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Sample records for prognosis remains poor

  1. Isolated microalbuminuria indicates a poor medical prognosis.

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    Scheven, Lieneke; Van der Velde, Marije; Lambers Heerspink, Hiddo J; De Jong, Paul E; Gansevoort, Ron T

    2013-07-01

    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 cardiovascular disease (CVD) history, hypertension and diabetes has clinical relevance. Included were 8356 subjects who participated in the first four screening rounds of the PREVEND study, a prospective, community-based, observational cohort study. Isolated microalbuminuria was defined as microalbuminuria (30-300 mg/24 h), in the absence of a CVD history, hypertension (blood pressuredefinition of isolated microalbuminuria, in which 2250 person-years of follow-up were available. In subjects with isolated microalbuminuria, the incidence rates of cardiovascular events and mortality, hypertension and diabetes were 15.3, 28.9 and 8.9 per 1000 person-year follow-up, respectively. Subjects with isolated microalbuminuria had an increased risk for cardiovascular events and mortality [crude HR 2.23 (1.63-3.07); Phypertension [OR 1.95 (1.47-2.59); Phypertension and/or diabetes. This increased risk remained significant after adjustment for age and gender. The relative risk held by isolated microalbuminuria was similar to the relative risk held by microalbuminuria in subjects that did have a CVD history, hypertension and/or diabetes. Isolated microalbuminuria indicates a poor prognosis and warrants medical attention.

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

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    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...

  3. Predictors of Poor Prognosis in Aluminum Phosphide Intoxication

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    Fakhredin Taghaddosi Nejad

    2012-05-01

    Full Text Available Background: Aluminum phosphide as a fumigant is extensively used for wheat preservation from rodents and bugs especially in silos worldwide. There is increasing number of acute intoxication with this potentially lethal compound because of its easy availability. We have tried to locate predictors of poor prognosis in patients with aluminum phosphide intoxication in order to find patients who need more strict medical cares. Methods: All cases of aluminum phosphide intoxication that had been referred to our hospital during April 2008 to March 2010 were studied by their medical dossiers. Pertinent data including vital signs, demographic features, clinical and lab findings, and incidence of any complication were collected and analyzed by the relevant statistical methods. Results: Sixty seven cases of aluminum phosphide intoxication were included in the study. 44.8% of them were male. 97% of cases were suicidal. Mean amount of ingestion was 1.23+/- 0.71 tablets. Mortality rate was 41.8%. ECG abnormality and need for mechanical ventilation had negative relation with outcome. Conclusion: Correlation between some findings and complications with outcome in aluminum phosphide intoxication can be used as guidance for risk assessment and treatment planning in the patients.

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

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    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.

  5. Modified optimal fractionation for poor prognosis malignant gliomas: An elusive search

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    Gupta, Tejpal; Dinshaw, Ketayun

    2005-01-01

    The prognosis of malignant gliomas has not changed much over the last few decades despite refinements in neurosurgical techniques, high-precision radiotherapy, and newer chemotherapeutic agents. The median survival of poor prognosis malignant gliomas (older and/or poor performance status patients) still remains in the range of 6-9 months following maximal safe resection and postoperative conventionally fractionated adjuvant radiotherapy with or without chemotherapy. However, six weeks of daily radiotherapy does seem inappropriate in relation to the short expected survival time in this subset and there is an increasing emphasis on reducing the overall treatment time and the number of hospital visits by such patients. This can be achieved either by accelerated radiotherapy or by hypofractionated radiation, both of which are equivalent to conventional fractionation in terms of palliative effect and survival, as in discussed in this review. Despite enough evidence, such alteration of fractionation has not gained widespread acceptance by the oncologic fraternity. This review has been conducted to collate the evidence that could help shift the paradigm from conventional to modified fractionation in poor prognosis malignant glioma patients

  6. Risk Factors of Poor Prognosis after Whiplash Injury

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    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.

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

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    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

  8. [Assessment of the prognosis in patients who remain comatose after resuscitation from cardiac arrest].

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    Ramberg, Emilie; Fedder, Anette Marianne; Dyrskog, Stig Eric; Degn, Niels Sanderhoff; Hassager, Christian; Jensen, Reinhold; Kirkegaard, Hans; Weber, Sven; Hoffmann-Petersen, Joachim Torp; Larsen, Niels Heden; Strange, Ditte Gry; Sonne, Morten; Lippert, Freddy K

    2014-06-30

    In Denmark there are around 3,500 unexpected cardiac arrests (CA) out of hospital each year. There is an unknown number of CA in hospitals. The survival rate after CA outside a hospital in Denmark is 10% after 30 days. There are varying data for the neurological outcome in this group of patients. The purpose of this work is to disseminate new knowledge and to help standardizing the treatment in the group of patients who remain comatose after being resuscitated from CA. Assessment of the prognosis for a patient in this group can be made after 72 hours and a multi-modal approach to the patient is required.

  9. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

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    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

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

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    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

  11. Podocalyxin Is a Marker of Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

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    Kapo Saukkonen

    Full Text Available Podocalyxin-like 1 is a transmembrane glyco-protein whose overexpression associates in many cancers with poor prognosis and unfavorable clinicopathological characteristics. Until now, its prognostic value has never been studied in pancreatic ductal adenocarcinoma (PDAC. The aim of this study was to investigate podocalyxin expression in PDAC by a novel monoclonal antibody and a commercially available polyclonal antibody.With tissue microarrays and immuno-histochemistry, podocalyxin expression evaluation involved 168 PDAC patients. The associations of the podocalyxin tumor expression with clinicopathological variables were explored by Fisher's exact test and the linear-by-linear test. Survival analyses were by Kaplan-Meier analysis and the Cox proportional hazard model.The polyclonal antibody revealed membranous podocalyxin expression in 73 (44.0% specimens and the monoclonal antibody was highly expressed in 36 (21.8% cases. Membranous expression by the polyclonal antibody was associated with T classification (p=0.045 and perineural invasion (p=0.005, and high expression by the mono-clonal antibody with poor differentiation (p=0.033. High podocalyxin expression associated significantly with higher risk of death from PDAC by both the polyclonal antibody (hazard ratio (HR = 1.62; 95% confidence interval (CI 1.12-2.33; p=0.01 and the monoclonal antibody (HR = 2.10, 95% CI 1.38-3.20; p<0.001. The results remained significant in multivariate analysis, adjusted for age, gender, stage, lymph node ratio (≥/< 20%, and perivascular invasion (respectively as HR = 2.03; 95% CI 1.32-3.13, p=0.001; and as HR = 2.36; 95% CI 1.47-3.80, p<0.001.We found podocalyxin to be an independent factor for poor prognosis in PDAC. To our knowledge, this is the first such report of its prognostic value.

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

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    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.

  13. DEK protein overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

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    Sun, Jie; Bi, Fangfang; Yang, Yang; Zhang, Yuan; Jin, Aihua; Li, Jinzi; Lin, Zhenhua

    2017-02-01

    DEK, a transcription factor, is involved in mRNA splicing, transcriptional control, cell division and differentiation. Recent studies suggest that DEK overexpression can promote tumorigenesis in a wide range of cancer cell types. However, little is known concerning the status of DEK in pancreatic ductal adenocarcinoma (PDAC). Based on the microarray data from Gene Expression Omnibus (GEO), the expression levels of DEK mRNA in PDAC tissues were significantly higher than levels in the adjacent non-tumor tissues. To explore the clinical features of DEK overexpression in PDAC, 87 PDAC and 52 normal pancreas tissues were selected for immunoenzyme staining of the DEK protein. Localization of the DEK protein was detected in PANC-1 pancreatic cancer cells using immunofluorescence (IF) staining. The correlations between DEK overexpression and the clinical features of PDAC were evaluated using the Chi-squared (χ2) and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. The expression levels of DEK mRNA in PDAC tissues were significantly higher than that in the adjacent non‑tumor tissues. The DEK protein showed a primarily nuclear staining pattern in PDAC. The positive rate of the DEK protein was 52.9% (46/87) in PDAC, which was significantly higher than that in the adjacent normal pancreatic tissues (7.7%, 4/52). DEK overexpression in PDAC was correlated with tumor size, histological grade, tumor‑node‑metastasis (TNM) stage and overall survival (OS) rates. In addition, multivariate analysis demonstrated that DEK overexpression was an independent prognostic factor along with histological grade and TNM stage in patients with PDAC. In conclusion, DEK overexpression is associated with PDAC progression and may be a potential biomarker for poor prognostic evaluation in PDAC.

  14. Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population.

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    Zhu, Xiaonian; Liu, Wei; Qiu, Xiaoqiang; Wang, Zhigang; Tan, Chao; Bei, Chunhua; Qin, Linyuan; Ren, Yuan; Tan, Shengkui

    2017-10-03

    Hepatocellular carcinoma (HCC) is a malignant cancer causing deleterious health effect worldwide, especially in China. So far clinical cure rate and long-term survival rate of HCC remains low. Most HCC patients after cancer resection have recurrence or metastasis within 5 years. This study aims to explore the genetic association of mutL homolog 1 ( MLH1 ) polymorphisms with HCC risk and prognosis. Four candidate MLH1 polymorphisms, rs1800734, rs10849, rs3774343 and rs1540354 were studied from a hospital-based case-control study including 1,036 cases (HCC patients) and 1,036 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. However, only rs1800734 had significant difference between cases and controls. Compared to the AA genotype, patients with AG, GG and AG/GG genotype of rs1800734 had an increased risk of HCC [ORs (95% CI) = 1.217 (1.074∼1.536), 1.745 (1.301∼2.591) and 1.291 (1.126∼1.687)] and a decreased survival time [co-dominant, HR (95% CI) = 1.553 (1.257∼1.920); dominant, HR (95% CI) = 2.207 (1.572∼3.100)]. Furthermore, we found that tumor number, tumor staging, metastasis and rs1800734 were associated with the overall survival of HCC patients by multivariate COX regression analysis. No significant difference was found between the other three MLH1 polymorphisms with HCC risk and prognosis. Our study suggests MLH1 SNP, rs1800734 as a new predictor for poor prognosis of HCC patients.

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

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    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.

  16. Aberrant membranous expression of β-catenin predicts poor prognosis in patients with craniopharyngioma.

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    Li, Zongping; Xu, Jianguo; Huang, Siqing; You, Chao

    2015-12-01

    The objective of this study is to investigate β-catenin expression in craniopharyngioma patients and determine its significance in predicting the prognosis of this disease. Fifty craniopharyngioma patients were enrolled in this study. Expression of β-catenin in tumor specimens collected from these patients was examined through immunostaining. In addition, mutation of exon 3 in the β-catenin gene, CTNNB1, was analyzed using polymerase chain reaction, denaturing high-pressure liquid chromatography, and DNA sequencing. Based on these results, we explored the association between membranous β-catenin expression, clinical and pathologic characteristics, and prognoses in these patients. Of all craniopharyngioma specimens, 31 (62.0%) had preserved membranous β-catenin expression, whereas the remaining 19 specimens (38.0%) displayed aberrant expression. Statistical analysis showed a significant correlation between aberrant membranous β-catenin expression and CTNNB1 exon 3 mutation, as well as between aberrant membranous β-catenin expression and the histopathologic type of craniopharyngioma and type of resection in our patient population. Furthermore, aberrant membranous β-catenin expression was found to be associated with poor patient survival. Results of Kaplan-Meier survival analysis and Cox regression analysis further confirmed this finding. In conclusion, our study demonstrated that aberrant membranous β-catenin expression was significantly correlated with poor survival in patients with craniopharyngioma. This raises the possibility for use of aberrant membranous β-catenin expression as an independent risk factor in predicting the prognosis of this disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Identifying subgroups among poor prognosis patients with nonseminomatous germ cell cancer by tree modelling: a validation study.

    NARCIS (Netherlands)

    M.R. van Dijk (Merel); E.W. Steyerberg (Ewout); S.P. Stenning; J.D.F. Habbema (Dik)

    2004-01-01

    textabstractBACKGROUND: In order to target intensive treatment strategies for poor prognosis patients with non-seminomatous germ cell cancer, those with the poorest prognosis should be identified. These patients might profit most from more intensive treatment strategies. For

  18. 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...

  19. ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

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    Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

    2014-08-01

    Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.

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

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    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.

  1. Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer

    International Nuclear Information System (INIS)

    Larsson, Anna; Fridberg, Marie; Gaber, Alexander; Nodin, Björn; Levéen, Per; Jönsson, Göran; Uhlén, Mathias; Birgisson, Helgi; Jirström, Karin

    2012-01-01

    Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman´;s Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS. No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels

  2. 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.

  3. 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.

  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 overexpression have a short overall survival (P = 0.0378, log-rank test), and a multivariate analysis revealed that WDR62 overexpression was an independent predictor of a poor survival outcome among LAC patients (hazard ratio, 2.032; 95% confidence interval, 1.071-3.777; P = 0.0305). Next, we examined the functional effect of WDR62 overexpression on the 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. KDM2B overexpression correlates with poor prognosis and regulates glioma cell growth

    Directory of Open Access Journals (Sweden)

    Wang Y

    2018-01-01

    Full Text Available Yiwei Wang,1 Jin Zang,1 Dongyong Zhang,2 Zhenxiang Sun,1 Bo Qiu,2 Xiaojie Wang1 1Department of Human Anatomy, Shenyang Medical College, Huanggu District, Shenyang City, 2Department of Neurosurgery, First Affiliated Hospital of China Medical University, Heping District, Shenyang City, Liaoning Province, ChinaBackground: Gliomas are one of the most lethal cancers in the human central nervous system. Despite clinical treatment advancements, the prognosis of patients with glioma remains poor. KDM2B is a histone lysine demethylase, which has been observed in multiple tumors. But the concrete role of KDM2B in gliomas remains to be further illustrated.Methods: The KDM2B expression in gliomas was detected with immunohistochemistry and Western blot assay. Furthermore, knockdown of KDM2B in U87 and U251 glioma cell lines, the proliferation capacity was evaluated by cell viability assay, colon formation assay and flow cytometry in vitro. Western blot assay was used to analyze the p21, EZH2 and cyclinD1 changes followed by knockdown of KDM2B.Results: KDM2B was upregulated in tissues of glioma patients, and the expression was correlated to cancer progression. Downregulation of KDM2B in U87 and U251 glioma cell lines inhibited cell proliferation and arrested cell cycle in G0/G1 phase. In addition, silencing KDM2B promoted the upregulation of p21 while reduced the expression of EZH2 and cyclinD1.Conclusion: Taken together, our results revealed that KDM2B might influence gliomas growth and act as a novel therapeutic target for glioma patients.Keywords: EZH2, glioma, KDM2B, P21

  6. Checkpoint Kinase 1 Expression Predicts Poor Prognosis in Nigerian Breast Cancer Patients.

    Science.gov (United States)

    Ebili, Henry Okuchukwu; Iyawe, Victoria O; Adeleke, Kikelomo Rachel; Salami, Babatunde Abayomi; Banjo, Adekunbiola Aina; Nolan, Chris; Rakha, Emad; Ellis, Ian; Green, Andrew; Agboola, Ayodeji Olayinka Johnson

    2018-02-01

    Checkpoint kinase 1 (CHEK1), a DNA damage sensor and cell death pathway stimulator, is regarded as an oncogene in tumours, where its activities are considered essential for tumourigenesis and the survival of cancer cells treated with chemotherapy and radiotherapy. In breast cancer, CHEK1 expression has been associated with an aggressive tumour phenotype, the triple-negative breast cancer subtype, an aberrant response to tamoxifen, and poor prognosis. However, the relevance of CHEK1 expression has, hitherto, not been investigated in an indigenous African population. We therefore aimed to investigate the clinicopathological, biological, and prognostic significance of CHEK1 expression in a cohort of Nigerian breast cancer cases. Tissue microarrays of 207 Nigerian breast cancer cases were tested for CHEK1 expression using immunohistochemistry. The clinicopathological, molecular, and prognostic characteristics of CHEK1-positive tumours were determined using the Chi-squared test and Kaplan-Meier and Cox regression analyses in SPSS Version 16. Nuclear expression of CHEK1 was present in 61% of breast tumours and was associated with tumour size, triple-negative cancer, basal-like phenotype, the epithelial-mesenchymal transition, p53 over-expression, DNA homologous repair pathway dysfunction, and poor prognosis. The rate expression of CHEK1 is high in Nigerian breast cancer cases and is associated with an aggressive phenotype and poor prognosis.

  7. Increased Expression of microRNA-17 Predicts Poor Prognosis in Human Glioma

    Directory of Open Access Journals (Sweden)

    Shengkui Lu

    2012-01-01

    Full Text Available Aim. To investigate the clinical significance of microRNA-17 (miR-17 expression in human gliomas. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR analysis was used to characterize the expression patterns of miR-17 in 108 glioma and 20 normal brain tissues. The associations of miR-17 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. Results. Compared with normal brain tissues, miR-17 expression was significantly higher in glioma tissues (P<0.001. In addition, the increased expression of miR-17 in glioma was significantly associated with advanced pathological grade (P=0.006 and low Karnofsky performance score (KPS, P=0.01. Moreover, Kaplan-Meier survival and Cox regression analyses showed that miR-17 overexpression (P=0.008 and advanced pathological grade (P=0.02 were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-17 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III~IV: P<0.001. Conclusions. Our data offer the convinced evidence that the increased expression of miR-17 may have potential value for predicting poor prognosis in glioma patients with high pathological grades, indicating that miR-17 may contribute to glioma progression and be a candidate therapeutic target for this disease.

  8. 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.□

  9. Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

    Science.gov (United States)

    Sánchez-Martínez, Diego; Lanuza, Pilar M; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A; Pardo, Julián

    2016-01-01

    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.

  10. 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.

  11. KDM2B overexpression correlates with poor prognosis and regulates glioma cell growth

    OpenAIRE

    Wang, Yiwei; Zang, Jin; Zhang, Dongyong; Sun, Zhenxiang; Qiu, Bo; Wang, Xiaojie

    2018-01-01

    Yiwei Wang,1 Jin Zang,1 Dongyong Zhang,2 Zhenxiang Sun,1 Bo Qiu,2 Xiaojie Wang1 1Department of Human Anatomy, Shenyang Medical College, Huanggu District, Shenyang City, 2Department of Neurosurgery, First Affiliated Hospital of China Medical University, Heping District, Shenyang City, Liaoning Province, ChinaBackground: Gliomas are one of the most lethal cancers in the human central nervous system. Despite clinical treatment advancements, the prognosis of patients with glioma remains ...

  12. 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.

  13. 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 pretreatment...... tumour samples from clinically high risk patients treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis with high resolution array comparative genomic hybridization (aCGH) and gene expression microarrays. Major finding was validated at the protein...

  14. Rectal malignant melanoma mistaken for thrombotic hemorrhoids - rare tumor with poor prognosis

    International Nuclear Information System (INIS)

    Kovacova, E.; Hvizdakova, A.; Vyskocil, M.; Kinova, S.; Sesovsky, V.; Kobzova, D.; Palkovic, M.

    2011-01-01

    Rectal malignant melanoma originates in the melanocytes of the anorectal area. Represent less than 1 % of all melanomas, and 4 % of all malignant tumors of the rectum and anus. The most common clinical manifestation is bleeding, the clinical examination may be mistaken for benign lesions or hemorrhoids. Given the rarity of the diagnosis are not well-defined therapeutic procedures. Prognosis for patient is poor. The authors present a case of 70-year old patient with rectal melanoma diagnosed at an advanced stage of disease, initially with diagnosis a thrombotic hemorrhoid. (author)

  15. In vitro downregulated hypoxia transcriptome is associated with poor prognosis in breast cancer.

    Science.gov (United States)

    Abu-Jamous, Basel; Buffa, Francesca M; Harris, Adrian L; Nandi, Asoke K

    2017-06-15

    Hypoxia is a characteristic of breast tumours indicating poor prognosis. Based on the assumption that those genes which are up-regulated under hypoxia in cell-lines are expected to be predictors of poor prognosis in clinical data, many signatures of poor prognosis were identified. However, it was observed that cell line data do not always concur with clinical data, and therefore conclusions from cell line analysis should be considered with caution. As many transcriptomic cell-line datasets from hypoxia related contexts are available, integrative approaches which investigate these datasets collectively, while not ignoring clinical data, are required. We analyse sixteen heterogeneous breast cancer cell-line transcriptomic datasets in hypoxia-related conditions collectively by employing the unique capabilities of the method, UNCLES, which integrates clustering results from multiple datasets and can address questions that cannot be answered by existing methods. This has been demonstrated by comparison with the state-of-the-art iCluster method. From this collection of genome-wide datasets include 15,588 genes, UNCLES identified a relatively high number of genes (>1000 overall) which are consistently co-regulated over all of the datasets, and some of which are still poorly understood and represent new potential HIF targets, such as RSBN1 and KIAA0195. Two main, anti-correlated, clusters were identified; the first is enriched with MYC targets participating in growth and proliferation, while the other is enriched with HIF targets directly participating in the hypoxia response. Surprisingly, in six clinical datasets, some sub-clusters of growth genes are found consistently positively correlated with hypoxia response genes, unlike the observation in cell lines. Moreover, the ability to predict bad prognosis by a combined signature of one sub-cluster of growth genes and one sub-cluster of hypoxia-induced genes appears to be comparable and perhaps greater than that of known

  16. Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

    Science.gov (United States)

    Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin

    2012-09-01

    Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

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

    Science.gov (United States)

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

    2014-06-01

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

  18. Remaining Useful Lifetime Prognosis of Controlled Systems: A Case of Stochastically Deteriorating Actuator

    Directory of Open Access Journals (Sweden)

    Danh Ngoc Nguyen

    2015-01-01

    Full Text Available This paper addresses the case of automatic controlled system which deteriorates during its operation because of components’ wear or deterioration. Depending on its specific closed-loop structure, the controlled system has the ability to compensate for disturbances affecting the actuators which can remain partially hidden. The deterioration modeling and the Remaining Useful Lifetime (RUL estimation for such closed-loop dynamic system have not been addressed extensively. In this paper, we consider a controlled system with Proportional-Integral-Derivative controller. It is assumed that the actuator is subject to shocks that occur randomly in time. An integrated model is proposed to jointly describe the state of the controlled process and the actuator deterioration. Only the output of the controlled system is available to assess its health condition. By considering a Piecewise Deterministic Markov Process, the RUL of the system can be estimated by a two-step approach. In the first step referred as the “Diagnosis” step, the system state is estimated online from the available monitoring observations by using a particle filtering method. In the second step referred as the “Prognosis” step, the RUL is estimated as a conditional reliability by Monte Carlo simulation. To illustrate the approach, a simulated tank level control system is used.

  19. Prognosis and cost-effectiveness of IVF in poor responders according to the Bologna Criteria.

    Science.gov (United States)

    Busnelli, Andrea; Somigliana, Edgardo

    2018-02-01

    Poor ovarian response (POR) to controlled ovarian hyperstimulation for in vitro fertilization (IVF) is one of the most challenging issue in the field of reproductive medicine. However, even if improving IVF outcome in poor responders (PORs) represents a main priority, the lack of a unique definition of POR has hampered research in this area. In order to overcome this impediment, an ESHRE Campus Workshop was organized in Bologna in 2010 and reached a consensus on the criteria for the diagnosis of POR ("Bologna Criteria"). In this review we aimed to estimate the prognostic potential of the ESHRE definition, to elucidate its possible weaknesses and to analyze the economic aspects of IVF in a population of poor responders (PORs). Available evidence confirmed that the Bologna criteria are able to select a population with a poor IVF prognosis thus supporting their validity. Nonetheless, different aspects of the definition have been criticized. The main points of debate concern the homogeneity of the population identified, the cut-off values chosen for the ovarian reserve tests and the risks factors other than age associated with POR. Data concerning the economic profile of IVF in PORs are scanty. The only published study on the argument showed that IVF in these cases is not cost-effective. However, considering the potential substantial impact of cost-effectiveness analyses on public health policies, there is the need for further and independent validations.

  20. 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.

  1. 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.

  2. Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer

    Science.gov (United States)

    Koishi, Kenji; Yoshikawa, Reigetsu; Tsujimura, Tohru; Hashimoto-Tamaoki, Tomoko; Kojima, Syoudou; Yanagi, Hidenori; Yamamura, Takehira; Fujiwara, Yoshinori

    2006-01-01

    AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence of CXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway. PMID:17171785

  3. Trisomy 11 as an Additional Chromosome Alteration in a Child with Acute Promyelocytic Leukemia with Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Elenice Ferreira Bastos

    2012-01-01

    Full Text Available The prognostic significance of the additional abnormalities to the t(15; 17 remains controversial. We report a case of promyelocytic leukemia (APL in a ten-year-old boy. Classical and molecular cytogenetic (FISH studies of a bone marrow sample obtained at diagnosis revealed the presence of trisomy of chromosome 11 as an additional chromosomal abnormality to the t(15; 17. The presence of the translocation t(15; 17, the cytogenetic marker of APL, is usually associated with good response to treatment with ATRA. In this case, although the patient had risk factors associated with good prognosis, he evolved and died quickly. So it seems that the presence of the trisomy 11 may be associated with disease progression and the poor outcome. To our knowledge, this is the first reported case of t(15; 17 associated with trisomy of chromosome 11 in a child with APL.

  4. Comorbidity predicts poor prognosis in nasopharyngeal carcinoma: Development and validation of a predictive score model

    International Nuclear Information System (INIS)

    Guo, Rui; Chen, Xiao-Zhong; Chen, Lei; Jiang, Feng; Tang, Ling-Long; Mao, Yan-Ping; Zhou, Guan-Qun; Li, Wen-Fei; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Ma, Jun

    2015-01-01

    Background and purpose: The impact of comorbidity on prognosis in nasopharyngeal carcinoma (NPC) is poorly characterized. Material and methods: Using the Adult Comorbidity Evaluation-27 (ACE-27) system, we assessed the prognostic value of comorbidity and developed, validated and confirmed a predictive score model in a training set (n = 658), internal validation set (n = 658) and independent set (n = 652) using area under the receiver operating curve analysis. Results: Comorbidity was present in 40.4% of 1968 patients (mild, 30.1%; moderate, 9.1%; severe, 1.2%). Compared to an ACE-27 score ⩽1, patients with an ACE-27 score >1 in the training set had shorter overall survival (OS) and disease-free survival (DFS) (both P < 0.001), similar results were obtained in the other sets (P < 0.05). In multivariate analysis, ACE-27 score was a significant independent prognostic factor for OS and DFS. The combined risk score model including ACE-27 had superior prognostic value to TNM stage alone in the internal validation set (0.70 vs. 0.66; P = 0.02), independent set (0.73 vs. 0.67; P = 0.002) and all patients (0.71 vs. 0.67; P < 0.001). Conclusions: Comorbidity significantly affects prognosis, especially in stages II and III, and should be incorporated into the TNM staging system for NPC. Assessment of comorbidity may improve outcome prediction and help tailor individualized treatment

  5. 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

    MDM2 is an oncoprotein involved in the regulation of p53. MDM2 exerts its tumorigenic potential through p53-dependent and -independent mechanisms. It is frequently overexpressed in various malignancies. Little is known about the prognostic value of MDM2 expression in non-Hodgkin's lymphomas (NHL...... overexpression was present in 42 (22%) of 188 cases. The frequency was highest in aggressive/very aggressive NHL (P lymphomas, MDM2 overexpression was 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 lymphomas (P = .0047). The relation to poor prognosis was maintained in a Cox regression analysis including known...

  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. 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

  8. Cancer in adolescents and young adults: Who remains at risk of poor social functioning over time?

    Science.gov (United States)

    Husson, Olga; Zebrack, Bradley J; Aguilar, Christine; Hayes-Lattin, Brandon; Cole, Steve

    2017-07-15

    The objective of the current study was to examine social functioning among adolescents and young adults (AYAs) within the first 2 years after a cancer diagnosis and compare their scores with population norms and identify trajectories of social functioning over time and its correlates. A multicenter, longitudinal study was conducted among 215 AYA patients with cancer aged 14 to 39 years. A total of 141 patients completed a self-report measure of social functioning within the first 4 months of diagnosis and again at 12 months and 24 months later. AYA patients with cancer were found to have significantly worse social functioning scores around the time of diagnosis (52.0 vs 85.1; Pcancer who had consistently low social functioning were more often off treatment at the time of follow-up, reported more physical symptoms and higher levels of distress at baseline and follow-up, and perceived less social support at baseline compared with the other 3 groups. Although improved over time, social functioning still was found to be compromised 24 months after the primary diagnosis. Nearly one-third of these patients remain at risk of poor social functioning. Reducing physical symptoms and psychological distress and enhancing social support by interventions during the period after treatment may potentially help these young survivors to better reintegrate into society. Cancer 2017;123:2743-51. © 2017 American Cancer Society. © 2017 American Cancer Society.

  9. 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.

  10. Echocardiographic screening for subclinical rheumatic heart disease remains a research tool pending studies of impact on prognosis.

    Science.gov (United States)

    Zühlke, Liesl; Mayosi, Bongani M

    2013-03-01

    The application of portable echocardiography to the screening of asymptomatic children and young adults for rheumatic heart disease (RHD) in developing countries indicates that the disease may affect 62 million to 78 million individuals worldwide, which could potentially result in 1.4 million deaths per year from RHD and its complications. The World Heart Federation has developed a guideline for the echocardiographic diagnosis of RHD in asymptomatic individuals without a history of acute rheumatic fever (ARF) in order to ensure the reliability, comparability, and reproducibility of findings of the echocardiographic screening studies. Early studies suggest that a third of individuals with asymptomatic subclinical RHD revert to normal echocardiographic findings on repeat testing after 6-12 months, suggesting that repeat echocardiography may be necessary to confirm the findings prior to consideration of interventions such as antibiotic prophylaxis. It is not known, however, whether echocardiographic screening for asymptomatic subclinical RHD or the introduction of antibiotic prophylaxis for affected individuals improves the prognosis of RHD. Furthermore, the cost-effectiveness of this screening method has not been established in the vast majority of affected countries. Therefore, echocardiographic screening for asymptomatic subclinical RHD remains a research tool until studies of impact on prognosis and cost-effectiveness are conducted.

  11. 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

  12. Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients.

    Science.gov (United States)

    Pang, Li; Wang, Da-Wei; Zhang, Nan; Xu, Da-Hai; Meng, Xiang-Wei

    2016-03-11

    Matrix metalloproteinase 11 (MMP11) has been shown to play a key role in human tumor progression and indicates poor clinical outcome in cancer patients. The current study aimed to evaluate the relationship between serum levels of MMP-11 and prognosis in colon cancer patients. Serum levels of MMP-11 were determined in 92 colon cancer patients and 92 healthy individuals using an enzyme-linked immunosorbent assay (ELISA). Associations between serum MMP-11 levels and clinicopathological characteristics of the patients and their outcomes were investigated. Survival analyses were performed to measure the 5-year overall survival (OS) and disease-free survival (DFS). Serum MMP-11 levels were substantially higher in colon cancer patients than in healthy controls. Moreover, serum MMP-11 levels were significantly higher in patients with advanced T status, lymph node metastasis, distant metastasis, and a higher TNM stage. Elevated serum levels of MMP-11 were identified as an independent prognostic factor for 5-year mortality and adverse events associated with colon cancer. Multivariate Cox regression analysis identified the serum MMP-11 level as an independent predictor of OS and DFS. Our study established that high serum levels of MMP-11 are associated with poor clinical outcome and may serve as a prognostic biomarker in colon cancer patients.

  13. Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Gao, Rui; Chen, Rui-Ze; Xia, Yi; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Zhu Wu, Jia-; Fan, Lei; Li, Jian-Yong; Yang, Tao; Xu, Wei

    2018-02-19

    Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL. © 2018 UICC.

  14. TROP2 correlates with microvessel density and poor prognosis in hilar cholangiocarcinoma.

    Science.gov (United States)

    Ning, Shanglei; Guo, Sen; Xie, Jianjun; Xu, Yunfei; Lu, Xiaofei; Chen, Yuxin

    2013-02-01

    Trophoblast cell surface antigen 2 (TROP2) was found to be associated with tumor progression and poor prognosis in a variety of epithelial carcinomas. The aim of the study was to investigate TROP2 expression and its prognostic impact in hilar cholangiocarcinoma. Immunohistochemistry and quantitative real-time PCR were used to determine TROP2 expression in surgical specimens from 70 hilar cholangiocarcinoma patients receiving radical resection. The relationship between TROP2 expression and microvessel density was investigated and standard statistical analysis was used to evaluate TROP2 prognosis significance in hilar cholangiocarcinoma. High TROP2 expression by immunohistochemistry was found in 43 (61.4 %) of the 70 tumor specimens. Quantitative real-time PCR confirmed that TROP2 level in tumor was significantly higher than in non-tumoral biliary tissues (P = 0.001). Significant correlations were found between TROP2 expression and histological differentiation (P = 0.016) and tumor T stage (P = 0.031) in hilar cholangiocarcinoma. TROP2 expression correlated with microvessel density in hilar cholangiocarcinoma (P = 0.026). High TROP2 expression patients had a significantly poorer overall survival rate than those with low TROP2 expression (30 vs. 68.5 %, P = 0.001), and multivariate Cox regression analysis indicated TROP2 as an independent prognostic factor for hilar cholangiocarcinoma (P = 0.004). TROP2 expression correlates with microvessel density significantly and is an independent prognostic factor in human hilar cholangiocarcinoma.

  15. Zinc finger protein ZBTB20 expression is increased in hepatocellular carcinoma and associated with poor prognosis

    International Nuclear Information System (INIS)

    Wang, Qing; Wang, Hong-yang; Tan, Ye-xiong; Ren, Yi-bin; Dong, Li-wei; Xie, Zhi-fang; Tang, Liang; Cao, Dan; Zhang, Wei-ping; Hu, He-ping

    2011-01-01

    Our previous studies showed that ZBTB20, a new BTB/POZ-domain gene, could negatively regulate α feto-protein and other liver-specific genes, concerning such as bio-transformation, glucose metabolism and the regulation of the somatotropic hormonal axis. The aim of this study is to determine the potential clinical implications of ZBTB20 in hepatocellular carcinoma (HCC). Quantitative real-time RT-PCR and Western blot analyses were used to detect expression levels of ZBTB20 in 50 paired HCC tumorous and nontumorous tissues and in 20 normal liver tissues. Moreover, expression of ZBTB20 was assessed by immunohistochemistry of paired tumor and peritumoral liver tissue from 102 patients who had undergone hepatectomy for histologically proven HCC. And its relationship with clinicopathological parameters and prognosis was investigated. Both messenger RNA and protein expression levels of ZBTB20 were elevated significantly in HCC tissues compared with the paired non-tumor tissues and normal liver tissues. Overexpressed ZBTB20 protein in HCC was significantly associated with vein invasion (P = 0.016). Importantly, the recurrence or metastasis rates of HCCs with higher ZBTB20 expression were markedly greater than those of HCCs with lower expression (P = 0.003, P = 0.00015, respectively). Univariate and multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. The disease-free survival period and over-all survival period in patients with overexpressed ZBTB20 in HCC was significantly reduced. The expression of ZBTB20 is increased in HCC and associated with poor prognosis in patients with HCC, implicating ZBTB20 as a candidate prognostic marker in HCC

  16. Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Sheng XR

    2018-02-01

    Full Text Available Xu-Ren Sheng,1,2,* Song-Ge Xing,2,3,* Run-Dong Wang,2 Kang Chen,2 Wei-Dong Jia1,2 1Department of Liver Surgery, Affiliated Provincial Hospital, Anhui Medical University, 2Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, 3CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, People’s Republic of China *These authors contributed equally to this work Purpose: The tumor suppressor candidate 3 (TUSC3 has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients. Materials and methods: Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients. Results: Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues (χ2=11.512, P=0.001. The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size (P=0.008, 0.009 and 0.020, respectively. Univariate analysis showed

  17. 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

  18. 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.

  19. Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma

    Science.gov (United States)

    Fiaschetti, G; Abela, L; Nonoguchi, N; Dubuc, A M; Remke, M; Boro, A; Grunder, E; Siler, U; Ohgaki, H; Taylor, M D; Baumgartner, M; Shalaby, T; Grotzer, M A

    2014-01-01

    Background: microRNA-9 is a key regulator of neuronal development aberrantly expressed in brain malignancies, including medulloblastoma. The mechanisms by which microRNA-9 contributes to medulloblastoma pathogenesis remain unclear, and factors that regulate this process have not been delineated. Methods: Expression and methylation status of microRNA-9 in medulloblastoma cell lines and primary samples were analysed. The association of microRNA-9 expression with medulloblastoma patients' clinical outcome was assessed, and the impact of microRNA-9 restoration was functionally validated in medulloblastoma cells. Results: microRNA-9 expression is repressed in a large subset of MB samples compared with normal fetal cerebellum. Low microRNA-9 expression correlates significantly with the diagnosis of unfavourable histopathological variants and with poor clinical outcome. microRNA-9 silencing occurs via cancer-specific CpG island hypermethylation. HES1 was identified as a direct target of microRNA-9 in medulloblastoma, and restoration of microRNA-9 was shown to trigger cell cycle arrest, to inhibit clonal growth and to promote medulloblastoma cell differentiation. Conclusions: microRNA-9 is a methylation-silenced tumour suppressor that could be a potential candidate predictive marker for poor prognosis of medulloblastoma. Loss of microRNA-9 may confer a proliferative advantage to tumour cells, and it could possibly contribute to disease pathogenesis. Thus, re-expression of microRNA-9 may constitute a novel epigenetic regulation strategy against medulloblastoma. PMID:24346283

  20. Epigenetic silencing of miRNA-9 is associated with HES1 oncogenic activity and poor prognosis of medulloblastoma.

    Science.gov (United States)

    Fiaschetti, G; Abela, L; Nonoguchi, N; Dubuc, A M; Remke, M; Boro, A; Grunder, E; Siler, U; Ohgaki, H; Taylor, M D; Baumgartner, M; Shalaby, T; Grotzer, M A

    2014-02-04

    microRNA-9 is a key regulator of neuronal development aberrantly expressed in brain malignancies, including medulloblastoma. The mechanisms by which microRNA-9 contributes to medulloblastoma pathogenesis remain unclear, and factors that regulate this process have not been delineated. Expression and methylation status of microRNA-9 in medulloblastoma cell lines and primary samples were analysed. The association of microRNA-9 expression with medulloblastoma patients' clinical outcome was assessed, and the impact of microRNA-9 restoration was functionally validated in medulloblastoma cells. microRNA-9 expression is repressed in a large subset of MB samples compared with normal fetal cerebellum. Low microRNA-9 expression correlates significantly with the diagnosis of unfavourable histopathological variants and with poor clinical outcome. microRNA-9 silencing occurs via cancer-specific CpG island hypermethylation. HES1 was identified as a direct target of microRNA-9 in medulloblastoma, and restoration of microRNA-9 was shown to trigger cell cycle arrest, to inhibit clonal growth and to promote medulloblastoma cell differentiation. microRNA-9 is a methylation-silenced tumour suppressor that could be a potential candidate predictive marker for poor prognosis of medulloblastoma. Loss of microRNA-9 may confer a proliferative advantage to tumour cells, and it could possibly contribute to disease pathogenesis. Thus, re-expression of microRNA-9 may constitute a novel epigenetic regulation strategy against medulloblastoma.

  1. The lower expression of gonadotropin-releasing hormone receptor associated with poor prognosis in gastric cancer

    Science.gov (United States)

    Lu, Mingzhu; Zhu, Jing; Ling, Yang; Shi, Wenping; Zhang, Changsong; Wu, Haorong

    2015-01-01

    Aims: Expression of gonadotropin-releasing hormone receptor (GnRHR) has been demonstrated in a number of malignancies. The aim is to investigate the expression of GnRHR and prognosis in gastric cancer. Methods and materials: GnRHR mRNA was examined in tumor and non-tumor tissues from 48 gastric cancer patients by Real-time PCR. The GnRHR protein expression was performed by immunohistochemical analysis. Results: The expression of GnRHR mRNA was higher (mean ± SD, -10.06 ± 1.28) in gastric tumor tissues than matched non-tumor tissues (mean ± SD, -12.43 ± 1.33). GnRHR mRNA expression was associated with lymph node metastasis, distant metastasis, and TNM stage. We found the decreased expression of GnRHR mRNA were significantly correlated with poor overall survival (P = 0.003). Immunocytochemical staining of GnRHR in tumor tissues showed mainly weak staining (43.48%, 10/23) and moderate staining (21.74%, 5/23) in high GnRHR mRNA patients, and mainly negative staining in low GnRHR mRNA patients. And the staining of GnRHR was not detection in tumor tissues for more than half of gastric patients (52.08%, 25/48). These results implied that the loss of GnRHR protein could be a main event in gastric cancer. Conclusion: The GnRHR expression is very low in gastric cancer, and the loss of GnRHR expression could be a poor prognostic factor, which implied that GnRHR could play an important role in the development of gastric cancer. PMID:26550267

  2. PRL-3, an emerging marker of carcinogenesis, is strongly associated with poor prognosis.

    Science.gov (United States)

    Guzińska-Ustymowicz, Katarzyna; Pryczynicz, Anna

    2011-01-01

    PRL-3 protein belongs to the family of protein tyrosine phosphatases with unique COOH-terminal prenylation motif, which determines the functions of this protein and its location in the cell. Numerous research studies revealed that apart from performing the poorly investigated physiological role, PRL-3 takes part in the process of carcinogenesis. Specifically, it is involved in reconstructing of the cytoskeleton, regulating adhesion and cell cycle of the cancer cells, and in epithelial-mesenchymal transition. Through these mechanisms PRL-3 protein participates in invasion, migration, metastasis and angiogenesis. Numerous studies indicate that PRL-3 expression is particularly important in colorectal, as well as in gastric, ovarian and breast carcinomas. Recently, several studies on PRL-3 protein in other types of cancer have been published. They reveal a significant role of this protein in the process of angiogenesis and metastasis. It has been proven that a higher expression of PRL-3 correlates with tumor progression and its severity. While the degree of overexpression of PRL-3 varies in different types of tumors, most research shows that in the metastases of these tumors, whether to the lymph nodes or to other organs, the level of expression is extremely high. Overexpression of PRL-3 protein was repeatedly confirmed in metastases, but not with primary tumors. PRL-3 seems to be an adequate marker in diagnosing the stage of tumor advancement for various types of carcinomas, especially for colorectal carcinoma investigated thoroughly in this study. PRL-3 overexpression predicts poor prognosis in patients with various carcinomas and is a promising target in the cancer treatment.

  3. Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

    Science.gov (United States)

    SHAN, YAN-SHEN; HSU, HUI-PING; LAI, MING-DERG; YEN, MENG-CHI; LUO, YI-PEY; CHEN, YI-LING

    2015-01-01

    Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin-embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer. PMID:25333458

  4. Decreased expression of GST pi is correlated with a poor prognosis in human esophageal squamous carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Junsheng

    2010-07-01

    Full Text Available Abstract Background Glutathione S-transferase pi (GST pi is a subgroup of GST family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Expression patterns of GST pi have been studied in several carcinomas and its down-regulation was implicated to be involved in malignant transformation in patients with Barrett's esophagus. However, neither the exact role of GST pi in the pathogenesis nor its prognostic impact in squamous esophageal carcinoma is fully characterized. Methods Immunohistochemistry was used to investigate GST pi expression on 153 archival squamous esophageal carcinoma specimens with a GST pi monoclonal antibody. Statistic analyses were performed to explore its association with clinicopathological factors and clinical outcome. Results The GST pi expression was greatly reduced in tissues of esophageal carcinomas compared to adjacent normal tissues and residual benign tissues. Absent of GST pi protein expression in cytoplasm, nuclear and cytoplasm/nucleus was found in 51%, 64.7% and 48% of all the carcinoma cases, respectively. GST pi deficiency in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to poor differentiation (p p p p p = 0.004, respectively and cytoplasm/nucleus (p = 0.017 and p = 0.031, respectively. In univariate analysis, absent of GST pi protein expression in cytoplasm, nucleus and cytoplasm/nucleus was significantly associated with a shorter overall survival (p p p p Conclusions Our results show that GST pi expression is down regulated in the squamous esophageal carcinoma, and that the lack of GST pi expression is associated with poor prognosis. Therefore, deficiency of GST pi protein expression may be an important mechanism involved in the carcinogenesis and progression of the squamous esophageal carcinoma, and the underlying mechanisms leading to decreased GST pi expression deserve further investigation.

  5. Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma.

    Science.gov (United States)

    Shi, Run; Sun, Qi; Sun, Jing; Wang, Xin; Xia, Wenjie; Dong, Gaochao; Wang, Anpeng; Jiang, Feng; Xu, Lin

    2017-03-01

    The cell division cycle 20, a key component of spindle assembly checkpoint, is an essential activator of the anaphase-promoting complex. Aberrant expression of cell division cycle 20 has been detected in various human cancers. However, its clinical significance has never been deeply investigated in non-small-cell lung cancer. By analyzing The Cancer Genome Atlas database and using some certain online databases, we validated overexpression of cell division cycle 20 in both messenger RNA and protein levels, explored its clinical significance, and evaluated the prognostic role of cell division cycle 20 in non-small-cell lung cancer. Cell division cycle 20 expression was significantly correlated with sex (p = 0.003), histological classification (p overexpression of cell division cycle 20 was significantly associated with bigger primary tumor size (p = 0.0023), higher MKI67 level (r = 0.7618, p Overexpression of cell division cycle 20 is associated with poor prognosis in lung adenocarcinoma patients, and its overexpression can also be used to identify high-risk groups. In conclusion, cell division cycle 20 might serve as a potential biomarker for lung adenocarcinoma patients.

  6. ALK gene amplification is associated with poor prognosis in colorectal carcinoma.

    Science.gov (United States)

    Bavi, P; Jehan, Z; Bu, R; Prabhakaran, S; Al-Sanea, N; Al-Dayel, F; Al-Assiri, M; Al-Halouly, T; Sairafi, R; Uddin, S; Al-Kuraya, K S

    2013-11-12

    Recently, the anaplastic lymphoma kinase (ALK) has been found to be altered in several solid and haematological tumours. ALK gene copy number changes and mutations in colorectal cancers (CRCs) are not well characterised. We aimed to study the prevalence of ALK copy number changes, translocations, gene mutations and protein expression in 770 CRC patients, and correlate these findings with molecular and clinico-pathological data. ALK gene copy number variations and ALK expression were evaluated by fluorescence in situ hybridisation (FISH) and immunohistochemistry, respectively. Translocations of the ALK gene were not observed; 3.4% (26 out of 756) of the CRC patients tested had an increase in ALK gene copy number either amplification or gain. Interestingly, increased ALK gene copy number alteration was associated with poor prognosis (P=0.0135) and was an independent prognostic marker in multivariate Cox proportional hazards model. The study reveals a significant impact of ALK gene copy number alterations on the outcome of patients with CRC. The findings of our study highlight a potential role of targeting ALK in advanced CRCs by using ALK FISH and ALK IHC as a screening tool to detect ALK alterations. Based on these findings, a potential role of ALK inhibitor as a therapeutic agent in a subset of CRC merits further investigation.

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

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    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.

  8. Elevated red cell distribution width contributes to a poor prognosis in patients with esophageal carcinoma.

    Science.gov (United States)

    Wan, Guo-Xing; Chen, Ping; Cai, Xiao-Jun; Li, Lin-Jun; Yu, Xiong-Jie; Pan, Dong-Feng; Wang, Xian-He; Wang, Xuan-Bin; Cao, Feng-Jun

    2016-01-15

    The red cell distribution width (RDW) has also been reported to reliably reflect the inflammation and nutrition status and predict the prognosis across several types of cancer, however, the prognostic value of RDW in esophageal carcinoma has seldom been studied. A retrospective study was performed to assess the prognostic value of RDW in patients with esophageal carcinoma by the Kaplan-Meier analysis and multivariate Cox regression proportional hazard model. All enrolled patients were divided into high RDW group (≧15%) and low RDW group (<15%) according to the detected RDW values. Clinical and laboratory data from a total of 179 patients with esophageal carcinoma were retrieved. With a median follow-up of 21months, the high RDW group exhibited a shorter disease-free survival (DFS) (p<0.001) and an unfavorable overall survival (OS) (p<0.001) in the univariate analysis. The multivariate analysis revealed that elevated RDW at diagnosis was an independent prognostic factor for shorter PFS (p=0.043, HR=1.907, 95% CI=1.020-3.565) and poor OS (p=0.042, HR=1.895, 95% CI=1.023-3.508) after adjustment with other cancer-related prognostic factors. The present study suggests that elevated preoperative RDW(≧15%) at the diagnosis may independently predict poorer disease-free and overall survival among patients with esophageal carcinoma. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 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.

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

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    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.

  11. 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.

  12. ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma

    International Nuclear Information System (INIS)

    Phi, Ji Hoon; Choi, Seung Ah; Lim, Sang-Hee; Lee, Joongyub; Wang, Kyu-Chang; Park, Sung-Hye; Kim, Seung-Ki

    2013-01-01

    The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma. ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels. Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas. High ID3 expression is associated with medullolbastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma

  13. Methylation of MGMT Is Associated with Poor Prognosis in Patients with Stage III Duodenal Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Tao Fu

    Full Text Available O6-methylguanine-DNA methyltransferase (MGMT methylation status has not been extensively investigated in duodenal adenocarcinoma (DA. The aim of this study was to evaluate the MGMT methylation status and examine its possible prognostic value in patients with stage III DA.Demographics, tumor characteristics and survival were available for 64 patients with stage III DA. MGMT methylation was detected by using MethyLight. A Cox proportional hazard model was built to predict survival, adjusted for clinicopathological characteristics and tumor molecular features, including the CpG island methylator phenotype (CIMP, microsatellite instability (MSI, and KRAS mutations.MGMT methylation was detected in 17 of 64 (26.6% patients, and was not correlated with sex, age, tumor differentiation, CIMP, MSI, or KRAS mutations. MGMT methylation was the only one factor associated with both overall survival (OS and disease-free survival (DFS on both univariate and multivariate analyses. In patients treated with surgery alone, MGMT-methylated group had worse OS and DFS when compared with MGMT-unmethylated group. However, in patients treated with chemotherapy/radiotherapy, outcomes became comparable between the two groups.Our results demonstrate MGMT methylation is a reliable and independent prognostic factor in DAs. Methylation of MGMT is associated with poor prognosis in patients with stage III DAs.

  14. Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

    Science.gov (United States)

    Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

    2017-09-15

    Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients

    NARCIS (Netherlands)

    de Sousa E Melo, Felipe; Colak, Selcuk; Buikhuisen, Joyce; Koster, Jan; Cameron, Kate; de Jong, Joan H.; Tuynman, Jurriaan B.; Prasetyanti, Pramudita R.; Fessler, Evelyn; van den Bergh, Saskia P.; Rodermond, Hans; Dekker, Evelien; van der Loos, Chris M.; Pals, Steven T.; van de Vijver, Marc J.; Versteeg, Rogier; Richel, Dick J.; Vermeulen, Louis; Medema, Jan Paul

    2011-01-01

    Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we

  16. Overexpression of high mobility group box 1 contributes to progressive clinicopathological features and poor prognosis of human bladder urothelial carcinoma

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    Huang CK

    2018-04-01

    Full Text Available Changkun Huang,* Zhichao Huang,* Xiaokun Zhao, Yinhuai Wang, Hongqing Zhao, Zhaohui Zhong, Lang Wang Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Background: High mobility group box 1 (HMGB1, a versatile protein with intranuclear and extracellular functions, plays an important role in a variety of human cancers. However, the clinical/prognostic significance of HMGB1 expression in human bladder urothelial carcinoma (BUC remains unclear. The aim of this study was to investigate the HMGB1 expression in human BUC with regard to its clinical and prognostic significance.Patients and methods: HMGB1 mRNA and protein expressions in tumor and paired normal bladder tissues were detected in 20 BUC cases by quantitative real-time polymerase chain reaction (qRT-PCR and Western blot. HMGB1 protein expression in 165 primary BUC tissues was evaluated by immunohistochemistry (IHC, and its correlations with clinicopathological characteristics and prognosis were also analyzed. Student’s t-test, χ2 test, Kaplan–Meier plots, and Cox proportional hazard regression model were performed to analyze the data. Results: By using qRT-PCR and Western blot, the upregulated expression of HMGB1 mRNA and protein was detected in BUC, compared with paired normal tissue (P<0.05. By using IHC, high HMGB1 expression was examined in 84 of 165 (51.0% BUC cases. High HMGB1 expression was significantly correlated with poorer differentiation and higher T and N classification (all P<0.05. Univariate analysis showed that high HMGB1 expression was significantly associated with a shortened patients’ overall survival (OS and disease-free survival (DFS; both P<0.001. In different subgroups of BUC patients, HMGB1 expression was a prognostic factor in patients with different histological grades or T classification (all P<0.05, pN− (both P<0.001 for OS and DFS, and

  17. CEP55 overexpression predicts poor prognosis in patients with locally advanced esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Wenpeng; Wang, Zhou; Jia, Yang

    2017-01-01

    Development of esophageal squamous cell carcinoma (ESCC) involves alterations in multiple genes with corresponding proteins. Recent studies have demonstrated that centrosomal protein 55 (CEP55) shares certain features with oncogenes, and CEP55 overexpression is associated with the development and progression of malignant tumors. The present study aimed to analyze, for the first time, whether CEP55 expression is related to clinicopothalogic features in the esophageal squamous cell carcinoma (ESCC), as well as patient survival. A total of 110 patients with mid-thoracic ESCC who suffered from Ivor-Lewis were enrolled. The CEP55 expression profile of these patients in tumour tissues and corresponding healthy esophageal mucosa (CHEM) was detected by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction analyses. Correlations between CEP55 expression and clinicopathological factors were analyzed using χ 2 test. The log-rank test was employed to calculate survival rate. A Cox regression multivariate analysis was performed to determine independent prognostic factors. The results demonstrated that CEP55 expression in ESCC was significantly higher than that of CHEM (POverexpression of CEP55 was significantly associated with differentiation degree (P=0.022), T stage (P=0.019), lymph node metastasis (P=0.033), clinicopathological staging (P=0.002) and tumor recurrence (P=0.021) in locally advanced ESCC patients. In addition, CEP55 overexpression was significantly associated with reduced overall survival of patients after surgery (P=0.012). The 5-year survival rate of patients without CEP55 overexpression was significantly higher than that of patients with CEP55 overexpression (P=0.012). Therefore, these findings suggest that CEP55 overexpression correlates with poor prognosis in locally advanced ESCC patients.

  18. Outcomes of infective endocarditis in the current era: Early predictors of a poor prognosis

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    Maria Carmo Pereira Nunes

    2018-03-01

    Full Text Available Background: The early identification of patients at risk of complications of infective endocarditis (IE using parameters obtained as part of routine practice is essential for guiding clinical decision-making. This study aimed to identify a parameter at hospital admission that predicts the outcome, adding value to other well-known factors of a poor prognosis in IE. Methods: Two hundred and three patients with IE were included in this study. Clinical evaluation, echocardiography, blood cultures, and routine laboratory tests were performed at hospital admission. The endpoint was in-hospital mortality. Results: The mean age of the patients was 48.2 ± 16.6 years; 62% were male and 38% had rheumatic heart disease. During treatment, cardiac surgery was performed in 111 patients (55%, and the overall in-hospital mortality rate was 32%. In the multivariable analysis, the independent predictors of death were age (odds ratio (OR 1.07, 95% confidence interval (CI 1.02–1.13, C-reactive protein (CRP at hospital admission (OR 1.12, 95% CI 1.04–1.21, length of the vegetation at diagnosis (OR 1.15, 95% CI 1.03–1.28, development of heart failure (OR 6.43, 95% CI 2.14–19.33, and embolic events during antimicrobial therapy (OR 12.14, 95% CI 2.11–71.89. Conclusions: An elevated CRP level at hospital admission and vegetation length at diagnosis were strong predictors of in-hospital mortality in IE, independent of other prognostic parameters, specifically taking into account patient characteristics and complications during therapy. Keywords: Infective endocarditis, C-reactive protein, Echocardiography, Mortality

  19. High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis.

    Science.gov (United States)

    Wu, Jianghong; Long, Ziwen; Cai, Hong; Du, Chunyan; Liu, Xiaowen; Yu, Shengjia; Wang, Yanong

    2016-08-02

    Colon cancer (CC) likes many epithelial-derived cancers, resulting from a complex tumorigenic process. However, the exactly mechanisms of development and progression of CC are still unknown. In this study, integrated analysis in the GSE33113 and Fudan University Shanghai Cancer Center Hospital datasets revealed that WISP1 expression was significantly increased in CC cases, positivity correlated with the advanced pathologic stage and a poor prognosis was more likely in CC patients with higher levels of WISP1. Downregulation of WISP1 inhibited cell proliferation and invasion through increasing apoptosis and blocking cell cycle at G1 phase in CC LOVO and RKO cells. Besides, Gene set enrichment analysis (GSEA) revealed that relative genes involved in the Cell adhesion molecules and Cytokine-cytokine receptor interaction pathways were enriched in WISP1-higher expression patients. Western blot analysis showed that Cell adhesion molecules pathway associated genes (ICAM- 1, VCAM-1, SDC2 and CDH2) and Cytokine-cytokine receptor interaction pathway associated genes (VEGFC, CCL18, CXCR4 and TGFBR1) were also modulated by WISP1 downregulation. Then, we found that the protein β-catenin was identified as a binding partner of WISP1 and mediated the functions of WISP1 through promoting cell proliferation and invasion in LOVO and RKO cells. Further in vivo tumor formation study in nude mice indicated that inhibition of WISP1 delayed the progress of tumor formation and inhibited PCNA expression. These results indicate that WISP1 could act as an oncogene and may serve as a promising therapeutic strategy for colon cancer.

  20. [Elevated expression of CLOCK is associated with poor prognosis in hepatocellular carcinoma].

    Science.gov (United States)

    Li, Bo; Yang, Xiliang; Li, Jiaqi; Yang, Yi; Yan, Zhaoyong; Zhang, Hongxin; Mu, Jiao

    2018-02-01

    Objective To evaluate the expression of circadian locomotor output cycles kaput (CLOCK) and its effects on cell growth in hepatocellular carcinoma (HCC). Methods The expression of CLOCK in 158 pairs of human HCC tissues and matched noncancerous samples was detected by immunohistochemical (IHC) staining. The expression of CLOCK in HCC patients was also verified using the data from GEO and TCGA (a total of 356 cases). The relationship between CLOCK expression and clinicopathological features of HCC patients was analyzed by single factor statistical analysis. Kaplan-Meier survival curves of HCC patients were drawn to study the relationship between the expression level of CLOCK and the survival state. The effect of CLOCK on the growth of HepG2 cells was detected by MTS assay. Results The expression of CLOCK in HCC tissues was significantly higher than that in the adjacent tissues, and the up-regulation of CLOCK expression in HCC tissue was also confirmed in the public data of HCC (356 cases). HCC patients were divided into low CLOCK expression group and high CLOCK expression group. Univariate analysis showed that the expression of CLOCK was related to tumor size, TNM stage, and portal vein invasion in HCC patients. HCC patients with low CLOCK expression had longer overall survival time and relapse-free survival time than those with high CLOCK expression. The proliferation of cells significantly decreased after the expression of CLOCK was knocked down in HepG2 cells. Conclusion The expression of CLOCK in HCC tissues was much higher than that in normal liver tissues, and the high expression of CLOCK indicated the poor prognosis. The knockdown of CLOCK in HCC cells could inhibit the proliferation of HepG2 cells.

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

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    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

  2. Decreased expression of GST pi is correlated with a poor prognosis in human esophageal squamous carcinoma

    International Nuclear Information System (INIS)

    Wang, Zhihui; He, Wei; Yang, Guanrui; Wang, Junsheng; Wang, Zhong; Nesland, Jahn M; Holm, Ruth; Suo, Zhenhe

    2010-01-01

    Glutathione S-transferase pi (GST pi) is a subgroup of GST family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Expression patterns of GST pi have been studied in several carcinomas and its down-regulation was implicated to be involved in malignant transformation in patients with Barrett's esophagus. However, neither the exact role of GST pi in the pathogenesis nor its prognostic impact in squamous esophageal carcinoma is fully characterized. Immunohistochemistry was used to investigate GST pi expression on 153 archival squamous esophageal carcinoma specimens with a GST pi monoclonal antibody. Statistic analyses were performed to explore its association with clinicopathological factors and clinical outcome. The GST pi expression was greatly reduced in tissues of esophageal carcinomas compared to adjacent normal tissues and residual benign tissues. Absent of GST pi protein expression in cytoplasm, nuclear and cytoplasm/nucleus was found in 51%, 64.7% and 48% of all the carcinoma cases, respectively. GST pi deficiency in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to poor differentiation (p < 0.001, p < 0.001 and p < 0.001, respectively). UICC stage and T stage were found significantly correlated to negative expression of GST pi in cytoplasm (p < 0.001 and p = 0.004, respectively) and cytoplasm/nucleus (p = 0.017 and p = 0.031, respectively). In univariate analysis, absent of GST pi protein expression in cytoplasm, nucleus and cytoplasm/nucleus was significantly associated with a shorter overall survival (p < 0.001, p < 0.001 and p < 0.001, respectively), whereas only GST pi cytoplasmic staining retained an independent prognostic significance (p < 0.001) in multivariate analysis. Our results show that GST pi expression is down regulated in the squamous esophageal carcinoma, and that the lack of GST pi expression is associated with poor prognosis. Therefore

  3. Why does Bangladesh remain so poor? Part I: the situation and efforts to change it.

    Science.gov (United States)

    Maloney, C

    1985-01-01

    This 1st part of the discussion of the poverty in Bangladesh reviews efforts on the part of individuals, donor agencies, and the government to alleviate poverty, and some goals of the new Third Five Year Plan. More than 3/4 of the people of Bangladesh live in poverty or close to it, according to development and economic criteria. Bangladesh society has hardly any parallel in the world if viewed from the perspective of its capacity, like a biological species, to adapt to an ecological niche and then reproduce to fill that niche. This defines success in biological terms. The Bangladesh society that developed was highly in tune with the natural environment of the rice growing plains. Social organization, kinship, settlement pattern, economic transactions, beliefs systems, and reproductive biology all developed in close symbiosis with the land. From a humanitarian perspective, Bangladesh is also highly successful. The human interaction, the expressive culture, the fullness of life, and the verbal arts all are more fully expressed than in many cultures. By "development" criteria, Bangladesh appears highly unsuccessful. Per capita income is about $130 a year. Bangladesh ranks very low in such indices as literacy, housing, roads, health services, infant survival, loan recovery, exportable goods, and control of the population growth rate. There is no question but that individuals usually are well aware if their situation is precarious, and they take rational action to improve their security; the government and private agencies have a multitude of programs aimed at alleviating poverty. For Bangladesh as a whole, domestic savings in 1984-85 was 8%, and during the Second Five Year Plan the rate of domestic savings increased faster than was expected, compared with income. Almost all the nongovernmental organizations (NGOs), many bilateral donor agencies, and huge segments of government target their efforts to the poor and the small farmers. There are over 150 NGOs of

  4. 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.

  5. [A Case of Endocrine Cell Carcinoma of the Transverse Colon with Very Poor Prognosis, Onset with Bowel Obstruction].

    Science.gov (United States)

    Yabe, Sakiko; Yamamoto, Eisuke; Masuda, Taiki; Sugimoto, Hitoshi; Koshiishi, Haruya; Yoshimura, Tetsunori

    2018-01-01

    We report a case of endocrine cell carcinoma of the colon with very poor prognosis, onset with bowel obstruction and multiple liver metastases. The patient was a 77-year-old man who underwent left hemicolectomy after a colon stent treatment for bowel obstruction due to cancer of the transverse colon with unresectable multiple liver metastases. Chemotherapy was not initiated because of his poor health. He died of primary cancer 52 days after the surgery. Endocrine cell carcinoma of the large intestine has a poor prognosis due to an early onset of liver and lymph node metastases, as well as peritoneal dissemination. A large-scale clinical study is needed to establish an effective adjuvant chemotherapy.

  6. 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.)

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

    International Nuclear Information System (INIS)

    Pietilae, M.; Ukkonen, H.; Malminiemi, K.; Saraste, M.; Naagren, K.; Lehikoinen, P.; Voipio-Pulkki, L.-M.

    2001-01-01

    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 ( 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 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 11 C-HED retention below the median and three in the group with 11 C-HED retention above the median (P 2 ), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that 11 C-HED PET provides independent prognostic information in patients with CHF. (orig.)

  8. Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Dai, Shun-Dong; Wang, Yan; Miao, Yuan; Zhao, Yue; Zhang, Yong; Jiang, Gui-Yang; Zhang, Peng-Xin; Yang, Zhi-Qiang; Wang, En-Hua

    2009-01-01

    expresses Kaiso in vitro, both proliferative and invasive abilities of three cancer cell lines were significantly enhanced, along with the up-regulation of Kaiso target gene, matrilysin. Our data suggest cytoplasmic Kaiso expression is associated with poor prognosis of NSCLC and various subcellular localizations of Kaiso may play differential biological roles in NSCLC

  9. Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis.

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    Svenja Thies

    Full Text Available The epithelioid and sarcomatoid histologic variants of malignant pleural mesothelioma (MPM can be considered as E- and M-parts of the epithelial-mesenchymal transition (EMT axis; the biphasic being an intermediate. EMT is associated with an increase of stem cell (SC traits. We correlated the neural crest SC marker nestin and the EMT marker periostin with histology, type of neo-adjuvant chemotherapy (CT and overall survival (OS of MPM patients.Tumor tissues of a historic cohort 1 (320 patients and an intended induction chemotherapy followed by extrapleural pneumonectomy (EPP cohort 2 (145 patients were immunohistochemically H-scored (intensity of immunoreactivity multiplied by frequency of stained cells. Paired chemo-naïve biopsies and -treated surgical specimens were available for 105/145 patients. CT included platinum/gemcitabine (Pla/Gem or platinum/pemetrexed (Pla/Pem.Expression of any cytosolic nestin progressively increased from epithelioid to biphasic to sarcomatoid MPM in cohort 1, whereas the diagnostic markers calretinin and podoplanin decreased. In cohort 2, Pla/Pem CT increased the expression level of nestin in comparison to Pla/Gem, whereas the opposite was found for periostin. In Pla/Pem treated patients, nestin was higher in biphasic MPM compared to epithelioid. In addition to non-epithelioid histology, any expression of nestin in chemo-naïve biopsies (median overall survival: 22 vs. 17 months and chemo-treated surgical specimens (18 vs. 12 months as well as high periostin in biopsies (23 vs. 15 months were associated with poor prognosis. In the multivariate survival analysis, any nestin expression in chemo-naïve biopsies proved to be an independent prognosticator against histology. In both pre- and post-CT situations, the combination of nestin or periostin expression with non-epithelioid histology was particularly/ dismal (all p-values <0.05.The SC marker nestin and the EMT marker periostin allow for further prognostic

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

    NARCIS (Netherlands)

    M.R. van Dijk (Merel); E.W. Steyerberg (Ewout); J.D.F. Habbema (Dik)

    2008-01-01

    textabstractBackground. 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

  11. CtBP2 overexpression promotes tumor cell proliferation and invasion in gastric cancer and is associated with poor prognosis.

    Science.gov (United States)

    Dai, Faxiang; Xuan, Yi; Jin, Jie-Jie; Yu, Shengjia; Long, Zi-Wen; Cai, Hong; Liu, Xiao-Wen; Zhou, Ye; Wang, Ya-Nong; Chen, Zhong; Huang, Hua

    2017-04-25

    C-terminal binding protein-2 (CtBP2), a transcriptional corepressor, has been reported to correlate with tumorigenesis and progression and predict a poor prognosis in several human cancers. However, few studies on CtBP2 in gastric cancer (GC) have been performed. In this research, we evaluated the correlations between CtBP2 expression and the clinicopathological characteristics, as well as prognosis of GC patients. The effects of silencing CtBP2 expression on GC cells biology activity were also assessed. The results showed that CtBP2 was overexpressed in GC tissues and closely correlated with poor differentiation, advanced tumor stage and poor prognosis in GC patients. CtBP2 induced epithelial-to-mesenchymal transition (EMT) and repressed PTEN to increase proliferation rate, migration, and invasion in GC cells. Silencing CtBP2 inhibited GC growth in nude mice model. In conclusion, CtBP2 is overexpressed in GC and may accelerate GC tumorigenesis and metastasis, which could represent an independent prognostic marker and promising therapeutic target for GC.

  12. FSTL5 is a marker of poor prognosis in non-WNT/non-SHH medulloblastoma

    NARCIS (Netherlands)

    Remke, Marc; Hielscher, Thomas; Korshunov, Andrey; Northcott, Paul A.; Bender, Sebastian; Kool, Marcel; Westermann, Frank; Benner, Axel; Cin, Huriye; Ryzhova, Marina; Sturm, Dominik; Witt, Hendrik; Haag, Daniel; Toedt, Grischa; Wittmann, Andrea; Schöttler, Anna; von Bueren, André O.; von Deimling, Andreas; Rutkowski, Stefan; Scheurlen, Wolfram; Kulozik, Andreas E.; Taylor, Michael D.; Lichter, Peter; Pfister, Stefan M.

    2011-01-01

    Integrated genomics approaches have revealed at least four distinct biologic variants of medulloblastoma: WNT (wingless), SHH (sonic hedgehog), group C, and group D. Because of the remarkable clinical heterogeneity of group D tumors and the dismal prognosis of group C patients, it is vital to

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

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    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.

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

    International Nuclear Information System (INIS)

    Ralhan, Ranju; Cao, Jun; Lim, Terence; MacMillan, Christina; Freeman, Jeremy L; Walfish, Paul G

    2010-01-01

    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. 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. 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 < 0.0004), median OS = 5 months as compared to 198 months for patients who did not show nuclear Ep-ICD or demonstrated only membranous EpE. 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

  15. Upregulated N-cadherin expression is associated with poor prognosis in epithelial-derived solid tumours: A meta-analysis.

    Science.gov (United States)

    Luo, Yong; Yu, Ting; Zhang, Qiongwen; Fu, Qingyu; Hu, Yuzhu; Xiang, Mengmeng; Peng, Haoning; Zheng, Tianying; Lu, Li; Shi, Huashan

    2018-04-01

    N-cadherin is an important molecular in epithelial-mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N-cadherin in solid malignancies remains controversially. The Pubmed/MELINE and EMBASE databases were used for a comprehensive literature searching. Pooled risk ratio (RR) and hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were employed to quantify the prognostic role. Involving 36 studies with 5705 patients were performed to investigate relationships between N-cadherin upregulation and clinicopathological features, survival. Results suggested upregulated N-cadherin was associated with lymph node metastasis (RR = 1.16, 95% CI [1.00, 1.35]), higher histological grade (RR = 1.36, 95%CI [1.14, 1.62]), angiolymphatic invasion (RR = 1.19, 95% CI [1.06, 1.34]) and advanced clinical stage (RR = 1.32, 95% CI [1.06, 1.64]), while upregulated N-cadherin was apt to be associated with distant metastasis (RR = 1.43, 95% CI [0.99, 2.05]). Moreover, N-cadherin was correlated with poor prognosis of 3-year survival (HR = 1.78, 95% CI [1.51, 2.10]), 5-year survival (HR = 1.57, 95% CI [1.17, 2.10]) and overall survival (OS) (HR = 1.32, 95% CI [1.20, 1.44]). Subgroup analyses according to cancer types were also conducted for applying these conclusions to some tumours more properly. No publication bias was found except subgroup analysis of distant metastasis (P = .652 for Begg's test and 0.023 for Egger's test). Taken together, upregulation of N-cadherin is associated with more aggressive behaviours of epithelial-derived solid malignancies and can be regarded as a predictor of poor survival. © 2018 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

  16. B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

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    Jiali Li

    2018-01-01

    Full Text Available Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37% expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031 and lymph node metastasis (P=0.012. Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289. β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227. Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT.

  17. A Rules-Based Algorithm to Prioritize Poor Prognosis Cancer Patients in Need of Advance Care Planning.

    Science.gov (United States)

    Bestvina, Christine M; Wroblewski, Kristen E; Daly, Bobby; Beach, Brittany; Chow, Selina; Hantel, Andrew; Malec, Monica; Huber, Michael T; Polite, Blase N

    2018-03-13

    Accurate understanding of the prognosis of an advanced cancer patient can lead to decreased aggressive care at the end of life and earlier hospice enrollment. Our goal was to determine the association between high-risk clinical events identified by a simple, rules-based algorithm and decreased overall survival, to target poor prognosis cancer patients who would urgently benefit from advanced care planning. A retrospective analysis was performed on outpatient oncology patients with an index visit from April 1, 2015, through June 30, 2015. We examined a three-month window for "high-risk events," defined as (1) change in chemotherapy, (2) emergency department (ED) visit, and (3) hospitalization. Patients were followed until January 31, 2017. A total of 219 patients receiving palliative chemotherapy at the University of Chicago Medicine with a prognosis of ≤12 months were included. The main outcome was overall survival, and each "high-risk event" was treated as a time-varying covariate in a Cox proportional hazards regression model to calculate a hazard ratio (HR) of death. A change in chemotherapy regimen, ED visit, hospitalization, and at least one high-risk event occurred in 54% (118/219), 10% (22/219), 26% (57/219), and 67% (146/219) of patients, respectively. The adjusted HR of death for patients with a high-risk event was 1.72 (95% confidence interval [CI] 1.19-2.46, p = 0.003), with hospitalization reaching significance (HR 2.74, 95% CI 1.84-4.09, p rules-based algorithm identified those with the greatest risk of death among a poor prognosis patient group. Implementation of this algorithm in the electronic health record can identify patients with increased urgency to address goals of care.

  18. 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.

  19. ITGBL1 promotes migration, invasion and predicts a poor prognosis in colorectal cancer.

    Science.gov (United States)

    Qiu, Xiao; Feng, Jue-Rong; Qiu, Jun; Liu, Lan; Xie, Yang; Zhang, Yu-Peng; Liu, Jing; Zhao, Qiu

    2018-05-14

    Colorectal cancer (CRC) is one of the most common malignancies worldwide; its progression and prognosis are associated with oncogenes. The present study aimed to identify differentially expressed genes (DEGs) and explore the role and potential mechanism of integrin subunit β like 1 (ITGBL1) in CRC. The microarray dataset GSE41258 was used to screen DEGs involved in CRC. Survival analysis was performed to predict the prognosis of CRC patients. To validate ITGBL1 expression, immunohistochemistry, quantitative real-time PCR and western blotting were performed in CRC tissues and cells. Subsequently, the effects of ITGBL1 were evaluated through colony formation, cell proliferation, migration and invasion assays. Finally, we took advantage of Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) to explore potential function and mechanism of ITGBL1 in CRC. In our study, 182 primary CRC tissues and 54 normal colon tissues were contained in GSE41258 dataset. A total of 318 DEGs were screened, among which ITGBL1 was found to be significantly up-regulated in CRC, and its high expression was associated with shortened survival of CRC patients. Moreover, knockdown of ITGBL1 promoted CRC cell proliferation, migration and invasion. Finally, GO analysis revealed that ITGBL1 was associated with cell adhesion. GSEA indicated that ITGBL1 was enriched in ECM receptor interaction and focal adhesion. In conclusion, a novel oncogene ITGBL1 was identified and demonstrated to be associated with the progression and prognosis of CRC, which might be a potential therapeutic target and prognostic biomarker for CRC patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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

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    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.

  1. Elevated plasma procalcitonin level predicts poor prognosis of ST elevation myocardial infarction in Asian elderly.

    Science.gov (United States)

    Dai, Junru; Xia, Bangbo; Wu, Xiaomiao

    Previous studies have focused on relationship between plasma procalcitonin level and myocardial infarction risk, but this relationship in Asian elderly has not been investigated. The aim of this study was to reveal the association of peripheral procalcitonin concentration (both immediate and average levels) with myocardial infarction prognosis in Asian elderly. A total of 400 ST-elevation myocardial infarction patients, 400 unstable angina patients and 400 controls were included. Plasma levels of high-sensitivity C-reactive protein and procalcitonin were measured using commercially available kits. Each myocardial infarction patient received a standard therapy and a 12-month follow-up unless major adverse cardiac events occurred. On admission, plasma procalcitonin level was higher in myocardial infarction patients than in unstable angina patients and controls (p < .001). In the follow-up period, 142 myocardial infarction patients suffered from major adverse cardiac events, and other 258 myocardial infarction patients did not. Higher admission, peak and average plasma levels of procalcitonin in the first week after chest pain onset were associated with elevated risk of major adverse cardiac events (HR: 1.46, 95%CI: 1.18-1.99; HR: 2.57, 95%CI: 1.99-3.52; HR: 2.36, 95%CI: 1.81-3.00). Plasma procalcitonin level had a positive linear correlation with plasma level of high-sensitivity C-reactive protein on admission (r = 0.650, p < .001). In conclusion, peripheral concentration of procalcitonin (both immediate and average levels) might be an independent predictor for prognosis in myocardial infarction patients. Prognostic significance of procalcitonin might be implicated in inflammation.

  2. Management of metastatic renal cell carcinoma in patients with poor prognosis

    International Nuclear Information System (INIS)

    Bullock, Andrea; McDermott, David F; Atkins, Michael B

    2010-01-01

    An improved understanding of renal cell carcinoma (RCC) biology has translated into major advances in the treatment of patients with metastatic RCC in recent years. Clinical and pathologic criteria can be used to identify RCC patients with poor prognoses. Such patients, however, are often excluded from the cancer clinical trials that guide treatment recommendations. This article reviews available information on the management of patients with metastatic RCC and poor risk features, focusing on the role of vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) inhibitors. While patients with poor risk features have a more guarded outcome, treatment with temsirolimus has produced meaningful improvements in overall survival for this population. Definitive phase III trial data are lacking for the VEGF pathway inhibitors in patients with poor prognostic features. However, available data suggest that such patients tolerate VEGF pathway blockade reasonably well and are likely to achieve some benefit relative to treatment with interferon. Ongoing translational research efforts may help to define novel treatment approaches specific for patients with metastatic RCC and poor prognostic features

  3. Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis

    International Nuclear Information System (INIS)

    Malfettone, Andrea; Saponaro, Concetta; Paradiso, Angelo; Simone, Giovanni; Mangia, Annita

    2012-01-01

    Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2. We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index. Grade 2 subgroup analysis showed that the PVI (p = 0.023) and the loss of membranous NHERF1 (p = 0.028) were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000). Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively). Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000), and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level. The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors

  4. High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Lin; Wang, Wenchao; Li, Guoli; Sun, Canlin; Ren, Zhenqin; Sheng, Haihui; Gao, Hengjun; Wang, Chaofu; Yu, Hong

    2016-08-01

    Long noncoding RNAs (lncRNAs) play critical roles in diverse biological processes such as tumorigenesis and metastasis. Taurine upregulated gene 1 (TUG1) is a cancer-related lncRNA that is associated with chromatin-modifying complexes and plays an important role in gene regulation. In this study, we determined the expression patterns of TUG1 in esophageal squamous cell carcinoma (ESCC) and evaluated its clinical significance. The expression level of TUG1 was examined in 218 pairs of ESCC and adjacent non-cancerous tissues by using quantitative real-time polymerase chain reaction. The relationship between TUG1 expression and clinical features and prognosis was statistically analyzed. The expression level of TUG1 was significantly upregulated in ESCC tissues compared with paired adjacent normal tissues. High TUG1 expression was significantly correlated with chemotherapy resistance. Survival analysis showed that patients with high TUG1 expression had poor prognosis, especially for cases with well and moderate differentiation, ulcerative type, smaller size, and chemotherapy-sensitive tumors. Our findings suggest that elevated TUG1 expression is related to chemotherapy resistance and may help predict a poor prognostic outcome of ESCC. TUG1 may provide a potential therapeutic target for ESCC.

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

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    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.

  6. Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis.

    Directory of Open Access Journals (Sweden)

    Richard Fristedt

    Full Text Available The polymeric immunoglobulin receptor (pIgR is a key component of the mucosal immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR expression has been reported to correlate with a less aggressive tumour phenotype and an improved prognosis in several human cancer types. Here, we examined the expression and prognostic significance of pIgR in pancreatic and periampullary adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients surgically treated with pancreaticoduodenectomy for pancreatic and periampullary adenocarcinoma in Malmö and Lund University Hospitals, Sweden, between 2001-2011. Tissue microarrays were constructed from primary tumours (n = 175 and paired lymph node metastases (n = 105. A multiplied score was calculated from the fraction and intensity of pIgR staining. Classification and regression tree analysis was used to select the prognostic cut-off. Unadjusted and adjusted hazard ratios (HR for death and recurrence within 5 years were calculated. pIgR expression could be evaluated in 172/175 (98.3% primary tumours and in 96/105 (91.4% lymph node metastases. pIgR expression was significantly down-regulated in lymph node metastases as compared with primary tumours (p = 0.018. Low pIgR expression was significantly associated with poor differentiation grade (p < 0.001, perineural growth (p = 0.027, lymphatic invasion (p = 0.016, vascular invasion (p = 0.033 and infiltration of the peripancreatic fat (p = 0.039. In the entire cohort, low pIgR expression was significantly associated with an impaired 5-year survival (HR = 2.99, 95% confidence interval (CI 1.71-5.25 and early recurrence (HR = 2.89, 95% CI 1.67-4.98. This association remained significant for survival after adjustment for conventional clinicopathological factors, tumour origin and adjuvant treatment (HR = 1.98, 95% CI 1.10-3.57. These results demonstrate, for the first time, that high tumour-specific pIgR expression signifies

  7. Overexpression of MMP21 and MMP28 is associated with gastric cancer progression and poor prognosis.

    Science.gov (United States)

    Zhang, Jizhen; Pan, Qi; Yan, Wenhui; Wang, Yiru; He, Xujun; Zhao, Zhongsheng

    2018-05-01

    Matrix metalloproteinase (MMP)-21 and MMP-28, or epilysin, are overexpressed during the invasion and metastasis of solid tumors. The present study investigated MMP-21 and MMP-28 expression levels in human gastric cancer using tissue microarray (TMA) analysis, and determined their association with clinicopathological characteristics and patient prognosis. TMA blocks, including 436 cases of gastric cancer and 92 non-cancerous adjacent gastric tissues, were investigated using immunohistochemistry. Staining results were analyzed statistically in association with various clinicopathological characteristics and overall survival. The MMP-21 and MMP-28 positive detection rate was 31.9% (139/436) and 34.4% (150/436), respectively, in the gastric carcinoma tissue specimens. MMP-21 and MMP-28 expression levels were negative in the 92 normal gastric tissue samples. In patients with gastric cancer, positive expression of MMP-21 and MMP-28 was correlated with tumor diameter, depth of invasion, vessel invasion, lymph node and distant metastases and tumor-node-metastasis stage. The overall survival rate was significantly lower in MMP-21 and MMP-28-positive compared with negative patients. Cox multivariate analysis revealed that MMP-21 and MMP-28 levels were independent predictors of survival in patients with gastric cancer. These findings emphasize the importance of MMP-21 and MMP-28, which may serve as novel and independent prognostic markers for the invasion and metastasis of human gastric cancer.

  8. Low Expression of TBX4 Predicts Poor Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

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    Meijuan Zong

    2011-08-01

    Full Text Available This study was designed to investigate the expression of the T-box transcription factor 4 (TBX4, a tumor biomarker that was previously identified by proteomics, in pancreatic ductal adenocarcinoma (PDAC and evaluate its clinical utility as a potential prognostic biomarkers for PDAC. The expression of TBX4 was detected in 77 stage II PDAC tumors by immunohistochemistry, and the results were analyzed with regard to clinicopathological characteristics and overall survival. Moreover, Tbx4 promoter methylation status in primary PDAC tumors and normal adjacent pancreas tissues was measured by bisulfite sequencing. Among 77 stage II PDAC tumors, 48 cases (62.3% expressed TBX4 at a high level. No significant correlation between TBX4 expression and other clinicopathological parameters, except tumor grade and liver metastasis recurrence, was found. The survival of patients with TBX4-high expression was significantly longer than those with TBX4-low expression (P = 0.010. In multivariate analysis, low TBX4 expression was an independent prognostic factor for overall survival in patients with stage II PDAC. TBX4 promoter methylation status was frequently observed in both PDAC and normal adjacent pancreas. We conclude that a low level of TBX4 expression suggests a worse prognosis for patients with stage II PDAC. Down-regulation of the TBX4 gene in pancreas is less likely to be regulated by DNA methylation.

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

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    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.

  10. Plasma serotonin level is a predictor for recurrence and poor prognosis in colorectal cancer patients.

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    Xia, Yan; Wang, Dawei; Zhang, Nan; Wang, Zhihao; Pang, Li

    2018-02-01

    To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC). Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5-year outcome. Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence-free survival and overall survival. Our results suggest that a high peri-operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival. © 2017 Wiley Periodicals, Inc.

  11. Lnc RNA H19 is associated with poor prognosis in breast cancer patients and promotes cancer stemness.

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    Shima, Hidetaka; Kida, Kumiko; Adachi, Shoko; Yamada, Akimitsu; Sugae, Sadatoshi; Narui, Kazutaka; Miyagi, Yohei; Nishi, Mayuko; Ryo, Akihide; Murata, Soichiro; Taniguchi, Hideki; Ichikawa, Yasushi; Ishikawa, Takashi; Endo, Itaru

    2018-04-24

    Aldehyde dehydrogenase1 (ALDH1) is widely accepted as a stem cell marker for normal breast as well as in breast cancer. Although the clinical impact of ALDH1 was observed in our previous study, we do not know how ALDH1 affects stem cell features resulting in worsening of prognosis in breast cancer. The purpose of this study is to explore ALDH1-related gene and its function on cancer stem cell (CSC). In five cases of ALDH1-positive triple-negative breast cancer, mRNA expression profile was compared between ALDH1-positive and ALDH1-negative cells by Affymetrix microarray analysis after microdissection. Among the genes modulated in ALDH1-positive cells, we focused on H19, which encodes a long non-coding RNA, in this study. An in-vitro study was conducted with H19 siRNA in HCC1934 and iCSCL10A cell lines. The association of H19 with prognosis was examined in 180 breast cancer cases. Network analysis revealed the existence of five genes related with H19, including miR-103, miR-107, let-7, miR-29b-1, and Trx. In-vitro analysis showed that suppression of H19 using siRNA reduces sphere formation capacity in both HCC1934 and iCSCL10A cell lines. In clinical studies, H19 expression was associated with hormone negativity, tumor size, and nodal status. Patients with H19 expression had significantly poor disease-free survival (DFS) (26.3 vs. 64.8% at 5 years, p = 0.001) and overall survival (OS) (28.9 vs. 68.3% at 5 years, p = 0.004). The effect of H19 expression on prognosis was the most significant in triple-negative breast cancer compared to that in other subtypes (20.0 vs. 65.4% at 5 years DFS, p = 0.012, 20.0 vs. 69.2% at 5 years OS, p = 0.016). This study indicated that H19 was associated with stem cell phenotype in ALDH1-positive breast cancer. H19 regulates CSC and is associated with poor prognosis in breast cancer patients, particularly in triple-negative subtype.

  12. Multimodality diagnostics and megatherapy in poor prognosis Ewing's tumor patients. A single-center report

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    Laws, H.J.; Kaick, B. van; Engel, B.; Dirksen, U.; Koerholz, D.; Goebel, U.; Burdach, S.; Pape, H.; Kahn, T.; Merck, H.; Schmitz, M.; Heyll, A.; Dockhorn-Dworniczak, B.D.; Juergens, H.

    1999-01-01

    Patients and Methods: Since 1988, 25 patients were treated with megatherapy consisting of melphalan, etoposide and total-body irradiation followed by stem cell transplantation. All patients received 6 courses of an induction therapy. Before the fourth therapy block, tumors that were bulky at initial diagnosis (>200 ml) were excised, as well as lung metastases which could still be detected after the third chemotherapy block. During the fifth and sixth chemotherapy block, patients received local irradiation on all infiltrated sites. Persisting immunosuppression after high-dose treatment may facilitate the incidence of relapse. To improve proliferation and cytotoxic activity of early regenerating NK-cells, adoptive immunotherapy with systemic IL-2 therapy after megatherapy is part of the treatment protocol. Results: Of 25 patients treated with megatherapy, 10 patients are still alive with a follow-up time of 6 months to 9 years after megatherapy. The time up to engraftment was decreased from 15±6 days down to 9±2 days through the use of G-CSF and CD34+ selected stem cells. At the same time, erythrocyte and platelet replacement was shortened. Frequently occurring complications were mucositis and infections. One patient died after developing septicemia and multiorgan failure, another patient developed a myelodysplastic syndrome 4.5 years after megatherapy. However, relapse is still the major cause of death. The influence of IL-2 on event-free survival cannot valued because 21 of 25 patients were treated with adoptive immunotherapy. Conclusion: The complex diagnostic and therapeutic strategy renders an EFS of 34% for a patient group with otherwise dismal prognosis. To clarify the efficiency of megatherapy in patients with advanced Ewing's tumors, a standardized treatment strategy is necessary to accumulate a sufficient number of patients for large cooperative studies in this subject. (orig.) [de

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

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    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

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

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    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.

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

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    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

  16. Overexpression of GEFT, a Rho family guanine nucleotide exchange factor, predicts poor prognosis in patients with rhabdomyosarcoma.

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    Sun, Chao; Liu, Chunxia; Li, Shugang; Li, Hongan; Wang, Yuanyuan; Xie, Yuwen; Li, Bingcheng; Cui, Xiaobin; Chen, Yunzhao; Zhang, Wenjie; Li, Feng

    2014-01-01

    Rhabdomyosarcoma (RMS) is one of the most common soft-tissue sarcomas in children and adolescents with poor prognosis. Yet, there is lack of effective prognostic biomarkers for RMS. The present study, therefore, aimed to explore potential biomarkers for RMS based on our previous findings using array comparative genomic hybridization. We investigated guanine nucleotide exchange factor, GEFT, at expression level in 45 RMS patients and 36 normal striated muscle controls using immunohistochemistry using tissue microarrays. The expression rate of GEFT in RMS samples (42/45, 93.33%) was significantly higher (Prate of GEFT in RMS (31/45, 68.89%) was also significantly higher (P<0.05) than that in normal controls (0/36, 0.00%). Increased expression of GEFT correlated significantly with advanced disease stages (stages III/IV) (P=0.001), lymph node metastasis (P=0.019), and distant metastasis (P=0.004), respectively, in RMS patients. In addition, RMS patients having overexpressed GEFT experienced worse overall survival (OS) than those having low levels of GEFT (P=0.001). GEFT overexpression was determined to be an independent prognostic factor for poor OS in RMS patients (hazard ratio: 3.491, 95% confidence interval: 1.121-10.871, P=0.004). In conclusion, these observations provide the first evidence of GEFT overexpression in RMS and its correlations with disease aggressiveness and metastasis. These findings suggest that GEFT may serve as a promising biomarker predicting poor prognosis in RMS patients, thus implying its potential as a therapeutic target.

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

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    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.

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

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    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.

  19. Cytokeratin 8/18 expression indicates a poor prognosis in squamous cell carcinomas of the oral cavity

    International Nuclear Information System (INIS)

    Fillies, Thomas; Werkmeister, Richard; Packeisen, Jens; Brandt, Burkhard; Morin, Philippe; Weingart, Dieter; Joos, Ulrich; Buerger, Horst

    2006-01-01

    Intermediary filaments are involved in cell motility and cancer progression. In a variety of organs, the expression of distinct intermediary filaments are associated with patient prognosis. In this study, we seeked to define the prognostic potential of cytokeratin and vimentin expression patterns in squamous cell carcinomas (SCC's) of the oral cavity. 308 patients with histologically proven and surgically treated squamous cell carcinomas of the oral cavity were investigated for the immunohistochemical expression of a variety of intermediary filaments including high- and low-molecular weight cytokeratins (Ck's), such as Ck 5/6, Ck 8/18, Ck 1, CK 10, Ck 14, Ck 19 and vimentin, using the tissue microarray technique. Correlations between clinical features and the expression of Cytokeratins and vimentin were evaluated statistically by Kaplan-Meier curves and multivariate Cox regression analysis. The expression of Ck 8/18 and Ck 19 were overall significantly correlated with a poor clinical prognosis (Ck 8/18 p = 0.04; Ck19 p < 0.01). These findings could also be reproduced for Ck 8/18 in primary nodal-negative SCC's and held true in multivariate-analysis. No significant correlation with patient prognosis could be found for the expression of the other cytokeratins and for vimentin. The expression of Ck 8/18 in SCC's of the oral cavity is an independent prognostic marker and indicates a decreased overall and progression free survival. These results provide an extended knowledge about the role of intermediary filament expression patterns in SCC's

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

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    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.

  1. High expression of testes-specific protease 50 is associated with poor prognosis in colorectal carcinoma.

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    Lei Zheng

    Full Text Available BACKGROUND: Testes-specific protease 50 (TSP50 is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: TSP50 mRNAs and proteins were detected in 7 CRC cell lines and 8 CRC specimens via RT-PCR and Western blot analysis. Immunohistochemical analysis of TSP50, p53 and carcinoembryonic antigen (CEA with tissue microarrays composed of 95 CRCs, 20 colorectal adenomas and 20 normal colorectal tissues were carried out and correlated with clinicopathological characteristics and disease-specific survival for CRC patients. There was no significant correlation between the expression levels of TSP50 and p53 (P = 0.751 or CEA (P = 0.663. Abundant expression of TSP50 protein was found in CRCs (68.4% while it was poorly expressed in colorectal adenomas and normal tissues (P<0.0001. Thus, CRCs can be distinguished from them with high specificity (92.5% and positive predictive value (PPV, 95.6%. The survival of CRC patients with high TSP50 expression was significantly shorter than that of the patients with low TSP50 expression (P = 0.010, specifically in patients who had early-stage tumors (stage I and II; P = 0.004. Multivariate Cox regression analysis indicated that high TSP50 expression was a statistically significant independent risk factor (hazard ratio  = 2.205, 95% CI = 1.214-4.004, P = 0.009. CONCLUSION: Our data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  3. Up-regulation of 91H promotes tumor metastasis and predicts poor prognosis for patients with colorectal cancer.

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    Qiwen Deng

    Full Text Available Long noncoding RNAs (lncRNAs play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA 91H expression in CRC and evaluate its clinical significance and biological roles in the development and progression of CRC.91H expression and copy number variation (CNV were measured in 72 CRC tumor tissues and adjacent normal tissues by real-time PCR. The biological roles of 91H were evaluated by MTT, scratch wound assay, migration and invasion assays, and flow cytometry.91H was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Moreover, 91H overexpression was closely associated with distant metastasis and poor prognosis in patients with CRC, except for CNV of 91H. Multivariate analysis indicated that 91H expression was an independent prognostic indicator, as well as distant metastasis. Our in vitro data indicated that knockdown of 91H inhibited the proliferation, migration, and invasiveness of CRC cells.91H played an important role in the molecular etiology of CRC and might be regarded as a novel prognosis indicator in patients with CRC.

  4. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

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    Nath, Aritro; Chan, Christina

    2016-01-04

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.

  5. Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers

    International Nuclear Information System (INIS)

    Li, Zhaomin; Dong, Zizheng; Myer, David; Yip-Schneider, Michele; Liu, Jianguo; Cui, Ping; Schmidt, C Max; Zhang, Jian-Ting

    2010-01-01

    Pancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which are now curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, the level of 14-3-3σ mRNA was found to be increased in pancreatic cancers and this increased expression may contribute to the failure in treatment of pancreatic cancers. In the present study, we tested this hypothesis. Western blot analysis was used to determine 14-3-3σ protein level in fresh frozen tissues and was correlated to clinical outcome. A stable cell line expressing 14-3-3σ was established and the effect of 14-3-3σ over-expression on cellular response to radiation and anticancer drugs were tested using SRB assay and clonogenic assays. Cell cycle distribution and apoptosis analyses were performed using propidium iodide staining and PARP cleavage assays. We found that 14-3-3σ protein level was increased significantly in about 71% (17 of 24) of human pancreatic cancer tissues and that the 14-3-3σ protein level in cancers correlated with lymph node metastasis and poor prognosis. Furthermore, we demonstrated that over-expression of 14-3-3σ in a pancreatic cancer cell line caused resistance to γ-irradiation as well as anticancer drugs by causing resistance to treatment-induced apoptosis and G2/M arrest. The increased level of 14-3-3σ protein likely contributes to the poor clinical outcome of human pancreatic cancers by causing resistance to radiation and anticancer drugs. Thus, 14-3-3σ may serve as a prognosis marker predicting survival of pancreatic cancer patients and guide the clinical treatment of these patients

  6. Overexpression of SOX18 correlates with accelerated cell growth and poor prognosis in human pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Wang, Yazhou; Guo, Huahu; Zhang, Dafang; Yu, Xin; Leng, Xisheng; Li, Shu; Zhu, Weihua

    2016-01-01

    Transcription factor SOX18 has been proved to play a significant role in carcinogenesis. However, no investigation was performed about the expression of SOX18 in pancreatic ductal adenocarcinoma (PDAC). In our work, we found that the PDAC tissues had higher level of SOX18 mRNA and protein expression than matched non-tumor pancreatic tissues and high level of SOX18 protein indicated poor prognosis for PDAC patients. After knockdown of SOX18 gene in PANC-1 and SW1990 cell lines, which showed higher expression level of SOX18 among five PDAC cell lines, the abilities of proliferation, migration and invasion were inhibited and the tumor growth was suppressed in vivo. In addition, the flow cytometry results indicated that down-regulation of SOX18 induced G1/S phase arrest. Furthermore, we found that the expression of cyclin D1, c-myc and MMP-7, three tumorigenesis promoters, was inhabited with downregulation of SOX18. In conclusion, our study reveals that SOX18 plays a significant role in promoting the growth of PDAC, and might serve as a promising target for PDAC therapy. - Highlights: • Overexpression of SOX18 correlates with poor prognosis for pancreatic cancer. • SOX18 promotes pancreatic cancer cell growth in vitro and in vivo. • SOX18 promotes pancreatic cancer cell migration and invasion. • Knockdown of SOX18 induces G1/S phase arrest. • Knockdown of SOX18 induces decrease of cyclin D1, c-myc and MMP-7.

  7. Monocarboxylate transporter 4 (MCT4 and CD147 overexpression is associated with poor prognosis in prostate cancer

    Directory of Open Access Journals (Sweden)

    Pereira Helena

    2011-07-01

    Full Text Available Abstract Background Monocarboxylate transporters (MCTs are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. Methods Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171, adjacent non-neoplastic tissues (n = 135, PIN lesions (n = 40 and normal prostatic tissue (n = 14. Protein expression was correlated with patients' clinicopathologic characteristics. Results In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. Conclusions Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and

  8. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer

    International Nuclear Information System (INIS)

    Pértega-Gomes, Nelma; Lopes, Carlos; Baltazar, Fátima; Vizcaíno, José R; Miranda-Gonçalves, Vera; Pinheiro, Céline; Silva, Joana; Pereira, Helena; Monteiro, Pedro; Henrique, Rui M; Reis, Rui M

    2011-01-01

    Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171), adjacent non-neoplastic tissues (n = 135), PIN lesions (n = 40) and normal prostatic tissue (n = 14). Protein expression was correlated with patients' clinicopathologic characteristics. In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in

  9. 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.

  10. Low expression of Mel-18 predicts poor prognosis in patients with breast cancer.

    Science.gov (United States)

    Guo, B-H; Zhang, X; Zhang, H-Z; Lin, H-L; Feng, Y; Shao, J-Y; Huang, W-L; Kung, H-F; Zeng, M-S

    2010-12-01

    Our previous study suggested that melanoma nuclear protein 18 (Mel-18) acted as a tumor suppressor in human breast cancer. This study was designed to investigate the clinical and prognostic significance of Mel-18 in breast cancer patients. Mel-18 was detected by immunohistochemistry in paraffin-embedded tissues from 287 breast cancer patients, of which 287 were from primary cancer sites, 63 from matched adjacent noncancerous sites, and 35 from metastatic lymph nodes. Differences in Mel-18 expression and clinical characteristics were compared by χ² test. Prognostic outcomes correlated with Mel-18 were examined using Kaplan-Meier analysis and Cox proportional hazards model. The decreased Mel-18 expression is incremental depending upon the magnitude of cancer progression (P Mel-18 was conversely correlated with the pathological classifications (P Mel-18 showed prolonged overall survivals (P Mel-18 expression may be a risk factor for the patients' survival (P Mel-18 expression is correlated with advanced clinicopathologic classifications and a poor overall survival in breast cancer patients. These findings suggest that Mel-18 may serve as a useful marker in prognostic evaluation for patients.

  11. Lack of pro-inflammatory cytokine mobilization predicts poor prognosis in patients with acute heart failure.

    Science.gov (United States)

    Vistnes, M; Høiseth, A D; Røsjø, H; Nygård, S; Pettersen, E; Søyseth, V; Hurlen, P; Christensen, G; Omland, T

    2013-03-01

    The aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients. Plasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n=22) on admission. Low levels of MCP-1, IL-1β and a low IL-1β/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1β had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E' and inferior caval vein diameter, than patients with high levels. Immune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1β and MCP-1 during AHF is associated with poor outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Low EphA7 Expression Correlated with Lymph Node Metastasis and Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Bai, Yu-Qin; Zhang, Jun-Yi; Bai, Chun-Ying; Xu, Xiu-E; Wu, Jian-Yi; Chen, Bo; Wu, Zhi-Yong; Wang, Shao-Hong; Shen, Jian; Shen, Jin-Hui; Yao, Xiao-Dong; Gao, Lian-Zhu; Wu, Bao; Gu, Hong-Li; Liu, Xiao-Hui; Li, Xin; Li, En-Min; Xu, Li-Yan

    2015-01-01

    As a member of the Eph family of receptor tyrosine kinases, EphA7 plays an important role in cancer. However, the expression and significance of Eph receptors in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we detected the expression of EphA7 by immunohistochemistry in a sample of 352 patients with ESCC, and aimed to investigate the expression status of EphA7 in ESCC and its impact on prognosis. The results showed that low EphA7 expression significantly correlated with lymph node metastases (N0: 29%; N1: 64%. p<0.001), poor degree of tumor differentiation (G1: 31%; G2: 49%; G3: 58%. p=0.009) and pTNM staging (I+II: 33%; III+IV: 58%. p<0.001). Furthermore, in a combined analysis, patients with low EphA7-expressing tumors showed a shorter overall survival than those with high expression, resulting in a five-year overall survival rate of 47.4% vs. 52.6%, respectively (p=0.016). Consequently, patients with a low EphA7 expression have poorer prognosis in ESCC compared with those manifesting high expression

  13. 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...... and miR-18a) expression levels were evaluated by quantitative real-time PCR (RT-qPCR) in 52 BC and 3 normal breast samples. ATM protein expression was assessed by immunohistochemistry in 968 BC and 35 adjacent normal breast tissues. ATM copy number alteration was detected by array comparative genomic...... hybridization (aCGH) in 42 tumours. RESULTS: Low ATM levels were associated with tumour grade. Absence of ATM protein expression was associated with distant metastasis (P ATM...

  14. “Frequent exacerbator” is a phenotype of poor prognosis in Japanese patients with chronic obstructive pulmonary disease

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    Tomioka R

    2016-02-01

    Full Text Available Ryusuke Tomioka,1,2 Tomotaka Kawayama,1 Masashi Suetomo,1,2 Takashi Kinoshita,1 Yoshihisa Tokunaga,1 Haruki Imaoka,1 Kazuko Matsunaga,1 Masaki Okamoto,1 Tomoaki Hoshino1 1Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, 2Respiratory Medicine, Chikugo City Hospital, Chikugo, JapanBackground: The prognosis of Japanese patients with COPD who suffer repeated exacerbations is unclear, although Westerners with such episodes have a poor prognosis.Materials and methods: We conducted a 1-year prospective observational trial involving 90 Japanese patients with COPD: 58 nonexacerbators, 12 infrequent exacerbators, and 20 frequent exacerbators classified on the basis of exacerbation frequency (zero, one, and two or more exacerbations/year, respectively, during the previous year were observed prospectively for 1 year. The characteristics of frequent exacerbators, the frequency of exacerbation, and the period until the first event were then compared among the groups.Results: A total of 78 patients completed the study. Frequent exacerbators had a significantly higher risk of frequent exacerbation in the following year than the case for nonexacerbators (odds ratio [95% confidence interval] 2.94 [1.21–7.17], P=0.0340, but not in comparison with infrequent exacerbators (1.51 [0.49–4.63], P>0.05. The mean annual frequency of exacerbations in the following year was significantly (P=0.0020 higher in the frequent exacerbators (1.4 exacerbations/year than in the nonexacerbators (0.4, but not in the infrequent exacerbators (0.9, P>0.05. The mean period until the first exacerbation was significantly shorter in the frequent exacerbators than in the infrequent or nonexacerbators (P=0.0012. Independent risk factors for future frequent exacerbation included the presence of gastroesophageal reflux disease, more severe airflow obstruction, and use of inhaled corticosteroids.Conclusion: Our present

  15. Association between Low Free Triiodothyronine Levels and Poor Prognosis in Patients with Acute ST-Elevation Myocardial Infarction

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    Yuanbin Song

    2018-01-01

    Full Text Available Background. Low free triiodothyronine (fT3 levels are generally associated with poor prognosis in patients with heart diseases, but this is controversial and there is a lack of data about ST-elevation myocardial infarction (STEMI in Chinese patients. Objective. To assess the association between fT3 levels and the prognosis of patients with STEMI. Methods. This was a prospective observational study of 699 consecutive patients with STEMI treated at the Xinqiao Hospital between January 1, 2013, and December 31, 2014. The patients were divided into the low fT3 (fT3 < 3.1 pmol/L; n=179, 27.5% and normal fT3 (fT3 ≥ 3.1 pmol/L; n=473, 72.5% groups according to fT3 levels at admission. Patients were followed up at 1, 3, 6, and 12 months for all-cause death and major adverse cardiac events (MACE. Results. During the 1-year follow-up, there were 70 all-cause deaths (39.1% in the low fT3 group and 40 (8.5% in the normal fT3 group (P<0.001. MACE occurred in 105 patients (58.7% in the low fT3 group and 74 (15.6% in the normal fT3 group (P<0.001. Multivariate Cox proportional hazards regression analysis indicated that fT3 levels were independently associated with 30-day and 1-year all-cause death [30-day: hazard ratio (HR = 0.702, 95% confidence interval (95% CI: 0.501–0.983, P=0.04; 1-year: HR = 0.557, 95% CI: 0.411–0.755, P<0.001] and MACE (30-day: HR = 0.719, 95% CI: 0.528–0.979, P=0.036; 1-year: HR = 0.557, 95% CI: 0.445–0.698, P<0.001. Conclusion. Low fT3 levels were strongly associated with poor prognosis in patients with STEMI. Measurement of fT3 levels may be a valuable and simple way to identify high-risk STEMI patients.

  16. 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

  17. WWC3 downregulation correlates with poor prognosis and inhibition of Hippo signaling in human gastric cancer

    Directory of Open Access Journals (Sweden)

    Hou J

    2017-06-01

    Full Text Available Jiabin Hou, Jin Zhou The First Affiliated Hospital, Harbin Medical University, Harbin, People’s Republic of China Abstract: The aim of this study was to investigate the clinicopathological significance and biological roles of WWC3 in human gastric cancer (GC. Clinical significance of WWC3 in human GCs was examined by using immunohistochemistry (IHC. WWC3 was downregulated in 48 of 111 human GCs, and its downregulation was associated with advanced stage, positive nodal status, and higher relapse rate. Importantly, WWC3 downregulation correlated with poor survival. It was also found that WWC3 protein expression was downregulated in GC cell lines compared with normal cell line GES-1. On one hand, WWC3 overexpression inhibited the cell growth rate and invading ability in HGC-27 cell line. On the other hand, depleting WWC3 by small interfering RNA (siRNA promoted proliferation rate and invading ability in the SGC-7901 cell line. In addition, cell cycle analysis showed that WWC3 overexpression inhibited while its depletion accelerated cell cycle progression at the G1/S transition. Western blot (WB analysis demonstrated that WWC3 repressed cyclin D1 and cyclin E while upregulated p27 expression. Luciferase reporter assay showed that WWC3 activated Hippo signaling pathway by suppressing TEAD transcription activity, with downregulation of total and nuclear YAP and its target CTGF. WWC3 siRNA depletion exhibited the opposite effects. In conclusion, this study indicates that WWC3 serves as a tumor suppressor in GC by activating Hippo signaling. Keywords: WWC3, gastric cancer, cell cycle, Hippo, YAP

  18. DEK over expression as an independent biomarker for poor prognosis in colorectal cancer

    International Nuclear Information System (INIS)

    Lin, Lijuan; Piao, Junjie; Gao, Wenbin; Piao, Yingshi; Jin, Guang; Ma, Yue; Li, Jinzi; Lin, Zhenhua

    2013-01-01

    The DEK protein is related to chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. High expression levels of the human DEK gene have been correlated with numerous human malignancies. This study explores the roles of DEK in tumor progression and as a prognostic determinant of colorectal cancer. Colorectal cancer specimens from 109 patients with strict follow-up, and colorectal adenomas from 52 patients were selected for analysis of DEK protein by immunohistochemistry. The correlations between DEK over expression and the clinicopathological features of colorectal cancers were evaluated by Chi-square test and Fisher’s exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. DEK protein showed a nuclear immunohistochemical staining pattern in colorectal cancers. The strongly positive rate of DEK protein was 48.62% (53/109) in colorectal cancers, which was significantly higher than that in either adjacent normal colon mucosa (9.17%, 10/109) or colorectal adenomas (13.46%, 7/52). DEK over expression in colorectal cancers was positively correlated with tumor size, grade, lymph node metastasis, serosal invasion, late stage, and disease-free survival- and 5-year survival rates. Further analysis showed that patients with late stage colorectal cancer and high DEK expression had worse survival rates than those with low DEK expression. Moreover, multivariate analysis showed high DEK expression, serosal invasion, and late stage are significant independent risk factors for mortality in colorectal cancer. DEK plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor of colorectal cancers

  19. Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

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    Sheng-Dean Luo

    2015-01-01

    Full Text Available Background. Osteopontin (OPN is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients’ biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin. Results. Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF. An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin. Conclusions. A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.

  20. Elevated levels of serum amyloid A indicate poor prognosis in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Wang, Jun-Ye; Zheng, Yu-Zhen; Yang, Juan; Lin, Yue-Hao; Dai, Shu-Qin; Zhang, Ge; Liu, Wan-Li

    2012-01-01

    Increase of Serum amyloid A (SAA) level has been observed in patients with a variety of cancers. The objective of this study was to determined whether SAA level could be used as a prognostic parameter in patients with esophageal squamous cell carcinoma (ESCC). SAA levels were measured by rate nephelometry immunoassay in 167 healthy controls and 167 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and SAA levels were determined using the Mann–Whitney U test. The clinical value of SAA level as a prognostic parameter was evaluated using the Cox’s proportional hazards model. SAA levels were significantly higher in patients with ESCC compared to levels in healthy controls (13.88 ± 15.19 mg/L vs. 2.26 ± 1.66 mg/L, P < 0.001). Elevation of SAA levels (≥ 8.0 mg/L) was observed in 54.5% (91/167) of patients with ESCC but not in healthy controls. SAA levels were associated with tumor size (P < 0.001), histological differentiation (P = 0.015), T classification (P < 0.001), clinical stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P < 0.001), but not with the age and gender of the patients or tumor location. Multivariate analysis revealed that patients with an elevated level of SAA (≥ 8.0 mg/L) had significantly lower 5-year survival rate than those with non-elevated SAA (< 8.0 mg/L, log-rank P < 0.0001). An elevated level of preoperative SAA was found to associate with tumor progression and poor survival in patients with ESCC

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

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    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.

  2. Strategies for improving the outcome of patients with poor prognosis prostate cancers

    International Nuclear Information System (INIS)

    Hanks, G.E.

    1998-01-01

    We can identify groups of patients with a poor outcome when treated with radiation therapy alone. Patterns of failure indicate the problem in these patients, including both excessive local regional failure and metastatic disease. The latter is probably present in 30-60% of these patients at the time of treatment but is not detectable by present diagnostic means. There is a clear dose response for 4-year biochemical and clinical freedom from failure and dose is an independent variable on multivariate analysis. The relative ineffectiveness of conventional dose level radiation (<70 Gy) vs 76 Gy is clearly demonstrated. If possible, despite the technological requirements of 3D conformal treatment technique (3 DCRT), future trials of adjuvant treatments should be combined with radiation-delivering doses of 75-80 Gy by 3 DCRT. The reduction in the later morbidity associated with 3 DCRT is impressive and on its own justifies adopting this technology. Adjuvant androgen deprivation with radiation in prostate cancer was originally thought to perhaps be similar to the addition of tamoxifen to breast cancer management with an opportunity for eliminating micro-metastasis. It appears that this result may have been achieved in prostate cancer, but the magnitude of effect (17%) is much more than one would expect and this trial needs to be confirmed. It is worth noting from both a cost and morbidity viewpoint that LHRH agonist used alone with radiation is the only adjuvant hormone manipulation associated with a survival advantage. The addition of androgen blockers with their cost, GI, liver and other toxicities has yet to be proven in the adjuvant setting. (orig./MG)

  3. NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Ma, Yue; Kong, Jienan; Yan, Guanghai; Ren, Xiangshan; Jin, Dan; Jin, Tiefeng; Lin, Lijuan; Lin, Zhenhua

    2014-01-01

    NQO1 (NAD(P)H: quinone oxidoreductase-1), located on chromosome 16q22, functions primarily to protect normal cells from oxidant stress and electrophilic attack. Recent studies have revealed that NQO1 is expressed at a high level in most human solid tumors including those of the colon, breast, pancreas, ovaries and thyroid, and it has also been detected following the induction of cell cycle progression and proliferation of melanoma cells. In this study, we aimed to investigate the clinicopathological significance of upregulated NQO1 protein expression in squamous cell carcinomas (SCCs) of the uterine cervix. The localization of the NQO1 protein was determined in the SiHa cervical squamous cancer cell line using immunofluorescence (IF) staining, and immunohistochemical (IHC) staining performed on paraffin-embedded cervical SCC specimens from 177 patients. For comparison, 94 cervical intraepithelial neoplasia (CIN) and 25 normal cervical epithelia samples were also included. QRT-PCR was performed on RNA from fresh tissues to detect NQO1 mRNA expression levels, and HPV infection status was genotyped using oligonucleotide microarray. Disease-free survival (DFS) and 5-year overall survival (OS) rates for all cervical SCC patients were calculated using the Kaplan–Meier method, and univariate and multivariate analysis was performed using the Cox proportional hazards regression model. The NQO1 protein showed a mainly cytoplasmic staining pattern in cervical cancer cells, and only three cases of cervical SCC showed a nuclear staining pattern. The strongly positive rate of NQO1 protein expression was significantly higher in cervical SCCs and CINs than in normal cervical epithelia. High-level NQO1 expression was closely associated with poor differentiation, late-stage, lymph node metastasis and high-risk for HPV infection. Additionally, high-level NQO1 expression was associated with lower DFS and 5-year OS rates, particularly for patients with early-stage cervical SCCs

  4. High expression of Rac1 is correlated with partial reversed cell polarity and poor prognosis in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Liu, Bingbing; Xiong, Jianhua; Liu, Guiqiu; Wu, Jing; Wen, Likun; Zhang, Qin; Zhang, Chuanshan

    2017-07-01

    The change of cell polarity is usually associated with invasion and metastasis. Partial reverse cell polarity in IDC-NOS may play a role in lymphatic tumor spread. Rac1 is a kind of polarity related protein. It plays an important role in invasion and metastasis in tumors. We here investigated the expression of Rac1 and partial reverse cell polarity status in breast cancer and evaluated their value for prognosis in breast cancer. The association of the expression of Rac1 and MUC-1 with clinicopathological parameters and prognostic significance was evaluated in 162 cases of IDC-NOS paraffin-embedded tissues by immunohistochemical method. The Rac1 messenger RNA expression was measured by real-time polymerase chain reaction in 30 breast cancer patients, which was divided into two groups of partial reverse cell polarity and no partial reverse cell polarity. We found that lymph node metastasis of partial reverse cell polarity patients was higher than no partial reverse cell polarity patients (Z = -4.030, p = 0.000). Rac1 was upregulated in partial reverse cell polarity group than no partial reverse cell polarity group (Z = -3.164, p = 0.002), and there was correlationship between the expression of Rac1 and partial reverse cell polarity status (r s  = 0.249, p = 0.001). The level of Rac1 messenger RNA expression in partial reverse cell polarity group was significantly higher compared to no partial reverse cell polarity group (t = -2.527, p = 0.017). Overexpression of Rac1 and partial reverse cell polarity correlates with poor prognosis of IDC-NOS patients (p = 0.011). Partial reverse cell polarity and lymph node metastasis remained as independent predictors for poor disease-free survival of IDC-NOS (p = 0.023, p = 0.046). Our study suggests that partial reverse cell polarity may lead to poor prognosis of breast cancer. Overexpression of Rac1 may lead to polarity change in IDC-NOS of the breast. Therefore, Rac1 could be a

  5. 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

  6. Factors for poor prognosis of near-fatal asthma after recovery from a life-threatening asthma attack.

    Science.gov (United States)

    Kim, Myung Shin; Cho, Young Joo; Moon, Hee Bom; Cho, Sang Heon

    2008-12-01

    The aim of this study was to investigate poor prognostic factors associated with a near-fatal asthma attack following patient recovery. We enrolled 68 patients who suffered near-fatal asthma attacks and were admitted to the intensive care units of five university hospitals. The patients were divided into two groups. The first group was comprised of patients who discontinued oral corticosteroids within 6 months after being discharged from the hospital and who maintained a forced expiratory volume in 1 s (FEV(1)) >/=60% of the maximum or estimated values of the corresponding patients. The second group included patients who continued on oral corticosteroids for >/=6 months or who maintained a FEV(1) asthma, factors for a poor prognosis included older age [48.47+/-3.53 vs. 64.69+/-2.59 years, pasthma, high values for inflammation-related laboratory markers (ESR, 8.75+/-2.05 vs. 23.88+/-4.40 mm/h, p=0.004; CRP, 1.72+/-0.46 vs. 6.68+/-9.36 mg/dL, pasthma exacerbated by pneumonia (28.1 vs. 52.8%, pasthma or the need for continual oral corticosteroids after being discharged from the hospital. Patients with these factors should be treated appropriately, under close surveillance.

  7. Nephronectin is Correlated with Poor Prognosis in Breast Cancer and Promotes Metastasis via its Integrin-Binding Motifs

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    Tonje S. Steigedal

    2018-04-01

    Full Text Available Most cancer patients with solid tumors who succumb to their illness die of metastatic disease. While early detection and improved treatment have led to reduced mortality, even for those with metastatic cancer, some patients still respond poorly to treatment. Understanding the mechanisms of metastasis is important to improve prognostication, to stratify patients for treatment, and to identify new targets for therapy. We have shown previously that expression of nephronectin (NPNT is correlated with metastatic propensity in breast cancer cell lines. In the present study, we provide a comprehensive analysis of the expression pattern and distribution of NPNT in breast cancer tissue from 842 patients by immunohistochemical staining of tissue microarrays from a historic cohort. Several patterns of NPNT staining were observed. An association between granular cytoplasmic staining (in <10% of tumor cells and poor prognosis was found. We suggest that granular cytoplasmic staining may represent NPNT-positive exosomes. We found that NPNT promotes adhesion and anchorage-independent growth via its integrin-binding and enhancer motifs and that enforced expression in breast tumor cells promotes their colonization of the lungs. We propose that NPNT may be a novel prognostic marker in a subgroup of breast cancer patients.

  8. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

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    Zheng, Long-Yi; Zhou, Dong-Xun; Lu, Jin; Zhang, Wen-Jun; Zou, Da-Jin

    2012-01-01

    Highlights: ► PTP1B protein showed decreased expression in 67.79% of the HCC patients. ► Low PTP1B expression predicts poor prognosis of HCC. ► Low PTP1B expression is correlated with expansion of OV6 + tumor-initiating cells. ► Down-regulation of PTP1B is associated with activation of Wnt/β-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6 + tumor-initiating cells (T-ICs) and high frequency of nuclear β-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/β-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

  9. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

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    Zheng, Long-Yi [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zhou, Dong-Xun [Department of Comprehensive Treatment II, Eastern Hepatobiliary Surgery Hospital, 225 Changhai Road, Shanghai 200438 (China); Lu, Jin [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zhang, Wen-Jun [Department of Emergency, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zou, Da-Jin, E-mail: dajinzou@hotmail.com [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer PTP1B protein showed decreased expression in 67.79% of the HCC patients. Black-Right-Pointing-Pointer Low PTP1B expression predicts poor prognosis of HCC. Black-Right-Pointing-Pointer Low PTP1B expression is correlated with expansion of OV6{sup +} tumor-initiating cells. Black-Right-Pointing-Pointer Down-regulation of PTP1B is associated with activation of Wnt/{beta}-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6{sup +} tumor-initiating cells (T-ICs) and high frequency of nuclear {beta}-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/{beta}-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

  10. Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and poor prognosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Kurihara-Shimomura, Miyako; Sasahira, Tomonori; Nakamura, Hiroshi; Nakashima, Chie; Kuniyasu, Hiroki; Kirita, Tadaaki

    2018-05-01

    Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear. In this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC. High cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001). These results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

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    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

  12. Compensating effect of minor portal hypertension on the muscle mass loss-related poor prognosis in cirrhosis.

    Science.gov (United States)

    Maruyama, Hitoshi; Kobayashi, Kazufumi; Kiyono, Soichiro; Ogasawara, Sadahisa; Suzuki, Eichiro; Ooka, Yoshihiko; Chiba, Tetsuhiro; Yamaguchi, Tadashi

    2017-01-01

    Background: To examine the influence of the severity of portal hemodynamic abnormality on the prognosis of cirrhosis with respect to the muscle mass loss (MML). Methods: The study involved a subgroup analysis in 98 cirrhosis patients (63.5 ± 11.8 years) who prospectively underwent both Doppler ultrasound and hepatic venous catheterization. The prognostic influence of MML diagnosed by computed tomography using the L3 skeletal muscle index was evaluated (median observation period, 32.7 months). Results: The cumulative survival rate showed difference between patients with MML (n = 34; 82.2%/1year, 41.2%/3years and 36.1%/5years) and those without (n = 64; 92.1%/1year, 74.9%/3years and 69.4%/5years; P = 0.005). When divided with respect to the portal velocity, the survival rate showed differences between patients with and without MML in the cohort 12 mmHg. However, in the cohort with HVPG ≤ 12 mmHg, survival rate showed no difference between patients with MML (n=10; 100%/1year, 61.9%/3years and 61.9%/5years) and those without (n=19; 93.8%/1year, 71.2%/3years and 59.4%/5years; p = 0.493) Conclusion: Lower HVPG has a compensating effect on the MML-induced poor prognosis of cirrhosis. Care should be taken in the evaluation of the influence of MML in consideration of the severity of portal hypertension.

  13. Influence of neutrophile granulocyte/lymphocyte ratio (NLR on poor prognosis of elderly AECOPD patients during hospital stay

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    Jian-Rong Cui

    2016-01-01

    Full Text Available Objective: To discuss the influence of neutrophile granulocyte/lymphocyte ratio(NLR to the poor prognosis of elderly AECOPD patients during the stay in hospital. Method: A total of 133 cases elderly patients with AECOPD admitted in our hospital from March 2013 to September 2014 were selected, and divided them into death group (31 cases and survival group (102 cases according to in-hospital death occurrence; To compare the on admission general clinical data, therapy method, lung function, blood routine examination [white blood cell count (WBC, neutrophile granulocyte/lymphocyte ratio(NLR], C-reactive protein (CRP, blood gas analysis and blood biochemical indexes in both groups, and drew ROC curve for a analysis of the clinical value of NLR in the prediction of death. Results: Among 133 cases of elderly AECOPD patients: the proportion of combined pulmonary heart disease and mechanical ventilation in death group was higher than that in survival group, PaCO2, WBC count, neutrophil count, NLR, CRP level in death group was higher, but lymphocyte count, serum albumin(ALB in death group was lower; multiple logistic regression analysis showed that NLR presented independent positive correlation with the in-hospital death in elderly AECOPD patients; ROC curve analysis showed that the ROCAUC of NLR to the inhospital death in elderly AECOPD patients was 0.787, the best diagnostic node value was 7.3, sensitivity and specificity were 77.4% and 74.5% respectively; bounded by NLR(7.3, divided patients into NLR≥7.3 group and NLR<7.3 group, hospital stays, CRP level and mortality in NLR≥7.3 group were higher than that in NLR<7.3 group. Conclusion: NLR was the high risk factor of the in-hospital death in elderly AECOPD patients, early detection of NLR level had a certain difference to the evaluation for short-term prognosis of elderly AECOPD patients and guide treatment.

  14. Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients

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    Gaber Alexander

    2010-09-01

    Full Text Available Abstract Background There is an insufficient number of reliable prognostic and response predictive biomarkers in colorectal cancer (CRC management. In a previous study, we found that high tumour tissue expression of tumour-associated trypsin inhibitor (TATI correlated with liver metastasis and an impaired prognosis in CRC. The aim of this study was to investigate the prognostic validity of serum TATI (s-TATI in CRC. We further assessed the prognostic value of carcino-embryonic antigen in serum (s-CEA and the interrelationship between s-TATI and TATI in tissue (t-TATI. Methods Using an immunofluorometric assay, s-TATI levels were analysed in 334 preoperatively collected serum samples from patients with CRC. Spearman's Rho and Chi-square test were used for analysis of correlations between s-TATI and clinicopathological parameters, s-CEA and t-TATI. Kaplan-Meier analysis and Cox uni- and multivariate regression analysis were used to estimate disease free survival (DFS and overall survival (OS according to quartiles of s-TATI and cut-offs derived from ROC-analysis of s-TATI and s-CEA. Results Increased levels of s-TATI were associated with a reduced DFS (HR = 2.00; 95% CI 1.40-2.84, P P P = 0.034 for DFS and HR = 1.78; 95% CI 1.25-2.53, P = 0.001 for OS. There was no significant association between s-TATI and t-TATI. The prognostic value of s-CEA was also evident, but somewhat weaker than for s-TATI. Conclusions High preoperative s-TATI levels predict a poor prognosis in patients with CRC, and the prognostic value is independent of established prognostic parameters and t-TATI expression. These data suggest that s-TATI might be a useful marker for prognostic stratification in CRC.

  15. The Controlling Nutritional Status Score Is a Significant Independent Predictor of Poor Prognosis in Patients With Malignant Pleural Mesothelioma.

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    Takamori, Shinkichi; Toyokawa, Gouji; Taguchi, Kenichi; Edagawa, Makoto; Shimamatsu, Shinichiro; Toyozawa, Ryo; Nosaki, Kaname; Seto, Takashi; Hirai, Fumihiko; Yamaguchi, Masafumi; Shoji, Fumihiro; Okamoto, Tatsuro; Takenoyama, Mitsuhiro; Ichinose, Yukito

    2017-07-01

    Malignant pleural mesothelioma (MPM) is a devastating neoplasm; however, some patients exhibit a good response to chemotherapy or multidisciplinary therapy, including surgery and chemotherapy. It is therefore important to discover the factors that can be used to select patients who will benefit from such treatment. Although the Controlling Nutritional Status (CONUT) score has been used to predict the prognosis in other types of malignancy, its utility in patients with MPM is unknown. The aim of this study was to clarify the clinical significance of the CONUT in patients with MPM. The data of 83 patients, who were treated with surgery, chemotherapy, or multidisciplinary therapy, were analyzed in the present study. A cut-off CONUT score of 2 was used to classify all of the patients into low or high CONUT groups. Fifty-two of the 83 patients were classified into the low CONUT group. A high CONUT score was significantly correlated with chemotherapy alone (P = .011). The high CONUT group had significantly poorer overall survival (OS) (P clinical stage and the CONUT score were found to be independent predictive factors for the OS: clinical stage, I/II and III/IV; P = .001 and CONUT score, ≥ 3 and ≤ 2; P = .011, respectively. The clinical stage and the CONUT score were also independent predictive factors for DFS/PFS: clinical stage, I/II and III/IV; P = .006 and CONUT score, ≥ 3 and ≤ 2; P = .013, respectively. The CONUT score was an independent predictor of a poor prognosis in the patients with MPM. This score provides useful information for selecting patients who will benefit from the treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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    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.

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

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    Punt, Simone; Fleuren, Gert Jan; Kritikou, Eva; Lubberts, Erik; Trimbos, J Baptist; Jordanova, Ekaterina S; Gorter, Arko

    2015-01-01

    The 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 using immunohistochemical double and immunofluorescent triple stainings. In the tumor stroma, IL-17 was found to be predominantly expressed by neutrophils (66%), mast cells (23%), and innate lymphoid cells (8%). Remarkably, T-helper 17 (Th17) cells were a minor IL-17 expressing population (4%). A similar distribution was observed in the tumor epithelium. The Th17 and granulocyte fractions were confirmed in head and neck, ovarian, endometrial, prostate, breast, lung, and colon carcinoma. An above median number of total IL-17 expressing cells was an independent prognostic factor for poor disease-specific survival in early stage disease ( p = 0.016). While a high number of neutrophils showed at trend toward poor survival, the lowest quartile of mast cells correlated with poor survival ( p = 0.011). IL-17 expressing cells and neutrophils were also correlated with the absence of vaso-invasion ( p < 0.01). IL-17 was found to increase cell growth or tightness of cervical cancer cell lines, which may be a mechanism for tumorigenesis in early stage disease. These data suggest that IL-17, primarily expressed by neutrophils, predominantly promotes tumor growth, correlated with poor prognosis in early stage disease. Strikingly, a high number of Th17 cells was an independent prognostic factor for improved survival ( p = 0.026), suggesting Th17 cells are part of a tumor suppressing immune response.

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

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    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

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

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    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.

  20. Cytoplasmic expression of survivin is an independent predictor of poor prognosis in patients with salivary gland cancer.

    Science.gov (United States)

    Stenner, Markus; Weinell, Antje; Ponert, Tobias; Hardt, Aline; Hahn, Moritz; Preuss, Simon F; Guntinas-Lichius, Orlando; Klussmann, Jens Peter

    2010-11-01

    The expression of the inhibitor of apoptosis protein survivin has been shown to be a significant prognostic indicator in various human cancers. The aim was to assess its expression and prognostic value in salivary gland adenocarcinoma and muco-epidermoid carcinoma. Survivin expression was analysed in 48 patients with parotid gland cancer (21 muco-epidermoid, 27 adenocarcinomas) by means of immunohistochemistry. The experimental findings were correlated with clinicopathological and survival parameters. A high cytoplasmic expression of survivin was found in 30% of the examined tumours without any significant correlation with the patients' clinicopathological characteristics (P > 0.05). Within all patients, the estimated overall survival rate of muco-epidermoid carcinomas was significantly better than that of adenocarcinomas (P = 0.013). A high cytoplasmic survivin expression significantly indicated a poor 5-year disease-free survival rate compared to patients with a low cytoplasmic survivin expression in the whole group (P = 0.001) and in adenocarcinomas (P = 0.004). In a multivariate analysis, a high cytoplasmic survivin expression was the only independent prognostic indicator for a significantly poorer 5-year disease-free survival rate (P = 0.001). The correlation between cytoplasmic survivin expression and survival in salivary gland malignancies might make this an effective tool in patient follow-up, prognosis and targeted therapy in future. © 2010 Blackwell Publishing Limited.

  1. The expression of CD56 antigen is associated with poor prognosis in patients with acute myeloid leukemia

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    Ana Paula Alegretti

    2011-06-01

    Full Text Available BACKGROUND: The expression of CD56 is considered a bad prognostic factor for overall survival, lower rates or short complete remission and extramedullary invasion but the results are controversial. The importance of validating new prognostic parameters in acute leukemias was the reason to investigate the CD56 expression in blast cells of patients with acute myeloid leukemia. METHODS: A cohort of 48 patients treated at Hospital de Clinicas de Porto Alegre and diagnosed with acute myeloid leukemia as classified by the French-American-British group (FAB criteria using cell morphology, cytochemistry and flow cytometry were evaluated. RESULTS: Eight cases (16.7% were CD56 positive without correlation to age or gender. The highest incidence of CD56 positivity was in FAB subtypes M4 and M5. The death rate during induction was not significantly different between patients with and without CD56 expression (62.5% vs. 27.5%; p-value = 0.097. However, patients that expressed CD56 had significantly lower overall survival than those who did not (mean 4.0 months vs. 14.5 months; p-value = 0.03. CONCLUSIONS: The data suggest that expression of CD56 in acute myeloid leukemia may be indicative of poor prognosis because it is associated with a shorter overall survival. The death rate during induction was not significantly different despite an apparent difference in proportions between groups.

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

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    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.

  3. LncRNA-SNHG16 predicts poor prognosis and promotes tumor proliferation through epigenetically silencing p21 in bladder cancer.

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    Cao, Xianxiang; Xu, Jing; Yue, Dong

    2018-02-01

    More and more evidences have ensured the crucial functions of long non-coding RNAs (lncRNAs) in multiple tumors. It has been discovered that lncRNA-SNHG16 is involved in many tumors. Even so, it is still necessary to study SNHG16 comprehensively in bladder cancer. In terms of our study, the level of SNHG16 both in the tumor tissues and cell lines was measured and the relationship among SNHG16, clinicopathological traits and prognosis was explored. Interference assays were applied to determine the biological functions of SNHG16. It was discovered that the level of SNHG16 was evidently enhanced both in tissues and cell lines of bladder cancer. Patients with highly expressed SNHG16 suffered from poor overall survival. Multivariable Cox proportional hazards regression analysis implied that highly expressed SNHG16 could be used as an independent prognostic marker. It could be known from functional assays that silenced SNHG16 impaired cell proliferation, owing to the effects of SNHG16 on cell cycle and apoptosis. Finally, mechanism experiments revealed that SNHG16 could epigenetically silence the expression of p21. The facts above pointed out that lncRNA-SNHG16 might be quite vital for the diagnosis and development of bladder cancer, and could even become an important therapeutic target for bladder cancer.

  4. Integrin α4 Enhances Metastasis and May Be Associated with Poor Prognosis in MYCN-low Neuroblastoma.

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    Shanique A Young

    Full Text Available High-risk neuroblastoma is associated with an overall survival rate of 30-50%. Neuroblastoma-expressed cell adhesion receptors of the integrin family impact cell adhesion, migration, proliferation and survival. Integrin α4 is essential for neural crest cell motility during development, is highly expressed on leukocytes, and is critical for transendothelial migration. Thus, cancer cells that express this receptor may exhibit increased metastatic potential. We show that α4 expression in human and murine neuroblastoma cell lines selectively enhances in vitro interaction with the alternatively spliced connecting segment 1 of fibronectin, as well as vascular cell adhesion molecule-1 and increases migration. Integrin α4 expression enhanced experimental metastasis in a syngeneic tumor model, reconstituting a pattern of organ involvement similar to that seen in patients. Accordingly, antagonism of integrin α4 blocked metastasis, suggesting adhesive function of the integrin is required. However, adhesive function was not sufficient, as mutants of integrin α4 that conserved the matrix-adhesive and promigratory function in vitro were compromised in their metastatic capacity in vivo. Clinically, integrin α4 is more frequently expressed in non-MYNC amplified tumors, and is selectively associated with poor prognosis in this subset of disease. These results reveal an unexpected role for integrin α4 in neuroblastoma dissemination and identify α4 as a potential prognostic indicator and therapeutic target.

  5. Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma.

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    Ma, Bing; Li, Meng; Zhang, Lei; Huang, Ming; Lei, Jun-Bin; Fu, Gui-Hong; Liu, Chun-Xin; Lai, Qi-Wen; Chen, Qing-Quan; Wang, Yi-Lian

    2016-04-01

    The pathogenesis of osteosarcoma involves complex genetic and epigenetic factors. This study was to explore the impact and clinical relevance of long non-coding RNA (lncRNA), Taurine up-regulated gene 1 (TUG1) on patients with osteosarcoma. Seventy-six osteosarcoma tissues and matched adjacent normal tissues were included for analysis. The plasma samples were obtained from 29 patients with osteosarcoma at pre-operation and post-operation, 42 at newly diagnosed, 18 who experienced disease progression or relapse, 45 post-treatment, 36 patients with benign bone tumor, and 20 healthy donors. Quantitative real-time reverse transcript polymerase chain reactions were used to assess the correlation of the expression levels of TUG1 with clinical parameters of osteosarcoma patients. TUG1 was significantly overexpressed in the osteosarcoma tissues compared with matched adjacent normal tissues (P TUG1 strongly correlated with poor prognosis and was an independent prognostic indicator for overall survival (HR = 2.78, 95% CI = 1.29-6.00, P = 0.009) and progression-free survival (HR = 1.81, 95% CI = 1.01-3.54, P = 0.037). Our constructed nomogram containing TUG1 had more predictive accuracy than that without TUG1 (c-index 0.807 versus 0.776, respectively). In addition, for plasma samples, TUG1 expression levels were obviously decreased in post-operative patients (mean ΔCT -4.98 ± 0.22) compared with pre-operation patients (mean ΔCT -6.09 ± 0.74), and the changes of TUG1 expression levels were significantly associated with disease status. Receiver operating characteristic (ROC) curve analysis demonstrated that TUG1 could distinguish patients with osteosarcoma from healthy individuals compared with alkaline phosphatase (ALP) (the area under curve 0.849 versus 0.544). TUG1 was overexpressed in patients with osteosarcoma and strongly correlated with disease status. In addition, TUG1 may serve as a molecular indicator in maintaining surveillance

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

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    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

  7. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Xu, Chuan; Xie, Dan; Yu, Shi-Cang; Yang, Xiao-Jun; He, Li-Ru; Yang, Jing; Ping, Yi-Fang; Wang, Bin; Yang, Lang; Xu, Sen-Lin; Cui, Wei; Wang, Qing-Liang; Fu, Wen-Juan; Liu, Qing; Qian, Cheng; Cui, You-Hong; Rich, Jeremy N; Kung, Hsiang-Fu; Zhang, Xia; Bian, Xiu-Wu

    2013-05-15

    Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression; however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma showed that high expression of insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was positively correlated with the expressions of cancer stem cell markers CD133 and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like cells (LACSLC) through PI3K/AKT/GSK3β/β-catenin cascade. POU5F1 could form a novel complex with β-catenin and SOX2 to bind Nanog promoter for transcription to maintain self-renewal of LACSLCs, which was dependent on the functional IGF-IR. Genetic and pharmacologic inhibition of IGF-IR abrogated LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo xenograft tumor model, knockdown of either IGF-IR or POU5F1 impeded tumorigenic potentials of LACSLCs. By analyzing pathologic specimens excised from 200 patients with lung adenocarcinoma, we found that colocalization of highly expressed IGF-IR with β-catenin and POU5F1 predicted poor prognosis. Taken together, we show that IGF-IR-mediated POU5F1 expression to form a complex with β-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of LACSLCs, and the integrative clinical detection of the expressions of IGF-IR, β-catenin, and POU5F1 is indicatory for predicting prognosis in the patients of lung adenocarcinoma. ©2013 AACR.

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

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    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.

  9. Co-expression of podoplanin and fibroblast growth factor 1 predicts poor prognosis in patients with lung squamous cell carcinoma.

    Science.gov (United States)

    Li, Juan; Chen, Han; Li, Xiaoqing; Wang, Linlin; Gao, Aiqin; Zhang, Pei; Lin, Wenli; Gao, Wei; Yang, Dong; Guo, Xiaosun; Liu, Jie; Dang, Qi; Sun, Yuping

    2017-08-01

    demonstrated that podoplanin was co‑expressed with FGF1 in lung SQCC and this co‑expression was correlated with poor prognosis.

  10. Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer.

    Science.gov (United States)

    Beg, Shaham; Siraj, Abdul K; Prabhakaran, Sarita; Jehan, Zeenath; Ajarim, Dahish; Al-Dayel, Fouad; Tulbah, Asma; Al-Kuraya, Khawla S

    2015-06-01

    PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow-up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN loss in triple-negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.

  11. Overexpression of Zwint predicts poor prognosis and promotes the proliferation of hepatocellular carcinoma by regulating cell-cycle-related proteins

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    Ying H

    2018-02-01

    Full Text Available Hanning Ying,1,2 Zhiyao Xu,3 Mingming Chen,1,2 Senjun Zhou,1,2 Xiao Liang,1,2 Xiujun Cai1,2 1Department of General Surgery, 2Key Laboratory of Endoscopic Technique Research of Zhejiang Province, 3Central Lab of Biomedical Research Center, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China Introduction: Zwint, a centromere-complex component required for the mitotic spindle checkpoint, has been reported to be overexpressed in different human cancers, but it has not been studied in human hepatocellular carcinoma (HCC.Materials and methods: The role of Zwint in hepatocellular carcinoma cell proliferation capacities was evaluated by using cell counting kit-8 (CCK8, flow cytometry, clone formation and tumor formation assay in nude mice. Western blot analysis and qPCR assay were performed to assess Zwint interacting with cell-cycle-related proteins.Results: We report that ZWINT mRNA and protein expression were upregulated in HCC samples and cell lines. An independent set of 106 HCC-tissue pairs and corresponding noncancerous tissues was evaluated for Zwint expression using immunohistochemistry, and elevated Zwint expression in HCC tissues was significantly correlated with clinicopathological features, such as tumor size and number. Kaplan–Meier survival and Cox regression analysis revealed that high expression of Zwint was correlated with poor overall survival and a greater tendency for tumor recurrence. Ectopic expression of Zwint promoted HCC-cell proliferation, and Zwint expression affected the expression of several cell-cycle proteins, including PCNA, cyclin B1, Cdc25C and CDK1.Conclusion: Our findings suggest that upregulation of Zwint may contribute to the progression of HCC and may be a prognostic biomarker and potential therapeutic target for treating HCC. Keywords: Zwint, hepatocellular carcinoma, HCC, prognosis, cell proliferation, cell cycle

  12. 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.

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

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    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

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

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    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

  15. A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancer

    International Nuclear Information System (INIS)

    Pértega-Gomes, Nelma; Vizcaíno, José R; Attig, Jan; Jurmeister, Sarah; Lopes, Carlos; Baltazar, Fátima

    2014-01-01

    In a malignant tumour, cancer cells are embedded in stromal cells, namely cancer-associated fibroblasts (CAFs). These CAFs are now accepted as important players in cancer dynamics, being involved in tumour growth and progression. Although there are various reports on the interaction between tumour and stromal cells, the clinico-pathological significance of this cross-talk is still largely unknown. In this study, we aimed to characterise the expression of key metabolic proteins involved in glucose transport, pyruvate/lactate shuttle system, glycolytic metabolism and fatty acid oxidation in CAFs and tumour cells in different stages of malignant transformation. We further aimed to contextualise the clinico-pathological significance of these protein expression profiles with reference to known prognostic indicators, including biochemical recurrence in pT stage. Prostate tissues were obtained from 480 patients with a median age of 64 years following radical prostatectomy with no previous hormonal therapy. Tissues were analysed for the expression of several key metabolism-related proteins in glands and surrounding fibroblasts by immunohistochemistry. Reliable markers of prognosis such as pT stage and biochemical recurrence were assessed for each case. We observed that prostate cancer cells did not rely mainly on glycolytic metabolism, while there was a high expression of MCT4 and CAIX - in CAFs. This corroborates the hypothesis of the “Reverse Warburg effect” in prostate cancer, in which fibroblasts are under oxidative stress and express CAIX, an established hypoxia marker. We found that alterations in the expression of metabolism-related proteins were already evident in the early stages of malignant transformation, suggesting the continuing alteration of CAFs from an early stage. Additionally, and for the first time, we show that cases showing high MCT4 expression in CAFs with concomitant strong MCT1 expression in prostate cancer (PCa) cells are associated with poor

  16. 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.

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

    International Nuclear Information System (INIS)

    Zhang, Zijian; Huang, Shanzhou; Wang, Huanyu; Wu, Jian; Chen, Dong; Peng, Baogang; Zhou, Qi

    2016-01-01

    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. DNA Amplifications and Aneuploidy, High Proliferative Activity and Impaired Cell Cycle Control Characterize Breast Carcinomas with Poor Prognosis

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    Harald Blegen

    2003-01-01

    Full Text Available In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short‐term survivors showed a higher average number of chromosomal copy alterations compared to the long‐term survivors. Of note, the number of sub‐chromosomal high‐level copy number increases (amplifications was significantly increased in the group of short‐term survivors. In both short‐ and long‐term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short‐term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low‐ and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki‐67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.

  19. Tumor-Endothelial Interaction Links the CD44+/CD24- Phenotype with Poor Prognosis in Early-Stage Breast Cancer

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    Martin Buess

    2009-10-01

    Conclusions Our results suggest that the interaction of endothelial cells with tumor cells that express the CD44+/CD24- signature, which indicates a low proliferative potential, might explain the unexpected and paradoxical association of the CD44+/CD24- signature with highly proliferative tumors that have an unfavorable prognosis.

  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. 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

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

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    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

  3. 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.

  4. Prognosis of Combining Remaining Teeth and Implants in Double-Crown-Retained Removable Dental Prostheses: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Lian, Meifei; Zhao, Kai; Feng, Yunzhi; Yao, Qian

    The reliability of combining natural teeth and implants in one removable prosthesis is controversial. This systematic review was conducted to evaluate the prognosis of combined tooth/implant-supported double-crown-retained removable dental prostheses (DCR-RDPs) and to compare them with solely implant-supported prostheses with a minimum observation period of 3 years. Electronic database (PubMed, Embase, Central, and SCI) and manual searches up to August 2016 were conducted to identify human clinical studies on tooth/implant-supported DCR-RDPs. Literature selection and data extraction were accomplished by two independent reviewers. Meta-analyses of survival and complication rates were performed separately for combined tooth/implant-supported and solely implant-supported DCRRDPs. Among the initially identified 366 articles, 17 were included in a quantitative analysis. The estimated overall cumulative survival rate (CSR) for implants in combined tooth/implant-supported DCRRDPs was 98.72% (95% confidence interval [95% CI]: 96.98% to 99.82%), and that for implants in solely implant-supported DCR-RDPs was 98.83% (95% CI: 97.45% to 99.75%). The summary CSR for abutment teeth was 92.96% (95% CI: 85.38% to 98.12%). Double-crown-retained dentures with both abutment types showed high CSRs, most of which were approximately 100%. Regarding prosthetic maintenance treatment, the estimated incidence for patients treated with combined tooth/implant-supported RDPs was 0.164 (95% CI: 0.089 to 0.305) per patient per year (T/P/Y) and that for patients restored with solely implant-supported RDPs was 0.260 (95% CI: 0.149 to 0.454) T/P/Y. Based on four studies with combined tooth/implant-supported DCR-RDPs, no intrusion phenomena were encountered. Subject to the limitations of the present review, combining remaining teeth and implants in DCR-RDPs is a reliable and predictable treatment modality for partially edentulous patients. Comparable high survival rates and minor biologic or

  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 [ adj OR = 3.4, 95% CI (1.12-10.60), p = 0.031], poor ovarian response (POR) according to the Bologna criteria [ adj OR = 11.5, 95% CI (1.37-96.83), p = 0.024], and rAFS stage IV [ adj OR = 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 endometriosis had a negative impact on the 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. Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Cai, Shao-Hang; Lu, Shi-Xun; Liu, Li-Li; Zhang, Chris Zhiyi; Yun, Jing-Ping

    2017-10-01

    Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4α and clinical features of HCC patients were analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of P2-HNF4α. The results showed that the expression of P2-HNF4α in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4α expression was negatively correlated with P2-HNF4α expression ( p  = 0.023). High P2-HNF4α expression was significantly associated with poor differentiation of HCC ( p = 0.002) and vascular invasion ( p = 0.017). Kaplan-Meier analysis showed that P2-HNF4α expression was closely correlated with overall survival in the training group ( p = 0.01), validation group ( p = 0.034), and overall group of patients with HCC ( p P2-HNF4α, different from P1-HNF4α, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

  7. Upregulation of c-mesenchymal epithelial transition expression and RAS mutations are associated with late lung metastasis and poor prognosis in colorectal carcinoma.

    Science.gov (United States)

    Liu, Jianhua; Zeng, Weiqiang; Huang, Chengzhi; Wang, Junjiang; Xu, Lishu; Ma, Dong

    2018-05-01

    The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with RAS (including KRAS, NRAS and HRAS ) or BRAF mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC). A total of 374 patients with stage III CRC were classified into 4 groups based on RAS/BRAF and C-MET status for comprehensive analysis. Mutations in RAS / BRAF were determined using Sanger sequencing and C-MET expression was examined using immunohistochemistry. The associations between RAS/BRAF mutations in combination with C-MET overexpression and clinicopathological variables including survival were evaluated. In addition, their predictive value for late distant metastases were statistically analyzed via logistic regression and receiver operating characteristic analysis. Among 374 patients, mutations in KRAS, NRAS, HRAS, BRAF and C-MET overexpression were observed in 43.9, 2.4, 0.3, 5.9 and 71.9% of cases, respectively. Considering RAS/BRAF mutations and C-MET overexpression, vascular invasion (P=0.001), high carcino-embryonic antigen level (P=0.031) and late distant metastases (PC-MET overexpression, although they were both predictive factors for adverse prognosis. Further logistic regression suggested that RAS/BRAF mutations and C-MET overexpression may predict late distant metastases. In conclusion, RAS/BRAF mutations and C-MET overexpression may serve as predictive indicators for metastatic behavior and poor prognosis of CRC.

  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

    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...... of NOTCH1 was PCR amplified and directly sequenced. RESULTS: LPL gene expression could be measured as a categorical variable (LPL+/LPL-) and was associated with time to treatment (p... 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. Cytoplasmic CXCR4 expression in breast cancer: induction by nitric oxide and correlation with lymph node metastasis and poor prognosis

    International Nuclear Information System (INIS)

    Yasuoka, Hironao; Tsujimoto, Masahiko; Yoshidome, Katsuhide; Nakahara, Masaaki; Kodama, Rieko; Sanke, Tokio; Nakamura, Yasushi

    2008-01-01

    Lymph nodes constitute the first site of metastasis for most malignancies, and the extent of lymph node involvement is a major criterion for evaluating patient prognosis. The CXC chemokine receptor 4 (CXCR4) has been shown to play an important role in lymph node metastasis. Nitric oxide (NO) may also contribute to induction of metastatic ability in human cancers. CXCR4 expression was analyzed in primary human breast carcinoma with long-term follow-up. The relationship between nitrotyrosine levels (a biomarker for peroxynitrate formation from NO in vivo) and lymph node status, CXCR4 immunoreactivity, and other established clinico-pathological parameters, as well as prognosis, was analyzed. Nitrite/nitrate levels and CXCR4 expressions were assessed in MDA-MB-231 and SK-BR-3 breast cancer cell lines after induction and/or inhibition of NO synthesis. CXCR4 staining was predominantly cytoplasmic; this was observed in 50%(56/113) of the tumors. Cytoplasmic CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis. Kaplan-Meier survival curves showed that cytoplasmic CXCR4 expression was associated with reduced disease-free and overall survival. In multivariate analysis, cytoplasmic CXCR4 expression emerged as a significant independent predictor for overall and disease-free survival. Cytoplasmic expression of functional CXCR4 in MDA-MB-231 and SK-BR-3 cells was increased by treatment with the NO donor DETA NONOate. This increase was abolished by L-NAME, an inhibitor of NOS. Our data showed a role for NO in stimulating cytoplasmic CXCR4 expression in vitro. Formation of the biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in vivo. In addition, cytoplasmic CXCR4 expression may serve as a significant prognostic factor for long-term survival in breast cancer

  10. Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression

    International Nuclear Information System (INIS)

    Yasuoka, Hironao; Kodama, Rieko; Tsujimoto, Masahiko; Yoshidome, Katsuhide; Akamatsu, Hiroki; Nakahara, Masaaki; Inagaki, Michiya; Sanke, Tokio; Nakamura, Yasushi

    2009-01-01

    Neuropilin-2 (Nrp2) is a receptor for vascular endothelial growth factor-C (VEGF-C), which is a well-known lymphangiogenic factor and plays an important role in lymph node metastasis of various human cancers, including breast cancer. Recently, Nrp2 was shown to play a role in cancer by promoting tumor cell metastasis. CXC chemokine receptor 4 (CXCR4) also promotes tumor metastasis. In the previous studies, we demonstrated that VEGF-C and cytoplasmic CXCR4 expressions were correlated with poorer patient prognosis (BMC Cancer 2008,8:340; Breast Cancer Res Treat 2005, 91:125–132). The relationship between Nrp2 expression and lymph node metastasis, VEGF-C expression, CXCR4 expression, and other established clinicopathological variables (these data were cited in our previous papers), including prognosis, was analyzed in human breast cancer. Effects of neutralizing anti-Nrp2 antibody on CXCR4 expression and chemotaxis were assessed in MDA-MB-231 breast cancer cells. Nrp2 expression was observed in 53.1% (60 of 113) of the invasive breast carcinomas. Nrp2 expression was significantly correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Survival curves determined by the Kaplan-Meier method showed that Nrp2 expression was associated with reduced overall survival. In multivariate analysis, Nrp2 expression emerged as a significant independent predictor for overall survival. Neutralizing anti-Nrp2 antibody blocks cytoplasmic CXCR4 expression and CXCR4-induced migration in MDA-MB-231 cells. Nrp2 expression was correlated with lymph node metastasis, VEGF-C expression, and cytoplasmic CXCR4 expression. Nrp2 expression may serve as a significant prognostic factor for long-term survival in breast cancer. Our data also showed a role for Nrp2 in regulating cytoplasmic CXCR4 expression in vitro

  11. SMAD4 and NF1 mutations as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese metastatic colorectal cancer patients.

    Science.gov (United States)

    Mei, Zhu; Shao, Yang W; Lin, Peinan; Cai, Xiaomin; Wang, Biao; Ding, Yan; Ma, Xiangyuan; Wu, Xue; Xia, Yewei; Zhu, Dongqin; Shu, Yongqian; Fu, Zan; Gu, Yanhong

    2018-04-27

    Cetuximab, an anti-EGFR monoclonal antibody, is used in combination with chemotherapy in clinic to enhance the outcome in metastatic colorectal cancer (mCRC) patients with only ~ 20% response rate. To date only activating mutations in KRAS and NRAS have been identified as poor prognosis biomarkers in cetuximab-based treatment, which makes an urgent need for identification of novel prognosis biomarkers to precisely predict patients' response in order to maximize the benefit. In this study, we analysed the mutation profiles of 33 Chinese mCRC patients using comprehensive next-generation sequencing (NGS) targeting 416 cancer-relevant genes before cetuximab treatment. Upon receiving cetuximab-based therapy, patients were evaluated for drug response, and the progression-free survival (PFS) was monitored. The association of specific genetic alterations and cetuximab efficacy was analyzed. Patients carrying SMAD4 mutations (SMAD4 mut , n = 8) or NF1 mutations (NF1 mut , n = 4) had significantly shorter PFS comparing to those carrying wildtype SMAD4 (SMAD4 wt , n = 25) (P = 0.0081) or wildtype NF1 (NF1 wt , n = 29) (P = 0.0028), respectively. None of the SMAD4 mut or NF1 mut patients showed response to cetuximab when assessed at 12-week post-treatment. Interestingly, two patients carrying both SMAD4 mut and NF1 mut showed the shortest PFS among all the patients. Our results demonstrated that SMAD4 and NF1 mutations can serve as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese mCRC patients.

  12. Overexpression of the E2F target gene CENPI promotes chromosome instability and predicts poor prognosis in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Thangavelu, Pulari U; Lin, Cheng-Yu; Vaidyanathan, Srividya; Nguyen, Thu H M; Dray, Eloise; Duijf, Pascal H G

    2017-09-22

    During cell division, chromosome segregation is facilitated by the mitotic checkpoint, or spindle assembly checkpoint (SAC), which ensures correct kinetochore-microtubule attachments and prevents premature sister-chromatid separation. It is well established that misexpression of SAC components on the outer kinetochores promotes chromosome instability (CIN) and tumorigenesis. Here, we study the expression of CENP-I, a key component of the HIKM complex at the inner kinetochores, in breast cancer, including ductal, lobular, medullary and male breast carcinomas. CENPI mRNA and protein levels are significantly elevated in estrogen receptor-positive (ER+) but not in estrogen receptor-negative (ER-) breast carcinoma. Well-established prognostic tests indicate that CENPI overexpression constitutes a powerful independent marker for poor patient prognosis and survival in ER+ breast cancer. We further demonstrate that CENPI is an E2F target gene. Consistently, it is overexpressed in RB1 -deficient breast cancers. However, CENP-I overexpression is not purely due to cell cycle-associated expression. In ER+ breast cancer cells, CENP-I overexpression promotes CIN, especially chromosome gains. In addition, in ER+ breast carcinomas the degree of CENPI overexpression is proportional to the level of aneuploidy and CENPI overexpression is one of the strongest markers for CIN identified to date. Our results indicate that overexpression of the inner kinetochore protein CENP-I promotes CIN and forecasts poor prognosis for ER+ breast cancer patients. These observations provide novel mechanistic insights and have important implications for breast cancer diagnostics and potentially therapeutic targeting.

  13. Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2

    International Nuclear Information System (INIS)

    Cicenas, Jonas; Urban, Patrick; Vuaroqueaux, Vincent; Labuhn, Martin; Küng, Willy; Wight, Edward; Mayhew, Mark; Eppenberger, Urs; Eppenberger-Castori, Serenella

    2005-01-01

    Akt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers. Using a two-site chemiluminescence-linked immunosorbent assay, we measured the quantitative expression levels of total phosphorylated (P-S473) Akt (Akt1/Akt2/Akt3) on cytosol fractions obtained from fresh frozen tissue samples of 156 primary breast cancer patients. Akt phosphorylation was not associated with nodal status or ErbB-2 protein expression levels. High levels of phosphorylated Akt correlated (P < 0.01) with poor prognosis, and the significance of this correlation increased (P < 0.001) in the subset of patients with ErbB-2 overexpressing tumours. In addition, phosphorylated Akt was found to be associated with mRNA expression levels of several proliferation markers (e.g. thymidylate synthase), measured using quantitative real-time RT-PCR. Our findings demonstrate that, in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours

  14. High Platelet-to-Lymphocyte Ratio Predicts Poor Prognosis and Clinicopathological Characteristics in Patients with Breast Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Miao Zhang

    2017-01-01

    Full Text Available Background. We aimed to evaluate the correlation of platelet-to-lymphocyte ratio (PLR with prognosis and clinicopathological characteristics of breast cancer. Methods. The PubMed and Embase databases were searched. Hazard ratio (HR with 95% confidence interval (CI was used to summarize disease-free survival (DFS and overall survival (OS. Odds ratio (OR was used to summarize tumor clinicopathological characteristics. Results. High PLR was associated with poor DFS and OS (DFS: HR = 1.47, 95% CI = 1.16–1.85, and Tau2 = 0.070; OS: HR = 1.88, 95% CI = 1.27–2.80, and Tau2 = 0.192. A Galbraith plot indicated that the studies by Allan et al. and Cihan et al. contributed the heterogeneity of DFS and OS, respectively. There were significant differences in the incidence of high PLR between stage II–IV and stage I groups (OR = 1.86, 95% CI = 1.20–2.90, and Tau2 < 0.001, between lymph node-positive and lymph node-negative groups (OR = 1.52, 95% CI = 1.22–1.91, and Tau2 =0.014, and between metastasis-positive and metastasis-negative groups (OR = 4.24, 95% CI = 2.73–6.59, and Tau2 < 0.001. Conclusions. Our results indicated that PLR was associated with poor prognosis of breast cancer and adequately predicted clinicopathological characteristics.

  15. CD147-CD98hc complex contributes to poor prognosis of non-small cell lung cancer patients through promoting cell proliferation via the PI3K/Akt signaling pathway.

    Science.gov (United States)

    Fei, Fei; Li, Xiaofei; Xu, Li; Li, Deyang; Zhang, Zhipei; Guo, Xu; Yang, Hushan; Chen, Zhinan; Xing, Jinliang

    2014-12-01

    It has been reported that CD147 and CD98 heavy chain (CD98hc) form a complex on the cell plasma membrane of several cancers; however, whether this complex exists in non-small cell lung cancer (NSCLC) cells and affects the prognosis of patients remains to be elucidated. The expression of CD147 and CD98hc was assessed in tissue samples from 241 NSCLC patients and NSCLC cell lines. The correlation between CD147 and CD98hc expression and their association with the prognosis of NSCLC patients were analyzed. We also evaluated the impact of CD147 and CD98hc on the growth of NSCLC cells as well as Akt phosphorylation. Both CD147 and CD98hc were significantly upregulated in NSCLC cells, and their expression levels were significantly correlated (p CD147 and CD98hc could form a complex on NSCLC cells. Compared with NSCLC patients with CD147-/CD98hc-, those with CD147+/CD98hc+ exhibited a significantly poor overall survival (OS) with a hazard ratio (HR) of 1.92 (p = 0.010), and a significantly increased risk of recurrence with a HR of 1.97 (p = 0.004). Also, we demonstrated that the proliferation of lung cancer cell lines was significantly affected by knockdown and force-expression of the CD147-CD98hc complex. Western blot analysis indicated that the phosphorylation of Akt in NSCLC cells was significantly affected by knockdown and overexpression of either or both CD147 and CD98hc. Our findings indicate that the CD147-CD98hc complex significantly contributes to poor prognosis of NSCLC patients through promoting cell proliferation via the PI3K/Akt pathway.

  16. Reduced expression of ZDHHC2 is associated with lymph node metastasis and poor prognosis in gastric adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Shu-Mei Yan

    Full Text Available BACKGROUND: Zinc finger, DHHC-type containing 2 (ZDHHC2, originally named as reduced expression associated with metastasis protein (REAM, has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative Real-Time PCR (qRT-PCR and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472 of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001 and histological grade (p<0.001. Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001. CONCLUSIONS/SIGNIFICANCE: Our data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.

  17. 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.

  18. Low Platelet to White Blood Cell Ratio Indicates Poor Prognosis for Acute-On-Chronic Liver Failure.

    Science.gov (United States)

    Jie, Yusheng; Gong, Jiao; Xiao, Cuicui; Zhu, Shuguang; Zhou, Wenying; Luo, Juan; Chong, Yutian; Hu, Bo

    2018-01-01

    Background. Platelet to white blood cell ratio (PWR) was an independent prognostic predictor for outcomes in some diseases. However, the prognostic role of PWR is still unclear in patients with hepatitis B related acute-on-chronic liver failure (ACLF). In this study, we evaluated the clinical performances of PWR in predicting prognosis in HBV-related ACLF. Methods. A total of 530 subjects were recruited, including 97 healthy controls and 433 with HBV-related ACLF. Liver function, prothrombin time activity (PTA), international normalized ratio (INR), HBV DNA measurement, and routine hematological testing were performed at admission. Results . At baseline, PWR in patients with HBV-related ACLF (14.03 ± 7.17) was significantly decreased compared to those in healthy controls (39.16 ± 9.80). Reduced PWR values were clinically associated with the severity of liver disease and the increased mortality rate. Furthermore, PWR may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 0.660, 95% CI: 0.438-0.996, p = 0.048) as well as model for end-stage liver disease (MELD) score. Conclusions . The PWR values were markedly decreased in ACLF patients compared with healthy controls and associated with severe liver disease. Moreover, PWR was an independent prognostic indicator for the mortality rate in patients with ACLF. This investigation highlights that PWR comprised a useful biomarker for prediction of liver severity.

  19. Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer

    International Nuclear Information System (INIS)

    Shin, Na Ri; Lee, Jae Hyuk; Park, Do Youn; Jeong, Eun Hui; Choi, Chang In; Moon, Hyun Jung; Kwon, Chae Hwa; Chu, In Sun; Kim, Gwang Ha; Jeon, Tae Yong; Kim, Dae Hwan

    2012-01-01

    Epithelial–mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer. We examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail’s clinicopathological and prognostic significance. Differential gene expression in 45 GC specimens with Snail overexpression was investigated using cDNA microarray analysis. Silencing of Snail by shRNA decreased invasion and migration in GC cell lines. Conversely, Snail overexpression increased invasion and migration of gastric cancer cells, in line with increased VEGF and MMP11. Snail overexpression (≥75% positive nuclear staining) was also significantly associated with tumor progression (P < 0.001), lymph node metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P = 0.023). cDNA microarray analysis revealed 213 differentially expressed genes in GC tissues with Snail overexpression, including genes related to metastasis and invasion. Snail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs

  20. 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.

  1. A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria.

    Science.gov (United States)

    Busnelli, Andrea; Papaleo, Enrico; Del Prato, Diana; La Vecchia, Irene; Iachini, Eleonora; Paffoni, Alessio; Candiani, Massimo; Somigliana, Edgardo

    2015-02-01

    Do the Bologna criteria for poor responders successfully identify women with poor IVF outcome? The Bologna criteria effectively identify a population with a uniformly low chance of success. Women undergoing IVF who respond poorly to ovarian hyper-stimulation have a low chance of success. Even if improving IVF outcome in this population represents a main priority, the lack of a unique definition of the condition has hampered research in this area. To overcome this impediment, a recent expert meeting in Bologna proposed a new definition of poor responders ('Bologna criteria'). However, data supporting the relevance of this definition in clinical practice are scanty. Retrospective study of women undergoing IVF-ICSI between January 2010 and December 2012 in two independent infertility units. Women could be included if they fulfilled the definition of poor ovarian response (POR) according to Bologna criteria prior to initiation of the cycle. Women were included only for one cycle. The main outcome was the live birth rate per started cycle. The perspective of the cost analysis was the one of the health provider. Three-hundred sixty-two women from two independent Infertility Units were selected. A binomial distribution model was used to calculate the 95% CI of the rate of success. Characteristics of women who did and did not obtain a live birth were compared. A logistic regression model was used to adjust for confounders. The economic analysis included costs for pharmacological compounds and for the IVF procedure. The benefits were estimated on quality-adjusted life years (QALY). To develop the model, we used the local life-expectancy tables, we applied a 3% discount of life years gained and we used a 0.07 improvement in quality of life associated with parenthood. Sensitivity analyses were performed varying the improvement of the quality of life and including/excluding the male partner. The reference values for cost-effectiveness were the Italian and the local (Lombardy

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... treatments being used today. Still, your doctor may tell you that you have a good prognosis if ... to respond well to treatment. Or, he may tell you that you have a poor prognosis if ...

  3. Decreased expression of CIAPIN1 is correlated with poor prognosis in patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zheng, Xiushan; Zhao, Yunping; Wang, Xin; Li, Yunming; Wang, Ruwen; Jiang, Yaoguang; Gong, Taiqian; Li, Mengbin; Sun, Li; Hong, Liu; Li, Xiaohua; Liang, Jie; Luo, Guanhong; Jin, Bin; Yang, Jianjun; Zhang, Hongwei; Fan, Daiming

    2010-12-01

    CIAPIN1, a newly identified antiapoptotic molecule, is a downstream effector of the receptor tyrosine kinase-Ras signaling pathway in the mouse Ba/F3 pro-B cell line. Neither CIAPIN1 expression nor its clinical significance has been previously examined in esophageal squamous cell carcinoma (ESCC), and the present immunohistochemical analysis is the first study on CIAPIN1 distribution in ESCC. To investigate the relationships between the expression of CIAPIN1 and clinicopathological characteristics of ESCC, and evaluate the relationship between the expression of this gene and prognosis in ESCC patients. The expression of CIAPIN1 was investigated in 112 surgically resected specimens of ESCC by immunohistochemistry using a specific monoclonal antibody. The relations of CIAPIN1 expression with clinicopathological characteristics and the postoperative survival rate were statistically analyzed. We found that the expression of CIAPIN1 was statistically correlated with the degree of differentiation, depth of invasion, and lymph node metastasis of ESCC. Consistently, the survival rates of patients with CIAPIN1-negative tumors tended to be statistically lower than those with CIAPIN1-positive tumors. However, no significant difference was observed between CIAPIN1 expression and the patient age, sex, tumor location, and distant metastasis. Furthermore, multivariate analysis was performed by using Cox's proportional hazards model, and the results showed that lymph node metastases and CIAPIN1 expression were two independent prognostic factors. CIAPIN1 might play an important role in esophageal carcinogenesis, and it could be considered as a valuable prognostic indicator in ESCC. Finally, functional enhancement of CIAPIN1 might lead to a novel strategy for the treatment of SCC in the esophagus.

  4. 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.

  5. AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

    Science.gov (United States)

    Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne

    2010-02-01

    The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor

  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...... Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2a expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC). Also the kinase activity of CK2 was significantly increased in ccRCC compared to normal...... 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. Rac1 overexpression is correlated with epithelial mesenchymal transition and predicts poor prognosis in non-small cell lung cancer.

    Science.gov (United States)

    Zhou, Yujuan; Liao, Qianjin; Han, Yaqian; Chen, Jie; Liu, Zhigang; Ling, Hang; Zhang, Jing; Yang, Wenjuan; Oyang, Linda; Xia, Longzheng; Wang, Li; Wang, Heran; Xue, Lei; Wang, Hui; Hu, Bingqiang

    2016-01-01

    Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype. Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors. The correlation of Rac1 and EMT markers with clinicopathological characteristics and the relationship between the protein levels and progression-free survival (PFS) and overall survival (OS) were analyzed. Results: Compared with non-tumor tissues, the NSCLC tissues showed marked elevation in the levels of Rac1, Snail1, Twist1, N-cad, and Vim levels, whereas the E-cad levels were significantly decreased (P Rac1 and EMT markers was significantly associated with TNM stage and metastasis (P Rac1 may be associated with poor OS and PFS compared with low expression (PRac1, Snail1, Twist1, N-cad, Vim, and E-cad was an independent prognostic factor in NSCLC. Interestingly, Rac1 expression was positively correlated with Snail1, Twist1, N-cad, and Vim levels (r=0.563, r=0.440, r=0.247 r=0.536, PRac1, Twist, Snail1, Vim and N-cad were highly expressed in lung cancer patients resistant to radiotherapy, while E-cad was poorly expressed. Conclusion: Rac1 may promote NSCLC progression and metastasis via EMT, which may be considered as a potential therapeutic target.

  8. 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. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  9. Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma

    OpenAIRE

    Cai, Shao-hang; Lu, Shi-xun; Liu, Li-li; Zhang, Chris Zhiyi; Yun, Jing-ping

    2017-01-01

    Background: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. Methods: A total of 615 HCC specimens were obtained to construct tissue microarrays and pe...

  10. 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...... hospitalization could improve management and ultimately reduce mortality levels. The aim of this study was to evaluate CRP on the 3rd day (CRP3) of hospitalization as a predictor for 30 days mortality. METHODS: A retrospective multicentre cohort study of adult patients admitted with CAP at three Danish hospitals....... 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...

  11. Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios Are More Effective than the Fournier's Gangrene Severity Index for Predicting Poor Prognosis in Fournier's Gangrene.

    Science.gov (United States)

    Yim, Sang Un; Kim, Sun Woo; Ahn, Ji Hoon; Cho, Yang Hyun; Chung, Hoseok; Hwang, Eu Chang; Yu, Ho Song; Oh, Kyung Jin; Kim, Sun-Ouck; Jung, Seung Il; Kang, Taek Won; Kwon, Dong Deuk; Park, Kwangsung

    2016-04-01

    We investigated the value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as markers of mortality in patients with Fournier's gangrene. Records from 62 patients treated for Fournier's gangrene between 2003 and 2014 were reviewed retrospectively. Data were collected regarding medical history, symptoms, physical examination findings, admission laboratory tests, and the extent of body surface area involved (%). Fournier's Gangrene Severity Index score, NLR, and PLR were calculated. The data were assessed separately for surviving and deceased patients. Of the 62 patients, 36 survived (58%, group 1) and 26 died (42%, group 2). Parameters that were statistically different between the two groups (p Fournier's Gangrene Severity Index score, and admission laboratory parameters, including body temperature, heart rate, bicarbonate, albumin, and serum calcium. The average body surface area affected in group 2 was statistically different from that of group 1 (6.0% versus 2.3%, p = 0.001). A high Fournier's Gangrene Severity Index score (>9), high NLR (>8), and high PLR (>140) were associated more frequently with group 2 patients. Multivariable regression analysis showed that high NLR (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.25-17.3; p = 0.022) and high PLR (adjusted OR, 11.6; 95% CI, 2.7-49.5; p = 0.001) were independent prognostic factors for poor prognosis from Fournier's gangrene. However, the Fournier's Gangrene Severity Index score did not shown any statistically significant effect on mortality (p = 0.086). The Fournier's Gangrene Severity Index scoring system was not associated with determining poor prognosis, however, high NLR and high PLR were associated with predictors of mortality in patients with Fournier's gangrene.

  12. The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Liu, Xiang-hua; Liu, Zhi-li; Sun, Ming; Liu, Jing; Wang, Zhao-xia; De, Wei

    2013-01-01

    The identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of cancer. HOTAIR (HOX transcript antisense intergenic RNA) has been implicated in several cancers; however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of HOTAIR in NSCLC and to evaluate its biological role and clinical significance in tumor progression. Expression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of HOTAIR. The effect of HOTAIR on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Tail vein injection of cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). HOTAIR was highly expressed both in NSCLC samples and cell lines compared with corresponding normal counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi decreased the migration and invasion of NSCLC cells in vitro and impeded cell metastasis in vivo. HOXA5 levels were affected by HOTAIR knockdown or over-expression in vitro. Our findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC

  13. Intra-tumour IgA1 is common in cancer and is correlated with poor prognosis in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    2016-08-01

    Full Text Available A high frequency of IgA1-positive tumour cells was found in tissue micro-arrays of oesophagus, colon, testis, lung, breast, bladder and ovarian cancer. IgA1 was observed in the cytoplasm and the plasma membrane. A correlation was found between intra-tumour IgA1 and poor overall survival in a large cohort of bladder cancer patients (n = 99, p = 0.011, log-rank test. The number of IgA1-positive tumour cells was also found to be higher in female than male bladder cancer patients. The presence of IgA1 was confirmed in formalin-fixed paraffin-embedded ovarian carcinoma samples using LC-MS/MS analysis. Uptake of IgA1 was also observed in breast cancer and melanoma cell lines when cultivated in the presence of serum from healthy individuals, indicating a possible origin of the IgA1 antibodies in cancer cells.

  14. FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis.

    Science.gov (United States)

    Goldie, Stephen J; Mulder, Klaas W; Tan, David Wei-Min; Lyons, Scott K; Sims, Andrew H; Watt, Fiona M

    2012-07-01

    New therapeutic strategies are needed to improve treatment of head and neck squamous cell carcinoma (HNSCC), an aggressive tumor with poor survival rates. FRMD4A is a human epidermal stem cell marker implicated previously in epithelial polarity that is upregulated in SCC cells. Here, we report that FRMD4A upregulation occurs in primary human HNSCCs where high expression levels correlate with increased risks of relapse. FRMD4A silencing decreased growth and metastasis of human SCC xenografts in skin and tongue, reduced SCC proliferation and intercellular adhesion, and stimulated caspase-3 activity and expression of terminal differentiation markers. Notably, FRMD4A attenuation caused nuclear accumulation of YAP, suggesting a potential role for FRMD4A in Hippo signaling. Treatment with the HSP90 inhibitor 17-DMAG or ligation of CD44 with hyaluronan caused nuclear depletion of FRMD4A, nuclear accumulation of YAP and reduced SCC growth and metastasis. Together, our findings suggest FRMD4A as a novel candidate therapeutic target in HNSCC based on the key role in metastatic growth we have identified. ©2012 AACR.

  15. 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.

  16. High expression of SDF-1 and VEGF is associated with poor prognosis in patients with synovial sarcomas.

    Science.gov (United States)

    Feng, Qi; Guo, Peng; Wang, Jin; Zhang, Xiaoyu; Yang, Hui-Chai; Feng, Jian-Gang

    2018-03-01

    Stromal cell-derived factor-1 (SDF-1) predicts poor clinical outcomes of certain types of cancer. Furthermore, vascular endothelial growth factor (VEGF) promotes the growth and metastasis of solid tumors. The aim of the present study was to examine the expression of SDF-1 and VEGF in patients with synovial sarcoma and to determine their expression is correlated with unfavorable outcomes. Levels of SDF-1 and VEGF proteins were evaluated in 54 patients with synovial sarcoma using immunohistochemical and immunofluorescence staining. Potential associations between the expression of SDF-1 and VEGF and various clinical parameters were analyzed using Pearson's χ 2 test and the Spearman-rho test. Additionally, univariate and multivariate Cox regression analyses were used to identify potential prognostic factors, and the Kaplan-Meier method was used to analyze the overall survival rates of patients. Low SDF-1 and VEGF expression was detected in 20.4% (11/54) and 22.2% (12/54) of patients with synovial sarcoma; moderate expression was detected in 35.2% (19/54) and 37.0% (20/54) of patients and high expression was detected in 44.4% (24 of 54) and 40.7% (22 of 54) of patients, respectively. Levels of SDF-1 and VEGF proteins were significantly associated with histological grade (P<0.05), metastasis (P<0.05) and American Joint Committee on Cancer staging (P<0.05). In addition, levels of SDF-1 and VEGF expression were positively correlated with each other (P<0.001). Univariate analysis also indicated that VEGF expression was associated with shorter overall survival rates in (P<0.05), whereas multivariate analysis demonstrated that SDF-1 expression was associated with shorter patient survival rates (P<0.05). Finally, both SDF-1 and VEGF expression were associated with various characteristics of synovial sarcoma. Therefore, SDF-1 expression may be a potential independent prognostic indicator in patients with synovial sarcomas.

  17. HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

    International Nuclear Information System (INIS)

    Bitu, Carolina Cavalcante; Destro, Maria Fernanda de Souza Setúbal; Carrera, Manoela; Silva, Sabrina Daniela da; Graner, Edgard; Kowalski, Luiz Paulo; Soares, Fernando Augusto; Coletta, Ricardo D

    2012-01-01

    HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA) containing 127 oral squamous cell carcinomas (OSCC) was performed to determine the prognostic role of HOXA1 expression. We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells) decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026). Our findings indicate that HOXA1 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and suggest that HOXA1

  18. HOXA1 is overexpressed in oral squamous cell carcinomas and its expression is correlated with poor prognosis

    Directory of Open Access Journals (Sweden)

    Bitu Carolina

    2012-04-01

    Full Text Available Abstract Background HOX genes encode homeodomain-containing transcription factors involved in the regulation of cellular proliferation and differentiation during embryogenesis. However, members of this family demonstrated oncogenic properties in some malignancies. The present study investigated whether genes of the HOXA cluster play a role in oral cancer. Methods In order to identify differentially expressed HOXA genes, duplex RT-PCR in oral samples from healthy mucosa and squamous cell carcinoma was used. The effects of HOXA1 on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT and anchorage-independent growth were assessed in cells with up- and down-regulation of HOXA1. Immunohistochemical analysis using a tissue microarray (TMA containing 127 oral squamous cell carcinomas (OSCC was performed to determine the prognostic role of HOXA1 expression. Results We showed that transcripts of HOXA genes are more abundant in OSCC than in healthy oral mucosa. In particular, HOXA1, which has been described as one of the HOX members that plays an important role in tumorigenesis, was significantly more expressed in OSCCs compared to healthy oral mucosas. Further analysis demonstrated that overexpression of HOXA1 in HaCAT human epithelial cells promotes proliferation, whereas downregulation of HOXA1 in human OSCC cells (SCC9 cells decreases it. Enforced HOXA1 expression in HaCAT cells was not capable of modulating other events related to tumorigenesis, including apoptosis, adhesion, invasion, EMT and anchorage-independent growth. A high number of HOXA1-positive cells was significantly associated with T stage, N stage, tumor differentiation and proliferative potential of the tumors, and was predictive of poor survival. In multivariate analysis, HOXA1 was an independent prognostic factor for OSCC patients (HR: 2.68; 95% CI: 1.59-2.97; p = 0.026. Conclusion Our findings indicate that HOXA1 may contribute to oral carcinogenesis

  19. Dexamethasone administration during definitive radiation and temozolomide renders a poor prognosis in a retrospective analysis of newly diagnosed glioblastoma patients

    International Nuclear Information System (INIS)

    Shields, Lisa B. E.; Shelton, Brent J.; Shearer, Andrew J.; Chen, Li; Sun, David A.; Parsons, Sarah; Bourne, T. David; LaRocca, Renato; Spalding, Aaron C.

    2015-01-01

    Dexamethasone (DXM) is commonly used in the management of cerebral edema in patients diagnosed with glioblastoma multiforme (GBM). Bevacizumab (BEV) is FDA-approved for the progression or recurrence of GBM but has not been shown to improve survival when given for newly diagnosed patients concurrently with radiation (RT) and temozolomide (TMZ). Both DXM and BEV reduce cerebral edema, however, DXM has been shown to induce cytokine cascades which could interfere with cytotoxic therapy. We investigated whether DXM would reduce survival of GBM patients in the setting of concurrent TMZ and BEV administration. We reviewed the treatment of all 73 patients with GBM who received definitive therapy at our institution from 2005 to 2013 with RT (60 Gy) delivered with concurrent daily TMZ (75 mg/m 2 ). Of these, 34 patients also were treated with concurrent BEV (10 mg/kg every two weeks). Patients received adjuvant therapy (TMZ or TMZ/Bev) until either progression, discontinuation due to toxicity, or 12 months after radiation completion. All patients who had GBM progression with TMZ were offered BEV for salvage therapy, with 19 (56 %) receiving BEV. With a median follow-up of 15.6 months, 67 (91.8 %) patients were deceased. The OS for the entire cohort was 15.9 months, while the PFS was 7.7 months. The extent of resection was a prognostic indicator for OS (p = .0044). The median survival following gross tumor resection (GTR) was 22.5 months, subtotal resection (STR) was 14.9 months, and biopsy was 12.1 months. The addition of BEV to TMZ with RT was borderline significantly associated with increased PFS (9.4 vs. 5.1 months, p = 0.0574) although was not significantly associated with OS (18.1 vs. 15.3 months respectively, p = 0.3064). In patients receiving TMZ, DXM use concurrent with RT was a poor prognostic indicator of both OS (12.7 vs. 22.6 months, p = 0.003) and PFS (3.6 vs. 8.4 months, p <0.0001). DXM did not reduce OS in patients who received TMZ and BEV concurrently with RT

  20. Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    An, Jun; Liu, Zhiyong; Liang, Qiong; Pan, Yuhang; Li, Haifeng; Wang, Ruizhi; Jin, Yi

    2017-09-01

    The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain cancers. However, the relationship of this expression with hepatocellular carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7 and to evaluate their role in hepatocarcinogenesis, in 162 cases of hepatocellular carcinoma, we used immunohistochemistry to investigate the expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic tissues around the hepatocellular carcinoma. The results demonstrated that the rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%, respectively, in hepatocellular carcinoma tissues. However, the rates of positive Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues (Phepatocellular carcinoma tissues of patients with lymph node metastasis, tumor thrombi in the portal vein and an advanced clinical stage (Phepatocellular carcinoma cohort. Moreover, patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins (Phepatocellular carcinoma and could be used as a prognostic indicator in patients with hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. Low Expression of DYRK2 (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2 Correlates with Poor Prognosis in Colorectal Cancer.

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    Haiyan Yan

    Full Text Available Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2 is a member of dual-specificity kinase family, which could phosphorylate both Ser/Thr and Tyr substrates. The role of DYRK2 in human cancer remains controversial. For example, overexpression of DYRK2 predicts a better survival in human non-small cell lung cancer. In contrast, amplification of DYRK2 gene occurs in esophageal/lung adenocarcinoma, implying the role of DYRK2 as a potential oncogene. However, its clinical role in colorectal cancer (CRC has not been explored. In this study, we analyzed the expression of DYRK2 from Oncomine database and found that DYRK2 level is lower in primary or metastatic CRC compared to adjacent normal colon tissue or non-metastatic CRC, respectively, in 6 colorectal carcinoma data sets. The correlation between DYRK2 expression and clinical outcome in 181 CRC patients was also investigated by real-time PCR and IHC. DYRK2 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues. Functional studies confirmed that DYRK2 inhibited cell invasion and migration in both HCT116 and SW480 cells and functioned as a tumor suppressor in CRC cells. Furthermore, the lower DYRK2 levels were correlated with tumor sites (P = 0.023, advanced clinical stages (P = 0.006 and shorter survival in the advanced clinical stages. Univariate and multivariate analyses indicated that DYRK2 expression was an independent prognostic factor (P < 0.001. Taking all, we concluded that DYRK2 a novel prognostic biomarker of human colorectal cancer.

  4. The lncRNA PVT1 Contributes to the Cervical Cancer Phenotype and Associates with Poor Patient Prognosis.

    Directory of Open Access Journals (Sweden)

    Marissa Iden

    Full Text Available The plasmacytoma variant translocation 1 gene (PVT1 is an lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Although the mechanism by which PVT1 influences disease processes has been studied in multiple cancer types, its role in cervical tumorigenesis remains unknown. Thus, the present study was designed to investigate the role of PVT1 in cervical cancer in vitro and in vivo. PVT1 expression was measured by quantitative PCR (qPCR in 121 invasive cervical carcinoma (ICC samples, 30 normal cervix samples, and cervical cell lines. Functional assays were carried out using both siRNA and LNA-mediated knockdown to examine PVT1's effects on cervical cancer cell proliferation, migration and invasion, apoptosis, and cisplatin resistance. Our results demonstrate that PVT1 expression is significantly increased in ICC tissue versus normal cervix and that higher expression of PVT1 correlates with poorer overall survival. In cervical cancer cell lines, PVT1 knockdown resulted in significantly decreased cell proliferation, migration and invasion, while apoptosis and cisplatin cytotoxicity were significantly increased in these cells. Finally, we show that PVT1 expression is augmented in response to hypoxia and immune response stimulation and that this lncRNA associates with the multifunctional and stress-responsive protein, Nucleolin. Collectively, our results provide strong evidence for an oncogenic role of PVT1 in cervical cancer and lend insight into potential mechanisms by which PVT1 overexpression helps drive cervical carcinogenesis.

  5. Overexpression of prostate tumor overexpressed 1 correlates with tumor progression and predicts poor prognosis in breast cancer

    International Nuclear Information System (INIS)

    Lei, Fangyong; Zhang, Longjuan; Li, Xinghua; Lin, Xi; Wu, Shu; Li, Fengyan; Liu, Junling

    2014-01-01

    Prostate tumor overexpressed 1 (PTOV1) was demonstrated to play an important role in cancer progression and was correlated with unfavorable clinical outcome. However, the clinical role of PTOV1 in cancer remains largely unknown. This study aimed to investigate the expression and clinicopathological significance of PTOV1 in breast cancer. The mRNA and protein expression levels of PTOV1 were analyzed in 12 breast cancer cell lines and eight paired breast cancer tumors by semi-quantitative real time-PCR and western blotting, respectively. Immunohistochemistry was performed to assess PTOV1 protein expression in 169 paraffin-embedded, archived breast cancer samples. Survival analysis and Cox regression analysis were performed to investigate the clinicopathological significance of PTOV1 expression. Our data revealed that PTOV1 was frequently overexpressed in breast cancer cell lines compared to normal human breast epithelial cells and in primary breast cancer samples compared to adjacent noncancerous breast tissues, at both the mRNA and protein levels. Moreover, high expression of PTOV1 in breast cancer is strongly associated with clinicopathological characteristics and estrogen receptor expression status (P = 0.003). Breast cancer patients with higher PTOV1 expression had substantially shorter survival times than patients with lower PTOV1 expression (P < 0.001). Univariate and multivariate analysis revealed that PTOV1 might be an independent prognostic factor for breast cancer patients (P = 0.005). Our study showed that PTOV1 is upregulated in breast cancer cell lines and clinical samples, and its expression was positively associated with progression and aggressiveness of breast cancer, suggesting that PTOV1 could serve as an independent prognostic marker

  6. Signatures derived from increase in SHARPIN gene copy number are associated with poor prognosis in patients with breast cancer

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    Diane Ojo

    2017-12-01

    Full Text Available We report three signatures produced from SHARPIN gene copy number increase (GCN-Increase and their effects on patients with breast cancer (BC. In the Metabric dataset (n = 2059, cBioPortal, SHARPIN GCN-Increase occurs preferentially or mutual exclusively with mutations in TP53, PIK3CA, and CDH1. These genomic alterations constitute a signature (SigMut that significantly correlates with reductions in overall survival (OS in BC patients (n = 1980; p = 1.081e−6. Additionally, SHARPIN GCN-Increase is associated with 4220 differentially expressed genes (DEGs. These DEGs are enriched in activation of the pathways regulating cell cycle progression, RNA transport, ribosome biosynthesis, DNA replication, and in downregulation of the pathways related to extracellular matrix. These DEGs are thus likely to facilitate the proliferation and metastasis of BC cells. Additionally, through forward (FWD and backward (BWD stepwise variate selections among the top 160 downregulated and top 200 upregulated DEGs using the Cox regression model, a 6-gene (SigFWD and a 50-gene (SigBWD signature were derived. Both signatures robustly associate with decreases in OS in BC patients within the Curtis (n = 1980; p = 6.16e−11 for SigFWD; p = 1.06e−10, for SigBWD and TCGA cohort (n = 817; p = 4.53e−4 for SigFWD and p = 0.00525 for SigBWD. After adjusting for known clinical factors, SigMut (HR 1.21, p = 0.0297, SigBWD (HR 1.25, p = 0.0263, and likely SigFWD (HR 1.17, p = 0.062 remain independent risk factors of BC deaths. Furthermore, the proportion of patients positive for these signatures is significantly increased in ER−, Her2-enriched, basal-like, and claudin-low BCs compared to ER+ and luminal BCs. Collectively, these SHARPIN GCN-Increase-derived signatures may have clinical applications in management of patients with BC.

  7. Low Serum Complement C3 Levels at Diagnosis of Renal ANCA-Associated Vasculitis Is Associated with Poor Prognosis.

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    Jean-François Augusto

    Full Text Available Recent studies have demonstrated the key role of the complement alternative pathway (cAP in the pathophysiology of experimental ANCA-associated vasculitis (AAV. However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes.We conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3<120 mg/dL and the high C3 level group (C3≥120 mg/dL. Patient and renal survivals, association between C3 level and renal pathology were analysed.Serum complement C3 concentration remained in the normal range [78-184 mg/dL]. Compared with the high C3 level, the patients in the low C3 level group had lower complement C4 concentrations (P = 0.008 and lower eGFR (P = 0.002 at diagnosis. The low C3 level group had poorer patient and death-censored renal survivals, compared with the high C3 level group (P = 0.047 and P = 0.001, respectively. We observed a significant negative correlation between C3 levels and the percentage of glomeruli affected by cellular crescent (P = 0.017, r = -0.407. According to the Berden et al renal histologic classification, patients in the crescentic/mixed category had low C3 levels more frequently (P<0.01. Interestingly, we observed that when patients with the crescentic/mixed histologic form were analysed according to C3 level, long term renal survival was significantly greater in the high C3 level group than in the low C3 level group (100% vs 40.7% at 6 years, p = 0.046. No relationship between serum C4 and renal outcome was observed.A Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival.

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

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    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

  9. Borealin/Dasra B is a cell cycle-regulated chromosomal passenger protein and its nuclear accumulation is linked to poor prognosis for human gastric cancer

    International Nuclear Information System (INIS)

    Chang, J.-L.; Chen, T.-H.; Wang, C.-F.; Chiang, Y.-H.; Huang, Y.-L.; Wong, F.-H.; Chou, C.-K.; Chen, C.-M.

    2006-01-01

    Chromosomal passenger proteins including Aurora B, Survivin, and Borealin/Dasra B, also called CDCA8/FLJ10468, are known to play crucial roles during mitosis and cell division. Inappropriate chromosomal segregation and cell division may cause auneuploidy leading to cancer. However, it is still unclear how the expression of chromosomal passenger proteins may be linked to cancer. In this study, we demonstrated that Borealin is a cell cycle-regulated gene and is upregulated at G2-M phases of the cell cycle. We showed that Borealin interacts with Survivin but not with Aurora B. The interaction domain of Survivin in Borealin was mapped to the N-terminal 92 amino-acid residues of Borealin. To examine the linkage between expression of Borealin and cancer, we performed immunohistochemistry analysis using anti-Borealin specific antibody on the paraffin-embedded gastric cancer tissues. Our results showed that Borealin expression is significantly correlated with Survivin (P = 0.003) and Ki67 (P = 0.007) in gastric cancer. Interestingly, an increased nuclear Borealin level reveals borderline association with a poor survival rate (P = 0.047). Taken together, our results demonstrated that Borealin is a cell cycle-regulated chromosomal passenger protein and its aberrant expression is linked to a poor prognosis for gastric cancer

  10. Overexpression of long non-coding RNA colon cancer-associated transcript 2 is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer.

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    Zhang, Junling; Jiang, Yong; Zhu, Jing; Wu, Tao; Ma, Ju; Du, Chuang; Chen, Shanwen; Li, Tengyu; Han, Jinsheng; Wang, Xin

    2017-12-01

    The aim of the present study was to explore the clinicopathological and prognostic significance of long non-coding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) expression in human colorectal cancer (CRC). Expression levels of lncRNA CCAT2 in CRC, adjacent non-tumor and healthy colon mucosa tissues were detected by quantitative polymerase chain reaction. The disease-free survival and overall survival rates were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using Cox proportional hazard analysis. The expression level of lncRNA CCAT2 in CRC tissues was increased significantly compared with adjacent normal tissues or non-cancerous tissues. CCAT2 expression was observed to be progressively increased between tumor-node-metastasis (TNM) stages I and IV. A high level of CCAT2 expression was revealed to be associated with poor cell differentiation, deeper tumor infiltration, lymph node metastasis, distance metastasis, vascular invasion and advanced TNM stage. Compared with patients with low levels of CCAT2 expression, patients with high levels of CCAT2 expression had shorter disease-free survival and overall survival times. Multivariate analyses indicated that high CCAT2 expression was an independent poor prognostic factor. Therefore, increased lncRNA CCAT2 expression maybe a potential diagnostic biomarker for CRC, and an independent predictor of prognosis in patients with CRC.

  11. CpG Island Methylator Phenotype Positive Tumors in the Absence of MLH1 Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis

    Science.gov (United States)

    Fu, Tao; Pappou, Emmanouil P.; Guzzetta, Angela A.; Jeschke, Jana; Kwak, Ruby; Dave, Pujan; Hooker, Craig M.; Morgan, Richard; Baylin, Stephen B.; Iacobuzio-Donahue, Christine A.; Wolfgang, Christopher L.; Ahuja, Nita

    2012-01-01

    Purpose Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis. Experimental Design Demographics, tumor characteristics and survival were available for 99 duodenal adenocarcinoma patients. Testing for KRAS and BRAF mutations, MSI, MLH1 methylation and CpG island methylator phenotype (CIMP) status was performed. A Cox proportional hazard model was built to predict survival. Results CIMP+ was detected in 27 of 99 (27.3%) duodenal adenocarcinomas, and was associated with MSI (P = 0.011) and MLH1 methylation (P CIMP− tumors. No BRAF V600E mutation was detected. Among the CIMP+ tumors, 15 (55.6%) were CIMP+/MLH1-unmethylated (MLH1-U). Kaplan-Meier analysis showed tumors classified by CIMP, CIMP/MLH1 methylation status or CIMP/MSI status could predict overall survival (OS; P = 0.047, 0.002, and 0.002, respectively), while CIMP/MLH1 methylation status could also predict time-to-recurrence (TTR; P = 0.016). In multivariate analysis, CIMP/MLH1 methylation status showed a significant prognostic value regarding both OS (P CIMP+/MLH1-U tumors had the worst OS and TTR. Conclusions Our results demonstrate existence of CIMP in duodenal adenocarcinomas. The combination of CIMP+/MLH1-U appears to be independently associated with poor prognosis in patients with duodenal adenocarcinomas. This study also suggests that BRAF mutations are not involved in duodenal tumorigenesis, MSI or CIMP development. PMID:22825585

  12. Low expression of Mda-7/IL-24 and high expression of C-myb in tumour tissues are predictors of poor prognosis for Burkitt lymphoma patients.

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    Ma, Ming; Zhao, Riyang; Yang, Xingxiao; Zhao, Lianmei; Liu, Lihua; Zhang, Cong; Wang, Xuexiao; Shan, Baoen

    2018-02-08

    Burkitt lymphoma is one of the most common types of haematopoietic malignancy in children and adolescents. Mda-7/IL-24 had been identified as a differentiation inducer of Burkitt lymphoma cells. Previous studies have revealed that knockdown of C-myb can also lead to the terminal differentiation of Burkitt lymphoma cells. The aim of the present study was to investigate the correlation between the expression of Mda-7/IL-24 and C-myb, as well as their prognostic significance, for Burkitt lymphoma patients. The tumour tissues were collected from 59 cases of Burkitt lymphoma patients and detected with Western blotting and immunohistochemistry. The results showed that the expression of Mda-7/IL-24 was lower, whereas the expression of C-myb was higher in Burkitt lymphoma tissues compared to specimens of normal lymph node tissues. Furthermore, C-myb expression was negatively correlated with Mda-7/IL-24 expression at the protein level in Burkitt lymphoma tissues and cell lines. Both the expression of Mda-7/IL-24 and C-myb in Burkitt lymphoma tissues was associated with some clinicopathological parameters, such as clinical stage, infiltration in the bone marrow, Ki67 and overall survival rates. These results indicated that low expression of Mda-7/IL-24 along with high expression of C-myb are predictors for poor prognosis of Burkitt lymphoma patients; this outcome suggests that Mda-7/IL-24 and C-myb might be potential targets for clinical treatment of Burkitt lymphoma. Mda-7/IL-24: melanoma differentiation associated gene7/interleukin 24; FCM: flow cytometry; Ecog: Eastern Cooperative Oncology Group; IPI: International lymphoma prognosis index.

  13. Can loco-regional irradiation be a routine supplement to high dose chemotherapy with autologous bone marrow transplant in women with poor prognosis breast cancer

    International Nuclear Information System (INIS)

    Wobeck, Linda K.; Holland, H. Kent; Landry, Jerome C.; Lynn, Michael J.; Hughes, Lorie L.

    1997-01-01

    Purpose: High dose chemotherapy followed by bone marrow transplantation (BMT) is currently being performed in many women with localized, poor prognosis breast cancer. The purpose of this study was to examine patterns of care in radiation treatment as well as acute side effects in women who received breast or chest wall and regional nodal irradiation (XRT) post BMT. Methods: The records of 126 consecutive women with localized, poor prognosis breast cancer who received an autologous BMT at Emory University between (3(90)) and (7(96)) were retrospectively reviewed. Results: All 126 women underwent high dose chemotherapy with cyclophosphamide, carboplatinum and thiotepa followed by BMT. Loco - regional XRT after BMT was routinely recommended for patients with 10 or more positive axillary lymph nodes or inflammatory carcinoma. Overall, 90 patients received local +/- regional XRT; 11 patients prior to BMT and 79 patients post BMT. Three of these patients had a local relapse prior to beginning XRT post BMT. Thirty six patients did not receive XRT for the following reasons: major post BMT morbidity or insufficient hematological recovery (15 patients), less than 10 positive axillary lymph nodes (12 patients), or refusal/not referred (9 patients). Therefore, of the 103 patients (excludes those with less than 10 positive nodes) intended to receive post BMT irradiation, 14.5 % (15 patients- 2 with inflammatory carcinoma) were unable to receive it secondary to post BMT morbidity and 9% (9 patients) refused or were not referred. Of these 79 patients irradiated post BMT, 16 had stage IIA, 20 stage IIB, 27 stage IIIA and 16 inflammatory carcinoma (IIIB). The median time from transplant to irradiation was 82 days (range 44 - 641). Average dose to breast or chest wall was 49.5 Gy (range 42-55.8 Gy). Boost dose (mean 12 Gy, range 10-22 Gy) was given in 62% of patients. The median tumor bed/mastectomy scar dose was 60 Gy (range 42-72 Gy). Supraclavicular, posterior axillary and

  14. Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma

    International Nuclear Information System (INIS)

    Liang, Yu; Bollen, Andrew W; Aldape, Ken D; Gupta, Nalin

    2006-01-01

    nuclear FABP7 immunoreactivity increases the risk of poor prognosis In this study, we identified a possible mechanism as the basis of the association between nuclear FABP7 and poor prognosis of GBM. FABP7 expression can be found in all grades of astrocytoma, but neoplastic cells with nuclear FABP7 were only seen in infiltrative types of tumors. Nuclear FABP7 may be induced by EGFR activation to promote migration of GBM tumor cells. Positive nuclear FABP7 and EGFR overexpression correlated with short survival in EGFR-positive GBM patients. Therefore, nuclear FABP7 immunoreactivity could be used to monitor the progression of EGFR-overexpressed GBM

  15. Long-Term Clinical Outcomes and Factors That Predict Poor Prognosis in Athletes After a Diagnosis of Acute Spondylolysis: A Retrospective Review With Telephone Follow-up.

    Science.gov (United States)

    Selhorst, Mitchell; Fischer, Anastasia; Graft, Kristine; Ravindran, Reno; Peters, Eric; Rodenberg, Richard; MacDonald, James

    2016-12-01

    Study Design Retrospective review with telephone follow-up. Background Acute spondylolytic injuries have a dramatic impact on the young athlete. Excellent short-term clinical outcomes have been observed, but not enough is known about long-term clinical outcomes. Objectives (1) To report long-term clinical outcomes for patients diagnosed with acute spondylolysis, and (2) to assess the prognostic ability of retrospective variables for long-term outcomes. Methods Patients from 2010 through 2013 were retrospectively reviewed to identify patients and to obtain demographic, baseline, and short-term outcomes. Long-term follow-up data were collected by telephone from patients diagnosed with acute spondylolysis to assess recurrence rate of low back pain, perceived outcome, pain, and functional ability. Patients were categorized as having a good or poor long-term outcome based on these measures. Logistic regression analysis was performed to assess the prognostic ability of the retrospective variables for long-term outcomes 3.4 years (range, 1.5-5.6 years) after treatment. Results One hundred twenty-one (71.6%) patients completed the follow-up questionnaire (48 female; mean age at baseline, 14.4 years). At follow-up, 81 (66.9%) patients were able to maintain their same or a higher level of sport. Recurrence of significant symptoms was reported by 55 (45.5%) patients, with 41 (33.9%) requiring medical treatment. The final logistic regression model revealed that female sex, adverse reaction during care, and multilevel injury were significant predictors of poor long-term outcome (R 2 = 0.22). Conclusion Although excellent short-term outcomes were noted, 42% of patients reported a poor outcome at long-term follow-up. Female sex, multilevel injury, and experiencing an adverse reaction during care were significant predictors of poor long-term clinical outcome for patients diagnosed with acute spondylolysis. Level of Evidence Prognosis, level 4. Registered January 15, 2015 at www

  16. Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery.

    Science.gov (United States)

    Garvin, Stina; Oda, Husam; Arnesson, Lars-Gunnar; Lindström, Annelie; Shabo, Ivan

    2018-05-03

    Cancer cell fusion with macrophages results in highly tumorigenic hybrids that acquire genetic and phenotypic characteristics from both maternal cells. Macrophage traits, exemplified by CD163 expression, in tumor cells are associated with advanced stages and poor prognosis in breast cancer (BC). In vitro data suggest that cancer cells expressing CD163 acquire radioresistance. Tissue microarray was constructed from primary BC obtained from 83 patients treated with breast-conserving surgery, 50% having received postoperative radiotherapy (RT) and none of the patients had lymph node or distant metastasis. Immunostaining of CD163 in cancer cells and macrophage infiltration (MI) in tumor stroma were evaluated. Macrophage:MCF-7 hybrids were generated by spontaneous in vitro cell fusion. After irradiation (0, 2.5 and 5 Gy γ-radiation), both hybrids and their maternal MCF-7 cells were examined by clonogenic survival. CD163-expression by cancer cells was significantly associated with MI and clinicopathological data. Patients with CD163-positive tumors had significantly shorter disease-free survival (DFS) after RT. In vitro generated macrophage:MCF-7 hybrids developed radioresistance and exhibited better survival and colony forming ability after radiation compared to maternal MCF-7 cancer cells. Our results suggest that macrophage phenotype in tumor cells results in radioresistance in breast cancer and shorter DFS after radiotherapy.

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

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    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.

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

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    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.

  19. Combined overexpression of cadherin 6, cadherin 11 and cluster of differentiation 44 is associated with lymph node metastasis and poor prognosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Ma, Chao; Zhao, Ji-Zhi; Lin, Run-Tai; Zhou, Lian; Chen, Yong-Ning; Yu, Li-Jiang; Shi, Tian-Yin; Wang, Mu; Liu, Man-Man; Liu, Yao-Ran; Zhang, Tao

    2018-06-01

    Oral squamous cell carcinoma (OSCC) is a highly invasive lesion that frequently metastasizes to the cervical lymph nodes and is associated with a poor prognosis. Several adhesion factors, including cadherin 6 (CDH6), cadherin 11 (CDH11) and cluster of differentiation 44 (CD44), have been reported to be involved in the invasion and metastasis of multiple types of cancer. Therefore, the aim of the present study was to determine the expression of CDH6, CDH11 and CD44 in tumor tissues from patients with OSCC, and whether this was associated with the metastasis and survival of OSCC. The mRNA expression of the human tumor metastasis-related cytokines was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in OSCC tumors with or without lymph node metastasis (n=10/group). The expression of CDH6, CDH11 and CD44 in 101 OSCC and 10 normal oral mucosa samples was examined by immunohistochemical staining. The association between overall and disease-specific survival times of patients with OSCC and the expression of these three proteins was evaluated using Kaplan-Meier curves and the log-rank test. RT-qPCR results indicated that the mRNA expression of CDH6, CDH11 and CD44 was increased in OSCC patients with lymph node metastasis (2.93-, 2.01- and 1.92-fold; P<0.05). Overexpression of CDH6, CDH11 and CD44 was observed in 31/35 (89%), 25/35 (71%) and 31/35 (89%) patients, respectively. The number of OSCC patients with lymph node metastasis exhibiting CDH6, CDH11 and CD44 overexpression was significantly higher than the number of patients without lymph node metastasis exhibiting overexpression of these proteins (P=0.017, P=0.038 and P=0.007, respectively). OSCC patients with high co-expression of CDH6, CDH11 and CD44 exhibited lower disease-specific survival times (P=0.047; χ 2 =3.933) when compared with OSCC patients with low co-expression of these adhesion factors. CDH6, CDH11 and CD44 serve important roles in OSCC metastasis and the combined use

  20. Downregulation of miR-15a due to LMP1 promotes cell proliferation and predicts poor prognosis in nasal NK/T-cell lymphoma.

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    Komabayashi, Yuki; Kishibe, Kan; Nagato, Toshihiro; Ueda, Seigo; Takahara, Miki; Harabuchi, Yasuaki

    2014-01-01

    Nasal NK/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-associated malignancy and has distinct clinical and histological features. However, its genetic features are hitherto unclear. MicroRNAs (miRNAs) play a crucial role in the pathogenesis of several malignancies via regulating gene expression. In this study, we investigated whether the specific microRNAs were related to the tumor behaviors in NNKTL. MiRNA array and Quantitative RT-PCR analyses revealed that miR-15a was expressed at a much lower level in NNKTL cells (SNK-1, SNK-6, and SNT-8) than in normal peripheral NK cells and EBV-negative NK cell line KHYG-1. Quantitative PCR and western blot analyses showed that the expression of MYB and cyclin D1, which are validated targets of miR-15a, was higher in NNKTL cells. Transfection of NNKTL cells (SNK-6 and SNT-8) with a miR-15a precursor decreased MYB and cyclin D1 levels, thereby blocking G1/S transition and cell proliferation. Knockdown of EBV-encoded latent membrane protein 1 (LMP1) significantly increased miR-15a expression in SNK-6 cells. In NNKTL tissues, we found that reduced miR-15a expression, which correlated with MYB and cyclin D1 expression, was associated with poor prognosis of NNKTL patients. These data suggest that downregulation of miR-15a, possibly due to LMP1, implicates in the pathogenesis of NNKTL by inducing cell proliferation via MYB and cyclin D1. Thus, miR-15a could be a potential target for antitumor therapy and a prognostic predictor for NNKTL. Copyright © 2013 Wiley Periodicals, Inc.

  1. KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer.

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    Deng, Yanhong; Wang, Li; Tan, Shuyun; Kim, George P; Dou, Ruoxu; Chen, Dianke; Cai, Yue; Fu, Xinhui; Wang, Lei; Zhu, Jun; Wang, Jianping

    2015-08-01

    The KRAS gene frequently mutates in colorectal cancer (CRC). Here we investigated the prognostic and predictive role of KRAS mutation in patients with stage II or III CRC. A consecutive cohort of patients with stage II or III CRC from a single center database was studied. The association between KRAS status, adjuvant FOLFOX therapy, and 3-year disease-free survival (3-y DFS) was analyzed. Of our 433 patients, 166 (38.3%) exhibited the KRAS mutation. Among the 190 patients who did not receive adjuvant therapy, those with KRAS mutation tumors had a worse 3-y DFS (hazard ratio [HR], 1.924; 95% confidence interval [CI], 1.078-3.435; P = 0.027). Among patients who received adjuvant chemotherapy, KRAS mutation was not correlated with worse 3-y DFS (HR, 1.083; 95% CI, 0.618-1.899; P = 0.781). Adjuvant chemotherapy improved 3-y DFS only among patients with KRAS mutant tumors (78.0% vs 69.2%) on multivariate analysis adjusted for age, stage, grade, site, vessel invasion, and carcinoembryonic antigen level (HR, 0.454; 95% CI, 0.229-0.901; P = 0.024). In contrast, there was no benefit of adjuvant chemotherapy in the KRAS wild-type group (84.3% vs 82.0%). KRAS mutation indicates poor prognosis. FOLFOX adjuvant chemotherapy benefits patients with stage II or III colorectal cancer with KRAS mutant tumors and is worth further investigation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. 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.

  3. Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.

    Science.gov (United States)

    Zhao, Xiangshan; Mirza, Sameer; Alshareeda, Alaa; Zhang, Ying; Gurumurthy, Channabasavaiah Basavaraju; Bele, Aditya; Kim, Jun Hyun; Mohibi, Shakur; Goswami, Monica; Lele, Subodh M; West, William; Qiu, Fang; Ellis, Ian O; Rakha, Emad A; Green, Andrew R; Band, Hamid; Band, Vimla

    2012-07-01

    Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.

  4. 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 Caregivers with lower health responsibility, spiritual growth, interpersonal relation, and stress management scores had lower preparedness and decision-making self-efficacy. A significant proportion of caregivers simultaneously report low engagement in all forms of self-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.

  5. A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.

    Science.gov (United States)

    Holkova, Beata; Supko, Jeffrey G; Ames, Matthew M; Reid, Joel M; Shapiro, Geoffrey I; Perkins, Edward Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Honeycutt, Connie; McGovern, Renee M; Kmieciak, Maciej; Shrader, Ellen; Wellons, Martha D; Sankala, Heidi; Doyle, Austin; Wright, John; Roberts, John D; Grant, Steven

    2013-04-01

    This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination. Patients received vorinostat (200 mg orally, three times a day, for 14 days) on a 21-day cycle, combined with 2 different alvocidib administration schedules: a 1-hour intravenous infusion, daily × 5; or a 30-minute loading infusion followed by a 4-hour maintenance infusion, weekly × 2. The alvocidib dose was escalated using a standard 3+3 design. Twenty-eight patients were enrolled and treated. The alvocidib MTD was 20 mg/m(2) (30-minute loading infusion) followed by 20 mg/m(2) (4-hour maintenance infusion) on days one and eight, in combination with vorinostat. The most frequently encountered toxicities were cytopenias, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, and QT prolongation. Dose-limiting toxicities (DLT) were cardiac arrhythmia-atrial fibrillation and QT prolongation. No objective responses were achieved although 13 of 26 evaluable patients exhibited stable disease. Alvocidib seemed to alter vorinostat pharmacokinetics, whereas alvocidib pharmacokinetics were unaffected by vorinostat. Ex vivo exposure of leukemia cells to plasma obtained from patients after alvocidib treatment blocked vorinostat-mediated p21(CIP1) induction and downregulated Mcl-1 and p-RNA Pol II for some specimens, although parallel in vivo bone marrow responses were infrequent. Alvocidib combined with vorinostat is well tolerated. Although disease stabilization occurred in some heavily pretreated patients, objective responses were not obtained with these schedules. ©2013 AACR.

  6. lncRNA H19 predicts poor prognosis in patients with melanoma and regulates cell growth, invasion, migration and epithelial–mesenchymal transition in melanoma cells

    Directory of Open Access Journals (Sweden)

    Shi G

    2018-06-01

    Full Text Available Gaofeng Shi,1,2 Hu Li,2 Fengshan Gao,2 Qian Tan1 1Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Plastic Surgery, the Affiliated Wuxi No 4 People’s Hospital of Jiangnan University, Wuxi, People’s Republic of China Introduction: Melanoma is a deadly malignancy and the poor prognosis of patients with advanced disease is relatively poor. Recent studies indicate that long non-coding RNAs are involved in the pathogenesis of malignant melanoma. This study aims to investigate the role of the long non-coding RNA H19 in melanoma and to explore the underlying molecular mechanisms. Materials and methods: The expression levels of H19 in clinical samples and melanoma cells were determined by quantitative real-time PCR. The cell growth and cell metastasis were assessed by Cell Counting Kit 8, cell invasion and wound healing assays. Cell apoptosis and cell cycle were determined by flow cytometry. Protein levels were determined by Western blotting assay. Results: H19 was highly expressed in melanoma tissues compared to normal adjacent skin tissues, and the tissue expression level of H19 from melanoma patients with metastasis was significantly higher than that from patients without distant metastasis. In addition, the high expression of H19 in melanoma tissues was associated with advanced tumor invasion and TNM stage, distal metastasis, lymph node metastasis and shorter overall survival in patients with melanoma. The in vitro functional assays showed that knockdown of H19 inhibited cell growth, invasion and migration and also induced cell apoptosis as well as G0/G1 arrest in melanoma cells. Further quantitative real-time PCR and Western blot experiments showed that knockdown of H19 differentially regulated the epithelial–mesenchymal transition (EMT-related gene expressions and reversed EMT in melanoma cell lines. Knockdown of H19 suppressed in vivo tumor growth and modulated the

  7. Notwithstanding High Prevalence of Overweight and Obesity, Smoking Remains the Most Important Factor in Poor Self-rated Health and Hospital Use in an Australian Regional Community

    Directory of Open Access Journals (Sweden)

    Helen Mary Haines

    2017-08-01

    Full Text Available Objective: To classify a rural community sample by their modifiable health behaviours and identify the prevalence of chronic conditions, poor self-rated health, obesity and hospital use. Method: Secondary analysis of a cross- sectional self-report questionnaire in the Hume region of Victoria, Australia. Cluster analysis using the two-step method was applied to responses to health behaviour items. Results: 1,259 questionnaires were completed. Overall 63% were overweight or obese. Three groups were identified: ‘Healthy Lifestyle’ (63%, ‘Non Smoking, Unhealthy Lifestyle’ (25% and ‘Smokers’ (12%. ‘Healthy lifestyle’ were older and more highly educated than the other two groups while ‘Non Smoking, Unhealthy Lifestyle’ were more likely to be obese. ‘Smokers’ had the highest rate of poor self-rated health. Prevalence of chronic conditions was similar in each group (>20%. ‘Smokers’ were twice as likely to have had two or more visits to hospital in the preceding year even after adjustment for age, gender and education. Conclusion: High rates of overweight and obesity were identified but ‘Smokers’ were at the greatest risk for poor self-rated health and hospitalisation. Implications for Public Health: Within an environment of high rates of chronic ill health and obesity, primary care clinicians and public health policy makers must maintain their vigilance in encouraging people to quit smoking.

  8. 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

  9. Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis

    Science.gov (United States)

    Majumdar, Gaurav; Majumdar, Abha; Lall, Meena; Verma, Ishwar C.; Upadhyaya, Kailash C.

    2016-01-01

    CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case–control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis. PMID:27382234

  10. 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 ... poor prognosis if the cancer is harder to control. Whatever your doctor tells you, keep in mind ...

  11. 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...

  12. 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.

  13. Elevated tumor-to-liver uptake ratio (TLR) from 18F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    International Nuclear Information System (INIS)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin; Duan, Yinghua; Zhang, Zhanwen; Hu, Ping; Wang, Xiaoyan

    2017-01-01

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from 18 F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent 18 F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative 18 F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with elevated TLR. Cox

  14. Elevated tumor-to-liver uptake ratio (TLR) from {sup 18}F-FDG-PET/CT predicts poor prognosis in stage IIA colorectal cancer following curative resection

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jun; Huang, Liang; Zhou, Jiaming; Huang, Pinzhu; Tan, Shuyun; Wang, Jianping; Huang, Meijin [6th Affiliated Hospital, Sun Yat-sen University, Department of Colorectal Surgery, Guangzhou, Guangdong (China); Duan, Yinghua [1st Affiliated Hospital, Sun Yat-sen University, Department of Traditional Chinese Medicine, Guangzhou (China); Zhang, Zhanwen; Hu, Ping [6th Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China); Wang, Xiaoyan [1st Affiliated Hospital, Sun Yat-sen University, Department of Nuclear Medicine, Guangzhou (China)

    2017-11-15

    The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from {sup 18}F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent {sup 18}F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative {sup 18}F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with

  15. 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.

  16. A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604).

    Science.gov (United States)

    Huddart, Robert A; Gabe, Rhian; Cafferty, Fay H; Pollock, Philip; White, Jeff D; Shamash, Jonathan; Cullen, Michael H; Stenning, Sally P

    2015-03-01

    Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required. To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial. We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres. BEP (bleomycin 30,000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15,000 IU). Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates. A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61-85) with CBOP/BEP, 61% with BEP (90% CI, 48-73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33-1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS. The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data

  17. If you had less than a year to live, would you want to know? A seven-country European population survey of public preferences for disclosure of poor prognosis.

    Science.gov (United States)

    Harding, R; Simms, V; Calanzani, N; Higginson, I J; Hall, S; Gysels, M; Meñaca, A; Bausewein, C; Deliens, L; Ferreira, P; Toscani, F; Daveson, B A; Ceulemans, L; Gomes, B

    2013-10-01

    With increasing European cancer deaths, clinicians must manage information regarding poor prognosis. This study aimed to determine European citizens' preferences, within a scenario of serious illness such as cancer with less than a year to live, for information disclosure regarding poor prognosis, the likely symptoms and problems, and the care options available, to measure variations between countries and to identify factors associated with preferences. A population-based cross-national telephone survey using random digit dialling in seven countries was conducted. Among 9344 respondents, data revealed an international preference (73.9%) to always be informed in the scenario of having a serious illness such as cancer with less than a year to live. This varied from 67.6% in Italy to 80.7% in Flanders. A minority (21.1%) did not want such information unless they ask, or at all. People younger than 70 years (OR 0.72, 95% CI 0.62-0.83, p < 0.001), men (OR 1.23, 95% CI 1.10-1.37, p < 0.001), those with experience of illness (OR = 1.20. 95% CI 1.01-1.43, p < 0.05) and with more education (OR = 1.20, 95% CI 1.09-1.32, p < 0.001) were more likely to want to know of limited time left. The models confirmed the influence of four factors in more than one country (age, gender, education and most concerning problem) and added 11 country-specific factors to which national policies and clinical practice should respond. These findings confirm a majority public preference to be informed in a scenario of poor prognosis. Policy clinical practice should facilitate elucidation and delivery of preferences. Evidence for effective communication skills-building interventions for clinicians is required. Copyright © 2013 John Wiley & Sons, Ltd.

  18. MicroRNA-218 functions as a tumor suppressor in lung cancer by targeting IL-6/STAT3 and negatively correlates with poor prognosis.

    Science.gov (United States)

    Yang, Yan; Ding, Lili; Hu, Qun; Xia, Jia; Sun, Junjie; Wang, Xudong; Xiong, Hua; Gurbani, Deepak; Li, Lianbo; Liu, Yan; Liu, Aiguo

    2017-08-22

    Aberrant expression of microRNAs in different human cancer types has been widely reported. MiR-218 acts as a tumor suppressor in diverse human cancer types impacting regulation of multiple genes in oncogenic pathways. Here, we evaluated the expression and function of miR-218 in human lung cancer and ALDH positive lung cancer cells to understand the potential mechanisms responsible for disease pathology. Also, the association between its host genes and the target genes could be useful towards the better understanding of prognosis in clinical settings. Publicly-available data from The Cancer Genome Atlas (TCGA) was mined to compare the levels of miR-218 and its host gene SLIT2/3 between lung cancer tissues and normal lung tissues. Transfection of miR-218 to investigate its function in lung cancer cells was done and in vivo effects were determined using miR-218 expressing lentiviruses. Aldefluor assay and Flow cytometry was used to quantify and enrich ALDH positive lung cancer cells. Levels of miR-218, IL-6R, JAK3 and phosphorylated STAT3 were compared in ALDH1A1 positive and ALDH1A1 negative cells. Overexpression of miR-218 in ALDH positive cells was carried to test the survival by tumorsphere culture. Finally, utilizing TCGA data we studied the association of target genes of miR-218 with the prognosis of lung cancer. We observed that the expression of miR-218 was significantly down-regulated in lung cancer tissues compared to normal lung tissues. Overexpression of miR-218 decreased cell proliferation, invasion, colony formation, and tumor sphere formation in vitro and repressed tumor growth in vivo. We further found that miR-218 negatively regulated IL-6 receptor and JAK3 gene expression by directly targeting the 3'-UTR of their mRNAs. In addition, the levels of both miR-218 host genes and the components of IL-6/STAT3 pathway correlated with prognosis of lung cancer patients. MiR-218 acts as a tumor suppressor in lung cancer via IL-6/STAT3 signaling pathway

  19. Long non-coding RNA taurine-upregulated gene 1 correlates with poor prognosis, induces cell proliferation, and represses cell apoptosis via targeting aurora kinase A in adult acute myeloid leukemia.

    Science.gov (United States)

    Wang, Xinfeng; Zhang, Lina; Zhao, Fan; Xu, Ruirong; Jiang, Jie; Zhang, Chenglu; Liu, Hong; Huang, Hongming

    2018-04-13

    This study aimed to investigate the correlation of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) with clinicopathological feature and prognosis, and to explore its effect on cell proliferation and apoptosis as well as the relevant target genes in adult acute myeloid leukemia (AML). LncRNA TUG1 expression was detected in bone marrow samples from 186 AML patients and 62 controls. Blank mimic, lncRNA TUG1 mimic, blank inhibitor, and lncRNA TUG1 inhibitor lentivirus vectors were transfected in KG-1 cells. Rescue experiment was performed by transfection of lncRNA TUG1 inhibitor and aurora kinase A (AURKA) mimic lentivirus vectors. Cell proliferation, apoptosis, RNA, and protein expressions were determined by CKK-8, annexin V-FITC-propidium iodide, quantitative polymerase chain reaction, and western blot assays. LncRNA TUG1 expression was higher in AML patients compared to controls and correlated with higher white blood cell counts, monosomal karyotype, FLT3-ITD mutation, poor-risk stratification, and poor prognosis, which independently predicted worse event-free survival and overall survival. In vitro, lncRNA TUG1 expression was higher in AML cell lines (KG-1, MOLM-14, HL-60, NB-4, and THP-1 cells) compared to controls. LncRNA TUG1 mimic promoted cell proliferation and decreased cell apoptosis rate, while lncRNA TUG1 inhibitor repressed cell proliferation and increased cell apoptosis rate. Rescue experiment showed that AURKA attenuated the influence of lncRNA TUG1 on AML cell proliferation and apoptosis. In conclusion, lncRNA TUG1 associates with advanced disease and worse prognosis in adult AML patients, and it induces AML cell proliferation and represses cell apoptosis via targeting AURKA.

  20. 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

  1. 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

  2. Baseline β-catenin, programmed death-ligand 1 expression and tumour-infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor-treated melanoma patients.

    Science.gov (United States)

    Massi, Daniela; Romano, Emanuela; Rulli, Eliana; Merelli, Barbara; Nassini, Romina; De Logu, Francesco; Bieche, Ivan; Baroni, Gianna; Cattaneo, Laura; Xue, Gongda; Mandalà, Mario

    2017-06-01

    The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome. Quantitative assessment of mRNA transcripts associated with Wnt/β-catenin pathway and immune response was performed in 51 patients. We found an inverse correlation between tumoural β-catenin expression and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio, OR 0.12, 95% confidence interval, CI 0.03-0.53, p = 0.005) and the presence of CD8+ T cells (OR 18.27, 95%CI 2.54-131.52, p = 0.004) were significantly associated with a higher probability of response to MAPKi monotherapy. Responding patients showed a significantly increased expression of mRNA transcripts associated with adaptive immunity and antigen presentation. By multivariate analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10-0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09-0.67, p = 0.006) were longer in patients with high density of CD8+ T cells and β-catenin <10% than those without CD8+ T cells infiltration and β-catenin ≥10%. Our findings provide evidence that in the context of MAPKi monotherapy, immune subsets in the (TME) and

  3. Clinicopathologic and gene expression parameters predict liver cancer prognosis

    International Nuclear Information System (INIS)

    Hao, Ke; Zhong, Hua; Greenawalt, Danielle; Ferguson, Mark D; Ng, Irene O; Sham, Pak C; Poon, Ronnie T; Molony, Cliona; Schadt, Eric E; Dai, Hongyue; Luk, John M; Lamb, John; Zhang, Chunsheng; Xie, Tao; Wang, Kai; Zhang, Bin; Chudin, Eugene; Lee, Nikki P; Mao, Mao

    2011-01-01

    The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model. Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction. HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis. When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome

  4. The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

    International Nuclear Information System (INIS)

    Kang, Chung-Jan; Lin, Chien-Yu; Wang, Hung-Ming; Fan, Kang-Hsing; Ng, Shu-Hang; Lee, Li-Yu; Chen, I-How; Huang, Shiang-Fu

    2011-01-01

    Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes (≥4 vs. ≤3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of ≥11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth ≥11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.

  5. 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.

  6. Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer.

    Science.gov (United States)

    Jie, Ding; Zhongmin, Zhang; Guoqing, Liao; Sheng, Liu; Yi, Zhang; Jing, Wen; Liang, Zeng

    2013-06-01

    The first identified lysine-specific demethylase, LSD1, plays an important role in the metastatic progression of several types of cancer. The aim of this study was to investigate LSD1, E-cadherin, and N-cadherin expression in colon cancer specimens and their clinical significance. The expression of LSD1, E-cadherin, and N-cadherin in colon cancer specimens was determined by immunohistochemistry, and the relationship between the expression of the respective molecules and clinicopathological characteristics was analyzed. The positive expression rates of LSD1, E-cadherin, and N-cadherin in colon cancer specimens were 66.7 % (72/108), 85.2 % (92/108), and 41.7 % (45/108), respectively. LSD1 was significantly more highly expressed in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P clinical and pathological characteristics (P > 0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression (r s = -0.318, P = 0.001), but not evidently correlated with N-cadherin expression (r s = 0.182, P = 0.06). Colon cancer specimens with positive LSD1 expression and negative E-cadherin expression were correlated with significantly lower overall survival. LSD1 showed a significantly higher expression, in contrast to the significantly lower expression of E-cadherin, in colon cancer specimens classified as high TNM stage lesions and with distant metastasis. Positive expression of LSD1 and negative expression of E-cadherin may be predictors of a worse colon cancer prognosis.

  7. 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

  8. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  9. Long non-coding RNA CCAT2 is associated with poor prognosis in hepatocellular carcinoma and promotes tumor metastasis by regulating Snail2-mediated epithelial–mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Xu Y

    2017-02-01

    Full Text Available Yongfu Xu,* Binfeng Wang,* Fabiao Zhang, Aidong Wang, Xuefeng Du, Peng Hu, Yu Zhu, Zheping Fang Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China *These authors contributed equally to this work Abstract: Increasing evidence has demonstrated that aberrant expressions of long non-coding RNAs (lncRNAs are involved in various malignancies, including hepatocellular carcinoma (HCC. This study aimed to investigate the role of lncRNA colon cancer-associated transcript 2 (CCAT2 in the progression of HCC. Quantitative real-time polymerase chain reaction analysis confirmed that CCAT2 was upregulated in HCC cell lines and cancerous tissues compared with normal liver cell line and adjacent normal tissue samples. The level of CCAT2 was positively associated with tumor–node–metastasis stages and vessel invasion. Survival analyses revealed that high CCAT2 expression predicted poor prognostic outcomes, serving as an independent prognostic factor for HCC patients. Patients with high CCAT2 expression had a 1.849-fold increased risk of death compared with those with low CCAT2 expression. Moreover, we also found that knockdown of CCAT2 expression reduced cell migration and invasion in vitro. We further demonstrated that CCAT2 played a key role in enhancing the epithelial–mesenchymal transition (EMT through the regulation of vimentin, E-cadherin and transcription factor snail2 expression. Taken together, our findings showed that high CCAT2 expression is associated with poor survival in HCC patients. CCAT2 promotes HCC progression by regulating Snail2-induced EMT. CCAT2 may be a prognostic biomarker and therapeutic target for HCC. Keywords: long non-coding RNA, CCAT2, hepatocellular carcinoma, epithelial–mesenchymal transition, survival

  10. The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition

    OpenAIRE

    Sun, Junfeng; Ding, Chaohui; Yang, Zhen; Liu, Tao; Zhang, Xiefu; Zhao, Chunlin; Wang, Jiaxiang

    2016-01-01

    Background Long intergenic non-coding RNAs (lncRNAs) are a class of non-coding RNAs that are involved in gene expression regulation. Taurine up-regulated gene 1 (TUG1) is a cancer progression related lncRNA in some tumor oncogenesis; however, its role in colorectal cancer (CRC) remains unclear. In this study, we determined the expression patterns of TUG1 in CRC patients and explored its effect on CRC cell metastasis using cultured representative CRC cell lines. Methods The expression levels o...

  11. 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

    screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin's lymphomas (NHLs). On the basis of p53 gene mutation status and immunohistochemically detected p53 and p21Waf1 expression in 34 lymphomas, we established an immunophenotype (delta p53......) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry and was correlated with clinical parameters. Delta p53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis...... of advanced stage lymphomas showed that delta p53 was independently associated with treatment failure (relative risk, 3.8; P = 0.001). Delta p53 predicted poor survival when analyzing all patients (P = 0.0001), as well as B-cell (P = 0.04) and T-cell NHL (P = 0.000002). In multivariate analysis, delta p53...

  12. Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.

    Science.gov (United States)

    Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P; Iacobuzio-Donahue, Christine A; Kerner, Zachary; Baylin, Stephen B; Wolfgang, Christopher L; Ahuja, Nita

    2016-12-27

    We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes.

  13. High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation.

    Science.gov (United States)

    Shen, Chao-Qin; Yan, Ting-Ting; Liu, Wei; Zhu, Xiao-Qiang; Tian, Xiang-Long; Fu, Xue-Liang; Hua, Rong; Zhang, Jun-Feng; Huo, Yan-Miao; Liu, De-Jun; Yang, Jian-Yu; Sun, Yong-Wei; Fang, Jing-Yuan; Chen, Hao-Yan; Hong, Jie

    2017-01-01

    FAM83B (family with sequence similarity 83, member B) seems to emerge as a new class of players involved in the development of a variety of malignant tumors. Yet the molecular mechanisms are not well understood. The present study is intended to investigate the expression and function of FAM83B in pancreatic ductal adenocarcinoma (PDAC). In this study, we found that the expression of FAM83B was significantly increased both in PDAC cell lines and PDAC tumor tissues. FAM83B expression was positively related with advanced clinical stage and poor vital status. Higher FAM83B expression predicted shorter overall survival in PDAC patients, regardless of lymphatic metastasis status and histological differentiation. Actually, FAM83B may act as an independent prognostic indicator as well. What's more, down-regulation of FAM83B in PDAC cells contributed to G0/G1 phase arrest and inhibition of cell proliferation. Finally, a subcutaneous xenograft model indicated that knockdown of FAM83B significantly reduced the tumor volume in vivo . Our findings have provided supporting evidence for the potential molecular biomarker role of FAM83B in PDAC. It's of great interest and broad significance to target FAM83B in PDAC, which may conduce to develop a meaningful and effective strategy in the diagnosis and treatment of PDAC.

  14. High preoperative serum CA19-9 level is predictive of poor prognosis for patients with colorectal liver oligometastases undergoing hepatic resection.

    Science.gov (United States)

    Lu, Zhenhai; Peng, Jianhong; Wang, Zhiqiang; Pan, Zhizhong; Yuan, Yunfei; Wan, Desen; Li, Binkui

    2016-11-01

    Oligometastasis is defined as a transitional state between localized and widespread systemic metastatic cancers. In colorectal cancer, the prognostic factors and prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for patients with colorectal liver oligometastases (CLOM) undergoing hepatic resection have not been well explored. Therefore, the present study included 141 patients with CLOM (≤5 liver metastases) who underwent R0 resection from 2005 to 2012. The association of clinicopathological factors including preoperative CA19-9 and CEA levels with overall survival (OS) was analyzed with univariate and multivariate analyses. Kaplan-Meier analysis showed that patients with high CA19-9 levels tended to have poorer OS than those with low levels (median OS 21.5 vs. 64.0 months, P = 0.002). Preoperative CEA levels were not significantly associated with OS (P > 0.05). Univariate and multivariate analyses demonstrated that larger tumor size of liver metastases (HR 1.911; 95 % CI 1.172-3.114; P = 0.009), bilobar distribution (HR 1.776; 95 % CI 1.097-2.873; P = 0.019), and higher preoperative CA19-9 levels (HR 1.954; 95 % CI 1.177-3.242; P = 0.010) were independent predictors of poor OS for patients with CLOM. Our study identified tumor size, distribution, and preoperative CA19-9 levels as independent prognostic factors for OS of patients with CLOM. In particular, measurement of preoperative CA19-9 levels offers an easy tool that could help identify high-risk patients and aid in improving the management of patients with CLOM.

  15. PRRX2 as a novel TGF-β-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer.

    Science.gov (United States)

    Juang, Yu-Lin; Jeng, Yung-Ming; Chen, Chi-Long; Lien, Huang-Chun

    2016-12-01

    TGF-β and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-β biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-β continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-β and identified TGF-β-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage-independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by partial fibroblastoid morphology of cells, upregulation of EMT markers and partially disrupted acinar structure in a three-dimensional culture. We further identified PLAT, the gene encoding tissue-type plasminogen activator (tPA), as the highest differentially expressed gene in PRRX2-overexpressing MCF10A cells, and demonstrated direct binding and transactivation of the PLAT promoter by PRRX2. Furthermore, PLAT knockdown inhibited PRRX2-mediated enhanced migration and invasion, suggesting that tPA may mediate PRRX2-induced migration and invasion. Finally, the significant correlation of PRRX2 expression with poor survival in 118 primary breast tumour samples (P = 0.027) and the increased PRRX2 expression in metaplastic breast carcinoma samples, which is pathogenetically related to EMT, validated the biological importance of PRRX2-enhanced migration and invasion and PRRX2-induced EMT. Thus, our data suggest that upregulation of PRRX2 may be a mechanism contributing to TGF-β-induced invasion and EMT in breast cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. 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.

  17. Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer.

    Science.gov (United States)

    Namani, Akhileshwar; Matiur Rahaman, Md; Chen, Ming; Tang, Xiuwen

    2018-01-06

    NRF2 is the key regulator of oxidative stress in normal cells and aberrant expression of the NRF2 pathway due to genetic alterations in the KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2 like 2)-CUL3 (cullin 3) axis leads to tumorigenesis and drug resistance in many cancers including head and neck squamous cell cancer (HNSCC). The main goal of this study was to identify specific genes regulated by the KEAP1-NRF2-CUL3 axis in HNSCC patients, to assess the prognostic value of this gene signature in different cohorts, and to reveal potential biomarkers. RNA-Seq V2 level 3 data from 279 tumor samples along with 37 adjacent normal samples from patients enrolled in the The Cancer Genome Atlas (TCGA)-HNSCC study were used to identify upregulated genes using two methods (altered KEAP1-NRF2-CUL3 versus normal, and altered KEAP1-NRF2-CUL3 versus wild-type). We then used a new approach to identify the combined gene signature by integrating both datasets and subsequently tested this signature in 4 independent HNSCC datasets to assess its prognostic value. In addition, functional annotation using the DAVID v6.8 database and protein-protein interaction (PPI) analysis using the STRING v10 database were performed on the signature. A signature composed of a subset of 17 genes regulated by the KEAP1-NRF2-CUL3 axis was identified by overlapping both the upregulated genes of altered versus normal (251 genes) and altered versus wild-type (25 genes) datasets. We showed that increased expression was significantly associated with poor survival in 4 independent HNSCC datasets, including the TCGA-HNSCC dataset. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and PPI analysis revealed that most of the genes in this signature are associated with drug metabolism and glutathione metabolic pathways. Altogether, our study emphasizes the discovery of a gene signature regulated by the KEAP1-NRF2-CUL3 axis which is strongly associated with

  18. Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57.

    Science.gov (United States)

    Zhang, E; He, X; Yin, D; Han, L; Qiu, M; Xu, T; Xia, R; Xu, L; Yin, R; De, W

    2016-02-25

    Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC.

  19. Decreased expression of miR‑490‑3p in colorectal cancer predicts poor prognosis and promotes cell proliferation and invasion by targeting RAB14.

    Science.gov (United States)

    Wang, Bo; Yin, Mujun; Cheng, Cheng; Jiang, Hongpeng; Jiang, Kewei; Shen, Zhanlong; Ye, Yingjiang; Wang, Shan

    2018-06-19

    Growing evidence indicates a potential role for miR‑490‑3p in tumorigenesis. However, its function in colorectal carcinoma (CRC) remains undefined. In this study, miR‑490‑3p was markedly downregulated in fifty colorectal cancer tissue samples compared with the corresponding adjacent non‑cancerous specimens, by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of miR‑490‑3p were closely associated with tumor differentiation and distant metastasis. In addition, both Kaplan-Meier and multivariate analyses indicated CRC patients with elevated miR‑490‑3p amounts had prolonged overall survival. Overexpression of miR‑490‑3p markedly reduced proliferation, colony formation and invasion in CRC cells by enhancing apoptosis and promoting G2/M phase arrest. Furthermore, ectopic expression of miR‑490‑3p resulted in decreased expression of RAB14, which was directly targeted by miR‑490‑3p, as shown by the dual-luciferase reporter gene assay. Finally, in a nude mouse model, miR‑490‑3p overexpression significantly suppressed the growth of CRC cells. The above results indicated that miR‑490‑3p might constitute a prognostic indicator and a novel molecular target for miRNA-based CRC therapy.

  20. Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients

    International Nuclear Information System (INIS)

    Walker, B A; Wardell, C P; Brioli, A; Boyle, E; Kaiser, M F; Begum, D B; Dahir, N B; Johnson, D C; Ross, F M; Davies, F E; Morgan, G J

    2014-01-01

    Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including IGH, IGK and IGL, which juxtapose the immunoglobulin (Ig) enhancers next to MYC in 8/23 samples. The remaining samples had partner loci including XBP1, FAM46C, CCND1 and KRAS, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of MYC in these samples. Patients with MYC translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near MYC result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of MYC and an aggressive disease phenotype

  1. The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition.

    Science.gov (United States)

    Sun, Junfeng; Ding, Chaohui; Yang, Zhen; Liu, Tao; Zhang, Xiefu; Zhao, Chunlin; Wang, Jiaxiang

    2016-02-08

    Long intergenic non-coding RNAs (lncRNAs) are a class of non-coding RNAs that are involved in gene expression regulation. Taurine up-regulated gene 1 (TUG1) is a cancer progression related lncRNA in some tumor oncogenesis; however, its role in colorectal cancer (CRC) remains unclear. In this study, we determined the expression patterns of TUG1 in CRC patients and explored its effect on CRC cell metastasis using cultured representative CRC cell lines. The expression levels of TUG1 in 120 CRC patients and CRC cells were determined using quantitative real-time PCR. HDACs and epithelial-mesenchymal transition (EMT)-related gene expression were determined using western blot. CRC cell metastasis was assessed by colony formation, migration assay and invasion assay. Our data showed that the levels of TUG1 were upregulated in both CRC cell lines and primary CRC clinical samples. TUG1 upregulation was closely correlated with the survival time of CRC patients. Overexpression of TUG1 in CRC cells increased their colony formation, migration, and invasion in vitro and promoted their metastatic potential in vivo, whereas knockdown of TUG1 inhibited the colony formation, migration, and invasion of CRC cells in vitro. It is also worth pointing out that TUG1 activated EMT-related gene expression. Our data suggest that tumor expression of lncRNA TUG1 plays a critical role in CRC metastasis. TUG1 may have potential roles as a biomarker and/or a therapeutic target in colorectal cancer.

  2. IκBζ, an atypical member of the inhibitor of nuclear factor kappa B family, is induced by γ-irradiation in glioma cells, regulating cytokine secretion and associated with poor prognosis.

    Science.gov (United States)

    Brennenstuhl, Heiko; Armento, Angela; Braczysnki, Anne Kristin; Mittelbronn, Michel; Naumann, Ulrike

    2015-11-01

    The inhibitor of nuclear factor kappa B zeta (IκBζ) is an atypical member of the IκB protein family. Its function in regulating the activity of the transcription factor nuclear factor kappa B (NFκB) as well as its involvement in cancer-associated processes is poorly understood. In glioma patients, enhanced expression of IκBζ in tumor specimen is associated with poor prognosis. Here we report that IκBζ is upregulated in a glioma cell line resistant towards NFκB-dependent non-apoptotic cell death. Upon γ-irradiation of glioma cells, IκBζ expression is enhanced, and subsequently serves as a transcriptional activator of the tumor promoting cytokines interleukin (IL-6), IL-8 and chemokine (C-X-C motif) ligand 1 (CXCL1) that are known to be involved in glioma associated inflammatory processes. In contrast, shRNA-mediated knockdown of IκBζ reduces the expression of the aforementioned cytokines. We propose a previously unappreciated role of IκBζ in the inflammatory micromilieu as well as progression in glioma.

  3. 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.

  4. 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

  5. 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 .

  6. Evaluación de la válvula de Ahmed en el glaucoma de mal pronóstico quirúrgico Evaluation of Ahmed valve in the glaucoma of poor surgical prognosis

    Directory of Open Access Journals (Sweden)

    Francisco García González

    2001-12-01

    Full Text Available Se intervinieron 8 pacientes con glaucoma de mal pronóstico quirúrgico a los que se les implantaron una válvula de Ahmed con la técnica quirúrgica convencional. Se logró controlar la presión intraocular (PIO. Las complicaciones fueron: hipotonía (75 %, desprendimiento coroideo (37,5 %, hifema (25,0 %, contacto tubo iridiano (25, 0 %, hipotalamia (12,5 % y congestión en el área del implante (12,5 %. No hubo complicaciones intraoperatorias. Se obtuvieron resultados satisfactorios a mediano plazo.8 patients with glaucoma of poor surgical prognosis were implanted an Ahmed valve by using the conventional surgical technique. It was possible to control the intraocular pressure (IOP. The complications were: hypotony (75 %, choroidal detachment (37.5 %, hyphaemia (25.0 %, contact with the iridian tube (25.0 %, hypothalamia (12.5 % and congestion in the area of the implantation (12.5 %. There were no intraoperative complications. Medium term results were satisfactory.

  7. 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.

  8. Mitogen activated protein kinase kinase kinase 3 (MAP3K3/MEKK3) overexpression is an early event in esophageal tumorigenesis and is a predictor of poor disease prognosis

    International Nuclear Information System (INIS)

    Hasan, Raghibul; Sharma, Rinu; Saraya, Anoop; Chattopadhyay, Tushar K; DattaGupta, Siddartha; Walfish, Paul G; Chauhan, Shyam S; Ralhan, Ranju

    2014-01-01

    Mitogen-activated protein kinase kinase kinase3 (MAP3K3/MEKK3) was identified to be differentially expressed in esophageal squamous cell carcinoma (ESCC) using cDNA microarrays by our laboratory. Here in we determined the clinical significance of MEKK3 in ESCC. Immunohistochemical analysis of MEKK3 expression was carried out in archived tissue sections from 93 ESCCs, 47 histologically normal and 61 dysplastic esophageal tissues and correlated with clinicopathological parameters and disease prognosis over up to 7.5 years for ESCC patients. MEKK3 expression was significantly increased in esophageal dysplasia and ESCC in comparison with normal mucosa (p trend < 0.001). Kaplan Meier survival analysis showed significantly reduced median disease free survival median DFS = 10 months in patients with MEKK3 positive ESCCs compared to patients with no immunopositivity (median DFS = 19 months, p = 0.04). ESCC patients with MEKK3 positive and lymph node positive tumors had median DFS = 9 months, as compared to median DFS = 21 months in patients who did not show the alterations (p = 0.01). In multivariate Cox regression analysis, combination of MEKK3 overexpression and node positivity [p = 0.015, hazard ratio (HR) = 2.082, 95% CI = 1.154 - 3.756] emerged as important predictor of reduced disease free survival and poor prognosticator for ESCC patients. Alterations in MEKK3 expression occur in early stages of development of ESCC and are sustained during disease progression; MEKK3 in combination with lymph node positivity has the potential to serve as adverse prognosticator in ESCC

  9. 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 ...

  10. 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 ...

  11. Understanding Your Cancer Prognosis

    Science.gov (United States)

    Understanding Your Cancer Prognosis is the main video in the NCI Prognosis Video Series, which offers the perspectives of three cancer patients and their doctor, an oncologist who is also a national expert in doctor-patient communication.

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... your situation is in the best position to discuss your prognosis and explain what the statistics may ... situation best is in the best position to discuss your prognosis. Survival statistics most often come from ...

  17. Sugarcane outgrowers in Ethiopia: ’Forced’ to remain poor?

    OpenAIRE

    Mengistu Assefa Wendimu; Arne Henningsen; Peter Gibbon

    2015-01-01

    Contract farming is often seen as a panacea to many of the challenges faced by agricultural production in developing countries. Given the large heterogeneity of contract farming arrangements, it is debatable whether all kinds of contract farming arrangements offer benefits to participating smallholders. We apply matching methods to analyze the effects of a public sugarcane outgrower scheme in Ethiopia. Participation in the outgrower scheme significantly reduces the income and asset stocks of ...

  18. Care seeking for maternal health: challenges remain for poor women

    African Journals Online (AJOL)

    Data were analysed using Nudist software. Important findings: The location of childbirth involves retaining control of the process and outcome, and securing a safe delivery. The pregnant woman is influenced by her attendants; families only seek care for complications if local or herbal, remedies and prayer are defeated.

  19. Care seeking for maternal health: challenges remain for poor women

    African Journals Online (AJOL)

    Bernt Lindtjorn

    Timely care seeking is reliant on the knowledge, understanding and financial ... on the relative heterogeneity and security situation of that region. ... adolescent girls and boys, newly delivered mothers, older ... such as the mother in-law or older sister in-laws. The main overriding factors that contribute to the decisions and ...

  20. Cerebral circulation and prognosis of the patients with hypoxic encephalopathy

    International Nuclear Information System (INIS)

    Nogami, Kenichiro; Fujii, Masami; Kashiwagi, Shiro; Sadamitsu Daikai; Maekawa, Tsuyoshi

    2000-01-01

    Recent progress in cardiopulmonary resuscitation techniques improved the survival rate of patients with acute cardiopulmonary disturbances. However, severe cerebral complications remained frequently in patients who survived the acute stage. Early prediction of cerebral prognosis is important to optimize the management of these patients. We examined the relations between radiological findings (Xe-CT and MRI) and cerebral prognosis. Patients included in this study were selected from all patients with hypoxic encephalopathy admitted to our hospital. There were 11 men and 10 women. Causes of hypoxic encephalopathy were heart disease (11 cases), suffocation (4 cases), CO intoxication (2 cases), asthma (1 case), pneumothorax (1 case), anaphyraxy shock (1 case) and electric shock (1 case). Xe-CT and MRI were carried out 3 weeks after the onset. Cerebral blood flow (CBF) of the patients was measured at rest and 15 minutes after intravenous administration of acetazolamide (1 g). The prognosis was evaluated 3 months after the onset in accordance with Glasgow Outcome Scale (GOS). Low hemispheric CBF (30 ml/100 g/min), poor reactivity of acetazolamide challenge test (10 ml/100 g/min), presence of hyperintensity areas in the basal ganglia in T1 weighted images (T1WI) and T2 weighted images (T2WI) are the factors associated with poor outcome in hypoxic encephalopathy. (author)

  1. High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.

    Directory of Open Access Journals (Sweden)

    Makoto Emori

    Full Text Available Epithelioid sarcoma (ES is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high cells correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009. In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.

  2. Prognosis and submandibular gland function

    International Nuclear Information System (INIS)

    Ino, Chiyonori; Yamashita, Toshio; Hanaoka, Mako; Kumazawa, Tadami

    1984-01-01

    Submandibular gland function was tested with sup(99m)Tc-pertechnetate scan 10 days and 3-4 weeks after the onset Bell's palsy, and the results and prognoses were correlated. In the first report we divided the cases into groups A, B and C, and this time group D classified in S.S.R. was poor. Groups A and D can be differentiated by submandibular gland scan within 10 days after the onset; that is to say, the prognosis of more than half the cases can be determined in this early phase. Especially, it is noticeable that group D showing the poor prognosis is differentiated within 10 days after the onset. This method was compared with other tests of facial palsy. Four to five weeks after the onset all tests were of equal accuracy in predicting the prognosis of each group. Within 10 days after the onset, however, submandibular gland scan seems to be more useful than the other tests. (author)

  3. Poor Prognosis of Lower Inner Quadrant in Lymph Node-negative Breast Cancer Patients Who Received No Chemotherapy: A Study Based on Nationwide Korean Breast Cancer Registry Database.

    Science.gov (United States)

    Hwang, Ki-Tae; Kim, Jongjin; Kim, Eun-Kyu; Jung, Sung Hoo; Sohn, Guiyun; Kim, Seung Il; Jeong, Joon; Lee, Hyouk Jin; Park, Jin Hyun; Oh, Sohee

    2017-07-01

    We aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer. Data of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer-specific survival (BCSS) according to primary tumor site. Central portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P < .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P < .001) and 1.215 (95% CI, 1.097-1.345, P < .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P < .001). For lymph node-negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P < .001), but that effect disappeared in the subgroup with chemotherapy (P = .058). LIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node-negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil; Thompson, Lora M.; Yue, Binglin; Stevens, Craig W.; Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee; Kim, Sungjune; Chiappori, Alberto

    2014-01-01

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause

  5. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dilling, Thomas J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Extermann, Martine [Department of Senior Adult Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Jongphil [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Thompson, Lora M. [Department of Supportive Care Medicine, Moffitt Cancer Center, Tampa, Florida (United States); Yue, Binglin [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Stevens, Craig W. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Sungjune [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Chiappori, Alberto, E-mail: alberto.chiappori@moffitt.org [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States)

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  6. 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.

  7. Presence of pleural effusion is associated with a poor prognosis in patients with epidermal growth factor receptor-mutated lung cancer receiving tyrosine kinase inhibitors as first-line treatment.

    Science.gov (United States)

    Wang, Tso-Fu; Chu, Sung-Chao; Lee, Jen-Jyh; Yang, Gee-Gwo; Huang, Wei-Han; Chang, En-Ting; Low, Tissot; Wu, Yi-Feng; Kao, Ruey-Ho; Lin, Chih-Bin

    2017-08-01

    This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs). Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively. A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively]. The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients. © 2017 John Wiley & Sons Australia, Ltd.

  8. Understanding Cancer Prognosis

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    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 ...

  9. Understanding Cancer Prognosis

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    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 ...

  10. [Impact of postoperative pathological features of esophageal squamous cell carcinoma on the prognosis].

    Science.gov (United States)

    Xu, Lei; Li, Yin; Sun, Haibo; Zheng, Yan; Wang, Zongfei; Chen, Xiankai

    2017-12-25

    Esophageal cancer is located in the 8th position of the incidence of malignant tumors and the 6th most common cause of cancer-related mortality in the world, while China has the highest incidence and mortality of esophageal cancer. Esophageal squamous cell carcinoma (ESCC), the predominant histologic type of esophageal cancer in China, accounts for about 90%. Despite recent improvement of surgical techniques and philosophy, however, the prognosis of ESCC patients treated with surgery is still poor, and 5-year survival remains unsatisfactorily low. So far, the pathogenesis of esophageal squamous cell carcinoma is still unclear, and effective prevention is also out of the question. To find the main factors affecting the prognosis of esophageal squamous cell carcinoma, and to improve the survival of patients, are the main directions of all scholars. Postoperative pathology of esophageal squamous cell carcinoma is considered to be one of the most important predictors of prognosis. Currently, the evaluation of postoperative esophageal prognosis mainly depends on TNM staging, but some criteria of its specific content and staging remains controversial. In this paper recent domestic and foreign related researches and clinical trials reports are collected, and the postoperative pathological features affecting esophageal squamous cell carcinoma prognosis were reviewed.

  11. Mining novel biomarkers for prognosis of gastric cancer with serum proteomics

    Directory of Open Access Journals (Sweden)

    Sui Mei-Hua

    2009-09-01

    Full Text Available Abstract Background Although gastric caner (GC remains the second cause of cancer-related death, useful biomarkers for prognosis are still unavailable. We present here the attempt of mining novel biomarkers for GC prognosis by using serum proteomics. Methods Sera from 43 GC patients and 41 controls with gastritis as Group 1 and 11 GC patients as Group 2 was successively detected by Surface Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0 and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS. CEA level were evaluated by chemiluminescence immunoassay. Results After median follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into 20 good-prognosis GC patients (overall survival more than 24 months and 19 poor-prognosis GC patients (no more than 24 months. The established prognosis pattern consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0% specificity, which were significantly higher than those of carcinoembryonic antigen (CEA and TNM stage. We also tested prognosis pattern blindly in Group 2 with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da peak elevated significantly in GC and was associated with advanced stage (III+IV and short survival (p Conclusion We have identified a number of novel biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak showed very promising to be developed into a novel biomarker associated with biologically aggressive features of GC.

  12. Therapeutic rationale to target highly expressed CDK7 conferring poor outcomes in triple-negative breast cancer

    NARCIS (Netherlands)

    Li, Bo; Chonghaile, Triona Ni; Fan, Yue; Madden, Stephen F.; Klinger, Rut; O'Connor, Aisling E.; Walsh, Louise; O'Hurley, Gillian; Udupi, Girish Mallya; Joseph, Jesuchristopher; Tarrant, Finbarr; Conroy, Emer; Gaber, Alexander; Chin, Suet-Feung; Bardwell, Helen A; Provenzano, Elena; Crown, John; Dubois, Thierry; Linn, Sabine; Jirstrom, Karin; Caldas, Carlos; O'Connor, Darran P; Gallagher, William M

    2017-01-01

    Triple-negative breast cancer (TNBC) patients commonly exhibit poor prognosis and high relapse after treatment, but there remains a lack of biomarkers and effective targeted therapies for this disease. Here, we report evidence highlighting the cell-cycle–related kinase CDK7 as a driver and candidate

  13. 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....

  14. Understanding Cancer Prognosis

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    Full Text Available ... talk about, even for doctors. Many Factors Can Affect Your Prognosis Some of the factors that affect prognosis include: The type of cancer and where ... at the National Institutes of Health FOLLOW US Facebook Twitter Instagram YouTube Google+ LinkedIn GovDelivery RSS CONTACT ...

  15. Understanding Cancer Prognosis

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    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 ...

  16. Understanding Cancer Prognosis

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    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 ... that cancer will come back later. For this reason, doctors cannot say for sure that you are ...

  17. Understanding Cancer Prognosis

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    Full Text Available ... D., a national expert on doctor-patient communications, talks with one of his patients about what she'd like to ... how to discuss cancer prognosis (the likely course of the disease). Learn key points about prognosis and how to talk about it, and gain valuable insight from the ...

  18. Lymphovascular invasion, ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes.

    Science.gov (United States)

    Ma, B; Li, H; Zhang, C; Yang, K; Qiao, B; Zhang, Z; Xu, Y

    2013-10-01

    To identify predictive factors underlying recurrence and survival after partial cystectomy for pelvic lymph node-negative muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) and to report the results of partial cystectomy among select patients. We retrospectively reviewed 101 cases that received partial cystectomy for MIBC (pT2-3N0M0) between 2000 and 2010. The log-rank test and a Cox regression analyses were performed to identify factors that were predictive of recurrence and survival. With a median follow-up of 53.0 months (range 9-120), the 5-year overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were 58%, 65% and 50%, respectively. A total of 33 patients died of bladder cancer and 52 patients survived with intact bladder. Of the 101 patients included, 55 had no recurrence, 12 had non-muscle-invasive recurrence in the bladder that was treated successfully, and 34 had recurrence with advanced disease. The multivariate analysis showed that prior history of urothelial carcinoma (PH.UC) was associated with both CSS and RFS and weakly associated with OS; lymphovascular invasion (LVI) and ureteral reimplantation (UR) were associated with OS, CSS and RFS. Among patients with pelvic lymph node-negative MIBC, PH.UC and UR should be considered as contraindications for partial cystectomy, and LVI is predictive of poor outcomes after partial cystectomy. Highly selective partial cystectomy is a rational alternative to radical cystectomy for the treatment of MIBC with negative pelvic lymph nodes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. 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

    Directory of Open Access Journals (Sweden)

    Rima eMoghnieh

    2015-02-01

    Full Text Available 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 Klebsiellapneumoniae(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 value<0.05.

  20. [PALEOPATHOLOGY OF HUMAN REMAINS].

    Science.gov (United States)

    Minozzi, Simona; Fornaciari, Gino

    2015-01-01

    Many diseases induce alterations in the human skeleton, leaving traces of their presence in ancient remains. Paleopathological examination of human remains not only allows the study of the history and evolution of the disease, but also the reconstruction of health conditions in the past populations. This paper describes the most interesting diseases observed in skeletal samples from the Roman Imperial Age necropoles found in urban and suburban areas of Rome during archaeological excavations in the last decades. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumours, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, the palaeopathological study allowed to highlight the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

  1. Understanding Cancer Prognosis

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    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 ...

  2. Understanding Cancer Prognosis

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    Full Text Available ... your cancer and knowing what to expect can help you and your loved ones make decisions. Some ... what the statistics may mean. If you need help coping with your prognosis, you may find our ...

  3. Understanding Cancer Prognosis

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    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 ...

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    Full Text Available ... to know more, the doctor who knows the most about your situation is in the best position ... statistics may be used to estimate prognosis. The most commonly used statistics include: Cancer-specific survival This ...

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    Full Text Available ... Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer ... need for different kinds of information about her colorectal cancer prognosis. Diving Out of the Dark View ...

  6. Understanding Cancer Prognosis

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    Full Text Available ... treatment Seeking Information About Your Prognosis Is a Personal Decision When you have cancer, you and your ... think they are too impersonal to be of value to you. It is up to you to ...

  7. Understanding Cancer Prognosis

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    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 ...

  8. Understanding Cancer Prognosis

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    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 ...

  9. Understanding Cancer Prognosis

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    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. ...

  10. Understanding Cancer Prognosis

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    Full Text Available ... D., a national expert on doctor-patient communications, talks with one of his patients about what she' ... understand what prognosis means and also hard to talk about, even for doctors. Many Factors Can Affect ...

  11. Understanding Cancer Prognosis

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    Full Text Available ... that cancer will come back later. For this reason, doctors cannot say for sure that you are ... about how to discuss prognosis with their patients. Good communication, he says, is part of providing good ...

  12. Understanding Cancer Prognosis

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    Full Text Available ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... Staging Prognosis Questions to Ask ... This statistic is another method used to estimate cancer-specific survival that does ...

  13. Understanding Cancer Prognosis

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    Full Text Available ... how to discuss prognosis with their patients. Good communication, he says, is part of providing good ... Please note that blog posts that are written by individuals from outside the ...

  14. Understanding Cancer Prognosis

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    Full Text Available ... to deal with financial and legal matters Many people want to know their prognosis. They find it ... that researchers have collected over many years about people with the same type of cancer. Several types ...

  15. Understanding Cancer Prognosis

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    Full Text Available ... spread. Certain traits of the cancer cells Your age and how healthy you were before cancer How ... how to discuss prognosis with their patients. Good communication, he says, is part of providing good care. ...

  16. Understanding Cancer Prognosis

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    Full Text Available ... Many people want to know their prognosis. They find it easier to cope when they know more ... this information on your own. Or, you may find statistics confusing and frightening, and think they are ...

  17. Understanding Cancer Prognosis

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    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. ...

  18. Understanding your cancer prognosis

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    ... about: Treatment Palliative care Personal matters such as finances Knowing what to expect may make it easier ... treatment. www.cancer.net/navigating-cancer-care/cancer-basics/understanding-statistics-used-guide-prognosis-and-evaluate-treatment . ...

  19. Understanding Cancer Prognosis

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    Full Text Available ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Funding for ... Staging Prognosis Questions to Ask about ... This statistic is another method used to estimate cancer-specific survival that does ...

  20. Understanding Cancer Prognosis

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    Full Text Available ... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... Staging Prognosis Questions to Ask about ... This statistic is another method used to estimate cancer-specific survival that does ...

  1. Understanding Cancer Prognosis

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    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 ...

  2. Understanding Cancer Prognosis

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    Full Text Available ... manage treatment side effects How to deal with financial and legal matters Many people want to know ... most about your situation is in the best position to discuss your prognosis and explain what the ...

  3. Understanding Cancer Prognosis

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    Full Text Available ... 2 years, 5 years, etc., with 5 years being the time period most often used. Cancer-specific ... a prognosis may not be based on treatments being used today. Still, your doctor may tell you ...

  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. 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 .... An adverse outcome was defined as deaths or myocardial infarction. Median follow-up was 6.3 years. RESULTS: Fourteen subjects (2.1%, group A) had s-Na ..., smoking, diabetes, low-density lipoprotein cholesterol, and blood pressure. The hazard ratios were robust for additional adjusting for variables showing univariate association to hyponatremia (ie, beta-blocker and diuretic use, heart rate variability, creatinine, C-reactive protein, and NT-pro brain...

  6. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; McHugh, Jonathan B.; Schipper, Matthew; Walline, Heather M.; Komarck, Christine; Feng, Felix Y.; Worden, Francis P.; Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R.; Mukherji, Suresh K.; Eisbruch, Avraham; Carey, Thomas E.

    2014-01-01

    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

  7. 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

  8. Prognosis of status epilepticus in elderly patients.

    Science.gov (United States)

    Vilella, L; González Cuevas, M; Quintana Luque, M; Toledo, M; Sueiras Gil, M; Guzmán, L; Salas Puig, J; Santamarina Pérez, E

    2018-03-01

    To evaluate the clinical features and prognosis of status epilepticus (SE) in patients above 70 years old. Retrospective analysis of all patients ≥70 years old with SE registered prospectively during 4 years. Follow-up after discharge was performed. Ninety patients were evaluated. Acute symptomatic etiology was the most prevalent. The mean number of antiepileptic drugs (AEDs) used was 2.7 ± 1.2, and 21% of the patients required sedation. A poor outcome was considered when death (31.1%) or developing of new neurological impairment at discharge (32.2%) occurred. After multivariate analysis, four variables predicted a poor outcome: acute symptomatic etiology (OR: 6.320; 95% CI: 1.976-20.217; P = .002), focal motor SE type (OR: 9.089; 95% CI: 2.482-33.283; P = .001), level of consciousness (OR: 4.596; 95% CI: 1.903-11.098; P = .001), and SE duration >12 hours (OR: 3.763; 95% CI: 1.130-12.530; P = .031). Independent predictive factors of mortality were SE duration >12 hours (OR: 4.306; 95% CI: 1.044-17.757; P = .043), modified Status Epilepticus Severity Score (mSTESS) (OR: 2.216; 95% CI: 1.313-3.740; P = .003), and development of complications (OR: 3.334; 95% CI: 1.004-11.070, P = .049). Considering long-term mortality, age (HR 1.036; 95% CI 1.001-1.071; P = .044), a potentially fatal underlying cause (HR 2.609; 95% CI 1.497- 4.548; P = .001), and mSTESS score >4 (HR 1.485; 95% CI 1.158-1.903; P = .002) remained as predictive factors. There was no association between sedation and the number of AEDs used with outcome at discharge or long-term mortality (P > .05). SE above 70 years old has a high morbimortality. Prognosis is not related to treatment aggressiveness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Understanding Cancer Prognosis

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    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 ...

  10. Understanding Cancer Prognosis

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    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 ...

  11. Understanding Cancer Prognosis

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    Full Text Available ... you received. Video Series This video series offers the perspectives of three cancer patients and their doctor. The ... Three cancer patients and their doctor share their perspectives on how to discuss cancer prognosis (the likely course of the disease). Learn key points ...

  12. Understanding Cancer Prognosis

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    Full Text Available ... Your Cancer Prognosis Video View this video on YouTube. Three cancer patients and their doctor share their ... One Couple's Creative Response View this video on YouTube. Vanessa, an artist, and her husband Roy discover ...

  13. Symposium summary and prognosis

    International Nuclear Information System (INIS)

    Bjorken, J.D.

    1975-11-01

    The summary of the symposium on high energy physics experiments includes phenomena at low energies, the foundations of physics (considered to be mainly gravitation and quantum electrodynamics), standards of reference used for interpretation of experimental data, the new physics, particle proliferation, theoretical development, and a prognosis for the future

  14. 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

  15. Understanding Cancer Prognosis

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    Full Text Available ... control. Whatever your doctor tells you, keep in mind that a prognosis is an educated guess. Your ... Website Cancer.gov en español Multimedia Publications Site Map Digital Standards for NCI Websites POLICIES Accessibility Comment ...

  16. Understanding Cancer Prognosis

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    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 ...

  17. Understanding Cancer Prognosis

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    Full Text Available ... a link to this page included, e.g., “Understanding Cancer Prognosis was originally published by the National Cancer Institute.” Please note that blog posts that are written by individuals from outside the government may be owned by the writer, and graphics ...

  18. 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.

  19. 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.

  20. Apoptosis and microvessel density in gastric cancer: correlation with tumor stage and prognosis.

    Science.gov (United States)

    Aurello, Paolo; Bellagamba, Riccardo; Rossi Del Monte, Simone; D'Angelo, Francesco; Nigri, Giuseppe; Cicchini, Claudia; Ravaioli, Matteo; Ramacciato, Giovanni

    2009-12-01

    Gastric cancer remains one of the most common human malignancies with a poor prognosis. Apoptosis is known to be a programmed cell death and its inhibition is involved in the unregulated cellular growth that leads to neoplasms. Microvessel density (MVD) has been investigated as a promoting factor for angiogenesis with conflicting results about its relation to survival. The aim of our study was to search a correlation between these factors and some clinicopathological features and prognosis. Identification of apoptotic cells was performed applying the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and recorded as apoptotic index (A.I.), whereas monoclonal antibodies were used for the study of MVD. A significant correlation was found between low and high A.I. and the subgroup of patients in Stages I and II (P stage (P = 0.036) and to a poorer 5-year overall survival (P gastric cancer.

  1. 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...... until the end of 2009. To explore changes over time, the endometriosis cohorts were followed for 15 years from the years 1980, 1986, 1992 and 1998, with the corresponding control cohorts. All pregnancy outcomes were categorized into naturally or artificially conceived pregnancies. MAIN OUTCOME MEASURES...

  2. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... is likely to respond well to treatment. Or, he may tell you that you have a poor ... Hodgkin lymphoma, and has learned to ask until he gets the information he is looking for. From ...

  3. Prevalence, determinants and prognosis of pulmonary hypertension among hemodialysis patients

    Science.gov (United States)

    Agarwal, Rajiv

    2012-01-01

    Background The prevalence, determinants and prognosis of pulmonary hypertension among long-term hemodialysis patients in the USA are poorly understood. Methods A cross-sectional survey of prevalence and determinants of pulmonary hypertension was performed, followed by longitudinal follow-up for all-cause mortality. Pulmonary hypertension was defined as an estimated systolic pulmonary artery pressure of >35 mmHg using echocardiograms performed within an hour after the end of dialysis. Results Prevalent in 110/288 patients (38%), the independent determinants of pulmonary hypertension were the following: left atrial diameter (odds ratio 10.1 per cm/m2, P pulmonary hypertension (53%, CMR 168.9/1000 patient-years) and 39 among 178 without pulmonary hypertension (22%, CMR 52.5/1000 patient-years) [unadjusted hazard ratio (HR) for death 2.12 (95% confidence interval 1.41–3.19), P pulmonary hypertension remained an independent predictor for all-cause mortality [HR 2.17 (95% confidence interval 1.31–3.61), P pulmonary hypertension is common and is strongly associated with an enlarged left atrium and poor long-term survival. Reducing left atrial size such as through volume control may be an attractive target to improve pulmonary hypertension. Improving pulmonary hypertension in this group of patients may improve the dismal outcomes. PMID:22290987

  4. Immunoability and prognosis in the patients after radiotherapy

    International Nuclear Information System (INIS)

    Sako, Takashi; Sakurai, Tomoyasu; Nishio, Masamichi; Saito, Akio; Koshiba, Ryuzo.

    1978-01-01

    About two weeks after radiotherapy, PPD intracutaneous reaction (0.05 mg of general diagnostic tuberculin was used) was examined. The peripheral lymphocyte count and the immunoglobulin value were also measured in order to study the correlation between these results and the prognosis. Subjects were 359 patients with malignant tumors and 20 patients with double cancer. All the patients, in whom PPD reaction was positive, tended to show the good prognosis except for the patients with pulmonary cancer. The positive rate decreased according to an advance of the stage of uterine cancer. Fourteen of the 17 patients, in whom the peripheral lymphocyte count could be observed when PPD reaction turned out negative, showed the decrease of the lymphocyte count less than 20%. The patients, in whom no correlation was found and the lymphocyte count did not decrease showed the better prognosis than the patients with positive PPD. Poor prognosis was found in the patients, in whom IgG and IgA values were abnormally high, without regard to positive or negative PPD. IgM value had no correlation, but the poor prognosis was more frequently observed in the patients with abnormal low IgM value. In the patients with double cancer no specificity was found in the type of diseases and the doubled pattern, and PPD positive rate significantly increased in the patients with good prognosis. (Kanao, N.)

  5. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Science.gov (United States)

    Alejandre, Maria José; Palomino-Morales, Rogelio J.; Prados, Jose; Aránega, Antonia; Delgado, Juan R.; Irigoyen, Antonio; Martínez-Galán, Joaquina; Ortuño, Francisco M.

    2015-01-01

    The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease. PMID:26346854

  6. Prognosis Relevance of Serum Cytokines in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Torres

    2015-01-01

    Full Text Available The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients’ outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox’s proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

  7. Outcome, comorbidity and prognosis in anorexia nervosa.

    Science.gov (United States)

    Jagielska, Gabriela; Kacperska, Iwona

    2017-04-30

    Anorexia nervosa (AN) is a relatively common disorder, especially in adolescent and young adult women. The lifetime prevalence of AN in females ranges from 1.2 to 2.2%. The prevalence in males is 10-times lower. The condition is associated with a high risk of chronic course and poor prognosis in terms of treatment and the risk of death. Longer follow-up periods seemed to correspond with increased improvement rates and increased mortality. Onset of the disorder during adolescence is associated with better prognosis. It is reported that as much as 70% to over 80% of patients in this age group achieve remission. Worse outcomes are observed in patients who required hospitalization and in adults. Recent studies indicate improved prognosis for cure and lower mortality rates than previously reported. However, the recovery can take several years and AN is associated with high risk of developing other psychiatric disorders during the patients' lifetime, even after recovery from AN (mainly: affective disorders, anxiety disorders, obsessive-compulsive disorders, substance abuse disorders). Studies indicate that bulimic symptoms often occur in the course of anorexia nervosa (especially within 2-3 years from the onset of AN). The authors present a review of literature on the course, comorbidity, mortality, and prognostic factors in AN. Better knowledge of the course of anorexia can contribute to more realistic expectations of the pace of symptomatic improvement, as well as to a creation of therapeutic programs which are better adapted to the needs of the patients.

  8. 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...

  9. Idiopathic focal segmental glomerulosclerosis: a favourable prognosis in untreated patients?

    NARCIS (Netherlands)

    Deegens, J.K.J.; Assmann, K.J.M.; Steenbergen, E.; Hilbrands, L.B.; Gerlag, P.G.G.; Jansen, J.L.; Wetzels, J.F.M.

    2005-01-01

    BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently

  10. Hypoxic ischemic encephalopathy in children : CT findings related to prognosis

    International Nuclear Information System (INIS)

    Cho, Jae Min; Il, Yim Byung; Kim, Ok Hwa; Kang, Doo Kyoung; Suh, Jung Ho

    1997-01-01

    To evaluate prognosis-related CT findings in hypoxic ischemic encephalopathy. For the purpose of prognosis, 28 children with a clinical history and CT findings suggestive of hypoxic ischemic encephalopathy (HIE) were restrospectively reviewed. The diagnostic criteria for HIE, as seen on CT scanning, were as follows : 1, ventricular collapse;2, effacement of cortical sulci;3, prominent enhancement of cortical vessels;4, poor differentiation of gray and white matter;5, reversal sign;6, obliteration of perimesencephalic cistern;7, high density on tentorial edge, as seen on precontrast scans;and 8, low density in thalamus, brain stem and basal ganglia. On the basis of clinical outcome, we divided the patients into three groups, as follows:group I(good prognosis);group II(neurologic sequelae), and group III(vegetative state or expire), and among these, compared CT findings. There were thirteen patients in group I, six in group II, and nine in group III. Ventricular collapse, effacement of cortical sulci, and prominent enhancement of cortical vessels were noted in all groups, whereas poor differentiation of gray and white matter, reversal sign, obliteration of perimesencephalic cistern, high density on tentorial edge, on precontrast scan, and low density in brain stem and basal ganglia were observed only in groups II and III. CT findings showed distinct differences between groups in whom prognosis was good, and in whom it was poor. An awareness of poor prognostic CT findings may be clinically helpful in the evaluation of patients with hypoxic ischemic encephalopathy

  11. [Catatonia de novo, report on a case: immediate vital prognosis and psychiatric prognosis in longer term].

    Science.gov (United States)

    Patry, L; Guillem, E; Pontonnier, F; Ferreri, M

    2003-01-01

    We report on the case of a 20 year old woman with no previous psychiatric history, who displayed a first episode of catatonia with acute onset. Symptoms started plainly with sudden general impairment, intense asthenia, headache, abdominal pain and confusion. After 48 hours, the patient was first admitted to an emergency unit and transferred to an internal medicine ward afterwards. She kept confused. Her behaviour was bizarre with permanent swinging of pelvis, mannerism, answers off the point and increasingly poor. The general clinical examination was normal, except for the presence of a regular tachycardia (120 bpm). The paraclinical investigations also showed normal: biology, EEG, CT Scan, lumbar puncture. Confusion persisted. The patient remained stuporous, with fixed gazing and listening-like attitudes. She managed to eat and move with the help of nurses but remained bedridden. The neurological examination showed hypokinaesia, extended hypotonia, sweating, urinary incontinence, bilateral sharp reflexes with no Babinski's sign and an inexhaustible nasoorbicular reflex. The patient was mute and contrary, actively closed her eyes, but responded occasionally to simple instructions. For short moments, she suddenly engaged in inappropriate behaviors (wandering around) while connecting back to her environment answering the telephone and talking to her parents. The patient's temperature rose twice in the first days but with no specific etiology found. During the first 8 days of hospitalization, an antipsychotic treatment was administered: haloperidol 10 mg per os daily and cyamemazine 37.5 mg i.m. daily. Despite these medications, the patient worsened and was transferred to our psychiatric unit in order to manage this catatonic picture with rapid onset for which no organic etiology was found. On admission, the patient was stuporous, immobile, unresponsive to any instruction, with catalepsy, maintenance of postures, severe negativism and refusal to eat. A first treatment

  12. 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

  13. 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 ...

  14. 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.

  15. Clinicopathological Characteristics and Prognosis of Colorectal Cancer in Chinese Adolescent Patients

    Directory of Open Access Journals (Sweden)

    Feng Du

    2015-01-01

    Conclusions: Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage III/IV disease with signet ring cell carcinoma. The prognosis was relatively poor.

  16. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    International Nuclear Information System (INIS)

    Zhu, Qiu-Li; Xu, Wang-Hong; Tao, Meng-Hua

    2010-01-01

    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

  17. Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Qiu-Li; Xu, Wang-Hong [Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032 (China); Tao, Meng-Hua [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.

  18. Distinct Clinicopathological Features and Prognosis of Helicobacter pylori Negative Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Kun-Feng Tsai

    Full Text Available Whether the characteristics and prognosis of gastric cancer (GC are different in patients with and without Helicobacter pylori (HP remains controversial. The definitions of HP status in patients with atrophic gastritis but negative tests for HP are heterogeneous. We aimed to assess the impact of HP on the prognosis of GC using different definitions.From 1998 Nov to 2011 Jul, five hundred and sixty-seven consecutive patients with GC were included. HP status was determined by serology and histology. Patients with any positive test were defined as HP infection. Patients without HP infection whose serum pepsinogen (PG I <70 ng/dl and PG I/II ratio < 3.0 were defined as atrophic gastritis and they were categorized into model 1: HP positive; model 2: HP negative; and model 3: exclusion of these patients.We found four characteristics of HP negative GC in comparison to HP positive GC: (1 higher proportion of the proximal tumor location (24.0%, P = 0.004, (2 more diffuse histologic type (56.1%, p = 0.008, (3 younger disease onset (58.02 years, p = 0.008 and (4 more stage IV disease (40.6%, p = 0.03. Patients with negative HP had worse overall survival (24.0% vs. 35.8%, p = 0.035. In Cox regression models, the negative HP status is an independent poor prognostic factor (HR: 1.34, CI:1.04-1.71, p = 0.019 in model 1, especially in stage I, II and III patients (HR: 1.62; CI:1.05-2.51,p = 0.026.We found the distinct characteristics of HP negative GC. The prognosis of HP negative GC was poor.

  19. And the Dead Remain Behind

    Directory of Open Access Journals (Sweden)

    Peter Read

    2013-08-01

    Full Text Available In most cultures the dead and their living relatives are held in a dialogic relationship. The dead have made it clear, while living, what they expect from their descendants. The living, for their part, wish to honour the tombs of their ancestors; at the least, to keep the graves of the recent dead from disrepair. Despite the strictures, the living can fail their responsibilities, for example, by migration to foreign countries. The peripatetic Chinese are one of the few cultures able to overcome the dilemma of the wanderer or the exile. With the help of a priest, an Australian Chinese migrant may summon the soul of an ancestor from an Asian grave to a Melbourne temple, where the spirit, though removed from its earthly vessel, will rest and remain at peace. Amongst cultures in which such practices are not culturally appropriate, to fail to honour the family dead can be exquisitely painful. Violence is the cause of most failure.

  20. Red Assembly: the work remains

    Directory of Open Access Journals (Sweden)

    Leslie Witz

    installed. What to do at this limit, at the transgressive encounter between saying yes and no to history, remains the challenge. It is the very challenge of what insistently remains.

  1. Pathogenesis and prognosis of bilateral thalamic infarction

    International Nuclear Information System (INIS)

    Nakase, Taizen; Ogura, Naoko; Maeda, Tetsuya; Yamazaki, Takashi; Kameda, Tomoaki; Sato, Yuichi; Nagata, Ken

    2008-01-01

    Only a few reports have discussed the detailed clinical symptoms and pathogenesis of bilateral thalamic infarction. The thalamus is composed of different functional nuclei and supplied by vessels containing several variations from the main arteries, leading to difficulty in the precise evaluation of bilateral thalamic infarction. In the present study, we assessed the prognosis of bilateral thalamic infarction based on the distribution of stroke lesions. From among the consecutive ischemic stroke patients admitted to hospital between April 2001 and March 2005, cases of acute bilateral thalamic infarction were selected for this study (n=9; 65.1±13.6 y.o.). The stroke lesions and vascular abnormalities were investigated by magnetic resonance imaging and magnetic resonance angiography on admission. Outcome was evaluated from the modified Rankin scale (mRS) at discharge. Good outcome patients (mRS 0-2; n=5) showed memory disturbance, cognitive impairment and hypersomnia. On the other hand, quadriplegia, oculomotor disturbance and bulbar palsy were observed in the poor outcome patients (mRS≥4; n=4). The critical features of a poor outcome were the age at onset (72.0±15.3 vs. 58.2±11.9 y.o.), inclusion of brainstem lesions and total occlusion of the basilar artery. In conclusion, older age at onset and/or basilar artery occlusion may be critical factors for predicting a poor outcome in bilateral thalamic infarction cases. (author)

  2. Green business will remain green

    International Nuclear Information System (INIS)

    Marcan, P.

    2008-01-01

    It all started with two words. Climate change. The carbon dioxide trading scheme, which was the politicians' idea on solving the number one global problem, followed. Four years ago, when the project was begun, there was no data for project initiation. Quotas for polluters mainly from energy production and other energy demanding industries were distributed based on spreadsheets, maximum output and expected future development of economies. Slovak companies have had a chance to profit from these arrangements since 2005. Many of them took advantage of the situation and turned the excessive quotas into an extraordinary profit which often reached hundreds of million Sk. The fact that the price of free quotas offered for sale dropped basically to 0 in 2006 only proved that the initial distribution was too generous. And the market reacted to the first official measurements of emissions. Slovak companies also contributed to this development. However, when planning the maximum emission volumes for 2008-2012 period, in spite of the fact that actual data were available, their expectations were not realistic. A glance at the figures in the proposal of the Ministry of Environment is sufficient to realize that there will be no major change in the future. And so for many Slovak companies business with a green future will remain green for the next five years. The state decided to give to selected companies even more free space as far as emissions are concerned. The most privileged companies can expect quotas increased by tens of percent. (author)

  3. [Laron syndrome: Presentation, treatment and prognosis].

    Science.gov (United States)

    Latrech, Hanane; Polak, Michel

    2016-01-01

    Laron syndrome is a rare cause of short stature due to an abnormality of growth hormone receptor (GHR). It is characterized by poor phenotype-genotype correlation and geographic predilection essentially in the Mediterranean rim, the Middle East and Indian subcontinent. This syndrome corresponds to an endogenous and exogenous complete insensitivity of GH and manifests by early hypoglycemia, an extremely severe short stature and dysmorphic features contrasting with high levels of circulating GH. To date, treatment with recombinant IGF1 is the only treatment option that has improved the terrible prognosis in these patients but does not actually realize the conditions for genuine replacement therapy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. 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....

  5. Thrombocytopenia in leukemia: Pathogenesis and prognosis.

    Science.gov (United States)

    Shahrabi, Saeid; Behzad, Masumeh Maleki; Jaseb, Kaveh; Saki, Najmaldin

    2018-02-20

    Leukemias, a heterogeneous group of hematological disorders, are characterized by ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells. Thrombocytopenia is a common problem among leukemia types that can lead to hemorrhagic complications in patients. The purpose of this review article is to identify the conditions associated with the incidence of thrombocytopenia in leukemias. It can be stated that although translocations have been considered responsible for this complication in many studies, other factors such as bone marrow failure, genes polymorphism, a mutation in some transcription factors, and the adverse effects of treatment could be associated with pathogenesis and poor prognosis of thrombocytopenia in leukemias. Considering the importance of thrombocytopenia in leukemias, it is hoped that the recognition of risk factors increasing the incidence of this complication in leukemic patients would be useful for prevention and treatment of this disorder.

  6. Silicon photonics: some remaining challenges

    Science.gov (United States)

    Reed, G. T.; Topley, R.; Khokhar, A. Z.; Thompson, D. J.; Stanković, S.; Reynolds, S.; Chen, X.; Soper, N.; Mitchell, C. J.; Hu, Y.; Shen, L.; Martinez-Jimenez, G.; Healy, N.; Mailis, S.; Peacock, A. C.; Nedeljkovic, M.; Gardes, F. Y.; Soler Penades, J.; Alonso-Ramos, C.; Ortega-Monux, A.; Wanguemert-Perez, G.; Molina-Fernandez, I.; Cheben, P.; Mashanovich, G. Z.

    2016-03-01

    This paper discusses some of the remaining challenges for silicon photonics, and how we at Southampton University have approached some of them. Despite phenomenal advances in the field of Silicon Photonics, there are a number of areas that still require development. For short to medium reach applications, there is a need to improve the power consumption of photonic circuits such that inter-chip, and perhaps intra-chip applications are viable. This means that yet smaller devices are required as well as thermally stable devices, and multiple wavelength channels. In turn this demands smaller, more efficient modulators, athermal circuits, and improved wavelength division multiplexers. The debate continues as to whether on-chip lasers are necessary for all applications, but an efficient low cost laser would benefit many applications. Multi-layer photonics offers the possibility of increasing the complexity and effectiveness of a given area of chip real estate, but it is a demanding challenge. Low cost packaging (in particular, passive alignment of fibre to waveguide), and effective wafer scale testing strategies, are also essential for mass market applications. Whilst solutions to these challenges would enhance most applications, a derivative technology is emerging, that of Mid Infra-Red (MIR) silicon photonics. This field will build on existing developments, but will require key enhancements to facilitate functionality at longer wavelengths. In common with mainstream silicon photonics, significant developments have been made, but there is still much left to do. Here we summarise some of our recent work towards wafer scale testing, passive alignment, multiplexing, and MIR silicon photonics technology.

  7. Neuroblastoma: biology, prognosis, and treatment

    NARCIS (Netherlands)

    Park, Julie R.; Eggert, Angelika; Caron, Huib

    2010-01-01

    Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Neuroblastoma is a heterogeneous malignancy with prognosis ranging from near uniform survival to high risk for fatal demise.

  8. Neuroblastoma: biology, prognosis, and treatment

    NARCIS (Netherlands)

    Park, Julie R.; Eggert, Angelika; Caron, Huib

    2008-01-01

    Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Neuroblastoma is a heterogeneous malignancy with prognosis ranging from near uniform survival to high risk for fatal demise.

  9. Fluorescence in situ hybridization detection of cytogenetic abnormalities and prognosis in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Zhou Xu

    2015-01-01

    Full Text Available We evaluated the prognosis of patients with newly diagnosed multiple myeloma (MM and attempted to find a suitable treatment strategy for them. Interphase fluorescence in situ hybridization (FISH detection was performed on 57 patients with MM. The following probes: IgH, p53, 1q21, RB1, and D13S319 specific for the rearrangements of 14q32, 17p13, 1q21 and 13q14 were used. Fluorescent hybridization signals were observed using an Olympus BX60 epifluorescence microscope equipped with filters for detecting fluoroisothiocyanate (FITC, Texas red, and 4'-6-Diamidino-2-phenylindole (DAPI. Triple color clone-specific images were captured using a Quips XL genetic workstation. The mortalities in patients with moderate prognosis (66.7% and poor prognosis (50% were significantly higher compared with that in patients with good prognosis (15%, P<0.05. All the patients in good and moderate prognosis groups achieved complete remission (CR/very good partial remission (VGPR/partial remission (PR, whereas only half of the cases in the poor prognosis group reached this level. Patients 2 supported by autologous hematopoietic stem-cell transplantation presented CR/PR and long survival. For those with poor prognosis, a proper therapeutic regimen and timely transplantation, especially tandem transplantation, was necessary due to the rapid progression and complications.

  10. 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-progno...

  11. [Breast cancer: histological prognosis from biopsy material].

    Science.gov (United States)

    Veith, F; Picco, C

    1977-01-01

    Two histological factors to be taken into consideration for prognosis in pretreatment schedules of breast cancer have been studied on a group of 352 cases treated by non-mutilating therapeutics at the Fondation Curie between 1960 and 1970. The tumour material the slides of which we have reexamined "blindly", i.e. ignoring the evolution of the case had been obtained mostly by drill-biopsy. Histological groups and types have been determined following an analytical classification for computer purpose. The degree of malignancy was calculated with the method of Scarff-Bloom-Richardson. The analyzed data have been memorized on computer and then confronted with the elements of the T.N.M. classification and the survival of the patients involved. It appeared that if drill-biopsie have been performed correctly the histological type may be defined in eighty percent of cases. And it is likewise possible to calculate the histological grade of malignancy for each mammary cancer. With such a material the value for prognosis by means of the Scarff-Bloom-Richardson method still remains if applied only to adenocarcinoma of the "common infiltrating type".

  12. Towards in silico prognosis using big data

    Directory of Open Access Journals (Sweden)

    Ohs Nicholas

    2016-09-01

    Full Text Available Clinical diagnosis and prognosis usually rely on few or even single measurements despite clinical big data being available. This limits the exploration of complex diseases such as adolescent idiopathic scoliosis (AIS where the associated low bone mass remains unexplained. Observed low physical activity and increased RANKL/OPG, however, both indicate a mechanobiological cause. To deepen disease understanding, we propose an in silico prognosis approach using clinical big data, i.e. medical images, serum markers, questionnaires and live style data from mobile monitoring devices and explore the role of inadequate physical activity in a first AIS prototype. It employs a cellular automaton (CA to represent the medical image, micro-finite element analysis to calculate loading, and a Boolean network to integrate the other biomarkers. Medical images of the distal tibia, physical activity scores, and vitamin D and PTH levels were integrated as measured clinically while the time development of bone density and RANKL/OPG was observed. Simulation of an AIS patient with normal physical activity and patient-specific vitamin D and PTH levels showed minor changes in bone density whereas the simulation of the same AIS patient but with reduced physical activity led to low density. Both showed unchanged RANKL/OPG and considerable cortical resorption. We conclude that our integrative in silico approach allows to account for a variety of clinical big data to study complex diseases.

  13. Impact of serum SP-A and SP-D levels on comparison and prognosis of idiopathic pulmonary fibrosis

    OpenAIRE

    Wang, Kai; Ju, Qing; Cao, Jing; Tang, Wenze; Zhang, Jian

    2017-01-01

    Abstract Background and objective: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis in general; however, it is heterogeneous to detect relative biomarkers for predicting the disease progression. Serum biomarkers can be conveniently collected to detect and help to differentially diagnose IPF and predict IPF prognosis. This meta-analysis aimed to evaluate the use of serum surfactant proteins A and D (SP-A and SP-D) for differential diagnosis and prognosis of IPF. Methods: Relevant artic...

  14. The effect of silicone implants on the diagnosis, prognosis, and treatment of breast cancer.

    Science.gov (United States)

    Handel, Neal

    2007-12-01

    Because of the prevalence of breast cancer, many augmented women eventually will develop the disease. This article reviews what is known about the effect of implants on the detection, prognosis, and treatment of carcinoma of the breast. Observations were made on 4082 breast cancer patients (3953 nonaugmented and 129 augmented) treated over a 23-year time span. Findings in the two groups were compared and differences analyzed statistically. Mammograms of all women with palpable lesions were reviewed to assess mammographic sensitivity in patients with and without implants. Cosmetic outcomes in augmented patients treated with breast conservation therapy were reviewed. Augmented patients presented more frequently with palpable lesions, invasive tumors, axillary nodal metastases, and false-negative mammograms. However, there was no significant difference in stage of disease, tumor size, recurrence rates, or survival between the two groups. Augmented patients treated with breast conservation therapy often experienced poor cosmetic results and frequently required reoperation. Despite the diminished sensitivity of mammography in women with implants, augmented and nonaugmented patients are diagnosed at a similar stage of disease and have a comparable prognosis. Implants may impair mammography but appear to facilitate tumor detection on physical examination. Magnetic resonance imaging and breast ultrasound may be useful adjuncts, but conventional mammography remains the most reliable tool for diagnosing early breast cancer in augmented patients. Breast implants do not interfere with mastectomy or breast reconstruction but may compromise the outcome of breast conservation therapy.

  15. Prognosis

    DEFF Research Database (Denmark)

    Myers, Jonathan; Brawner, Clinton A; Haykowsky, Mark J F

    2015-01-01

    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 b...

  16. Association between H3K4 methylation and cancer prognosis: A meta-analysis.

    Science.gov (United States)

    Li, Simin; Shen, Luyan; Chen, Ke-Neng

    2018-05-08

    Histone H3 lysine 4 methylation (H3K4 methylation), including mono-methylation (H3K4me1), di-methylation (H3K4me2), or tri-methylation (H3K4me3), is one of the epigenetic modifications to histone proteins, which are related to the transcriptional activation of genes. H3K4 methylation has both tumor inhibiting and promoting effects, and the prognostic value of H3K4 methylation in cancer remains controversial. Therefore, we performed a systematic review and meta-analysis to examine the association between H3K4 methylation and cancer prognosis. A comprehensive search of PubMed, Web of Science, ScienceDirect, Embase, and Ovid databases was conducted to identify studies investigating the association between H3K4 methylation and prognosis of patients with malignant tumors. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. A total of 1474 patients in 10 studies were enrolled in this meta-analysis. The pooled HR of 1.52 (95% CI 1.02-2.26) indicated that patients with a lower level of H3K4me2 expression were expected to have shorter overall survival, while the pooled HR of 0.45 (95% CI 0.27-0.74) indicated that patients with a lower level of H3K4me3 expression were expected to have longer overall survival. This meta-analysis indicates that increased H3K4me3 expression and decreased H3K4me2 expression might be predictive factors of poor prognosis in cancer. Further large cohort studies are needed to confirm these findings. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  17. Diagnosis and prognosis of primary breast cancer

    International Nuclear Information System (INIS)

    Robertson, J. F. R.; Evans, A. J.

    1997-01-01

    The diagnosis of breast cancer should be made in the context of a multidisciplinary team: preoperative diagnosis can be made in over 90 % of patients with symptomatic and screen-detected cancers. A preoperative diagnosis allows patients the opportunity to come to terms with the diagnosis of breast cancer and to consider their treatment options before progressing to therapeutic surgery. Surgery remains the primary therapeutic treatment for operable breast cancer with radiotherapy and systemic therapies as adjuvant treatments. Surgery in addition provides pathological specimens from which important prognostic information may be obtained. The traditional TNM classification in itself is no longer sufficient although there is still c considerable prognostic information to be gained in staging patients. Markers of tumour biology provide prognostic data independent of TNM staging. Both need to be considered in any overall assessment of patient prognosis

  18. The prognosis and prognostic risk factors of patients with hepatic artery complications after liver transplantation treated with the interventional techniques

    International Nuclear Information System (INIS)

    Shan Hong; Huang Mingsheng; Jiang Zaipo; Zhu Kangshun; Yang Yang; Chen Guihua

    2008-01-01

    Objective: To investigate the prognosis and prognostic risk factors of hepatic artery complications after orthotopic liver transplantation (OLT) treated with the interventional techniques. Methods: The clinical data of 21 patients with hepatic artery complication after liver transplantation receiving thrombolysis, PTA, and stent placement in our institute from November 2003 to April 2007 were retrospectively analyzed. Based on the prognosis of grafts, 21 patients were divided into poor-prognosis group and non-poor-prognosis group. Fifteen variables (including biliary complication, hepatic artery restenosis, early or late artery complication, and so on) were analyzed in both groups with binary logistic regression analysis to screen out the risk factors related to prognosis of pereutaneous interventional treatment for hepatic artery complications after OLT. Results: Twenty-one patients were followed for mean 436 days, median 464 days (3-1037 days). The poor-prognosis group included 11 patients (5 cases received retransplantation, and 6 died). The mean survival time of grafts in poor-prognosis group was 191 days, and median survival time was 73 days (3-616 days). The mean survival time of grafts in non-poor-prognosis group which included 10 patients was 706 days, and median survival time was 692 days (245-1037 days). Univariate analysis showed there were significant difference in biliary complication, total bilimbin and indirect bilirubin between the two groups. The binary, logistic regression analysis showed the risk factor related to prognosis was with biliary complication before the interventional management (P=0.027, OR=22.818). Conclusion: Biliary complication before interventional management is the risk factor related to poor prognosis of patients with hepatic artery stenosis or thrombosis receiving interventional treatment. (authors)

  19. 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.

  20. Cerebro-costo-mandibular syndrome: prognosis and proposal for classification.

    Science.gov (United States)

    Nagasawa, Hiroyuki; Yamamoto, Yutaka; Kohno, Yoshinori

    2010-09-01

    Cerebro-costo-mandibular syndrome (CCMS) is a very rare syndrome characterized by micrognathia and posterior rib gap, with a poor prognosis. To date, only 75 cases have been reported worldwide. The overall survival rate for patients with this disorder has not been reported, and a classification of the patients on the basis of the prognosis is not yet available. The present study analyzed the figures and prognoses of past patients and documented a new case of CCMS. Formerly published case reports and personal communications were used to reveal the prognosis and classification of CCMS. The occurrence ratios of rib gap defects and of missing ribs were examined. Patients were divided into the following three groups according to their life span: lethal type, where the patients died before 1 month; severe type, where the patients lived for 1-12 months; and mild type, where they survived for more than 1 year. A comparison was made of the number of rib gaps, missing ribs, and the rib gap ratio (defined as the number of rib gaps divided by the number of all existing ribs) among these three groups. A significant difference in the number of rib defects between the lethal type and other types was noted. Short life span of severe type patients, compared to mild type, was attributed to their subjection to severe respiratory infection. CCMS can be classified into three categories--lethal, severe, and mild--according to the severity of the symptoms and prognosis.

  1. 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.

  2. 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...

  3. [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

  4. [The contribution of the clinical examination, electroencephalogram, and brain MRI in assessing the prognosis in term newborns with neonatal encephalopathy. A cohort of 30 newborns before the introduction of treatment with hypothermia].

    Science.gov (United States)

    Jadas, V; Brasseur-Daudruy, M; Chollat, C; Pellerin, L; Devaux, A M; Marret, S

    2014-02-01

    Perinatal asphyxia complicated by hypoxic ischemic brain injury remains a source of neurological lesions. A major aim of neonatologists is to evaluate the severity of neonatal encephalopathy (NE) and to evaluate prognosis. The purpose of this study was to determine the contribution of brain MRI compared to electroencephalogram (EEG) and clinical data in assessing patients' prognosis. Thirty newborns from the pediatric resuscitation unit at Rouen university hospital were enrolled in a retrospective study between January 2006 and December 2008, prior to introduction of hypothermia treatment. All 30 newborns had at least two anamnestic criteria of perinatal asphyxia, one brain MRI in the first 5 days of life and another after 7 days of life as well as an early EEG in the first 2 days of life. Then, the infants were seen in consultation to assess neurodevelopment. This study showed a relation between NE stage and prognosis. During stage 1, prognosis was good, whereas stage 3 was associated with poor neurodevelopment outcome. Normal clinical examination before the 8th day of life was a good prognostic factor in this study. There was a relationship between severity of EEG after the 5th day of life and poor outcome. During stage 2, EEG patterns varied in severity, and brain MRI provided a better prognosis. Lesions of the basal ganglia and a decreased or absent signal of the posterior limb of the internal capsule were poor prognostic factors during brain MRI. These lesions were underestimated during standard MRI in the first days of life but were visible with diffusion sequences. Cognitive impairment affected 40% of surviving children, justifying extended pediatric follow-up. This study confirms the usefulness of brain MRI as a diagnostic tool in hypoxic ischemic encephalopathy in association with clinical data and EEG tracings. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Nanosuspension Technology for Solubilizing Poorly Soluble Drugs

    OpenAIRE

    Deoli Mukesh

    2012-01-01

    Poor water solubility for many drugs and drug candidates remains a major obstacle to their development and clinical application. It is estimated that around 40% of drugs in the pipeline cannot be delivered through the preferred route or in some cases, at all owing to poor water solubility. Conventional formulations to improve solubility suffer from low bioavailability and poor pharmacokinetics, with some carriers rendering systemic toxicities (e.g. Cremophor1 EL). To date, nanoscale systems f...

  6. Prognosis of mucous naso-sinus melanomas

    International Nuclear Information System (INIS)

    Thariat, J.; Poissonnet, G.; Dassonville, O.; Santini, J.; Castillo, L.; Iattes, L.; Bensadoun, R.J.; Castillo, L.

    2009-01-01

    Purpose: The mucous melanoma of superior aero-digestive tracts represents 1-2% of malignant melanomas, 5-10% of head and neck melanomas, and concerns particularly, the nasal cavities and naso-sinus cavities. The recurrences are frequent, often local ones, sometimes multifocal ones, the survival rate at five years is ≤ 30%. The Ballantyne classification distinguishes three stages: 1 localised tumors, 2 ganglions attack, 3 metastases. Are pejorative: a stage number 3 ( deep invasion, muscles, bones, cartilages) according to the Prasad classification (1: in situ or micro invasive, 2: invasion of the lamina propria), the achromia sub-type, a pseudo papillary or sarcoma, vascular emboli, necrosis. The recommendations rest on evidence level at 4. The complete excision is the rule and must be counterbalanced with the morbidity in case of orbital, dura-mater, frontal lobe, and infra temporal fossa. The adjuvant irradiation is debated.We evaluated the prognosis of mucous naso-sinus melanomas. Conclusion: The principal cause of death was the local failure. The Ballantyne classification does not take into account the extensions and overestimates the prognosis impact of ganglions invasion that is yet ≤10% ( and does not justify a radiotherapy in lack of adenopathy). It underestimates probably the impact of adjuvant radiotherapy. One should be able to distinguish the unfavourable stage 1 tumors (receiving eventually a radiotherapy) and these ones of very localised stage 1 for which it could be omitted. The fractionation and the optimal dose remain to be defined. The volume ≥100 ml and the irradiation by carbon ions seem promising in term of local control but the metastases stay a problem in the recent series. (N.C.)

  7. 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.

  8. Exploiting the Poor

    DEFF Research Database (Denmark)

    Kamp Justesen, Mogens; 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...... often rely heavily on services provided by governments. We test this proposition using micro-level survey data from the Afrobaromenter. Multilevel regressions across 18 countries show that poor people are much more prone to experience having to pay bribes to government officials....

  9. Hypertensive emergencies remain a clinical problem and are associated with high mortality.

    Science.gov (United States)

    Roubsanthisuk, Weranuj; Wongsurin, Unticha; Buranakitjaroen, Peera

    2010-01-01

    We suspect that hypertensive emergencies remain a clinical problem and data on their long-term prognosis are lacking. This study was conducted in order to determine the frequency, management, and outcome of hypertensive emergencies in this era, in which hypertension treatment is more effective than in the past. We reviewed the medical records of patients with hypertensive emergencies admitted to the medical wards of Siriraj Hospital in 2003 and collected data on their characteristic, management, investigations, and follow-ups through 31 December 2007. There were 184 patients included. Hypertension has been previously diagnosed in 89% of cases. Nearly half also had diabetes mellitus and around a quarter had chronic kidney failure. Mean +/- SD of blood pressure at presentation was 205.96 +/- 21.36/114.60 +/- 20.59 mmHg. Cardiac complications and stroke accounted for 71% and 23% of all target organ damage, respectively. Intravenous nitroglycerine and furosemide were most frequently prescribed. Additional investigations to search for the causes of hypertension were performed in only 55 cases. The average hospital stay was 9.8 days. The in-hospital mortality rate was 15%. Some 26% of patients were lost to follow-up and another 20% died later. Only 19% of patients had regular follow-ups until the end of 2007 and remained on an average of 2.4 antihypertensive drugs. Hypertensive emergencies are usually found in patients with a history of hypertension and diabetes mellitus or kidney failure. Recommended investigations usually failed to identify the cause of hypertension. The mortality rate of these patients was extremely high while their adherence to treatment was extremely poor.

  10. Value of neutrophil-to-lymphocyte ratio for predicting lung cancer prognosis: A meta-analysis of 7,219 patients.

    Science.gov (United States)

    Yu, Yu; Qian, Lei; Cui, Jiuwei

    2017-09-01

    Current evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) may be a biomarker for poor prognosis in lung cancer, although this association remains controversial. Therefore, a meta-analysis was performed to evaluate the association between NLR and lung cancer outcome. A systematic literature search was performed through the PubMed, Embase and Cochrane Library databases (until July 30, 2016), to identify studies evaluating the association between NLR and overall survival (OS) and/or progression-free survival (PFS) among patients with lung cancer. Based on the results of this search, data from 18 studies involving 7,219 patients with lung cancer were evaluated. The pooled hazard ratio (HR) suggested that elevated pretreatment NLR predicted poor OS [HR=1.46, 95% confidence interval (CI): 1.30-1.64] and poor PFS (HR=1.42, 95% CI: 1.15-1.75) among patients with lung cancer. Subgroup analysis revealed that the prognostic value of NLR for predicting poor OS increased among patients who underwent surgery (HR=1.50, 95% CI: 1.21-1.84) or patients with early-stage disease (HR=1.64, 95% CI: 1.37-1.97). An NLR cut-off value of ≥4 significantly predicted poor OS (HR=1.56, 95% CI: 1.31-1.85) and PFS (HR=1.54, 95% CI: 1.13-1.82), particularly in the cases of small-cell lung cancer. Thus, the results of the present meta-analysis suggested that an elevated pretreatment NLR (e.g., ≥4) may be considered as a biomarker for poor prognosis in patients with lung cancer.

  11. 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

  12. Accounting for the Poor

    OpenAIRE

    Robert M. Townsend

    2013-01-01

    Economists and other social scientists have long tried to understand the nature of poverty and how poor people make decisions. For example, T.W. Schultz, a Nobel Laureate, former professor of economics at the University of Chicago, and former president of the American Economic Association, spent his career working in development and agricultural economics. In his 1980 Nobel Prize acceptance speech, Schultz suggests that there is some accounting for the behavior of the poor in agriculture. "Fa...

  13. The role of metallothionein in oncogenesis and cancer prognosis

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Larsen, Agnete; Stoltenberg, Meredin

    2009-01-01

    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...

  14. Radiotherapy in breast cancer and its prognosis

    International Nuclear Information System (INIS)

    Mitter, Mihir

    1980-01-01

    Various aspects of breast cancer are discussed. These include clinical staging, histological grading, site of growth, frequency and lactation, immunological response and prognosis, and survival of untreated cases. Importance of early detection is emphasised and prognosis after radiotherapy alone or in combination with surgery is briefly discussed. (M.G.B.)

  15. Probabilistic Prognosis of Non-Planar Fatigue Crack Growth

    Science.gov (United States)

    Leser, Patrick E.; Newman, John A.; Warner, James E.; Leser, William P.; Hochhalter, Jacob D.; Yuan, Fuh-Gwo

    2016-01-01

    Quantifying the uncertainty in model parameters for the purpose of damage prognosis can be accomplished utilizing Bayesian inference and damage diagnosis data from sources such as non-destructive evaluation or structural health monitoring. The number of samples required to solve the Bayesian inverse problem through common sampling techniques (e.g., Markov chain Monte Carlo) renders high-fidelity finite element-based damage growth models unusable due to prohibitive computation times. However, these types of models are often the only option when attempting to model complex damage growth in real-world structures. Here, a recently developed high-fidelity crack growth model is used which, when compared to finite element-based modeling, has demonstrated reductions in computation times of three orders of magnitude through the use of surrogate models and machine learning. The model is flexible in that only the expensive computation of the crack driving forces is replaced by the surrogate models, leaving the remaining parameters accessible for uncertainty quantification. A probabilistic prognosis framework incorporating this model is developed and demonstrated for non-planar crack growth in a modified, edge-notched, aluminum tensile specimen. Predictions of remaining useful life are made over time for five updates of the damage diagnosis data, and prognostic metrics are utilized to evaluate the performance of the prognostic framework. Challenges specific to the probabilistic prognosis of non-planar fatigue crack growth are highlighted and discussed in the context of the experimental results.

  16. [Ethics in clinical routine care: example of prognosis information].

    Science.gov (United States)

    Elger, Bernice S

    2002-09-15

    The article discusses from an ethical point of view the question whether a physician should tell the patient the whole truth about a poor prognosis. From a legal viewpoint, the therapeutic privilege gives physicians in most countries the right to limit information, if they are concerned that this information will severely harm the patient. An overview about empirical studies, especially surveys of physicians and patients, shows that most patients always wish to know their prognosis, while physicians would less often tell the whole truth. Physicians explain their attitudes by referring to the ethical principles of nonmaleficience and beneficience. These principles are apparently in conflict with the principles of veracity and respect of patient autonomy. However, it can be shown that this conflict does not persist when empirical data about consequences of truthful information are considered: telling the truth seems not to have negative, but rather positive consequences on the overall well-being of the patient. After having summarized the empirical studies that have examined the consequences of truthful information about severe and incurable diseases, the article argues for always telling patients the truth if they want to know it. Many conflicts in medical ethics are between prima facie principles. In cases where the principles of beneficience and nonmaleficience are used in the argumentation, some of the conflicts can be eliminated when the ethical judgment is made on a thorough empirical basis, as shown by the example of truth-telling about prognosis.

  17. Etiology, Localization and Prognosis in Cerebellar Infarctions

    Directory of Open Access Journals (Sweden)

    Yavuz Yücel

    2006-01-01

    Full Text Available Cerebrovasculer disease are the most frequent disease of the brain. Cerebellar infarct remains % 1.5-4.2 of these diseases. Etiological factors, lesion localization, symptoms and findings and relationship with prognosis of our patients with cerebellar infarct were investigated in our study. For this purpose, 32 patients were evaluated who were admitted to the Dicle University Medical School Department of Neurology in 1995-2001 hospitalized with the diagnosis of clinically and radiological confirmed cerebellar infarction.All of patients in the study group, 21 (%65.6 were male and 11 (%34.3 female. Age of overall patients ranged between 40 and 75 years with a mean of 57.8±10.2 years. Atherothrombotic infarct was the most frequent reason at the etiologic clinical classification. The most frequently found localization was the posterior inferior cerebellar artery infarct (%50. The leading two risk factors were hypertension (%78.1 and cigarette smoking (%50. The most common sign and symptoms were vertigo (%93.7, vomiting (%75, headache (%68.7 and cerebellar dysfunction findings (%50. The mean duration of hospitalization was 16.3±7.6 days. Overall mortality rate was found to be % 6.2. Finally, the most remarkable risk factors at cerebellar infarct patients are hypertension and atherosclerosis at etiology. We are considering that, controlling of these factors will reduce the appearance frequency of cerebellar infarcts.

  18. Quantifying prognosis with risk predictions.

    Science.gov (United States)

    Pace, Nathan L; Eberhart, Leopold H J; Kranke, Peter R

    2012-01-01

    Prognosis is a forecast, based on present observations in a patient, of their probable outcome from disease, surgery and so on. Research methods for the development of risk probabilities may not be familiar to some anaesthesiologists. We briefly describe methods for identifying risk factors and risk scores. A probability prediction rule assigns a risk probability to a patient for the occurrence of a specific event. Probability reflects the continuum between absolute certainty (Pi = 1) and certified impossibility (Pi = 0). Biomarkers and clinical covariates that modify risk are known as risk factors. The Pi as modified by risk factors can be estimated by identifying the risk factors and their weighting; these are usually obtained by stepwise logistic regression. The accuracy of probabilistic predictors can be separated into the concepts of 'overall performance', 'discrimination' and 'calibration'. Overall performance is the mathematical distance between predictions and outcomes. Discrimination is the ability of the predictor to rank order observations with different outcomes. Calibration is the correctness of prediction probabilities on an absolute scale. Statistical methods include the Brier score, coefficient of determination (Nagelkerke R2), C-statistic and regression calibration. External validation is the comparison of the actual outcomes to the predicted outcomes in a new and independent patient sample. External validation uses the statistical methods of overall performance, discrimination and calibration and is uniformly recommended before acceptance of the prediction model. Evidence from randomised controlled clinical trials should be obtained to show the effectiveness of risk scores for altering patient management and patient outcomes.

  19. Critical Appraisal of the Quality of Evidence Addressing the Diagnosis, Prognosis, and Management of Peripheral Artery Disease in Patients With Diabetic Foot Ulceration.

    Science.gov (United States)

    Ali, Stephen R; Ozdemir, Baris A; Hinchliffe, Robert J

    2018-06-13

    There is a paucity of robust evidence on prevention and management of diabetic foot ulcers (DFUs) to inform treatment. This study appraises the current quality of the evidence addressing diagnosis, prognosis, and management of peripheral artery disease (PAD) in patients with DFUs using a newly devised 21 point scoring (TOPS) disease specific research appraisal tool published by the International Working Group on the Diabetic Foot (IWGDF) and European Wound Management Association. The 2015 IWGDF guidance on diagnosis, prognosis, and management of PAD in patients with DFUs was used to identify studies pertaining to prevention and management. Two reviewers assessed these articles against TOPS, which examines study design, conduct, and outcome reporting. The overall median score was 8 (3-12/21). The median design total score was 2 (0-4/11). The median conduct total score was 2 (1-4/6). The median outcomes total score was 3 (1-4/4). There was improvement with time in overall total (Spearman Rho 0.39, p = .0005), design total (0.35, p = .0023), and outcomes total (0.35, p = .0002), but not conduct total (-0.03, p = .8132) scores. Although this analysis revealed an improvement over time in the overall calibre of studies, the present quality remains poor on which to inform the diagnosis, management, and prognosis of patients with PAD and diabetic foot ulceration. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  20. Clinicopathological features and prognosis of gastric cancer in young patients

    International Nuclear Information System (INIS)

    Liu, Shushang; Feng, Fan; Xu, Guanghui; Liu, Zhen; Tian, Yangzi; Guo, Man; Lian, Xiao; Cai, Lei; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    The clinicopathological features and prognosis of gastric cancer in young patients are both limited and controversial. Therefore, the aim of this study was to define the clinicopathological features and prognosis of gastric cancer in young patients after curative resection. From May 2008 to December 2014, 198 young patients (age ≤ 40 years) and 1096 middle-aged patients (55 ≤ age ≤ 64 years) were enrolled in this study. The clinicopathological features and prognosis of gastric cancer in these patients were analyzed. Compared with middle-aged patients, the proportion of females, lower third tumors, tumor size less than 5 cm, poorly differentiated tumors and T1 tumors were significantly higher in young patients (all P < 0.05). The proportions of comorbidity, upper third tumors, well and moderately differentiated tumors, T4 tumors, and positive carcinoembryonic antigen (CEA), alpha fetoprotein (AFP) and carbohydrate antigen (CA) 19–9 were significantly lower in young patients (all P < 0.05). The distributions of N status and CA125 were comparable between young and middle-aged patients (all P > 0.05). The five-year overall survival rates were comparable between young patients and middle-aged patients (62.8 vs 54.7 %, P = 0.307). The tumor location, T status, N status and CA125 were independent predictors of prognosis in young patients. The overall survival of patients with tumors located in the upper or middle third was significantly lower than for those located in the lower third (60.8 vs 50.6 % vs 68.4 %, P = 0.016). The overall survival of CA125-positive patients was significantly lower than CA125-negative patients (49.0 vs 64.4 %, P = 0.001). The clinicopathological features were significantly different between young and middle-aged patients. The prognosis of gastric cancer in young patients was equivalent to that of middle-aged patients. Tumor location, T status, N status and CA125 were independent risk factors for prognosis in young patients. The online

  1. Prognosis on follow-up CT of chronic subdural hematomas treated by burr hole evacuation

    International Nuclear Information System (INIS)

    Higeta, Toshiaki; Yamada, Hiroshi; Itoh, Hakuji

    1986-01-01

    A consecutive series of 47 adult patients with chronic subdural hematoma was studied in respect to postoperative follow-up CT after burr hole evacuation. In 15 of our patients, the CT scan was normalized within 60 days. Six patients required reoperation because of reaccumulation or of poor re-expansion, and in 13 patients the follow-up CT showed a persisting subdural fluid collection even after 60 postoperative days. Further studying the correlation between the prognosis on follow-up CT and various factors, such as patient's age, preoperative neurological condition and CT findings or others, authors found that the elderly, especially older than 70 years, had a poor prognosis, and that the prognosis was correlated to the density and the thickness of hematoma on preoperative CT scan. (author)

  2. Clinicopathologic characteristics and prognosis of proximal and distal gastric cancer

    Directory of Open Access Journals (Sweden)

    Yu X

    2018-02-01

    Full Text Available Xuefeng Yu,1,* Fulan Hu,2,* Chunfeng Li,1 Qiang Yao,1 Hongfeng Zhang,1 Yingwei Xue1 1Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China; 2Department of Epidemiology, Public Health College, Harbin Medical University, Harbin, China *These authors contributed equally to this work Background and objectives: The dismal prognosis of gastric cancer patients is a global problem. We aim to evaluate the clinicopathologic features and prognostic factors of proximal and distal gastric cancer.Materials and methods: Gastric cancer cases diagnosed and treated at the same surgical unit between 2007 and 2010 were reviewed. Follow-up data from all patients were collected for at least 5 years until 2015. A total of 964 patients were studied (distal gastric cancer [DG], n=777 and proximal gastric cancer [PG], n=187.Results: DG patients had a relatively higher percentage of females, more thorough therapy (R0 [D0/D1/D2], fewer combined organ resections, younger age, smaller tumors (<5 cm, shorter surgery durations, less blood loss during surgery, and a relatively lower percentage of nodal metastases and a TNM stage of 4 (p<0.05. A significantly higher 5-year survival rate was observed in DG patients compared to PG patients (DG: 51%, PG: 28%; p<0.001. A multivariate analysis demonstrated that tumor size, blood loss during surgery, surgery approach of lymph node dissection, treatment with palliative surgery, histopathologic type, TNM stage, and tumor location were independent predictors of poor outcome.Conclusion: The different characteristics and prognosis of DG and PG cases have implications for the development of guiding strategies for a surgical program and assessment of prognosis of gastric cancer patients based on tumor location. Keywords: gastric cancer, tumor location, clinicopathologic features, prognosis, distal gastric cancer, proximal gastric cancer 

  3. 9. Poor medication

    African Journals Online (AJOL)

    Sitwala

    Majority (60%) of the patients were reviewed at least twice in the last 6 months at the time of the interview. 195 (83%) patients reported that drugs prescribed were not available at the hospital pharmacy, but 186 (79%) of. Factors Associated With Poor Medication Adherence. In Hypertensive Patients In Lusaka, Zambia. 1,4. 1.

  4. 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.

  5. Prognosis of non traumatic coma: The role of some socio-economic ...

    African Journals Online (AJOL)

    Background : Coma occurring in the course of an illness, irrespective of cause, traditionally implies a poor prognosis and many factors may determine its outcome. These factors must be identified and possibly stratified in their order of importance. This research seeks to identify these factors and how they influenced the ...

  6. Status and prognosis of lymph node metastasis in patients with cardia cancer – A systematic review

    DEFF Research Database (Denmark)

    Okholm, Cecilie; Svendsen, Lars Bo; Achiam, Michael P

    2014-01-01

    BACKGROUND: Adenocarcinoma of the gastroesophageal junction (GEJ) has a poor prognosis and survival rates significantly decreases if lymph node metastasis is present. An extensive lymphadenectomy may increase chances of cure, but may also lead to further postoperative morbidity and mortality. The...

  7. Predicting Prognosis for the Conduct-Problem Boy: Can Family History Help?

    Science.gov (United States)

    Odgers, Candice L.; Milne, Barry J.; Caspi, Avshalom; Crump, Raewyn; Poulton, Richie; Moffitt, Terrie E.

    2007-01-01

    Objective: Many children with conduct disorder develop life-course persistent antisocial behavior; however, other children exhibit childhood-limited or adolescence-limited conduct disorder symptoms and escape poor adult outcomes. Prospective prediction of long-term prognosis in pediatric and adolescent clinical settings is difficult. Improved…

  8. 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...

  9. Diagnostic radiation and its prognosis of pineal region tumor

    International Nuclear Information System (INIS)

    Momose, Toshimitsu; Aoki, Yukimasa; Akanuma, Atsuo; Machida, Tohru; Iio, Masahiro; Takakura, Kimitomo

    1984-01-01

    20 Gy of local irradiation was performed for the patients with pineal region tumor. We evaluated the tumor volume on X-CT in the pre-radiation and 20 Gy of post-radiation state. If tumor is sensitive enough to radiation therapy, we add 40 Gy of whole brain and 30 to 40 Gy of whole spine irradiation. If not, we transfer patients to neurosurgeons for the purpose of tumor ressection. We call this procedure ''Diagnostic Radiation.'' We proposed the concept of TRR (Tumor Regression Ratio) in order to evaluate our protocol more objctively. TRR is as follows: TRR (%) = [1-Total Tumor Volume (at each dose) / Total Tumor Volume (at o Gy)] x 100 (%) Total Tumor Volume(mm 3 ) = slice thickness(mm) x siguma HDA (mm 2 ) on each slice: where HDA is high density area on enhanced CT. Eleven patients were studied and TRR of each patients was calculated. The relations between TRR, tumor markers, CSF seeding and prognoiss was discussed. From our study, (1) TRR at 20Gy was important and might predict approximate prognosis of each cae case. A) TRR = 100 → very good B) TRR < 20 → poor C) 20 <= TRR < 100 → high possibility (2) Majority of TRR < 100 cases have turned out to be histologically in teratoma category. (3) Good correlation between the level of tumor markers and prognosis was observed. Cases with elevated level of AFP and/or HCG were radio- resistant and had poor prognosis. (4) Distant metastasis must also be kept in mind in the treatment of pineal region tumor. (author)

  10. Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available BACKGROUND: The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT. METHODS: The karyopherin 2 (KPNA2 expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125, and the translation level (R = 0.6636, P<0.0001, was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS of OMGCT (P = 0.02. The 5-year overall survival (OS and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48 were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42(P = 0.0151, P = 0.0109, respectively. The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62 was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28(P = 0.0519, P = 0.0647, respectively. CONCLUSIONS: KPNA2 is a potential candidate molecular marker and important prognostic marker in OMGCT patients.

  11. Early Infantile Leigh-like Gene Defects Have a Poor Prognosis: Report and Review

    Directory of Open Access Journals (Sweden)

    Majid Alfadhel

    2017-10-01

    Full Text Available Solute carrier family 19 (thiamine transporter, member 3 ( SCL19A3 gene defect produces an autosomal recessive neurodegenerative disorder associated with different phenotypes and acronyms. One of the common presentations is early infantile lethal Leigh-like syndrome. We report a case of early infantile Leigh-like SLC19A3 gene defects of patients who died at 4 months of age with no response to a high dose of biotin and thiamine. In addition, we report a novel mutation that was not reported previously. Finally, we review the literature regarding early infantile Leigh-like SLC19A3 gene defects and compare the literature with our patient.

  12. 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.

  13. Live birth rates are satisfactory following multiple IVF treatment cycles in poor prognosis patients.

    Science.gov (United States)

    Mustafa, Kamarul B; Keane, Kevin N; Walz, Nikita L; Mitrovic, Katarina I; Hinchliffe, Peter M; Yovich, John L

    2017-03-01

    This seven-year retrospective study analysed the live birth rate (LBR) for women undergoing IVF treatment with various antral follicle counts (AFC). The LBR decreased with lower AFC ratings, and in 290 treatment cycles for women in the poorest AFC category, ≤4 follicles (group E), the LBR was the lowest at 10.7%. The pregnancy loss rate (PLR) significantly increased with poorer AFC categories, from 21.8% in AFC group A (≥20 follicles), to 54.4% in AFC group E (p<0.0001). This trend was repeated with advancing age, from 21.6% for younger women (<35years), to 32.9, 48.5 and 100% for ages 35-39, 40-44 and ≥45 years, respectively (p<0.0001). However, LBR within the specific AFC group E cohort was also age-dependent and decreased significantly from 30.0% for <35 years old, to 13.3, 3.9 and 0% for patients aged 35-39, 40-44 and ≥45 years, respectively. Most, importantly, LBR rates within these age groups were not dependent on the number of IVF attempts (1st, 2nd, 3rd or ≥4 cycles), which indicated that cycle number should not be the primary deciding factor for cessation of IVF treatment in responding women <45years old. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

    Directory of Open Access Journals (Sweden)

    Shahriar Koochekpour

    Full Text Available Reduction or depletion of mitochondrial DNA (mtDNA has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA and Caucasian American (CA men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients 7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

  15. Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

    Science.gov (United States)

    Koochekpour, Shahriar; Marlowe, Timothy; Singh, Keshav K; Attwood, Kristopher; Chandra, Dhyan

    2013-01-01

    Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA) and Caucasian American (CA) men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients 7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

  16. High ASMA+ Fibroblasts and Low Cytoplasmic HMGB1+ Breast Cancer Cells Predict Poor Prognosis.

    Science.gov (United States)

    Amornsupak, Kamolporn; Jamjuntra, Pranisa; Warnnissorn, Malee; O-Charoenrat, Pornchai; Sa-Nguanraksa, Doonyapat; Thuwajit, Peti; Eccles, Suzanne A; Thuwajit, Chanitra

    2017-10-01

    The influence of cancer-associated fibroblasts (CAFs) and high mobility group box 1 (HMGB1) has been recognized in several cancers, although their roles in breast cancer are unclear. The present study aimed to determine the levels and prognostic significance of α-smooth muscle actin-positive (ASMA + ) CAFs, plus HMGB1 and receptor for advanced glycation end products (RAGE) in cancer cells. A total of 127 breast samples, including 96 malignant and 31 benign, were examined for ASMA, HMGB1, and RAGE by immunohistochemistry. The χ 2 test and Fisher's exact test were used to test the association of each protein with clinicopathologic parameters. The Kaplan-Meier method or log-rank test and Cox regression were used for survival analysis. ASMA + fibroblast infiltration was significantly increased in the tumor stroma compared with that in benign breast tissue. The levels of cytoplasmic HMGB1 and RAGE were significantly greater in the breast cancer tissue than in the benign breast tissues. High ASMA expression correlated significantly with large tumor size, clinical stage III-IV, and angiolymphatic and perinodal invasion. In contrast, increased cytoplasmic HMGB1 correlated significantly with small tumor size, pT stage, early clinical stage, luminal subtype (but not triple-negative subtype), and estrogen receptor and progesterone receptor expression. The levels of ASMA (hazard ratio, 14.162; P = .010) and tumor cytoplasmic HMGB1 (hazard ratio, 0.221; P = .005) could serve as independent prognostic markers for metastatic relapse in breast cancer patients. The ASMA-high/HMGB1-low profile provided the most reliable prediction of metastatic relapse. We present for the first time, to the best of our knowledge, the potential clinical implications of the combined assessment of ASMA + fibroblasts and cytoplasmic HMGB1 in breast cancer. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Multigenerational Positive Family History of Psychiatric Disorders Is Associated With a Poor Prognosis in Bipolar Disorder

    NARCIS (Netherlands)

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

    2015-01-01

    The authors assessed how family history loading affected the course of illness in patients from the United States. A total of 676 outpatients with bipolar disorder from the United States rated their illness and provided a parental and grandparental history of mood disorder, substance abuse, and

  18. A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Fei Ma

    Full Text Available INTRODUCTION: Triple-negative breast cancer (TNBC is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs. MATERIALS AND METHODS: The surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed. RESULTS: Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014. The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003. Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS in both lymph node positive (LN+ and negative (LN- cases (both P<0.001. Similarly it was also associated with shorter overall survival (OS(P = 0.003 in LN+ cases; P = 0.018 in LN- cases. In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P = 0.008. Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002. However, neither CLDN4 nor CLDN7 expression was associated with survival. CONCLUSION: In TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor in this heterogeneous subtype of breast cancer.

  19. Downregulation of ZNF132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis

    DEFF Research Database (Denmark)

    Abildgaard, Mette Opstrup; Borre, Michael; Mørck Mortensen, Martin

    2012-01-01

    This study investigates the expression and biomarker potential of zinc finger protein 132 (ZNF132) in prostate cancer (PC) by transcriptional profiling and immunohistochemical analysis of tissue microarrays, including tumor specimens from 615 radical prostatectomy (RP) patients and 199...... conservatively treated patients. Primary clinical endpoints were time to PSA recurrence and cancer-specific death, respectively. Compared to normal prostate epithelial cells from men without PC, ZNF132 transcript levels were significantly reduced in PC cells from patients with localized PC and further...... immunoreactivity was significantly associated with high Gleason score and advanced T stage in both PC patient cohorts. By univariate analysis, no/weak ZNF132 staining was a significant adverse predictor of PSA recurrence after RP (p = 0.024) and cancer-specific death following conservative treatment (p = 0...

  20. Obesity and smoking are factors associated with poor prognosis in patients with bacteraemia

    Directory of Open Access Journals (Sweden)

    Vuento Risto

    2007-03-01

    Full Text Available Abstract Background Bacteraemia is still a major cause of case fatality in all age groups. Our aim was to identify the major underlying conditions constituting risk factors for case fatality in bacteraemia patients. Methods The study involved 149 patients (79 male and 70 female with bacteraemia caused by Staphylococcus aureus (S. aureus (41 patients, Streptococcus pneumoniae (Str. pneumoniae (42 patients, β-hemolytic streptococcae (β-hml str. (23 patients and Eschericia coli (E. coli (43 patients. Underlying diseases, alcohol and tobacco consumption and body mass index (BMI were registered. Laboratory findings and clinical data were registered on admission and 6 consecutive days and on day 10–14. Case fatality was studied within 30 days after positive blood culture. Associations between underlying conditions and case fatality were studied in univariate analysis and in a multivariate model. Results Nineteen patients (12.8% died of bacteraemia. We found obesity (p = 0.002, RR 9.8; 95% CI 2.3 to 41.3, smoking (p Conclusion Our results indicate that obesity and smoking are prominent risk factors for case fatality in bacteraemic patients. Identification of risk factors underlying fatal outcome in bacteraemia may allow targeting of preventive efforts to individuals likely to derive greatest potential benefit.

  1. Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer.

    Science.gov (United States)

    Takayama, Hitoshi; Nonomura, Norio; Nishimura, Kazuo; Oka, Daizo; Shiba, Masahiro; Nakai, Yasutomo; Nakayama, Masashi; Tsujimura, Akira; Aozasa, Katsuyuki; Okuyama, Akihiko

    2009-02-01

    The aim of this study is to evaluate the expression of the macrophage scavenger receptor (MSR) in prostate needle biopsy specimens as a possible prognostic factor for prostate cancer. As MSR reportedly has a role in recognizing foreign pathogenic substances, MSR-positive inflammatory cells are often detected in solid tumours, and there is a correlation between the relative risk of prostate cancer and polymorphism of the MSR gene. MSR was evaluated by immunostaining in needle biopsies of the prostate from 135 patients who were confirmed to have prostate cancer. Among these men, 70 were treated by radical prostatectomy or by radiotherapy as definitive therapy; the other 65 were treated by hormonal therapy because of advanced disease or age. Needle-biopsy specimens were sectioned at 5 microm and immunostained with a monoclonal antibody against MSR. Six microscopic (x400) fields around the cancer foci were selected in each case for analysis. The median number of MSR-positive cells (MSR count) in each case was 24. There was an inverse correlation between the MSR count and Gleason score and clinical stage. The MSR count was lower in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (P or =24) than that in those with low MSR count (<24, P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with a higher MSR count were higher than in those with a lower MSR count (P < 0.001 and 0.014, respectively). Cox multivariate analysis showed that the MSR count was a prognostic factor for prostate cancer in addition to extraprostatic extension and Gleason score (P = 0.002, 0.038 and 0.011, respectively). The results of immunostaining of MSR in needle-biopsy specimens is a prognostic factor for prostate cancer.

  2. Low incidence but poor prognosis of complicated coeliac disease: a retrospective multicentre study.

    Science.gov (United States)

    Biagi, Federico; Gobbi, Paolo; Marchese, Alessandra; Borsotti, Edoardo; Zingone, Fabiana; Ciacci, Carolina; Volta, Umberto; Caio, Giacomo; Carroccio, Antonio; Ambrosiano, Giuseppe; Mansueto, Pasquale; Corazza, Gino R

    2014-03-01

    Coeliac disease is a chronic enteropathy characterized by an increased mortality caused by its complications, mainly refractory coeliac disease, small bowel carcinoma and abdominal lymphoma. Aim of the study was to study the epidemiology of complications in patients with coeliac disease. Retrospective multicenter case-control study based on collection of clinical and laboratory data. The incidence of complicated coeliac disease was studied among coeliac patients directly diagnosed in four Italian centres. Patients referred to these centres after a diagnosis of coeliac disease and/or complicated coeliac disease in other hospitals were therefore excluded. Between 1/1999 and 10/2011, 1840 adult coeliac patients were followed up for 7364.3 person-years. Fourteen developed complications. Since five patients died, at the end of the observation period (10/2011), the prevalence of complicated coeliac disease was 9/1835 (1/204, 0.49%, 95% CI 0.2-0.9%). The annual incidence of complicated coeliac disease in the study period was 14/7364 (0.2%, 95% CI 0.1-0.31%). Although complications tend to occur soon after the diagnosis of coeliac disease, Kaplan-Meier curve analysis showed that they can actually occur at any time after the diagnosis of coeliac disease. Complications of coeliac disease in our cohort were quite rare, though characterised by a very high mortality. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. PRAF2 stimulates cell proliferation and migration and predicts poor prognosis in neuroblastoma

    NARCIS (Netherlands)

    Yco, Lisette P.; Geerts, Dirk; Koster, Jan; Bachmann, André S.

    2013-01-01

    Prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is a novel 19-kDa protein with four transmembrane-spanning domains that belongs to the PRAF protein family. Neuroblastoma (NB) is the most common malignant extracranial solid tumor of childhood that originates in primitive cells of the

  4. 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.

  5. True Local Recurrences after Breast Conserving Surgery have Poor Prognosis in Patients with Early Breast Cancer

    Science.gov (United States)

    Sarsenov, Dauren; Ilgun, Serkan; Ordu, Cetin; Alco, Gul; Bozdogan, Atilla; Elbuken, Filiz; Nur Pilanci, Kezban; Agacayak, Filiz; Erdogan, Zeynep; Eralp, Yesim; Dincer, Maktav

    2016-01-01

    Background: This study was aimed at investigating clinical and histopathologic features of ipsilateral breast tumor recurrences (IBTR) and their effects on survival after breast conservation therapy. Methods: 1,400 patients who were treated between 1998 and 2007 and had breast-conserving surgery (BCS) for early breast cancer (cT1-2/N0-1/M0) were evaluated. Demographic and pathologic parameters, radiologic data, treatment, and follow-up related features of the patients were recorded. Results: 53 patients (3.8%) had IBTR after BCS within a median follow-up of 70 months. The mean age was 45.7 years (range, 27-87 years), and 22 patients (41.5%) were younger than 40 years. 33 patients (62.3%) had true recurrence (TR) and 20 were classified as new primary (NP). The median time to recurrence was shorter in TR group than in NP group (37.0 (6-216) and 47.5 (11-192) months respectively; p = 0.338). Progesterone receptor positivity was significantly higher in the NP group (p = 0.005). The overall 5-year survival rate in the NP group (95.0%) was significantly higher than that of the TR group (74.7%, p 20 mm), high grade tumor and triple-negative molecular phenotype along with developing TR negatively affected overall survival (hazard ratios were 4.2 (CI 0.98-22.76), 4.6 (CI 1.07-13.03), 4.0 (CI 0.68-46.10), 6.5 (CI 0.03-0.68), and 6.5 (CI 0.02- 0.80) respectively, p 2 cm), high grade, triple negative phenotype, and having true recurrence were identified as independent prognostic factors with a negative impact on overall survival in this dataset of patients with recurrent breast cancer. In conjunction with a more intensive follow-up program, the role of adjuvant therapy strategies should be explored further in young patients with large and high-risk tumors to reduce the risk of TR. PMID:27158571

  6. Evaluation of Ahmed valve in the glaucoma of poor surgical prognosis

    OpenAIRE

    García González, Francisco; Novoa Sánchez, Ester; San Martín Geisse, Raúl

    2001-01-01

    Se intervinieron 8 pacientes con glaucoma de mal pronóstico quirúrgico a los que se les implantaron una válvula de Ahmed con la técnica quirúrgica convencional. Se logró controlar la presión intraocular (PIO). Las complicaciones fueron: hipotonía (75 %), desprendimiento coroideo (37,5 %), hifema (25,0 %), contacto tubo iridiano (25, 0 %), hipotalamia (12,5 %) y congestión en el área del implante (12,5 %). No hubo complicaciones intraoperatorias. Se obtuvieron resultados satisfactorios a media...

  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. Novel Biomarker for Prognosis, Treatment Response

    Science.gov (United States)

    An NCI Cancer Currents blog about a study of a new type of cancer biomarker that measures the extent of chromosomal instability as a way to potentially predict patient prognosis and help guide cancer treatment choices.

  9. Prognosis of breast cancer is associated with one-carbon metabolism related nutrients among Korean women

    Directory of Open Access Journals (Sweden)

    Lee Yunhee

    2012-08-01

    Full Text Available Abstract Background The 5-year survival rate for breast cancer among Korean women has increased steadily; however, breast cancer remains the leading cause of cancer mortality among women. One-carbon metabolism, which requires an adequate supply of methyl group donors and B vitamins, may affect the prognosis of breast cancer. This aim of this study was to investigate the associations of dietary intake of vitamin B2, vitamin B6 and folate before diagnosis on the prognosis of breast cancer. Methods We assessed the dietary intake using a food frequency questionnaire with 980 women who were newly diagnosed and histopathologically confirmed to have primary breast cancer from hospitals in Korea, and 141 disease progression events occurred. Cox’s proportional hazard regression models were used to estimate the hazard ratio (HR and 95% confidence interval (95% CI adjusting for age, education, recruitment sites, TNM stage, hormone status, nuclear grade and total calorie. Results There was no significant association between any one-carbon metabolism related nutrients (vitamin B2, B6 and folate and the progression of breast cancer overall. However, one-carbon metabolism related nutrients were associated with disease progression in breast cancer patients stratified by subtypes. In ER + and/or PR + breast cancers, no association was observed; however, in ER–/PR– breast cancers, a high intake of vitamin B2 and folate statistically elevated the HR of breast cancer progression (HR = 2.28; 95% CI, 1.20-4.35, HR = 1.84; 95% CI, 1.02-3.32, respectively compared to a low intake. This positive association between the ER/PR status and progression of the disease was profound when the nutrient intakes were categorized in a combined score (Pinteraction = 0.018. In ER–/PR– breast cancers, high combined scores were associated with a significantly poor DFS compared to those belonging to the low score group (HR = 3.84; 95% CI, 1

  10. Tc-99m-Labeled-rhTSH Analogue (TR1401) for Imaging Poorly Differentiated Metastatic Thyroid Cancer

    NARCIS (Netherlands)

    Galli, Filippo; Manni, Isabella; Piaggio, Giulia; Balogh, Lajos; Weintraub, Bruce D.; Szkudlinski, Mariusz W.; Fremont, Valerie; Dierckx, Rudi A. J. O.; Signore, Alberto

    2014-01-01

    Background: Differentiated thyroid carcinomas originating from thyroid follicular cells are frequent tumors of the thyroid with relatively good prognosis due to improved surgical techniques and follow-up procedures. Poorly differentiated thyroid cancers, which lose iodine uptake ability, in most

  11. Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

    Science.gov (United States)

    Zhao, Hongying; Yuan, Huating; Hu, Jing; Xu, Chaohan; Liao, Gaoming; Yin, Wenkang; Xu, Liwen; Wang, Li; Zhang, Xinxin; Shi, Aiai; Li, Jing; Xiao, Yun

    2017-12-12

    Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

  12. Machinery prognostics and prognosis oriented maintenance management

    CERN Document Server

    Yan, Jihong

    2014-01-01

    This book gives a complete presentatin of the basic essentials of machinery prognostics and prognosis oriented maintenance management, and takes a look at the cutting-edge discipline of intelligent failure prognosis technologies for condition-based maintenance.  Latest research results and application methods are introduced for signal processing, reliability moelling, deterioration evaluation, residual life prediction and maintenance-optimization as well as applications of these methods.

  13. Subtypes and Prognosis of Guillain-Barré Syndrome in Southwest China.

    Directory of Open Access Journals (Sweden)

    Gang Zhang

    Full Text Available The proportion of different subtypes of Guillain-Barré syndrome (GBS and their prognosis varied significantly among different regions. This study attempts to investigate the clinical subtypes and outcome of GBS in southwest China. Patients with GBS admitted to The First Affiliated Hospital of Chongqing Medical University from January 2006 to March 2013 were included in our study. Patients were classified into acute inflammatory demyelinating polyneuropathy (AIDP group, acute motor axonal neuropathy (AMAN group, Miller-Fisher syndrome (MFS group, cranial nerve variants(CNV, Bickerstaff's brainstem encephalitis overlaps with GBS (BBE-GBS group and unclassifiable group based on clinical features and electrophysiological findings. Hughes function grade score (HFGS was used to assess the prognosis at 3 and 6 months. The prognosis of different subtypes and outcome predictors were analyzed. The most common subtype of GBS was AIDP (57%, followed by AMAN (22% and MFS (7%. The prognosis of AMAN and BBE-GBS is similar at 3 month(P = 0.0704and 6 month (P = 0.1614 follow-up. The prognosis of AMAN group was poorer than that of AIDP group at 3 month and 6 month follow-up (P<0.001. Outcome of MFS group and that of CNV group at 6 months were both good(Hughes≤1. Hughes≥3(P<0.0001,OR = 6.650,95%CI = 2.865 to 15.023and dysautonomia (P = 0.043,OR = 2.820,95%CI = 1.031 to 7.715 were associated with poor outcome at 6 month follow-up. AIDP is the most common subtype of GBS. Prognosis of AMAN group and BBE-GBS group is poorer than that of AIDP group at 3 month and 6 month follow-up. Hughes≥3 at nadir and dysautonomia are predictors of poor prognosis at 6 month follow-up.

  14. Prognosis of occupational hand eczema

    DEFF Research Database (Denmark)

    Cvetkovski, Rikke Skoet; Zachariae, Robert; Jensen, Hans Henrik

    2006-01-01

    OBJECTIVE: To identify prognostic risk factors in patients with occupational hand eczema (OHE). DESIGN: Cohort study with 1-year follow-up. SETTING: Danish National Board of Industrial Injuries Registry. PATIENTS: All patients with newly recognized OHE (758 cases) from October 1, 2001, through...... it. MAIN OUTCOME MEASURES: Persistently severe or aggravated OHE, prolonged sick leave, and loss of job after 1-year follow-up. RESULTS: During the follow-up period, 25% of all patients with OHE had persistently severe or aggravated disease, 41% improved, and 34% had unchanged minimal or mild...... to moderate disease. Patients with atopic dermatitis fared poorly compared with other patients. Patients younger than 25 years fared clearly better than older groups. Furthermore, severe OHE, age 40 years or greater, and severe impairment of quality of life at baseline appeared to be important predictors...

  15. Savings for the Poor

    OpenAIRE

    Ignacio Mas

    2010-01-01

    This paper reviews the relevance of formal financial services – in particular, savings – to poor people, the economic factors that have hindered the mass-scale delivery of such services in developing countries, and the technology-based opportunities that exist today to make massive gains in financial inclusion. It also highlights the benefits to government from universal financial access, as well as the key policy enablers that would need to be put in place to allow the necessary innovati...

  16. Poorly Differentiated Thyroid Carcinoma.

    Science.gov (United States)

    Setia, Namrata; Barletta, Justine A

    2014-12-01

    Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. Published by Elsevier Inc.

  17. Protocol: a systematic review of studies developing and/or evaluating search strategies to identify prognosis studies.

    Science.gov (United States)

    Corp, Nadia; Jordan, Joanne L; Hayden, Jill A; Irvin, Emma; Parker, Robin; Smith, Andrea; van der Windt, Danielle A

    2017-04-20

    Prognosis research is on the rise, its importance recognised because chronic health conditions and diseases are increasingly common and costly. Prognosis systematic reviews are needed to collate and synthesise these research findings, especially to help inform effective clinical decision-making and healthcare policy. A detailed, comprehensive search strategy is central to any systematic review. However, within prognosis research, this is challenging due to poor reporting and inconsistent use of available indexing terms in electronic databases. Whilst many published search filters exist for finding clinical trials, this is not the case for prognosis studies. This systematic review aims to identify and compare existing methodological filters developed and evaluated to identify prognosis studies of any of the three main types: overall prognosis, prognostic factors, and prognostic [risk prediction] models. Primary studies reporting the development and/or evaluation of methodological search filters to retrieve any type of prognosis study will be included in this systematic review. Multiple electronic bibliographic databases will be searched, grey literature will be sought from relevant organisations and websites, experts will be contacted, and citation tracking of key papers and reference list checking of all included papers will be undertaken. Titles will be screened by one person, and abstracts and full articles will be reviewed for inclusion independently by two reviewers. Data extraction and quality assessment will also be undertaken independently by two reviewers with disagreements resolved by discussion or by a third reviewer if necessary. Filters' characteristics and performance metrics reported in the included studies will be extracted and tabulated. To enable comparisons, filters will be grouped according to database, platform, type of prognosis study, and type of filter for which it was intended. This systematic review will identify all existing validated

  18. Chalkley estimates of angiogenesis in early breast cancer--relevance to prognosis

    DEFF Research Database (Denmark)

    Offersen, Birgitte V; Sørensen, Flemming Brandt; Yilmaz, Mette

    2002-01-01

    The aim of this study was to investigate whether Chalkley estimates of angiogenesis add new knowledge regarding prediction of prognosis in 455 consecutive early breast carcinomas, both node-positive (52%) and node-negative (48%). Median follow-up was 101 months. Intense vascularization indicated......, high malignancy grade, negative oestrogen receptor, and increasing Chalkley counts (both tertiles and continuous) were independent markers of disease-specific death. Thus, in a univariate analysis it was found that high Chalkley estimates of angiogenesis indicated a poor prognosis, but high Chalkley...

  19. [Poor insight and psychosis].

    Science.gov (United States)

    Giotakos, O

    2017-01-01

    A variety of phenomena might be considered as reflecting impaired insight in psychosis, like failure to recognize signs, symptoms or disease, failure to derive appropriate cognitive representations, despite recognition of the disease, and misattribution of the source or cause of the disease. The unawareness of tardive dyskinesia symptoms in schizophrenic patients points that self-awareness deficits in schizophrenia may be domain specific. Poor insight is an independent phenomenological and a prevalent feature in psychotic disorders in general, and in schizophrenia in particular, but we don't know yet if delusions in schizophrenia are the result of an entirely normal attempt to account for abnormal perceptual experiences or a product of abnormal experience but of normal reasoning. The theoretical approaches regarding impaired insight include the disturbed perceptual input, the impaired linkage between thought and emotion and the breakdown of the process of self-monitoring and error checking. The inability to distinguish between internally and externally generated mental events has been described by the metarepresentation theory. This theory includes the awareness of ones' goals, which leads to disorders of willed action, the awareness of intention, which leads to movement disorders, and the awareness of intentions of others, which leads to paranoid delusions. The theory of metarepresentation implies mainly output mechanisms, like the frontal cortex, while the input mechanism implies posterior brain systems, including the parietal lobe. There are many similarities between the disturbances of awareness seen in schizophrenia and those seen as a result of known neurological impairment. Neuropsychological models of impaired insight typically attribute the disturbance to any of a variety of core deficits in the processing of information. In this respect, lack of insight is on conceptual par with alogia, apraxia or aphasia in reflecting disturbed cognitive processing. In

  20. Fish remains and humankind: part two

    Directory of Open Access Journals (Sweden)

    Andrew K G Jones

    1998-07-01

    Full Text Available The significance of aquatic resources to past human groups is not adequately reflected in the published literature - a deficiency which is gradually being acknowledged by the archaeological community world-wide. The publication of the following three papers goes some way to redress this problem. Originally presented at an International Council of Archaeozoology (ICAZ Fish Remains Working Group meeting in York, U.K. in 1987, these papers offer clear evidence of the range of interest in ancient fish remains across the world. Further papers from the York meeting were published in Internet Archaeology 3 in 1997.

  1. The 'poor man's laryngogram'

    International Nuclear Information System (INIS)

    Bartelt, D.

    1991-01-01

    This paper is reassessment of an old method improved by well-directed application of well-known maneuvers of laryngo-pharyngeal function. Although not as visually attractive as a dedicated laryngogram (now hardly ever requested), it does render similarly reliable diagnostic information, which, supported, as occasionally necessary, by conventional tomography, can even surpass that given by the older technique. Its main advantage lies in providing cheap, quick, noninvasive studies with minimal descomfort for the patient. Should further investigation be necessary, for analysis of deep extension, modern cross-sectional imaging methods (especially MR) far surpass even dedicated laryngography in diagnostic value and can be based adequately on 'poor mans's laryngography'. Ways in which this method may be optimised, especially those involving laryngopharyngeal function, are briefly presented - with emphasis on relevant practical aspects - as are normal and abnormal findings. (orig.) [de

  2. REMO poor man's reanalysis

    Science.gov (United States)

    Ries, H.; Moseley, C.; Haensler, A.

    2012-04-01

    Reanalyses depict the state of the atmosphere as a best fit in space and time of many atmospheric observations in a physically consistent way. By essentially solving the data assimilation problem in a very accurate manner, reanalysis results can be used as reference for model evaluation procedures and as forcing data sets for different model applications. However, the spatial resolution of the most common and accepted reanalysis data sets (e.g. JRA25, ERA-Interim) ranges from approximately 124 km to 80 km. This resolution is too coarse to simulate certain small scale processes often associated with extreme events. In addition, many models need higher resolved forcing data ( e.g. land-surface models, tools for identifying and assessing hydrological extremes). Therefore we downscaled the ERA-Interim reanalysis over the EURO-CORDEX-Domain for the time period 1989 to 2008 to a horizontal resolution of approximately 12 km. The downscaling is performed by nudging REMO-simulations to lower and lateral boundary conditions of the reanalysis, and by re-initializing the model every 24 hours ("REMO in forecast mode"). In this study the three following questions will be addressed: 1.) Does the REMO poor man's reanalysis meet the needs (accuracy, extreme value distribution) in validation and forcing? 2.) What lessons can be learned about the model used for downscaling? As REMO is used as a pure downscaling procedure, any systematic deviations from ERA-Interim result from poor process modelling but not from predictability limitations. 3.) How much small scale information generated by the downscaling model is lost with frequent initializations? A comparison to a simulation that is performed in climate mode will be presented.

  3. Why Agricultural Educators Remain in the Classroom

    Science.gov (United States)

    Crutchfield, Nina; Ritz, Rudy; Burris, Scott

    2013-01-01

    The purpose of this study was to identify and describe factors that are related to agricultural educator career retention and to explore the relationships between work engagement, work-life balance, occupational commitment, and personal and career factors as related to the decision to remain in the teaching profession. The target population for…

  4. Juveniles' Motivations for Remaining in Prostitution

    Science.gov (United States)

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

    Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…

  5. Kadav Moun PSA (:60) (Human Remains)

    Centers for Disease Control (CDC) Podcasts

    2010-02-18

    This is an important public health announcement about safety precautions for those handling human remains. Language: Haitian Creole.  Created: 2/18/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 2/18/2010.

  6. The Annuity Puzzle Remains a Puzzle

    NARCIS (Netherlands)

    Peijnenburg, J.M.J.; Werker, Bas; Nijman, Theo

    We examine incomplete annuity menus and background risk as possible drivers of divergence from full annuitization. Contrary to what is often suggested in the literature, we find that full annuitization remains optimal if saving is possible after retirement. This holds irrespective of whether real or

  7. Sarcopenia in COPD: relationship with COPD severity and prognosis

    Science.gov (United States)

    Costa, Tatiana Munhoz da Rocha Lemos; Costa, Fabio Marcelo; Moreira, Carolina Aguiar; Rabelo, Leda Maria; Boguszewski, César Luiz; Borba, Victória Zeghbi Cochenski

    2015-01-01

    Objective: To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD. Methods: A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution. The patients underwent dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height2 only for low-weight subjects and adjusted for fat mass in normal/overweight subjects. Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index. Results: We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m2. Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status. Sarcopenia was not associated with the GOLD stage or with FEV1 (used as an indicator of the degree of obstruction). The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001). Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009). The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage. Conclusions: In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis. PMID:26578132

  8. Association of Preoperative Nutritional Status with Prognosis in Patients with Esophageal Cancer Undergoing Salvage Esophagectomy.

    Science.gov (United States)

    Sakai, Makoto; Sohda, Makoto; Miyazaki, Tatsuya; Yoshida, Tomonori; Kumakura, Yuji; Honjo, Hiroaki; Hara, Keigo; Ozawa, Daigo; Suzuki, Shigemasa; Tanaka, Naritaka; Yokobori, Takehiko; Kuwano, Hiroyuki

    2018-02-01

    To investigate whether malnutrition is associated with poor prognosis of patients who undergo salvage esophagectomy. We examined the association between the preoperative prognostic nutritional index (PNI) and prognosis of patients who undergo salvage esophagectomy. We conducted a single-center retrospective study and reviewed hospital patient records for tumor characteristics and patient outcomes. Univariate and multivariate survival analyses were carried out using the Cox proportional hazards regression model. Thirty-two patients with esophageal squamous cell carcinoma (ESCC) who underwent salvage esophagectomy between 1998 and 2015 at our Institute were included in this study. Univariate analysis revealed that clinical response (p=0.045), preoperative PNI (pnutritional status is associated with the prognosis of patients undergoing salvage esophagectomy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Laryngeal Electromyography for Prognosis of Vocal Fold Paralysis.

    Science.gov (United States)

    Pardo-Maza, Adriana; García-Lopez, Isabel; Santiago-Pérez, Susana; Gavilán, Javier

    2017-01-01

    This study aimed to determine the value of laryngeal electromyography in the prognosis of vocal fold paralysis. This is a retrospective descriptive study. This study included 80 patients diagnosed with unilateral or bilateral vocal fold paralysis on flexible laryngoscopy between 2002 and 2014 in a tertiary medical center. Laryngeal electromyography using a standardized protocol was performed; the outcome measures were classified and analyzed into two groups according to the degree of injury. Group 1 included patients with mild to moderate injury, and group 2 included patients with severe to complete injury. Prognosis was correlated with vocal fold motion recovery status with a minimum of 6 months of follow-up since the symptoms onset using positive and negative predictive values. Sixty patients showed acute or chronic recurrent laryngeal neuropathy in laryngeal electromyography. Twelve of 41 patients included in group 1 recovered motion, and 30 of 35 patients included in group 2 did not recover, resulting in 88.2% of positive predictive value and 35.7% of negative predictive value. Our data confirm that laryngeal electromyography is a useful clinical tool in predicting poor recovery in patients with vocal fold paralysis. It allows identification of candidates for early intervention. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  10. Explosives remain preferred methods for platform abandonment

    International Nuclear Information System (INIS)

    Pulsipher, A.; Daniel, W. IV; Kiesler, J.E.; Mackey, V. III

    1996-01-01

    Economics and safety concerns indicate that methods involving explosives remain the most practical and cost-effective means for abandoning oil and gas structures in the Gulf of Mexico. A decade has passed since 51 dead sea turtles, many endangered Kemp's Ridleys, washed ashore on the Texas coast shortly after explosives helped remove several offshore platforms. Although no relationship between the explosions and the dead turtles was ever established, in response to widespread public concern, the US Minerals Management Service (MMS) and National Marine Fisheries Service (NMFS) implemented regulations limiting the size and timing of explosive charges. Also, more importantly, they required that operators pay for observers to survey waters surrounding platforms scheduled for removal for 48 hr before any detonations. If observers spot sea turtles or marine mammals within the danger zone, the platform abandonment is delayed until the turtles leave or are removed. However, concern about the effects of explosives on marine life remains

  11. Fasting blood glucose level and prognosis in non-small cell lung cancer (NSCLC) patients.

    Science.gov (United States)

    Luo, Juhua; Chen, Yea-Jyh; Chang, Li-Jung

    2012-05-01

    Diabetes has been consistently linked to many forms of cancers, such as liver, colorectal, pancreatic, and breast cancer, however, the role of diabetes in outcome among cancer patients remains unclear. In this study, we retrospectively reviewed electronic medical records of 342 inpatients newly diagnosed with NSCLC referred by a teaching hospital cancer center in southern Taiwan between 2005 and 2007 to examine the effects of fasting glucose levels at time of cancer diagnosis on overall survival in patients with non-small cell lung cancer (NSCLC). All patients were followed up until the end of 2010. The Kaplan-Meier method was used to compare survival curves for patients with and without diabetes. The Cox proportional hazards model was used to estimate hazard ratios for the association between diabetes, other prognostic factors and patient survival. We observed that significant prognostic factors for poor overall survival in patients with NSCLC included older age, smoking, poor performance status, advanced stage (stage IIIB or IV), and no cancer-directed surgery treatment. Particularly, we identified that diabetic state defined by fasting blood glucose level ≥126 mg/dl was another independent prognostic factor for these patients. Compared with those who had normal range of fasting glucose level (70-99 mg/dl), patients with high fasting glucose level (≥126 mg/dl) had 69% excess risk of all-cause mortality in patients with NSCLC. Diabetes as indicated by elevated fasting blood glucose was independently associated with a significantly higher risk of all-cause mortality in patients with NSCLC, indicating that diabetes or hyperglycemia effectively controlled may present an opportunity for improving prognosis in NSCLS patients with abnormal glucose level. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Serving the world's poor, profitably.

    Science.gov (United States)

    Prahalad, C K; Hammond, Allen

    2002-09-01

    By stimulating commerce and development at the bottom of the economic pyramid, multi-nationals could radically improve the lives of billions of people and help create a more stable, less dangerous world. Achieving this goal does not require MNCs to spearhead global social-development initiatives for charitable purposes. They need only act in their own self-interest. How? The authors lay out the business case for entering the world's poorest markets. Fully 65% of the world's population earns less than $2,000 per year--that's 4 billion people. But despite the vastness of this market, it remains largely untapped. The reluctance to invest is easy to understand, but it is, by and large, based on outdated assumptions of the developing world. While individual incomes may be low, the aggregate buying power of poor communities is actually quite large, representing a substantial market in many countries for what some might consider luxury goods like satellite television and phone services. Prices, and margins, are often much higher in poor neighborhoods than in their middle-class counterparts. And new technologies are already steadily reducing the effects of corruption, illiteracy, inadequate infrastructure, and other such barriers. Because these markets are in the earliest stages of economic development, revenue growth for multi-nationals entering them can be extremely rapid. MNCs can also lower costs, not only through low-cost labor but by transferring operating efficiencies and innovations developed to serve their existing operations. Certainly, succeeding in such markets requires MNCs to think creatively. The biggest change, though, has to come from executives: Unless business leaders confront their own preconceptions--particularly about the value of high-volume, low-margin businesses--companies are unlikely to master the challenges or reap the rewards of these developing markets.

  13. Outcome of poor response paediatric AML using early SCT.

    Science.gov (United States)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas; Forestier, Erik; Gustafsson, Britt; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Hasle, Henrik

    2013-03-01

    Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients treated with SCT. Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13, matched sibling donors in 6, cord blood donor in 4, and haploidentical donor in two. The median follow-up for the 31 poor responding patients was 2.6 years (range 0.4 - 8.1 years) and 3-year probability of survival 70% (95% CI 59-77%). The poor responders in the NOPHO-AML 2004 protocol had a favourable prognosis treated with time-intensive induction followed by SCT. © 2012 John Wiley & Sons A/S.

  14. Does age affect prognosis in salivary gland carcinoma patients?

    DEFF Research Database (Denmark)

    Bjørndal, Kristine; Larsen, Stine R; Therkildsen, Marianne H

    2016-01-01

    in the young group were WHO performance status 0 and in disease stage I + II, and they presented with significantly more histological low grade tumors. In multivariate analysis, chronological age seemed to be of no prognostic significance to salivary gland carcinoma patients as opposed to performance status......, disease stage and histological grade. CONCLUSIONS: Salivary gland carcinoma patients over the age of 70 years have a poor prognosis compared to younger patients, which can be explained by higher disease stages, more histological high grade subtypes and a poorer performance status at the time of diagnosis.......AIM: To compare incidence, histology, treatment modalities, disease stages, and outcome in elderly patients (≥70 years) compared to younger (

  15. Vocal fold motion outcome based on excellent prognosis with laryngeal electromyography.

    Science.gov (United States)

    Smith, Libby J; Rosen, Clark A; Munin, Michael C

    2016-10-01

    As laryngeal electromyography (LEMG) becomes more refined, accurate predictions of vocal fold motion recovery are possible. Focus has been on outcomes for patients with poor prognosis for vocal fold motion recovery. Limited information is available regarding the expected rate of purposeful vocal fold motion recovery when there is good to normal motor recruitment, no signs of denervation, and no signs of synkinetic activity with LEMG, termed excellent prognosis. The objective of this study is to determine the rate of vocal fold motion recovery with excellent prognosis findings on LEMG after acute recurrent laryngeal nerve injury. Retrospective review. Patients undergoing a standardized LEMG protocol, consisting of qualitative (evaluation of motor recruitment, motor unit configuration, detection of fibrillations, presence of synkinesis) and quantitative (turns analysis) measurements were evaluated for purposeful vocal-fold motion recovery, calculated after at least 6 months since onset of injury. Twenty-three patients who underwent LEMG for acute vocal fold paralysis met the inclusion criteria of excellent prognosis. Eighteen patients (78.3%) recovered vocal fold motion, as determined by flexible laryngoscopy. Nearly 80% of patients determined to have excellent prognosis for vocal fold motion recovery experienced return of vocal fold motion. This information will help clinicians not only counsel their patients on expectations but will also help guide treatment. 4. Laryngoscope, 126:2310-2314, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  16. [Clinical value of angiogenin in predicting the prognosis of patients with idiopathic pulmonary fibrosis].

    Science.gov (United States)

    Bai, Yanling; Zhu, Haiyan; Sun, Qiyu; Gu, Guozhong; Zhang, Lingyu; Li, Ying; Yang, Baofeng

    2017-09-01

    To explore the relationship between angiogenin-1/2 (Ang-1/2) and clinical parameters of idiopathic pulmonary fibrosis (IPF), and to assess the value of Ang-1/2 in predicting the prognosis of patients with IPF. A retrospective analysis was conducted. Ninety-one patients diagnosed as IPF by high resolution CT (HRCT) and lung biopsy admitted to Daqing Oil Field General Hospital from March 2014 to January 2015 were enrolled. The general data, serum parameters and pulmonary function parameters of all patients were collected. After treatment, all of the 91 patients were followed-up to 2 years. The patients were divided into favorable prognosis group and unfavorable <