in-hospital mortality. The discriminatory ability of proteinuria plus SOFA was even better than that of SOFA alone, especially on postoperative day 1. The presence of proteinuria before liver transplantation is supposed to be recognized as a negative predictor for in-hospital survival. Moreover, the presence of proteinuria after liver transplantation can assist in the early prediction of poor short-term prognosis for patients receiving liver transplantation.

  14. Prognosis of depression in the elderly.

    Science.gov (United States)

    Meats, P; Timol, M; Jolley, D

    1991-11-01

    Fifty-six consecutively admitted elderly (65 and over) patients with depression were assessed on mental, physical and social states. They were followed up and assessed at home one year later. A group of 24 depressed in-patients aged under 65 years admitted to the same ward during the same period was also assessed. Outcome was different for the two groups, with 68% of the elderly 'well' at one year, against 50% of the younger group. The younger group were more likely to have 'poor' outcome (41%) than the elderly (16%). However, there were more deaths than expected, particularly in the elderly. These findings differ from some previous studies, and indicate an excellent prognosis for depression in the elderly. Outcome in younger patients is less good.

  15. Prognosis of ventricular fibrillation in hospital

    DEFF Research Database (Denmark)

    Jensen, G V; Torp-Pedersen, C; Køber, L

    1992-01-01

    In a retrospective study of 520 patients with in-hospital ventricular fibrillation 421 (81%) had acute myocardial infarction (MI), 66 (13%) had ischaemic heart disease (IHD) without MI, 33 (6%) had no signs of IHD. The in-hospital mortality of these three groups was 51%, 52%, and 27%, respectively...... (P = 0.01). Logistic regression analysis demonstrated that heart failure and cardiogenic shock were significant risk factors for in-hospital death among patients with IHD. Among discharged patients 1 and 5 years survival was 78% and 51% for patients with MI, 63% and 25% for patients with IHD, 67...... with known IHD suffering in-hospital VF without AMI have a very poor short- and long-term prognosis. These patients need extensive cardiac examination....

  16. FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures

    DEFF Research Database (Denmark)

    Wong, Kah Keng; Gascoyne, Duncan M; Soilleux, Elizabeth J

    2016-01-01

    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor...... prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL....... In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against...

  17. Accidental Haemorrhage and Fetal Prognosis

    African Journals Online (AJOL)

    1974-04-17

    Apr 17, 1974 ... perinatal mortality associated with accidental haemorrhage. The importance of clinical signs in determining fetal prognosis is discussed. A suggested clinical approach to cases of accidental haemorrhage, where on admission the fetus is found to be alive in utero, is given. S. Afr. Med. l., 48, 764 (1974).

  18. Does hypertension remain after kidney transplantation?

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand

    2015-05-01

    Full Text Available Hypertension is a common complication of kidney transplantation with the prevalence of 80%. Studies in adults have shown a high prevalence of hypertension (HTN in the first three months of transplantation while this rate is reduced to 50- 60% at the end of the first year. HTN remains as a major risk factor for cardiovascular diseases, lower graft survival rates and poor function of transplanted kidney in adults and children. In this retrospective study, medical records of 400 kidney transplantation patients of Sina Hospital were evaluated. Patients were followed monthly for the 1st year, every two months in the 2nd year and every three months after that. In this study 244 (61% patients were male. Mean ± SD age of recipients was 39.3 ± 13.8 years. In most patients (40.8% the cause of end-stage renal disease (ESRD was unknown followed by HTN (26.3%. A total of 166 (41.5% patients had been hypertensive before transplantation and 234 (58.5% had normal blood pressure. Among these 234 individuals, 94 (40.2% developed post-transplantation HTN. On the other hand, among 166 pre-transplant hypertensive patients, 86 patients (56.8% remained hypertensive after transplantation. Totally 180 (45% patients had post-transplantation HTN and 220 patients (55% didn't develop HTN. Based on the findings, the incidence of post-transplantation hypertension is high, and kidney transplantation does not lead to remission of hypertension. On the other hand, hypertension is one of the main causes of ESRD. Thus, early screening of hypertension can prevent kidney damage and reduce further problems in renal transplant recipients.

  19. The Human Remains from HMS Pandora

    Directory of Open Access Journals (Sweden)

    D.P. Steptoe

    2002-04-01

    Full Text Available In 1977 the wreck of HMS Pandora (the ship that was sent to re-capture the Bounty mutineers was discovered off the north coast of Queensland. Since 1983, the Queensland Museum Maritime Archaeology section has carried out systematic excavation of the wreck. During the years 1986 and 1995-1998, more than 200 human bone and bone fragments were recovered. Osteological investigation revealed that this material represented three males. Their ages were estimated at approximately 17 +/-2 years, 22 +/-3 years and 28 +/-4 years, with statures of 168 +/-4cm, 167 +/-4cm, and 166cm +/-3cm respectively. All three individuals were probably Caucasian, although precise determination of ethnicity was not possible. In addition to poor dental hygiene, signs of chronic diseases suggestive of rickets and syphilis were observed. Evidence of spina bifida was seen on one of the skeletons, as were other skeletal anomalies. Various taphonomic processes affecting the remains were also observed and described. Compact bone was observed under the scanning electron microscope and found to be structurally coherent. Profiles of the three skeletons were compared with historical information about the 35 men lost with the ship, but no precise identification could be made. The investigation did not reveal the cause of death. Further research, such as DNA analysis, is being carried out at the time of publication.

  20. Stress cardiomyopathy: diagnosis, pathophysiology, management, and prognosis.

    Science.gov (United States)

    Sharma, Ajay K; Singh, Jagmeet P; Heist, E Kevin

    2011-09-01

    Stress cardiomyopathy is now a well-recognized reversible cardiomyopathy, with a clinical presentation mimicking Acute Coronary syndrome in the absence of significant coronary artery disease. It is often encountered in postmenopausal females and is usually precipitated by acute emotional or physical stressors. In this review, we have attempted to summarize relevant data regarding diagnosis, typical and atypical presentations, pathophysiology, management options, and prognosis. Typically, patients present with chest pain and shortness of breath, transient electrocardiographic changes, moderate troponin elevation, and are found to have wall motion abnormalities (apical and midventricular akinesis with preserved basal segment systolic function) without obstructive coronary lesions, with complete resolution in next few weeks. The precise pathophysiology remains unclear, but excessive catecholamine stimulation, metabolic disturbances, and dysfunction of microcirculation are thought to be the underlying mechanisms.

  1. Prognosis

    DEFF Research Database (Denmark)

    Myers, Jonathan; Brawner, Clinton A; Haykowsky, Mark J F

    2015-01-01

    benefits of exercise and the mechanisms underlying these benefits. Studies on the outcome benefits of exercise training, including mortality and hospitalization, have been convincing. This article reviews the physiologic benefits of exercise training in HF, studies on exercise training in women, results......Patients with heart failure (HF) were once discouraged from participating in exercise programs because of concerns regarding safety and the potential for harm to an already damaged myocardium. However, studies over the last 3 decades have provided extensive insights into both the health outcome...

  2. INTERRELATION BETWEEN PERSISTENT NECROSIS OF CARDIOMYOCYTES AND PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE

    OpenAIRE

    E. N. Golovenko; D. A. Napalkov; V. A. Sulimov

    2010-01-01

    Background. Chronic heart failure (CHF) progression is accompanied by remodeling of muscular, collagen and vascular elements of myocardium. This can lead to increase in serum concentrations of myocardial lesion markers (cardiac troponin I (TrI) and myoglobin) which seem to correlate with poor prognosis in patients with CHF.Aim. To estimate correlations between cardiac TrI, myoglobin, creatine phosphokinase MB-fraction (MB-CPK) serum concentrations and disease severity and prognosis in CHF pat...

  3. Estimating and communicating prognosis in advanced neurologic disease.

    Science.gov (United States)

    Holloway, Robert G; Gramling, Robert; Kelly, Adam G

    2013-02-19

    Prognosis can no longer be relegated behind diagnosis and therapy in high-quality neurologic care. High-stakes decisions that patients (or their surrogates) make often rest upon perceptions and beliefs about prognosis, many of which are poorly informed. The new science of prognostication--the estimating and communication "what to expect"--is in its infancy and the evidence base to support "best practices" is lacking. We propose a framework for formulating a prediction and communicating "what to expect" with patients, families, and surrogates in the context of common neurologic illnesses. Because neurologic disease affects function as much as survival, we specifically address 2 important prognostic questions: "How long?" and "How well?" We provide a summary of prognostic information and highlight key points when tailoring a prognosis for common neurologic diseases. We discuss the challenges of managing prognostic uncertainty, balancing hope and realism, and ways to effectively engage surrogate decision-makers. We also describe what is known about the nocebo effects and the self-fulfilling prophecy when communicating prognoses. There is an urgent need to establish research and educational priorities to build a credible evidence base to support best practices, improve communication skills, and optimize decision-making. Confronting the challenges of prognosis is necessary to fulfill the promise of delivering high-quality, patient-centered care.

  4. Inference in `poor` languages

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, S.

    1996-10-01

    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.

  5. Exploiting the Poor

    DEFF Research Database (Denmark)

    Justesen, Mogens Kamp; Bjørnskov, Christian

    2014-01-01

    While extant research has focused on the causes and consequences of corruption at the macro-level, less effort has been devoted to understanding the micro-foundation of corruption. We argue that poor people are more likely to be victims of corrupt behavior by street-level bureaucrats as the poor...

  6. HER family receptor expression and prognosis in pancreatic cancer.

    Science.gov (United States)

    Bittoni, Alessandro; Mandolesi, Alessandra; Andrikou, Kalliopi; Santoni, Matteo; Alfonsi, Simona; Lanese, Andrea; Loretelli, Cristian; Pellei, Chiara; Piva, Francesco; Scarpelli, Marina; Cascinu, Stefano

    2015-07-22

    HER family receptors play a key role in tumor progression in several malignancies, such as colorectal, lung or breast cancer. The aims of this study were to investigate expression of HER-1, HER-2 and HER-3 in pancreatic cancer (PC) samples and evaluate the association between HER-family receptor expression and patients' clinical outcomes. Tissue samples from 91 PC patients were subjected to immunohistochemical staining to assess the expression of HER-1, HER-2 and HER-3. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+ or 3+ were assigned to each sample based on the intensity of staining for HER receptors. Scores of 2+ or 3+ were defined as positive staining. HER-1 overexpression was observed in 41 out of 91 samples (45.1%), while HER-2 was not overexpressed in any of the analyzed samples. HER-3 was overexpressed in 37 samples (40.7%) and was found to be associated with advanced TNM stage. In particular, HER-3 was overexpressed in 12 out of 16 stage IV patients (75%) compared with only 33.3% of stage I-III patients (p = 0.02). Among 79 patients with available survival data, the 6 patients with strong HER-3 expression (score 3+) had a shorter survival compared with remaining patients (median overall survival 6.9 months vs. 12.3 months, respectively). HER-1 and HER-3 were found to be expressed in a significant proportion of PC patients. Strong HER-3 expression represents an indicator of poor prognosis in PC patients, being associated with advanced stage and shorter survival.

  7. [Neuroimaging and Blood Biomarkers in Functional Prognosis after Stroke].

    Science.gov (United States)

    Branco, João Paulo; Costa, Joana Santos; Sargento-Freitas, João; Oliveira, Sandra; Mendes, Bruno; Laíns, Jorge; Pinheiro, João

    2016-11-01

    Stroke remains one of the leading causes of morbidity and mortality around the world and it is associated with an important long-term functional disability. Some neuroimaging resources and certain peripheral blood or cerebrospinal fluid proteins can give important information about etiology, therapeutic approach, follow-up and functional prognosis in acute ischemic stroke patients. However, among the scientific community, there is currently more interest in the stroke vital prognosis over the functional prognosis. Predicting the functional prognosis during acute phase would allow more objective rehabilitation programs and better management of the available resources. The aim of this work is to review the potential role of acute phase neuroimaging and blood biomarkers as functional recovery predictors after ischemic stroke. Review of the literature published between 2005 and 2015, in English, using the terms "ischemic stroke", "neuroimaging" e "blood biomarkers". We included nine studies, based on abstract reading. Computerized tomography, transcranial doppler ultrasound and diffuse magnetic resonance imaging show potential predictive value, based on the blood flow study and the evaluation of stroke's volume and localization, especially when combined with the National Institutes of Health Stroke Scale. Several biomarkers have been studied as diagnostic, risk stratification and prognostic tools, namely the S100 calcium binding protein B, C-reactive protein, matrix metalloproteinases and cerebral natriuretic peptide. Although some biomarkers and neuroimaging techniques have potential predictive value, none of the studies were able to support its use, alone or in association, as a clinically useful functionality predictor model. All the evaluated markers were considered insufficient to predict functional prognosis at three months, when applied in the first hours after stroke. Additional studies are necessary to identify reliable predictive markers for functional

  8. Fertility prognosis for infertile couples

    DEFF Research Database (Denmark)

    Bostofte, E; Bagger, P; Michael, A

    1993-01-01

    OBJECTIVE: To develop a fertility prognosis model for infertile couples. DESIGN: Prospective follow-up study. PARTICIPANTS: In the period November 30, 1977 to June 1, 1985, 321 consecutive couples were investigated for infertility at Hvidovre University Hospital. Investigation of the female...... MEASURE: The Cox regression model was used to predict the time required to conceive based on informations provided by fertility investigations. RESULTS: Three of 16 prognostic variables (the period of infertility, the female infertility factor, and the P-test) possess significant prognostic information...

  9. Poor school performance

    National Research Council Canada - National Science Library

    Karande, Sunil; Kulkarni, Madhuri

    2005-01-01

    Education is one of the most important aspects of human resource development. Poor school performance not only results in the child having a low self-esteem, but also causes significant stress to the parents...

  10. Ethnic Variations in Prognosis of Patients with Dementia

    DEFF Research Database (Denmark)

    Agyemang, Charles; van de Vorst, Irene E.; Koek, Huiberdina L.

    2017-01-01

    rate, ethnic minority patients with dementia did not have a worse prognosis. Given the poor prognosis of dementia, timely and targeted advance care planning is essential, particularly in ethnic minority groups who are mired by cultural barriers and where uptake of advance care planning is known...... minority groups and the ethnic Dutch population in the NetherlandsMethods: Nationwide prospective cohorts of first hospitalized dementia patients (N = 55,827) from January 1, 2000 to December 31, 2010 were constructed. Differences in short-term and long-term mortality and readmission risk following...... and the Dutch attenuated and was no longer statistically significant after further adjustment for comorbidities. There were no ethnic differences in short-term and long-term risk of death, and risk of readmission among day clinic patients. CONCLUSION: Compared with Dutch patients with a comparable comorbidity...

  11. The role of metallothionein in oncogenesis and cancer prognosis

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Larsen, Agnete; Stoltenberg, Meredin

    2009-01-01

    The antiapoptotic, antioxidant, proliferative, and angiogenic effects of metallothionein (MT)-I+II has resulted in increased focus on their role in oncogenesis, tumor progression, therapy response, and patient prognosis. Studies have reported increased expression of MT-I+II mRNA and protein...... in various human cancers; such as breast, kidney, lung, nasopharynx, ovary, prostate, salivary gland, testes, urinary bladder, cervical, endometrial, skin carcinoma, melanoma, acute lymphoblastic leukemia (ALL), and pancreatic cancers, where MT-I+II expression is sometimes correlated to higher tumor grade....../stage, chemotherapy/radiation resistance, and poor prognosis. However, MT-I+II are downregulated in other types of tumors (e.g. hepatocellular, gastric, colorectal, central nervous system (CNS), and thyroid cancers) where MT-I+II is either inversely correlated or unrelated to mortality. Large discrepancies exist...

  12. Course prognosis of cervical osteochondrosis

    Directory of Open Access Journals (Sweden)

    Kolesov V.N.

    2012-06-01

    Full Text Available

    Today we can state that in spite of a considerable number of cervical osteochondrosis studies, there is a lack of research devoted to analysis of its course. There is no correlation between initial expert evaluations of cervical osteo-chondrosis cases and further course of pathological process. Goal of the research is to develop system of course prognosis of cervical osteochondrosis taking into account environmental infuence, heredity, living conditions, psychological profle of patient’s personality. Materials and methods. Dynamics of degenerative-dystrophic changes progressing of cervical vertebrae in 236 patients was analyzed. Results. Received data demonstrated that probability of stage I changing to stage II, III and IV depended on patients’ sex, age and type of labour activity, frequent supercooling and stress. Probability of fast progression of cervical osteochondrosis (5-year cycle of stage I changing to stage III and IV was to a great extent associated with heredity, urban living, presence of endocrine system diseases, syndrome of nonspecifc dysplasia of connective tissue and low indices of quality of life. Conclusion. Proposed system allows making prognosis of morphologic changes in spinal cord, and is based on radiation methods of verifcation without taking into consideration dynamics of neurological symptomatology.

  13. Scott's Lake Excavation Letters on Human Remains

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This is two letters written about the repatriation of Santee Indian human remains and funerary objects to Santee Sioux Tribe. Includes an inventory of human remains...

  14. New proposal for the treatment of poor prognosis young patients with advanced stage diffuse large B-cell lymphoma Nova proposta de tratamento no linfoma difuso de grandes células B no paciente jovem de mau prognóstico em estágio avançado

    Directory of Open Access Journals (Sweden)

    Sergio Cortelazzo

    2008-06-01

    Full Text Available Patients with DLBCL now have a better outcome with a longer survival because of two major developments: 1 increasing the dose of active drugs with shortening the time between cycles, resulting in dose-dense or dose-intense regimens; and 2 combining rituximab with chemotherapy. Both strategies were associated with a better clinical outcome, particularly in patients without adverse prognostic factors. Poor risk patients in the age range of 60 to 65 years may benefit from a combination of dose-dense or dose-intense regimens plus rituximab. Young patients with poor risk DLBCL defined by an aaIPI of 2 or 3 and age younger than 60 years, are characterized by truly refractory disease, evidenced by progression during or early after treatment, or later relapse. Attempts to modify treatment including immunotherapy to improve the response rate and reduce the proportion of patients with progressive disease have been only partially successful: to date: the best progression-free survival was 51%. In contrast, some attempts to decrease the high resistant and relapse rate with sequential high-dose chemotherapy with rituximab (R-HDS and autologous stem cell transplantation (ASCT have succeeded. On the basis of these promising results, GITIL launched a prospective phase III randomized trial comparing the efficacy and safety of dose-dense CHOP plus rituximab with R-HDS and ASCT. Preliminary data show that intensive programs such as dose-dense chemo-immunotherapy and R-HDS with ASCT are feasible until 65 years with a manageable toxic profile, also on multi-centre basis.Os pacientes com linforma de grande células B agora apresentam uma melhor evolução e longa sobrevida por causa de dois grandes desenvolvimentos: 1- Aumento da dose de drogas ativas e o espaço de tempo mais curto entre os ciclos, resultando deste fato uma dose mais consistente ou um regime com dose mais intensa. 2- Combinação da quimioterapia com o rituximab. Estas duas estratégias s

  15. First-line treatment of patients with disseminated poorly differentiated neuroendocrine carcinomas with carboplatin, etoposide, and vincristine: a single institution experience

    DEFF Research Database (Denmark)

    Olsen, Ingrid Holst; Langer, Seppo W; Jepsen, Ida

    2012-01-01

    Poorly differentiated neuroendocrine carcinomas (PDECs) represent highly malignant tumors with an immense tendency to metastasize and with a poor prognosis. The treatment consists of palliative chemotherapy and corresponds to the treatment of extensive stage small cell lung cancer....

  16. Fertility prognosis for infertile couples

    DEFF Research Database (Denmark)

    Bostofte, E; Bagger, P; Michael, A

    1993-01-01

    OBJECTIVE: To develop a fertility prognosis model for infertile couples. DESIGN: Prospective follow-up study. PARTICIPANTS: In the period November 30, 1977 to June 1, 1985, 321 consecutive couples were investigated for infertility at Hvidovre University Hospital. Investigation of the female...... MEASURE: The Cox regression model was used to predict the time required to conceive based on informations provided by fertility investigations. RESULTS: Three of 16 prognostic variables (the period of infertility, the female infertility factor, and the P-test) possess significant prognostic information....... The period of infertility and the P-test are best scored as continuous variables, whereas the female infertility factor are best categorized in four classes, i.e., normal, ovulation or cervical disorder, anatomic disorder, or a combination of disorders. CONCLUSIONS: The three prognostic variables...

  17. Poor school performance.

    Science.gov (United States)

    Karande, Sunil; Kulkarni, Madhuri

    2005-11-01

    Education is one of the most important aspects of human resource development. Poor school performance not only results in the child having a low self-esteem, but also causes significant stress to the parents. There are many reasons for children to under perform at school, such as, medical problems, below average intelligence, specific learning disability, attention deficit hyperactivity disorder, emotional problems, poor socio-cultural home environment, psychiatric disorders and even environmental causes. The information provided by the parents, classroom teacher and school counselor about the child's academic difficulties guides the pediatrician to form an initial diagnosis. However, a multidisciplinary evaluation by an ophthalmologist, otolaryngologist, counselor, clinical psychologist, special educator, and child psychiatrist is usually necessary before making the final diagnosis. It is important to find the reason(s) for a child's poor school performance and come up with a treatment plan early so that the child can perform up to full potential.

  18. Overexpression of LncRNA-ROR predicts a poor outcome in gallbladder cancer patients and promotes the tumor cells proliferation, migration, and invasion.

    Science.gov (United States)

    Wang, Shou-Hua; Zhang, Ming-Di; Wu, Xiao-Cai; Weng, Ming-Zhe; Zhou, Di; Quan, Zhi-Wei

    2016-09-01

    LncRNA-ROR has been reported to be involved in many kinds of human cancers. However, whether LncRNA-ROR is involved in gallbladder cancer progression remains largely unknown. The objective of this study is to investigate the role of LncRNA-ROR in gallbladder cancer. We found that LncRNA-ROR expression level was upregulated in gallbladder cancer tissues (P ROR was significantly associated with poor prognosis in gallbladder cancer patients (P ROR inhibited cell proliferation, migration, and invasion. The epithelial-mesenchymal transition (EMT) phenotype induced by TGF-β1 was reversed after LncRNA-ROR knocking down in SGC-996 and Noz cells. LncRNA-ROR plays an important role in the development of gallbladder cancer and mediates the EMT in gallbladder cancer. LncRNA-ROR might act as a marker of prognosis and therapeutic target for gallbladder cancer.

  19. The relationship between polymorphisms of XRCC5 genes with astrocytoma prognosis in the Han Chinese population

    Science.gov (United States)

    Li, Lei; Zhang, Jiayi; Wu, Ruipeng; Zhang, Yuan; Kang, Longli; Yuan, Dongya; Jin, Tianbo

    2016-01-01

    Background Gliomas are highly malignant with a poor prognosis. Studies have reported that DNA repair genes influence risk for glioma, but its relationship with prognosis is unclear. In this study, we want to explore the relationship between DNA repair genes (XRCC3, XRCC4 and XRCC5) and prognosis of astrocytoma in the Chinese Han population. Materials and Methods 160 astrocytoma cases were recruited in our study. Survival probabilities were estimated by using Kaplan–Meier analysis, and significant differences were analyzed by using the log-rank test. Cox proportional hazards models were used to analyze the associations between genotypes with astrocytoma survival. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable models. All tests were two-sided and p astrocytoma prognosis. Further, the “A/A” genotype of rs9288516 in XRCC5 (HR: 1.67, 95%CI: 1.02 - 2.72, p = 0.042) had significantly outcomes after adjusting for potential confounders, patients with poor tumor differentiation and the coexistence of the unfavorable genotypes. Conclusion These results suggest that polymorphisms of XRCC5 play an important role in astrocytoma prognosis in the Chinese Han population which could be used in the determination of astrocytoma prognosis in clinical researches. PMID:27852033

  20. 9. Poor medication

    African Journals Online (AJOL)

    Sitwala

    previous diagnosis of essential hypertension receiving out patient care in the University Teaching. Hospital (UTH) were ... self report and 70% using modified Hill-Bone scale. The mean age was ... Factors Associated With Poor Medication Adherence .... DM. Yes. No. 51. 183. 42(83). 151(83). 9(17). 32(17). 1. 1 (0. 5 -2. 4).

  1. Morphosyntax in Poor Comprehenders

    Science.gov (United States)

    Adlof, Suzanne M.; Catts, Hugh W.

    2015-01-01

    Children described as "poor comprehenders" (PCs) have reading comprehension difficulties in spite of adequate word reading abilities. PCs are known to display weakness with semantics and higher-level aspects of oral language, but less is known about their grammatical skills, especially with regard to morphosyntax. The purpose of this…

  2. to the poor?

    African Journals Online (AJOL)

    2006-03-01

    Mar 1, 2006 ... than better-off ones, the differences are relatively modest and arc generally high enough to confer immunity through the herd immunity effect. As elsewhere in ... with herd immunity in force, protecting all children, howev- er rich or poor ... by a medical professional (doctor, nurse, or trained midwife) at delivery ...

  3. A poor deal

    NARCIS (Netherlands)

    Breman, J.

    2010-01-01

    The proposed upward revision of the poverty line has failed to capture the Janus-faced deprivation experienced by the poor. The methodological foundation of the proposed poverty line fails to overcome the discrepancy between the macro-statistics and the micro-reality. The proposed report on the

  4. Breast cancer prognosis by combinatorial analysis of gene expression data.

    Science.gov (United States)

    Alexe, Gabriela; Alexe, Sorin; Axelrod, David E; Bonates, Tibérius O; Lozina, Irina I; Reiss, Michael; Hammer, Peter L

    2006-01-01

    The potential of applying data analysis tools to microarray data for diagnosis and prognosis is illustrated on the recent breast cancer dataset of van 't Veer and coworkers. We re-examine that dataset using the novel technique of logical analysis of data (LAD), with the double objective of discovering patterns characteristic for cases with good or poor outcome, using them for accurate and justifiable predictions; and deriving novel information about the role of genes, the existence of special classes of cases, and other factors. Data were analyzed using the combinatorics and optimization-based method of LAD, recently shown to provide highly accurate diagnostic and prognostic systems in cardiology, cancer proteomics, hematology, pulmonology, and other disciplines. LAD identified a subset of 17 of the 25,000 genes, capable of fully distinguishing between patients with poor, respectively good prognoses. An extensive list of 'patterns' or 'combinatorial biomarkers' (that is, combinations of genes and limitations on their expression levels) was generated, and 40 patterns were used to create a prognostic system, shown to have 100% and 92.9% weighted accuracy on the training and test sets, respectively. The prognostic system uses fewer genes than other methods, and has similar or better accuracy than those reported in other studies. Out of the 17 genes identified by LAD, three (respectively, five) were shown to play a significant role in determining poor (respectively, good) prognosis. Two new classes of patients (described by similar sets of covering patterns, gene expression ranges, and clinical features) were discovered. As a by-product of the study, it is shown that the training and the test sets of van 't Veer have differing characteristics. The study shows that LAD provides an accurate and fully explanatory prognostic system for breast cancer using genomic data (that is, a system that, in addition to predicting good or poor prognosis, provides an individualized

  5. Mammalian Remains from Indian Sites on Aruba

    NARCIS (Netherlands)

    Hooijer, D.A.

    1960-01-01

    Mr. H. R. VAN HEEKEREN and Mr. C. J. DU RY, of the Rijksmuseum voor Volkenkunde at Leiden, entrusted me with the identification of some animal remains collected from Indian sites on Aruba by Professor J. P. B. DE JOSSELIN DE JONG in 1923. These remains relate for the most part to marine turtles

  6. Luminescence of thermally altered human skeletal remains

    NARCIS (Netherlands)

    Krap, Tristan; Nota, Kevin; Wilk, Leah; van de Goot, Frank; Ruijter, Jan; Duijst, Wilma; Oostra, Roelof Jan

    2017-01-01

    Literature on luminescent properties of thermally altered human remains is scarce and contradictory. Therefore, the luminescence of heated bone was systemically reinvestigated. A heating experiment was conducted on fresh human bone, in two different media, and cremated human remains were recovered

  7. EDITORIAL MALARIA DIAGNOSIS Malaria remains the most ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-02

    Mar 2, 2005 ... Malaria remains the most significant parasitic disease affecting man. Prompt and accurate diagnosis of malaria is the key to cost effective management (1). Since the identification of Plasmodium parasites in human blood in 1880, the diagnosis of malaria has remained a hot bed of scientific discussion.

  8. Syncope: epidemiology, etiology and prognosis.

    Directory of Open Access Journals (Sweden)

    Rose M F Lisboa Da Silva

    2014-12-01

    Full Text Available Syncope is a common medical problem, with a frequency between 15% and 39%. In the general population, the annual number episodes are 18.1 to 39.7 per 1000 patients, with similar incidence between genders. The first report of the incidence of syncope is 6.2 per 1000 person-years. However, there is a significant increase in the incidence of syncope after 70 years of age with rate annual 19.5 per thousand individuals after 80 years. It presents a recurrence rate of 35% and 29% of physical injury. Among the causes of syncope, the mediated neural reflex, known as neurocardiogenic or vasovagal syncope, is the most frequent. The others are of cardiac origin, orthostatic hypotension, carotid sinus hypersensitivity, neurological and endocrinological causes and psychiatric disorders. The diagnosis of syncope can be made by clinical method associated with the electrocardiogram in up 50% of patients. Its prognosis is determined by the underlying etiology specifically the presence and severity of cardiac disease. The annual mortality can reach between 18 and 33% if cardiac cause, and between 0 and 12% if the noncardiac cause. Thus, it is imperative to identify its cause and risk stratification for positive impact in reducing morbidity and mortality.

  9. Tailored antiplatelet therapy to improve prognosis in patients exhibiting clopidogrel low-response prior to percutaneous coronary intervention for stable angina or non-ST elevation acute coronary syndrome

    DEFF Research Database (Denmark)

    Paarup Dridi, Nadia; Johansson, Pär I; Lønborg, Jacob T

    2015-01-01

    Abstract Aim: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI......). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis. Methods: In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR...... was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily, n = 55) or the newer P2Y12-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days...

  10. Usefulness Of Nutritional Parameters Based On Creatinine Kinetic Model In Predicting Prognosis In Severe Aki Patients Requring Crrt

    Directory of Open Access Journals (Sweden)

    Joon Ho Song

    2012-06-01

    In conclusion, nutritional state and chronic comorbidities were major factors predicting the clinical outcome of severe AKI patients requiring CRRT. CKM was a simple and useful method in the assessment of nutritional state during CRRT treatment. Low creatinine production reflecting poor nutrition and protein reserve was associated with poor prognosis in severely ill ARF patients.

  11. Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis.

    Science.gov (United States)

    Erson-Omay, E Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J; Sander, Chris; Günel, Murat

    2015-10-01

    Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these "ultramutated" tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Impact of invasive extranodal extension on the prognosis of patients with papillary thyroid carcinoma.

    Science.gov (United States)

    Moritani, Sueyoshi

    2014-12-01

    Although 20-50% of papillary thyroid carcinoma (PTC) patients initially present with lymph node metastases, prognosis is excellent. Thus, the significance of lymph node metastasis in PTC remains controversial. In this study, we examined the impact of extranodal extension to surrounding organs (invasive extranodal extension) on the prognosis for PTC patients. Medical records of PTC patients who underwent surgery as their initial treatment at our institution between 1981 and 2008 were retrospectively reviewed. Patients with or without invasive extranodal extension were selected. Our therapeutic strategy for PTC with invasive extranodal extension included complete resection and functional reconstruction. Intergroup comparison was performed using Student's t-test or the chi-square test as appropriate. Survival curves determined by the Kaplan-Meier method were compared for statistical significance using the log-rank test. A Cox-hazard regression model with the forward stepwise method was used for multivariate analysis. The study cohort included 60 (12.3%) patients with and 428 (87.7%) without invasive extranodal extension. The most common site of invasive extranodal extension in the central neck compartment was the recurrent laryngeal nerve, whereas the internal jugular vein was the most frequently invaded site in the lateral neck compartment. The locoregional recurrence rate did not differ significantly between patients with and without invasive extranodal extension, but the distant recurrence rate was higher for those with invasive extranodal extension. The 10-year disease-specific survival rate was significantly lower for patients with invasive extranodal extension than for those without invasive extranodal extension. Furthermore, multivariate analysis revealed that being aged ≥45 years, poor differentiation, and extrathyroidal extension were independent predictive factors for disease-specific death in PTC. Invasive extranodal extension had no effect on the

  13. Prognosis of symptomatic patients with the A3243G mutation of mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Chi-Hung Liu

    2012-09-01

    Conclusion: Our study found that seizures and status epilepticus are the most important predictive values for a poor outcome in patients with the mtA3243G mutation of mtDNA. Age of onset and visceral organ involvement had no prominent influence on the prognosis. Some medical complications could be well controlled or even reversed after management.

  14. Preoperative mannan-binding lectin pathway and prognosis in colorectal cancer

    DEFF Research Database (Denmark)

    Ytting, Henriette; Christensen, Ib Jarle; Jensenius, Jens Christian

    2005-01-01

    PURPOSE: Deficiency of the mannan-binding lectin (MBL) pathway of innate immunity is associated with increased susceptibility to infections. In patients with colorectal cancer (CRC), postoperative infection is associated with poor prognosis. The aim of the present study was to evaluate (1...

  15. Probabilistic Remaining Useful Life Prediction of Composite Aircraft Components Project

    Data.gov (United States)

    National Aeronautics and Space Administration — A composite fatigue damage assessment and risk informed prognosis toolkit will be developed by enhancing and integrating existing solution modules within a...

  16. Remaining Life Expectancy With and Without Polypharmacy

    DEFF Research Database (Denmark)

    Wastesson, Jonas W; Canudas-Romo, Vladimir; Lindahl-Jacobsen, Rune

    2016-01-01

    OBJECTIVES: To investigate the remaining life expectancy with and without polypharmacy for Swedish women and men aged 65 years and older. DESIGN: Age-specific prevalence of polypharmacy from the nationwide Swedish Prescribed Drug Register (SPDR) combined with life tables from Statistics Sweden...... was used to calculate the survival function and remaining life expectancy with and without polypharmacy according to the Sullivan method. SETTING: Nationwide register-based study. PARTICIPANTS: A total of 1,347,564 individuals aged 65 years and older who had been prescribed and dispensed a drug from July 1...... to September 30, 2008. MEASUREMENTS: Polypharmacy was defined as the concurrent use of 5 or more drugs. RESULTS: At age 65 years, approximately 8 years of the 20 remaining years of life (41%) can be expected to be lived with polypharmacy. More than half of the remaining life expectancy will be spent...

  17. Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO).

    Science.gov (United States)

    Valentin, T; Le Cesne, A; Ray-Coquard, I; Italiano, A; Decanter, G; Bompas, E; Isambert, N; Thariat, J; Linassier, C; Bertucci, F; Bay, J O; Bellesoeur, A; Penel, N; Le Guellec, S; Filleron, T; Chevreau, C

    2016-03-01

    Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently. Adult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study. A total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1-94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms. To our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Mass Remaining During Evaporation of Sessile Drop

    Science.gov (United States)

    2008-09-01

    oscillations in the mass remaining. • TRANSFORM ED t TRUEt TRUEtCont 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 TIMI (Hr) Figure 13. Effect of 3 min...2.5 2.55 2.8 TIMI (Hr) 2.86 2.1 275 2.8 Figure 14. Mass Remaining vs. Time Expanded Scale The assumed sinusoidal variation of the friction velocity

  19. Oncoprotein MDM2 Overexpression is Associated with Poor Prognosis in Distinct Non-Hodgkin's Lymphoma Entities

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Nielsen, O; Pedersen, Niels Tinggaard

    1999-01-01

    overexpression was present in 42 (22%) of 188 cases. The frequency was highest in aggressive/very aggressive NHL (P associated with higher-grade disease (P = .008). MDM2 overexpression was not related to a phenotype indicating...... altered p53. In univariate analysis MDM2 overexpression associated with short survival in follicle center lymphomas (P = .0256), extranodal marginal zone lymphomas (P

  20. High levels of c-Met is associated with poor prognosis in glioblastoma

    DEFF Research Database (Denmark)

    Petterson, Stine Asferg; Dahlrot, Rikke Hedegaard; Hermansen, Simon Kjær

    2015-01-01

    . Measurements of high c-Met intensity correlated with high WHO grade (p = 0.006) but no association with survival was observed in patients with WHO grade II (p = 0.09) or III (p = 0.17) tumors. High expression of c-Met was associated with shorter overall survival in patients with glioblastoma multiforme (p = 0...... and the clinical variables age (HR 1.01, 95 % CI 0.99-1.03, p = 0.30), performance status (HR 1.34, 95 % CI 1.17-1.53, p

  1. High MicroRNA-370 Expression Correlates with Tumor Progression and Poor Prognosis in Breast Cancer

    OpenAIRE

    Sim, Jongmin; Ahn, Hyein; Abdul, Rehman; Kim, Hyunsung; Yi, Ki-jong; Chung, Yu-Min; Chung, Min Sung; Paik, Seung Sam; Song, Young Soo; Jang, Kiseok

    2015-01-01

    Purpose Deregulation of microRNA-370 (miR-370) has been reported in various cancers, in which it can act as either an oncogene or a tumor suppressor gene. However, the clinicopathologic significance of miR-370 expression in breast cancer has not been studied. Methods The expression of miR-370 was determined with quantitative real-time polymerase chain reaction in 60 formalin-fixed, paraffin-embedded primary breast cancer tissues. Additionally, the protein expression levels of previously known...

  2. Elevated cholesterol levels have a poor prognosis in a cholestasis scenario.

    Science.gov (United States)

    Nuño-Lámbarri, Natalia; Barbero-Becerra, Varenka J; Uribe, Misael; Chávez-Tapia, Norberto C

    2017-01-01

    Cholestasis results from defective bile flow through the biliary ducts leading to the accumulation of bile acids (BAs) in hepatocytes and serum. It has been seen that cholestasis is associated with hypercholesterolemia, which is a prerequisite for gallstone formation and primary biliary cirrhosis, being some of the most common gastrointestinal disorders in Western societies. Cytotoxic BAs induce proinflammatory mediators, oxidative stress, and apoptosis in hepatocytes, whereas cytoprotective BAs prevent them; they can also modify the plasmatic membrane structure of cells or mitochondrial outer membrane properties as well as the distribution of cholesterol, altering various proteins involved in BAs homeostasis. © 2016 Wiley Periodicals, Inc.

  3. Monosomal karyotype in acute myeloid leukemia: A better indicator of poor prognosis than a complex karyotype

    NARCIS (Netherlands)

    Breems, Dimitri A.; van Putten, Wim L. J.; de Greef, Georgine E.; van Zelderen-Bhola, Shama L.; Gerssen-Schoorl, Klasien B. J.; Mellink, Clemens H. M.; Nieuwint, Aggie; Jotterand, Martine; Hagemeijer, Anne; Beverloo, H. Berna; Lowenberg, Bob

    2008-01-01

    Purpose To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML). Patients and Methods Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years. Results Besides AML with normal cytogenetics (CN)

  4. Expression of SIRT1 and DBC1 is associated with poor prognosis of soft tissue sarcomas.

    Directory of Open Access Journals (Sweden)

    Jung Ryul Kim

    Full Text Available Recently, the roles of SIRT1 and deleted in breast cancer 1 (DBC1 in human cancer have been extensively studied and it has been demonstrated that they are involved in many human carcinomas. However, their clinical significance for soft-tissue sarcomas has not been examined. In this study, we evaluated the expression and prognostic significance of the expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 in 104 cases of soft-tissue sarcomas.Immunohistochemical expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were seen in 71%, 74%, 53%, 48%, and 73% of sarcomas, respectively. The expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were significantly correlated with advanced clinicopathological parameters such as higher clinical stage, higher histological grade, increased mitotic counts, and distant metastasis. The expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 were significantly correlated with each other and positive expression of all of these predicted shorter overall survival and event-free survival by univariate analysis. Multivariate analysis revealed the expression of SIRT1 as an independent prognostic indicator for overall survival and event-free survival of sarcoma patients. In conclusion, this study demonstrates that SIRT1- and DBC1-related pathways may be involved in the progression of soft-tissue sarcomas and can be used as clinically significant prognostic indicators for sarcoma patients. Moreover, the SIRT1- and DBC1-related pathways could be new therapeutic targets for the treatment of sarcomas.

  5. Association of severe thrombocytopenia and poor prognosis in pregnancies with aplastic anemia.

    Directory of Open Access Journals (Sweden)

    Jae Eun Shin

    Full Text Available PURPOSE: We sought to estimate the risks of adverse obstetric outcomes and disease outcomes associated with severe thrombocytopenia in pregnant women with aplastic anemia (AA. METHODS: In a retrospective study, we compared demographics, clinical characteristics, laboratory results, and outcomes between severe thrombocytopenia (ST and non-severe thrombocytopenia (non-ST groups comprising pregnant women with AA. RESULTS: Of 61 AA patients, 43 (70% were diagnosed as AA before pregnancy and 18 (30% were AA during pregnancy. The ST group exhibited lower gestational age at nadir of platelet count (26.0 versus 37.0 weeks, p<0.001 and at delivery (37.3 versus 39.1 weeks, p = 0.008, and a higher rate of bleeding gums (33.8 versus 7.7%, p = 0.015 than the non-ST group. In addition, the ST group exhibited more transfusions during pregnancy (72.7 versus 15.4%, p<0.001 and postpartum period (45.0 versus 2.7%, p<0.001, and more bone marrow transplant after delivery (25.0 versus 0.0%, p<0.001 than the non-ST group. The ST group had a higher odds ratio of composite disease complications (OR, 9.63; 95% CI, 2.82-32.9; p<0.001 and composite obstetric complications (OR, 6.78; 95% CI, 2.11-21.8; p = 0.001 than the non-ST group. CONCLUSIONS: Severe thrombocytopenia is more associated with obstetric and disease complications than is non-severe thrombocytopenia in pregnant women with AA.

  6. Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis

    Science.gov (United States)

    Ma, Yuhua; Yang, Jie; Wang, Ruozheng; Zhang, Zegao; Qi, Xiaoli; Liu, Chunhua; Ma, Miaomiao

    2017-01-01

    Background Definitive radiation therapy (RT) (with or without cisplatin-based chemotherapy) is one of the most effective treatments for cervical squamous cell carcinoma (CSCC), but efficacy is limited due to resistance. In the present study, we investigated the relationship between the expression of Aurora kinase A (Aurora-A, AURKA)and response to RT in patients with CSCC. Methods The expression of Aurora-A in biopsy specimens of untreated primary tumors in 129 Uyghur patients with CSCC was investigated immunohistochemically. Primary treatment in these patients was definitive radical RT, which consisted of pelvic RT plus brachytherapy (total point A dose:70–85 Gy) (with or without cisplatin-based chemotherapy). The prognostic value of tumoral Aurora-A expression and patients’ clinical outcomes were evaluated. Results Aurora-A expression was significantly associated with lymph node metastasis (P<0.001), large tumor size (P<0.001), low hemoglobin (Hb) level (P=0.011) and recurrence (P<0.001), but not other clinicopathological factors. Definitive RT was unfavorable in patients with high Aurora-A expression (P < 0.001). In 129 enrolled patients, lymph node metastasis, large tumor size, low Hb level, and AURKA overexpression were prognostic factors for both recurrent free survival (RFS) and overall survival (OS) in univariate analysis. However, only high AURKA expression was an adverse independent risk factor for both RFS (hazard ratio, 3.953; 95% CI, 1.473-10.638; P = 0.006) and OS (hazard ratio 9.091; 95%CI 2.597-32.258; P<0.001) in multivariate analyses. Conclusions Aurora-A may serve as a predictive biomarker of radiation response and a therapeutic target to reverse radiation therapy resistance. PMID:28404933

  7. Depression is associated with poor prognosis in patients with chronic obstructive pulmonary disease - a systematic review

    DEFF Research Database (Denmark)

    Salte, Kim; Titlestad, Ingrid; Halling, Anders

    2015-01-01

    INTRODUCTION: Patients with depression have significantly increased mortality from somatic disease. The purpose of this article was to review studies that investigate if there is a prognostic association with depression as co-morbidity in patients with chronic obstructive pulmonary disease (COPD......). We chose the following outcomes: mortality, suicide behaviour, risk of COPD exacerbation, use of primary care and prescription data. METHODS: A literature review was performed on 16 December 2014 in PubMed, Embase, OVID Medline and Cochrane for cohort studies. Only studies with mortality...... was a combined retro- and prospective study. There was a tendency for studies with more patients and higher methodological quality to show a positive correlation. Sixteen of the studies showed that depression was associated with increased mortality (relative risk (RR): 1.02-3.6) and more COPD exacerbations (RR...

  8. Downregulation of polo-like kinase 4 in hepatocellular carcinoma associates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Lili Liu

    Full Text Available Polo-like kinase 4 (PLK4, belonging to serine/threonine kinase family, is critical for centriole replication and cell cycle progression. PLK4 has been proposed as a tumor suppressor in hepatocellular carcinoma (HCC. However, its expression and significance in HCC have not been well studied. In the present study, we found that PLK4 was markedly downregulated in both HCC cell lines and fresh cancer tissues, using quantitative real-time-PCR and western blot. Immunohistochemistry data also revealed that decreased expression of PLK4 was present in 72.4% (178/246 of HCC tissues, compared with the corresponding adjacent nontumorous tissues. Furthermore, PLK4 expression significantly correlated with clinicopathological parameters, including clinical stage (P=0.034, serum α-fetoprotein (AFP (P=0.019 and tumor size (P=0.032. Moreover, HCC patients with low PLK4 expression survived shorter than those with high PLK4 expression, as indicated by overall survival (P=0.002 and disease-free survival (P=0.012 assessed by the Kaplan-Meier method. In addition, multivariate analysis suggested PLK4 as an independent predictor of overall survival (HR, 0.556; 95%CI, 0.376-0.822; P=0.003 and disease-free survival (HR, 0.547; 95%CI, 0.382-0.783; P=0.001. Collectively, our study demonstrated that PLK4 was remarkably downregulated in HCC and could be served as a potential prognostic marker for patients with this deadly disease.

  9. Cool seasons are related to poor prognosis in patients with infective endocarditis

    Science.gov (United States)

    Chen, Su-Jung; Chao, Tze-Fan; Lin, Yenn-Jiang; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Hsu, Tsui-Lieh; Yu, Wen-Chung; Leu, Hsin-Bang; Chang, Shih-Lin; Chen, Shih-Ann

    2012-09-01

    Many cardiac diseases demonstrate seasonal variations in the incidence and mortality. This study was designed to investigate whether the mortality of infective endocarditis (IE) was higher in cool seasons and to evaluate the effects of cool climate for IE. We enrolled 100 IE patients with vegetations in our hospital. The temperatures of the IE episodes were defined as the monthly average temperatures of the admission days. The average temperatures in the cool (fall/winter) and warm seasons (spring/summer) were 19.2°C and 27.6°C, respectively. In addition, patients admitted with the diagnosis of IE were identified from the National Health Insurance Research Database (NHIRD) and the in-hospital mortality rates in cool and warm seasons were compared to validate the findings derived from the data of our hospital. The mortality rate for IE was significantly higher in fall/winter than in spring/summer which presents consistently in the patient population of our hospital (32.7% versus 12.5%, p = 0.017) and from NHIRD (10.4% versus 4.6%, p = 0.019). IE episodes which occurred during cool seasons presented with a higher rate of heart failure (44.2% versus 22.9%, p = 0.025) and D-dimer level (5.5 ± 3.8 versus 2.4 ± 1.8 μg/ml, p = 0.017) at admission than that of warm seasons. These results may reflect the impact of temperatures during the pre-hospitalized period on the disease process. In the multivariate analysis, Staphylococcal infection, left ventricular hypertrophy, left ventricular systolic dysfunction and temperature were the independent predictors of mortalities in IE patients.

  10. Over-expression of CD200 predicts poor prognosis in MDS.

    Science.gov (United States)

    Chen, Jia-Xi; Mei, Li-Ping; Chen, Bao-Guo; Wang, Dong-Lian; Luo, Wen-da; Luo, Li-Fei; Lu, Ruyue; Zheng, Rui; Zhang, Li

    2017-05-01

    We studied the expression of CD200 in a series of 101 patients with diagnosis of myelodysplastic syndrome (MDS), to evaluate its impact on outcome and its possible association with other known prognostic factors. The CD200 was detected by flow cytometry, and the chromosome karyotypes were determined by G banding respectively. The Mann-Whitney U test was used to analyze the association among CD200 expression and clinical features. In addition, the overall survival and AML transformation of the MDS patients according to the expression level of CD200 was also explored. Overall, the flow cytometric analyses confirmed that expression of CD200 was high in this patient cohort compared to normal BM (pMDS according to IPSS risk(PMDS in our study indicated that patients with high expression level of CD200 had a shorter overall survival and a high Leukemic transformation than those with low expression (pMDS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Do younger women with non-metastatic and non-inflammatory breast carcinoma have poor prognosis?

    Directory of Open Access Journals (Sweden)

    Rajan Balakrishnan

    2004-01-01

    Full Text Available Abstract Background Controversy abounds over whether breast cancer in younger women is more aggressive than those in older. The aim of the study was to assess the influence of age on long-term survival of women with breast carcinoma. Materials and Methods Patients with non-metastatic and non-inflammatory invasive breast carcinoma treated at the Regional Cancer Centre, Trivandrum, Kerala, India during 1990–93 were divided into 4 age groups as 60 years. The overall survival (OS for each age group was estimated using the Kaplan-Meier method in relation to the primary tumor (T and the axillary node status (N. The OS of the various age groups were compared using the log-rank test. Hazard ratio and 95% confidence interval for each age group was estimated using Cox-regression model after adjusting for T and N. Results Between 1990–1993, 1701 women (26%, Conclusion Women under 40 years with T3/ T4 breast lesions and/or positive axillary nodes were found to have a significantly poorer survival.

  12. Monosomal karyotype in acute myeloid leukemia : A better indicator of poor prognosis than a complex karyotype

    NARCIS (Netherlands)

    Breems, Dimitri A.; Van Putten, Wim L. J.; De Greef, Georgine E.; Van Zelderen-Bhola, Shama L.; Gerssen-Schoorl, Klasien B. J.; Mellink, Clemens H. M.; Nieuwint, Aggie; Jotterand, Martine; Hagemeijer, Anne; Beverloo, H. Berna; Lowenberg, Bob

    2008-01-01

    Purpose To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML). Patients and Methods Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years. Results Besides AML with normal cytogenetics (CN)

  13. Downregulation of osteoprotegerin expression in metastatic colorectal carcinoma predicts recurrent metastasis and poor prognosis.

    Science.gov (United States)

    Moon, Ahrim; Do, Sung-Im; Kim, Hyun-Soo; Kim, Youn-Wha

    2016-11-29

    We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression. In this study, we used immunohistochemical staining to evaluate osteoprotegerin expression in 81 colorectal liver metastasis tissue samples and investigated its possible association with the clinicopathological characteristics and outcomes of patients with colorectal liver metastasis. These tissues exhibited significantly reduced expression of osteoprotegerin compared to primary colorectal carcinomas and normal colorectal mucosa. This reduced expression was significantly associated with the extent of colorectal liver metastasis, including multiplicity of metastatic tumors, involvement of the bilateral hepatic lobes, and higher histological grade. In addition, reduced osteoprotegerin expression was an independent significant predictor of recurrent liver metastasis and prognostic factor for reduced patient survival. These findings suggest that osteoprotegerin expression may be a novel predictor of recurrent liver metastasis and a prognostic biomarker in patients with colorectal liver metastasis. Patients harboring colorectal liver metastasis with reduced osteoprotegerin expression should be carefully monitored after hepatic resection for colorectal liver metastasis to enable early detection of potentially resectable metastatic recurrences.

  14. Tumor budding correlates with poor prognosis and epithelial-mesenchymal transition in tongue squamous cell carcinoma.

    Science.gov (United States)

    Wang, Cheng; Huang, Hongzhang; Huang, Zhiquan; Wang, Anxun; Chen, Xiaohua; Huang, Lei; Zhou, Xiaofeng; Liu, Xiqiang

    2011-08-01

    Tumor budding is a readily detectable histopathological feature and has been recognized as an adverse prognostic factor in several human cancers. However, the prognostic value of tumor budding in tongue squamous cell carcinoma (TSCC) has not been reported. The purpose of this study was to assess the correlation of tumor budding with the clinicopathologic features, and the known molecular biomarkers (E-cadherin and Vimentin), as well as to evaluate its prognostic significance for TSCC. Archival clinical samples of 230 patients with TSCC were examined for tumor budding. Immunohistochemistry analyses were performed to examine the expression of E-cadherin and Vimentin. Statistical analyses were carried out to assess the correlation of tumor budding with clinicopathologic parameters and patient survival. The potential association between tumor budding and alterations of E-cadherin and Vimentin expression was also assessed. Of the 230 TSCC cases examined, tumor budding was observed in 165 cases (71.7%), with a mean tumor bud count of 7.5 (range from 1 to 48 buds). High-intensity budding (≥5 tumor buds) was observed in 111 cases (48.3%). Statistical analysis revealed that tumor budding was associated with tumor size (P tumor budding and the deregulation of E-cadherin (P Tumor budding, which associates with epithelial-mesenchymal transition, is a frequent event and appears to be an independent prognostic factor in TSCC. © 2011 John Wiley & Sons A/S.

  15. [Comorbid puffy hand syndrome and factitious disorders: an unusual association with poor prognosis].