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Sample records for adverse prognostic marker

  1. Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia

    PubMed Central

    Roumier, Christophe; Peyrouze, Pauline; Gonzales, Fanny; Berthon, Céline; Quesnel, Bruno; Preudhomme, Claude; Behal, Hélène; Duhamel, Alain; Roche-Lestienne, Catherine; Cheok, Meyling

    2016-01-01

    CD81 is a cell surface protein which belongs to the tetraspanin family. While in multiple myeloma its expression on plasma cells is associated with worse prognosis, this has not yet been explored in acute myeloid leukemia (AML). We measured membrane expression of CD81 on AML cells at diagnosis, evaluated its association with AML characteristics and its influence on patient outcome after intensive chemotherapy in a cohort of 134 patients. CD81 was detected in 92/134 (69%) patients. Patients with AML expressing CD81 had elevated leukocyte count (P=0.02) and were more likely classified as intermediate or adverse-risk by cytogenetics (P<0.001). CD81 expression had a negative impact on survival (event-free survival, overall survival and relapse-free survival) in univariate (P<0.001) and in multivariate analyses (P=0.003, 0.002 and <0.001, respectively). CD81 has a negative impact on OS in patients with NPM1 mutation (P=0.01) and in patients ELN-favorable (P=0.002). In conclusion, this cell surface marker may be a new prognostic marker for diagnostic risk classification and a potential therapeutic target for drug development in AML. PMID:27566555

  2. Checkpoint kinase 1 expression is an adverse prognostic marker and therapeutic target in MYC-driven medulloblastoma

    PubMed Central

    Shah, Monil; Mulcahy Levy, Jean M.; Griesinger, Andrea M.; Alimova, Irina; Harris, Peter S.; Birks, Diane K.; Donson, Andrew M.; Davidson, Nathan; Remke, Marc; Taylor, Michael D.; Handler, Michael H.; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

    2016-01-01

    Checkpoint kinase 1 (CHK1) is an integral component of the cell cycle as well as the DNA Damage Response (DDR) pathway. Previous work has demonstrated the effectiveness of inhibiting CHK1 with small-molecule inhibitors, but the role of CHK1 mediated DDR in medulloblastoma is unknown. CHK1, both at the mRNA and protein level, is highly expressed in medulloblastoma and elevated CHK1 expression in Group3 medulloblastoma is an adverse prognostic marker. CHK1 inhibition with the small-molecule drug AZD7762, results in decreased cell growth, increased DNA damage and cell apoptosis. Furthermore, AZD7762 acts in synergy with cisplatin in reducing cell proliferation in medulloblastoma. Similar phenotypic changes were observed with another CHK1 inhibitor, PF477736, as well as genetic knockdown using siRNA against CHK1. Treatments with small-molecule inhibitors of CHK1 profoundly modulated the expression of both upstream and downstream target proteins within the CHK1 signaling pathways. This suggests the presence of a feedback loop in activating CHK1. Overall, our results demonstrate that small-molecule inhibition of CHK1 in combination with, cisplatin, is more advantageous than either treatment alone, especially for Group 3 medulloblastoma, and therefore this combined therapeutic approach serves as an avenue for further investigation. PMID:27449089

  3. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas

    PubMed Central

    Hatanpaa, Kimmo J.; Foong, Chan; Raisanen, Jack M.; Oliver, Dwight; Hiemenz, Matthew C.; Burns, Dennis K.; White, Charles L.; Whitworth, L. Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A.; Fink, Karen; Maher, Elizabeth A.; Bachoo, Robert M.

    2015-01-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n=50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p=0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III). PMID:24519516

  4. High expression of the stem cell marker nestin is an adverse prognostic factor in WHO grade II-III astrocytomas and oligoastrocytomas.

    PubMed

    Hatanpaa, Kimmo J; Hu, Tianshen; Vemireddy, Vamsidhara; Foong, Chan; Raisanen, Jack M; Oliver, Dwight; Hiemenz, Matthew C; Burns, Dennis K; White, Charles L; Whitworth, L Anthony; Mickey, Bruce; Stegner, Martha; Habib, Amyn A; Fink, Karen; Maher, Elizabeth A; Bachoo, Robert M

    2014-03-01

    Infiltrating astrocytomas and oligoastrocytomas of low to anaplastic grade (WHO grades II and III), in spite of being associated with a wide range of clinical outcomes, can be difficult to subclassify and grade by the current histopathologic criteria. Unlike oligodendrogliomas and anaplastic oligodendrogliomas that can be identified by the 1p/19q codeletion and the more malignant glioblastomas (WHO grade IV astrocytomas) that can be diagnosed solely based on objective features on routine hematoxylin and eosin sections, no such objective criteria exist for the subclassification of grade II-III astrocytomas and oligoastrocytomas (A+OA II-III). In this study, we evaluated the prognostic and predictive value of the stem cell marker nestin in adult A+OA II-III (n = 50) using immunohistochemistry and computer-assisted analysis on tissue microarrays. In addition, the correlation between nestin mRNA level and total survival was analyzed in the NCI Rembrandt database. The results showed that high nestin expression is a strong adverse prognostic factor for total survival (p = 0.0004). The strength of the correlation was comparable to but independent of the isocitrate dehydrogenase 1/2 (IDH 1/2) mutation status. Histopathological grading and subclassification did not correlate significantly with outcome, although the interpretation of this finding is limited by the fact that grade III tumors were treated more aggressively than grade II tumors. These results suggest that nestin level and IDH 1/2 mutation status are strong prognostic features in A+OA II-III and possibly more helpful for treatment planning than routine histopathological variables such as oligodendroglial component (astrocytoma vs. oligoastrocytoma) and WHO grade (grade II vs. III).

  5. In Vivo Assessment of Pulmonary Arterial Wall Fibrosis by Intravascular Optical Coherence Tomography in Pulmonary Arterial Hypertension: A New Prognostic Marker of Adverse Clinical Follow-Up§

    PubMed Central

    Domingo, Enric; Grignola, Juan C; Aguilar, Rio; Montero, María Angeles; Arredondo, Christian; Vázquez, Manuel; López-Messeguer, Manuel; Bravo, Carlos; Bouteldja, Nadia; Hidalgo, Cristina; Roman, Antonio

    2013-01-01

    Background: The aim is to correlate pulmonary arterial (PA) remodeling estimated by PA fibrosis in PA hypertension (PAH) with clinical follow-up. Histology of PA specimens is also performed. Methods: 19 patients, aged 54±16 (4 men), functional class II-III were studied with right heart catheterization, PA Intravascular Ultrasound and optical coherence tomography (OCT) in inferior lobe segment. PA wall fibrosis was obtained by OCT ( area of fibrosis/PA cross sectional area × 100). Patients follow-up was blind to OCT. Events were defined as mortality, lung transplantation, need of intravenous prostaglandins or onset of right ventricular failure. Results: OCT measurements showed high intra- and interobserver agreement. There was a good correlation between OCT and histology in PA fibrosis from explanted lungs. Area of fibrosis was 1.4±0.8 mm2, % fibrosis was 22.3±8. Follow-up was 3.5 years (2.5-4.5). OCT %Fib was significantly correlated with PA capacitance (r=-0.536) and with pulmonary vascular rsistance (r=0.55). Patients were divided according to the median value of PA fibrosis. There were 10 patients with a high (≥ 22%) and 9 with a low fibrosis (<22%). Events occurred in 6 (1 death, 1 lung transplantation, 2 intravenous prostaglandins, 2 right heart failure) out of 10 patients with high and in 0 out of 9 patients with low fibrosis (p<0.01). Conclusions: In PAH, the severity of PA remodeling assessed by OCT wall fibrosis was significantly predictive of severely unfavorable clinical outcome. In vivo assessment of pulmonary arterial wall fibrosis by intravascular OCT in PAH is a promising new prognostic marker of adverse clinical outcome. PMID:23730366

  6. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  7. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2013-10-01

    aims. Ethics approval has been obtained for the samples collection of AIM1. The chromosome 16p13.3 gain was found to be associated with high Gleason...Prostate cancer, Genomic alteration, Fluorescence in situ hybridization (FISH), Prognostic markers, ectopic expression, gene silencing, cDNA cloning ...In regard to AIM1 and AIM2, we have recently obtained the final approval from the Ethics committee of our hospital after a lengthy process. We have

  8. New prognostic markers in liver cirrhosis

    PubMed Central

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-01-01

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of “inflammatory stress” and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value. PMID:26019739

  9. New prognostic markers in liver cirrhosis.

    PubMed

    Di Martino, Vincent; Weil, Delphine; Cervoni, Jean-Paul; Thevenot, Thierry

    2015-05-28

    Determining the prognosis of cirrhotic patients is not an easy task. Prognostic scores, like Child-Pugh and Model of End-stage Liver Disease scores, are commonly used by hepatologists, but do not always reflect superimposed events that may strongly influence the prognosis. Among them, bacterial intestinal translocation is a key phenomenon for the development of cirrhosis-related complications. Several biological variables (C-reactive protein, serum free cortisol, copeptin, von Willebrand factor antigen) are surrogates of "inflammatory stress" and have recently been identified as potential prognostic markers in cirrhotic patients. Most of these above mentioned markers were investigated in pilot studies with sometimes a modest sample size but allow us to catch a glimpse of the pathophysiological mechanisms leading to the worsening of cirrhosis. These new data should generate further well-designed studies to better assess the benefit for liver function of preventing intestinal bacterial translocation and microvascular thrombosis. The control of infection is vital and among all actors of immunity, vitamin D also appears to act as an anti-infective agent and therefore has probably a prognostic value.

  10. Lipoprotein Lipase as a Prognostic Marker in Chronic Lymphocytic Leukemia.

    PubMed

    Mátrai, Zoltán; Andrikovics, Hajnalka; Szilvási, Anikó; Bors, András; Kozma, András; Ádám, Emma; Halm, Gabriella; Karászi, Éva; Tordai, Attila; Masszi, Tamás

    2017-01-01

    The marked clinical heterogeneity of CLL makes early prognosis assessment important. Lipoprotein lipase (LPL) has been shown to confer adverse prognosis in CLL, recent data indicating it might also contribute to CLL cell survival and metabolism. We determined LPL mRNA expression in unselected peripheral blood of 84 CLL patients by RT PCR. Results were correlated with other prognostic markers and outcome. 30/84 (40 %) of cases were LPL positive based on the cutoff established by ROC analysis. In LPL positive patients significantly shorter median survival (136 vs 258 months, p < 0.0001) and time to first treatment intervals (36 vs 144 months, p < 0.002) were documented. LPL values correlated with male gender, higher stages, more treatment requirement, CD38 positivity and unmutated IgVH genes. Among cases with 13q deletion, LPL positivity identified a subcohort with poor outcome (median survival 108 months vs NR, p < 0.0001). In multivariate analysis, cytogenetic aberrations and LPL had significant impact on survival. Our results confirm that LPL is a strong predictor of outcome in CLL, able to improve prognostic accuracy in good risk cytogenetic subgroups. The relationship between its prognostic and functional role in CLL needs to be explored further.

  11. Prognostic significance of adverse events in patients with hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Granito, Alessandro; Marinelli, Sara; Negrini, Giulia; Menetti, Saverio; Benevento, Francesca; Bolondi, Luigi

    2016-01-01

    Sorafenib is the standard treatment for patients with hepatocellular carcinoma (HCC) with advanced stage disease. Although its effectiveness has been demonstrated by randomized clinical trials and confirmed by field practice studies, reliable markers predicting therapeutic response have not yet been identified. Like other tyrosine kinase inhibitors, treatment with sorafenib is burdened by the development of adverse effects, the most frequent being cutaneous toxicity, diarrhoea, arterial hypertension and fatigue. In recent years, several studies have analysed the correlation between off-target effects and sorafenib efficacy in patients with HCC. In this review, an overview of the studies assessing the prognostic significance of sorafenib-related adverse events is provided. PMID:26929785

  12. Prognostic markers of symptomatic congenital cytomegalovirus infection.

    PubMed

    Romanelli, Roberta Maia de Castro; Magny, Jean François; Jacquemard, François

    2008-02-01

    The objective of this research was to identify maternal and fetal characteristics as prognostic markers of congenital cytomegalovirus (CMV) infection. This is a descriptive study of 13 cases of congenital CMV infection referred to Institute de Puericulture et Perinatologie de Paris (IPP) from January 2005 to October 2006. Amniotic fluid puncture was performed to research CMV polimerase chain reaction (PCR). Cordocentesis and cord blood samples at delivery were also analyzed to determinate fetal platelets count, GGT, ASAT, ALAT, CMV-DNA and IgM antibody. Variables of symptomatic and asymptomatic infants were then compared. Data were analyzed by SPSS--15.0. Mean gestational age of amniocentesis was 24.6 weeks and there was no difference of mean viral load in amniotic fluid considering infant features. Mean gestational age of cordocentesis was 26.1 weeks. There were no statistical differences of fetal viral load, IgM, platelets, GGT, ASAT and ALAT analyzed at cordocentesis samples, but at delivery, mean values of IgM and ASAT of fetal blood were increased in symptomatic ones (p= 0.03 for both parameters). When considering groups with normal and abnormal parameters, ASAT of cordon samples was also increased in symptomatic infants (p= 0.02). Sensibility, specificity, positive and negative predictive value of fetal ultrasound anomalies to detect symptomatic infants were, respectively, 80%, 62.5%, 57.1% and 83.3%. Thus, identification of markers of CMV symptomatic infants should be aimed. Prenatal diagnosis, identification and follow up of congenital CMV infected infants are important to consider treatment for symptomatic infants, trying to avoid or reducing some possible sequels.

  13. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2014-10-01

    Assessment post- Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict early...operative PSA levels, GS, T-Stage and CAPRA -S risk scores respectively, improved the overall prognostication in these patients (log rank, Pɘ.001...Risk Assessment post-Surgical ( CAPRA -S) nomogram (pɘ.05 respectively). Importantly, the 16p13.3 gain status was found to significantly predict

  14. Prognostic markers and stratification of chronic lymphocytic leukemia.

    PubMed

    Furman, Richard R

    2010-01-01

    Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies and is characterized by a tremendously variable clinical course. Additionally, whereas the median age at diagnosis is 72 years, CLL is diagnosed with increasing frequency in younger patients. Given the toxicities associated with currently available therapies, being able to predict which patients will need treatment could play a significant role in preserving bone marrow function and reducing morbidity and mortality. While a great many prognostic markers have been identified that predict outcomes for patients with CLL. Learning how to use these prognostic markers to provide patient care is more difficult.

  15. Predictive and prognostic value of preoperative serum tumor markers in resectable adenosqamous lung carcinoma

    PubMed Central

    Yue, Dongsheng; Li, Kai; Jiang, Richeng

    2016-01-01

    Background Adenosquamous carcinoma is a rare and aggressive form of lung cancer. The prognostic and predictive value of preoperative serum tumor markers and frequency of EGFR mutations in adenosquamous lung carcinoma are unclear. Methods We retrospectively analyzed data and samples collected from 106 radically resected adenosquamous lung carcinoma patients with pathological stage I-IIIA between 2008 and 2013. Correlations between serum tumor marker levels and EGFR mutations as well as survival parameters were analyzed and prognostic factors were identified. Results Of the 106 adenosquamous lung carcinoma patients, 29 (27.4%) harbored EGFR mutations. By univariate analysis, advanced clinical stage (P = 0.009 for disease-free survival [DFS]; P = 0.046 for overall survival [OS]), larger tumor size (P = 0.001 for DFS; P = 0.002 for OS), regional lymph node metastasis (P = 0.024 for DFS; P = 0.030 for OS), higher NSE level (P = 0.002 for DFS; P < 0.001 for OS), and higher TMI (tumor marker index) (P = 0.009 for OS) were significantly correlated with a worse prognosis. By multivariate analysis, NSE (P = 0.014) was confirmed as independent predictor for DFS, while NSE (P = 0.001) and TMI (P = 0.038) were independent prognostic factors for OS. Conclusion Adenosquamous lung carcinoma is an aggressive malignancy with relatively high EGFR mutation frequency. Elevated preoperative NSE level and TMI are adverse predictive and prognostic indicators. PMID:27623437

  16. Prognostic value of preoperative serum tumor markers in gastric cancer

    PubMed Central

    Huang, Ze-Bo; Zhou, Xin; Xu, Jun; Du, Yi-Ping; Zhu, Wei; Wang, Jian; Shu, Yong-Qian; Liu, Ping

    2014-01-01

    AIM: To evaluate the prognostic value of preoperative carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and CA50 in patients undergoing D2 resection. METHODS: We evaluated 363 patients with gastric cancer who underwent gastrectomy at our hospital from January 2006 to December 2009. Blood samples were obtained from each patient within 1 wk before surgery. The cut-off values for serum CEA, CA19-9, and CA50 were 5 ng/mL, 37 U/mL, and 20 U/mL, respectively. The correlation between preoperative tumor marker levels and prognosis was studied by means of univariate and multivariate analyses. RESULTS: The preoperative serum positive rates of CEA, CA19-9 and CA50 were 24.0%, 18.9% and 24.5%, respectively. The positivity rate of serum CEA was significantly correlated with age (P < 0.001), sex (P = 0.022), tumor size (P = 0.007) and depth of invasion (P = 0.018); CA19-9 with tumor size (P = 0.042) and lymph node metastasis (P < 0.001); and CA50 only with lymph node metastasis (P = 0.001). In multivariate analysis, tumor size, T category, N category, vascular or neural invasion, and adjuvant chemotherapy were independent prognostic factors for overall survival. CA19-9 had an independent prognostic significance in patients without adjuvant chemotherapy (P = 0.027). CONCLUSION: Preoperative serum CEA, CA19-9 and CA50 are prognostic in patients with gastric cancer. Only CA19-9 is an independent prognostic factor after surgery without adjuvant chemotherapy. PMID:24829865

  17. Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.

    PubMed

    Gottardo, Nicholas G; Hoffmann, Katrin; Beesley, Alex H; Freitas, Joseph R; Firth, Martin J; Perera, Kanchana U; de Klerk, Nicolas H; Baker, David L; Kees, Ursula R

    2007-05-01

    In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.

  18. Nuclear osteopontin-c is a prognostic breast cancer marker

    PubMed Central

    Zduniak, K; Ziolkowski, P; Ahlin, C; Agrawal, A; Agrawal, S; Blomqvist, C; Fjällskog, M-L; Weber, G F

    2015-01-01

    Background: Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Methods: Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. Results: We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. Conclusions: The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis. PMID:25625274

  19. Prognostic markers in acute pancreatitis: can pancreatic necrosis be predicted?

    PubMed Central

    Leese, T.; Shaw, D.; Holliday, M.

    1988-01-01

    The value of six prognostic markers was assessed prospectively in 198 attacks of acute pancreatitis with specific attention to their ability to predict pancreatic necrosis. The Imrie Prognostic Score (IPS) was recorded within 48 h of diagnosis. The serum C-reactive protein (CRP) alpha 1 antiprotease (A1AP), alpha 2 macroglobulin (A2M), amylase and white cell count (WCC) were measured on days 1, 3 and 7. When comparing all severe clinical outcomes to mile outcomes, serum CRP concentrations were higher on all three days (P less than 0.02, less than 0.001, less than 0.001), A1AP concentrations were higher on day 3 (P less than 0.05), A2M concentrations were lower on day 7 (P less than 0.01) and WCC was higher on all three days (P less than 0.001, less than 0.001, less than 0.001). Serum amylase concentrations showed no significant differences. None of the measured parameters were helpful in distinguishing patients who subsequently developed pancreatic necrosis from patients who had other severe outcomes. Multivariate analysis revealed that the initial IPS showed greatest independent significance in predicting severe outcome followed by the WCC (days 1 and 7) and CRP (day 3). CRP and WCC may be clinically useful predictors of severe outcome to supplement the initial IPS. These methods are unlikely to distinguish pancreatic necrosis from other severe outcomes, but they may supplement clinical judgment in selecting a high risk group of patients for contrast enhanced computed tomography. PMID:2458063

  20. Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma.

    PubMed

    O'Connor, Kate; Li-Chang, Hector H; Kalloger, Steven E; Peixoto, Renata D; Webber, Douglas L; Owen, David A; Driman, David K; Kirsch, Richard; Serra, Stefano; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-04-01

    Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

  1. Prognostic factors in neuroendocrine carcinoma: biological markers are more useful than histomorphological markers

    PubMed Central

    Freis, Patricia; Graillot, Emmanuelle; Rousset, Pascal; Hervieu, Valérie; Chardon, Laurence; Lombard-Bohas, Catherine; Walter, Thomas

    2017-01-01

    Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are a very aggressive type of cancer, for which prognostic factors are lacking. We analysed clinical and histomorphological prognostic markers of overall survival (OS), completed with a record of biological and haematological data of patients diagnosed between December 2002 and December 2015. The median OS was 16 months (95% CI 13.9–18.1). After univariate analysis, performance status (PS) ≥ 2 and stage IV were associated with a worse outcome (9 months and 14 months, respectively), as well as patients with lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels ≥ 2 ULN (9 months and 8 months, respectively). After multivariate analysis, LDH and AST levels were the only factors that remained significantly associated with better survival: HR 0.36 (p = 0.04) and 0.31 (p = 0.03), respectively. When patients had elevated LDH and AST levels, OS was 20 months, when they had high LDH or AST levels, 13 months and 8 months in the group with low LDH and AST levels (p < 0.001). Therefore, biological data appeared to be more relevant prognostic factors than usual factors described in other studies (PS, stage, and Ki-67). Considering LDH and AST levels at diagnosis could help physicians to predict survival and to stratify patients for clinical trials. PMID:28074897

  2. Prognostic factors versus markers of response to treatment versus surrogate endpoints: Three different concepts.

    PubMed

    Sormani, Maria Pia

    2017-03-01

    Multiple sclerosis is a highly heterogeneous disease; the quantitative assessment of disease progression is problematic for many reasons, including the lack of objective methods to measure disability and the long follow-up times needed to detect relevant and stable changes. For these reasons, the importance of prognostic markers, markers of response to treatments and of surrogate endpoints, is crucial in multiple sclerosis research. Aim of this report is to clarify some basic definitions and methodological issues about baseline factors to be considered prognostic markers or markers of response to treatment; to define the dynamic role that variables must have to be considered surrogate markers in relation to specific treatments.

  3. Diagnostic and Prognostic Markers in Differentiated Thyroid Cancer

    PubMed Central

    Gómez Sáez, José M

    2011-01-01

    The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems as ligands, transmembrane receptors and cytoplasmic secondary messengers to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. The genes, coding the signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. Moreover, it is additionally pointed out that genetic, as well as epigenetic DNA changing via aberrant methylation of several tumor suppressor and thyroid-specific genes is associated with tumor aggressiveness, being a jointly responsible mechanism for thyroid tumorigenesis. In the present manuscript the currently developed diagnostic and prognostic genetic/epigenetic markers are presented; the understanding of this molecular mechanism provides access to novel molecular therapeutic strategies. PMID:22654559

  4. Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy

    PubMed Central

    Nakamura, Yoshio; Takahashi, Akira; Tsutsumida, Arata; Namikawa, Kenjiro; Tanese, Keiji; Abe, Takayuki; Funakoshi, Takeru; Yamamoto, Noboru; Amagai, Masayuki

    2016-01-01

    Background An anti-programmed cell death protein 1 monoclonal antibody, nivolumab, is one of the most effective drugs for advanced melanoma. Tumor cell-derived or immune cell-derived markers and clinical predictors such as serum lactate dehydrogenase (LDH) and cutaneous adverse events, have already been described as prognostic factors for advanced melanoma treated with nivolumab. We sought to identify further clinical predictors that can be determined in routine clinical practice. Methods We retrospectively analyzed clinical findings of 98 consecutive patients with unresectable stage III or IV melanoma treated with nivolumab, at the National Cancer Center Hospital or at Keio University Hospital, in Tokyo, Japan, between July 2014 and July 2016. These patients had been administered nivolumab at a dose of 2mg/kg every 3 weeks. Results As for pretreatment prognostic factors, ECOG performance status (PS) ≥1, maximum tumor diameters of ≥30mm, elevated LDH and elevated C-reactive protein were significantly associated with poor overall survival (OS) (hazard ratio [HR] 0.29 [P<0.001], HR 0.40 [p=0.003], HR 0.29 [P<0.001], HR 0.42 [P=0.004], respectively) on univariate analysis. Among these factors, PS and LDH were identified as independent variables by multivariate analysis. As for early markers examined during therapy, patients with absolute lymphocyte count (ALC) ≥ 1000/μl (Week3: HR 0.40 [P=0.004], Week6: HR 0.33 [P=0.001]) and absolute neutrophil count (ANC) <4000/μl (Week3: HR 0.46 [P=0.014], Week6: HR 0.51 [P=0.046]) had significantly better OS. Conclusion ALC≥1000/μl and ANC<4000/μl during treatment appear to be early markers associated with OS. Nivolumab might have minimal efficacy in patients with a massive tumor burden. PMID:27764805

  5. Circulating tumor cells and miRNA as prognostic markers in neuroendocrine neoplasms.

    PubMed

    Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria Al

    2017-04-07

    The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs.

  6. Prognostic markers of acute decompensated heart failure: the emerging roles of cardiac biomarkers and prognostic scores.

    PubMed

    Cohen-Solal, Alain; Laribi, Said; Ishihara, Shiro; Vergaro, Giuseppe; Baudet, Mathilde; Logeart, Damien; Mebazaa, Alexandre; Gayat, Etienne; Vodovar, Nicolas; Pascual-Figal, Domingo A; Seronde, Marie-France

    2015-01-01

    Rapidly assessing outcome in patients with acute decompensated heart failure is important but prognostic factors may differ from those used routinely for stable chronic heart failure. Multiple plasma biomarkers, besides the classic natriuretic peptides, have recently emerged as potential prognosticators. Furthermore, prognostic scores that combine clinical and biochemical data may also be useful. However, compared with the scores used in chronic heart failure, scores for acute decompensated heart failure have not been validated. This article reviews potential biomarkers, with a special focus on biochemical biomarkers, and possible prognostic scores that could be used by the clinician when assessing outcome in patients with acute heart failure.

  7. Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

    PubMed Central

    Lee, Nuri; Lee, Hyewon; Moon, Soo Young; Sohn, Ji Yeon; Hwang, Sang Mee; Yoon, Ok Jin; Youn, Hye Sun

    2015-01-01

    Background Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. Methods The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). Results Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including β2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). Conclusions Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID:26354343

  8. Serum Clusterin as a Prognostic Marker of Chronic Spontaneous Urticaria

    PubMed Central

    Kim, Ji-Hye; Lee, Hyung-Young; Ban, Ga-Young; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min

    2016-01-01

    Abstract A substantial proportion of patients with chronic spontaneous urticaria (CSU) are refractory to antihistamines. However, identifying the subpopulation whose urticaria is not completely controlled by antihistamines remains difficult. The response of autologous serum skin test (ASST), a clinical test for the detection of basophil histamine-releasing activity upon autoantibodies or autoreactive stimulation, has been suggested as a potential predictor in the control of urticaria. We sought to identify proteins that were differentially expressed in the sera of patients with positive and negative ASST results and to investigate their association with urticaria control. Proteomics analysis was performed using sera from 3 CSU patients with positive ASST results compared with those showing negative ASST results. Seven upregulated and 5 downregulated proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in the ASST-positive group compared with the ASST-negative group. Proteins that were differentially expressed according to the ASST results in CSU patients were classified into 6 groups: apolipoproteins, glycoproteins, modified albumin, haptoglobulin, plectin, and others. Among these, apolipoprotein J or clusterin was validated using an enzyme-linked immunosorbent assay. Clusterin levels in 69 ASST-positive patients were significantly higher than those in 69 ASST-negative patients and in 86 healthy controls (231.2 ± 44.0 vs 210.2 ± 36.1 vs 118.7 ± 71.9 μg/mL, P < 0.001). Furthermore, clusterin levels differed significantly between patients with responsive and refractory responses to antihistamine treatment within 3 months (231.0 ± 39.1 vs 205.1 ± 40.4 μg/mL, P < 0.001). ASST results and serum clusterin levels can predict 92.7% of CSU patients whose urticaria would be refractory to antihistamines. Serum clusterin can be a prognostic marker to determine the responsiveness to

  9. Serum Clusterin as a Prognostic Marker of Chronic Spontaneous Urticaria.

    PubMed

    Kim, Ji-Hye; Lee, Hyung-Young; Ban, Ga-Young; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min

    2016-05-01

    A substantial proportion of patients with chronic spontaneous urticaria (CSU) are refractory to antihistamines. However, identifying the subpopulation whose urticaria is not completely controlled by antihistamines remains difficult. The response of autologous serum skin test (ASST), a clinical test for the detection of basophil histamine-releasing activity upon autoantibodies or autoreactive stimulation, has been suggested as a potential predictor in the control of urticaria. We sought to identify proteins that were differentially expressed in the sera of patients with positive and negative ASST results and to investigate their association with urticaria control.Proteomics analysis was performed using sera from 3 CSU patients with positive ASST results compared with those showing negative ASST results. Seven upregulated and 5 downregulated proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in the ASST-positive group compared with the ASST-negative group.Proteins that were differentially expressed according to the ASST results in CSU patients were classified into 6 groups: apolipoproteins, glycoproteins, modified albumin, haptoglobulin, plectin, and others. Among these, apolipoprotein J or clusterin was validated using an enzyme-linked immunosorbent assay. Clusterin levels in 69 ASST-positive patients were significantly higher than those in 69 ASST-negative patients and in 86 healthy controls (231.2 ± 44.0 vs 210.2 ± 36.1 vs 118.7 ± 71.9 μg/mL, P < 0.001). Furthermore, clusterin levels differed significantly between patients with responsive and refractory responses to antihistamine treatment within 3 months (231.0 ± 39.1 vs 205.1 ± 40.4 μg/mL, P < 0.001). ASST results and serum clusterin levels can predict 92.7% of CSU patients whose urticaria would be refractory to antihistamines. Serum clusterin can be a prognostic marker to determine the responsiveness to antihistamine

  10. Prognostic Utility of Neutrophil-to-Lymphocyte Ratio on Adverse Clinical Outcomes in Patients with Severe Calcific Aortic Stenosis

    PubMed Central

    Cho, Kyoung Im; Cho, Sang Hoon; Her, Ae-Young; Singh, Gillian Balbir; Shin, Eun-Seok

    2016-01-01

    Background Inflammation is an important factor in the pathogenesis of calcific aortic stenosis (AS). We aimed to evaluate the association between an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) and major adverse cardiovascular events (MACE) in patients with severe calcific AS. Methods A total of 336 patients with isolated severe calcific AS newly diagnosed between 2010 and 2015 were enrolled in this study. Using Cox proportional hazards (PH) regression models, we investigated the prognostic value of NLR adjusted for baseline covariates including logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE-I) and undergoing aortic valve replacement (AVR). We also evaluated the clinical relevance of NLR risk groups (divided into low, intermediate, high risk) as categorized by NLR cutoff values. MACE was defined as a composite of all-cause mortality, cardiac death and non-fatal myocardial infarction during the follow-up period. Results The inflammatory marker NLR was an independent prognostic factor most significantly associated with MACE [hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.04–1.09; p-value <0.001]. The goodness-of-fit and discriminability of the model including EuroSCORE-I and AVR (loglikelihood difference, 15.49; p-value <0.001; c-index difference, 0.035; p-value = 0.03) were significantly improved when NLR was incorporated into the model. The estimated Kaplan-Meier survival rates at 5 years for the NLR risk groups were 84.6% for the low risk group (NLR ≤ 2), 67.7% for the intermediate risk group (2 < NLR ≤ 9), and 42.6% for the high risk group (NLR > 9), respectively. Conclusion The findings of the present study demonstrate the potential utility of NLR in risk stratification of patients with severe calcific AS. PMID:27548384

  11. REporting recommendations for tumour MARKer prognostic studies (REMARK).

    PubMed

    McShane, Lisa M; Altman, Douglas G; Sauerbrei, Willi; Taube, Sheila E; Gion, Massimo; Clark, Gary M

    2005-08-01

    Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomised trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

  12. REporting recommendations for tumor MARKer prognostic studies (REMARK).

    PubMed

    McShane, Lisa M; Altman, Douglas G; Sauerbrei, Willi; Taube, Sheila E; Gion, Massimo; Clark, Gary M

    2006-11-01

    Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

  13. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia

    PubMed Central

    Qiu, Yi Hua; Zhang, Nianxiang; Singh, Neera; Faderl, Stefan; Ferrajoli, Alessandra; York, Heather; Qutub, Amina A.; Coombes, Kevin R.; Watson, Dennis K.

    2011-01-01

    Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to acute myelogenous leukemia (AML) by chromosomal events at the FLI1 locus, but the biologic impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in peripheral blood (PB) and BM and higher at diagnosis than at relapse (P = .02). Compared with normal CD34+ cells, expression in AML was above or below normal in 32% and 5% of patients, respectively. Levels were negatively correlated with an antecedent hematologic disorder (P = .002) but not with age or cytogenetics. Mutated NPM1 (P = .0007) or FLT3-ITD (P < .02) had higher expression. FLI1 levels were negatively correlated with 10 of 195 proteins associated with proliferation and stromal interaction, and positively correlated (R > 0.3) with 19 others. The FLI1 level was not predictive of remission attainment, but patients with low or high FLI1 expression had shorter remission duration (22.6 and 40.3 vs 51.1 weeks, respectively; P = .01) and overall survival (45.2 and 35.4 vs 59.4 weeks, respectively; P = .03). High FLI1 levels were adverse in univariate and multivariate analysis. FLI1 expression is frequently abnormal and prognostically adverse in AML. FLI1 and/or its response genes may be therapeutically targetable to interfere with AML cell biology. PMID:21917756

  14. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia.

    PubMed

    Kornblau, Steven M; Qiu, Yi Hua; Zhang, Nianxiang; Singh, Neera; Faderl, Stefan; Ferrajoli, Alessandra; York, Heather; Qutub, Amina A; Coombes, Kevin R; Watson, Dennis K

    2011-11-17

    Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to acute myelogenous leukemia (AML) by chromosomal events at the FLI1 locus, but the biologic impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in peripheral blood (PB) and BM and higher at diagnosis than at relapse (P = .02). Compared with normal CD34(+) cells, expression in AML was above or below normal in 32% and 5% of patients, respectively. Levels were negatively correlated with an antecedent hematologic disorder (P = .002) but not with age or cytogenetics. Mutated NPM1 (P = .0007) or FLT3-ITD (P < .02) had higher expression. FLI1 levels were negatively correlated with 10 of 195 proteins associated with proliferation and stromal interaction, and positively correlated (R > 0.3) with 19 others. The FLI1 level was not predictive of remission attainment, but patients with low or high FLI1 expression had shorter remission duration (22.6 and 40.3 vs 51.1 weeks, respectively; P = .01) and overall survival (45.2 and 35.4 vs 59.4 weeks, respectively; P = .03). High FLI1 levels were adverse in univariate and multivariate analysis. FLI1 expression is frequently abnormal and prognostically adverse in AML. FLI1 and/or its response genes may be therapeutically targetable to interfere with AML cell biology.

  15. RON is not a prognostic marker for resectable pancreatic cancer

    PubMed Central

    2012-01-01

    Background The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. Methods RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. Results RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. Conclusions Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer. PMID:22958871

  16. Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma

    PubMed Central

    Koh, Hyun Min; Jang, Bo Geun; Hyun, Chang Lim; Kim, Young Sill; Hyun, Jin Won; Chang, Weon Young; Maeng, Young Hee

    2017-01-01

    Background Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. Methods AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues. Results AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001). Conclusions AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients. PMID:28013532

  17. Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors

    PubMed Central

    Hamzić-Mehmedbašić, Aida; Rašić, Senija; Balavac, Merima; Rebić, Damir; Delić-Šarac, Marina; Durak-Nalbantić, Azra

    2016-01-01

    Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome. PMID:27471736

  18. [Serum Erythropoietin as Prognostic Marker in Myelodysplastic Syndromes].

    PubMed

    Cortesão, Emília; Tenreiro, Rita; Ramos, Sofia; Pereira, Marta; César, Paula; Carda, José P; Gomes, Marília; Rito, Luís; Magalhães, Emília; Gonçalves, Ana C; Silva, Nuno C E; Geraldes, Catarina; Pereira, Amélia; Ribeiro, Letícia; Nascimento Costa, José M; Ribeiro, Ana B Sarmento

    2015-01-01

    Introdução: A síndrome mielodisplásica é uma doença heterogénea caracterizada por displasia, medula hipercelular, citopenias e risco de evolução para leucemia aguda. Outros factores de prognóstico, nomeadamente, fibrose medular, elevação da enzima desidrogenase do lactato e 2-microglobulina têm sido descritos, contudo, a decisão terapêutica baseia-se no score do International Prognostic Scoring System. Material e Métodos: Este trabalho teve como objectivo analisar a relevãncia da eritropoietina sérica ao diagnóstico, em doentes com síndrome mielodisplásica de novo, avaliando o seu impacto na sobrevivência global e a sua implementação como factor de prognóstico. Recolhemos dados clínicos e laboratoriais de 102 doentes com síndrome mielodisplásica de novo diagnosticada entre outubro/2009 e março/2014. A análise de sobrevivência foi efectuada recorrendo à metodologia de Kaplan-Meier, de acordo com os valores de eritropoietina. Resultados: A amostra, de 102 doentes, apresenta uma mediana de idades de 74 anos e relação masculino/feminino igual a 0,8. Os doentes com o subtipo citopenia refratária com displasia unilinha apresentam, em média, valores de eritropoietina significativamente mais baixos, em oposição aos doentes com o subtipo 5q- que apresentam a média de eritropoietina sérica mais elevada (p < 0,05). Onze doentes evoluíram para leucemia aguda; estes têm, em média, eritropoietina sérica superior (p < 0,05). Adicionalmente, a eritropoietina sérica acima do limite superior da normalidade associa-se a menor sobrevivência (p = 0,0336). Após ajuste do modelo de regressão de Cox, o valor preditivo da eritropoietina para a sobrevivência global manteve-se (p < 0,001). Em análise multivariada, a eritropoietina sérica demonstrou ser um factor de prognóstico independente (p < 0,001). Discussão: A eritropoietina sérica é um factor preditivo de resposta à terapêutica com eritropoietina subcut'nea, sendo que os doentes

  19. Bioinformatics analyses of significant prognostic risk markers for thyroid papillary carcinoma.

    PubMed

    Min, Xiao-Shan; Huang, Peng; Liu, Xu; Dong, Chao; Jiang, Xiao-Lin; Yuan, Zheng-Tai; Mao, Lin-Feng; Chang, Shi

    2015-09-01

    This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 (BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F (MAFF), SRY (sex-determining region Y)-box 4 (SOX4), and retinoic acid receptor, alpha (RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention.

  20. KIT is an independent prognostic marker for pancreatic endocrine tumors: a finding derived from analysis of islet cell differentiation markers.

    PubMed

    Zhang, Lizhi; Smyrk, Thomas C; Oliveira, Andre M; Lohse, Christine M; Zhang, Shuya; Johnson, Michele R; Lloyd, Ricardo V

    2009-10-01

    Prediction of the biologic behavior of pancreatic endocrine tumor (PET) without local invasion or metastasis is often difficult. The 2004 World Health Organization (WHO) classification uses size, angioinvasion, mitotic activity, and Ki-67 index as prognostic criteria. Recently, cytokeratin 19 (CK19) was shown to be another prognostic marker, but the mechanism by which CK19 predicts prognosis is unknown. As CK19 is the first cytokeratin expressed in all epithelial cells in fetal pancreas, we sought to test expression of other markers of islet cell differentiation including KIT, Pdx-1, Pax4, and Pax6 in PET and correlation of these markers with clinical behavior. Clinical information and histology was reviewed in 97 PETs. All tumors were classified according to WHO criteria and a tumor, node, and metastases stage system. Immunohistochemistry was performed using antibodies to Ki-67, KIT, CK19, Pdx-1, Pax4, and Pax6. Associations of clinicopathologic and immunohistochemical features with prognosis were evaluated using Cox proportional hazards regression models. WHO and tumor, node, and metastases classifications, mitotic counts and Ki-67 labeling, infiltrative border, necrosis, perineural invasion, extrapancreatic extension, tumor size, and positive CK19 and KIT expression were significantly associated with death from disease in a univariate setting. In multivariate analysis, only WHO criteria and KIT expression were shown to be independent. An immunohistochemical classification system was derived from a combination of KIT and CK19 expression: low risk (KIT-/CK19-), intermediate risk (KIT-/CK19+), and high risk (KIT+/CK19+). Survival, metastases, and recurrence of PET were significantly different among the 3 groups. These results indicate that KIT is a new and independent prognostic marker for PETs. The classification system derived from KIT and CK19 was able to predict clinical behavior of PET.

  1. New blood markers for staging and prognostics of atherosclerosis

    NASA Astrophysics Data System (ADS)

    Sicchieri, Leticia B.; Silva, Mônica Nascimento; Monteiro, Andrea Moreira; Figueiredo Neto, Antonio Martins; Courrol, Lilia C.

    2014-03-01

    Analysis from the plasmas of rabbits subjected to high-cholesterol diets were performed by fluorescence spectroscopy using three biossensors: Europium-Chlortetracycline (EuCTc), Evans Blue (EB), and Thioflavin T (ThT). For this purpose an animal experimentation was done with New Zealand rabbits divided into two groups: control group of 6 rabbits that received a regular diet for 60 days; and experimental group of 9 rabbits, that were fed with 1% cholesterol for 60 days. The results from spectroscopic analysis have shown that the EuCTc marker emission intensity increases in the presence of plaque formation. The EB emission intensity remained constant for control and experimental groups. The ThT presented an increase in the emission intensity and a modification in the spectra shape with 60 days of diet. The studied biomarkers may not yet be specific in the

  2. The Impact of Various Platelet Indices as Prognostic Markers of Septic Shock

    PubMed Central

    Yu, Xuezhong; Guo, Shigong; Ji, Xu; Sun, Tongwen; Lan, Chao; Lavergne, Valery; Ghannoum, Marc; Li, Li

    2014-01-01

    Introduction Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. Methods Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non-surviving patients. Results A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non-survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non-survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. Conclusion A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID:25118886

  3. Methylation of serum SST gene is an independent prognostic marker in colorectal cancer

    PubMed Central

    Liu, Yanqun; Chew, Min Hoe; Tham, Chee Kian; Tang, Choong Leong; Ong, Simon YK; Zhao, Yi

    2016-01-01

    There is an increasing demand for accurate prognostication for colorectal cancer (CRC). This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients. A total of 165 CRC patients were enrolled in this prospective study. Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR. Kaplan-Meier test, and univariate and multivariate Cox proportional hazards regression models were used for survival analyses. After a median follow-up of 56 months, 43 patients (28.7%) experienced tumor recurrence. In univariate survival analyses, serum methylation levels of SST and MAL were significantly predictive of cancer-specific death (P<0.005 for both). The former was also a significant predictor for tumor recurrence (P=0.007). Independent prognostic effects of serum methylation levels of SST were revealed by multivariate Cox regression model (P=0.031 and P=0.003 for cancer death and recurrence, respectively). When focusing on stage II and III patients, prognostication with serum methylated SST remained significant. Methylated SST detected in all serum samples can be traced back to the matched primary tumor tissues. We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification. PMID:27725914

  4. [New prognostic and predictive markers for breast cancer].

    PubMed

    Wachter, D L

    2016-11-01

    Breast cancer can be divided into four molecular subtypes with different prognoses using immunohistochemical markers in the routine clinicopathological work-up. The protein Ki-67 is of central importance in this context, in particular to distinguish between luminal A and luminal B carcinomas. Determination of the Ki-67 index of a carcinoma also allows a prediction of the likelihood of the response to chemotherapy. Additionally, the expression of certain cytokeratins in tumor cells is associated with a poor response to chemotherapy. The heterogeneity of molecular subtypes with regard to the histological appearance indicates an even greater diversity of breast cancer. We were able to show that a high proportion of luminal B carcinomas display neuroendocrine differentiation. Further studies with particular emphasis on histomorphological criteria should be performed to attain a more accurate classification of breast cancer and to pave the way towards targeted therapies for a better prognosis in the future.

  5. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Aust, Stefanie; Knogler, Thomas; Pils, Dietmar; Obermayr, Eva; Reinthaller, Alexander; Zahn, Lisa; Radlgruber, Ilja; Mayerhoefer, Marius Erik; Grimm, Christoph; Polterauer, Stephan

    2015-01-01

    Objective Tumor cachexia is an important prognostic parameter in epithelial ovarian cancer (EOC). Tumor cachexia is characterized by metabolic and inflammatory disturbances. These conditions might be reflected by body composition measurements (BCMs) ascertained by pre-operative computed tomography (CT). Thus, we aimed to identify the prognostically most relevant BCMs assessed by pre-operative CT in EOC patients. Methods We evaluated muscle BCMs and well established markers of nutritional and inflammatory status, as well as clinical-pathological parameters in 140 consecutive patients with EOC. Furthermore, a multiplexed inflammatory marker panel of 25 cytokines was used to determine the relationship of BCMs with inflammatory markers and patient’s outcome. All relevant parameters were evaluated in uni- and multivariate survival analysis. Results Muscle attenuation (MA)—a well established BCM parameter—is an independent prognostic factor for survival in multivariate analysis (HR 2.25; p = 0.028). Low MA—reflecting a state of cachexia—is also associated with residual tumor after cytoreductive surgery (p = 0.046) and with an unfavorable performance status (p = 0.015). Moreover, MA is associated with Eotaxin and IL-10 out of the 25 cytokine multiplex marker panel in multivariate linear regression analysis (p = 0.021 and p = 0.047, respectively). Conclusion MA—ascertained by routine pre-operative CT—is an independent prognostic parameter in EOC patients. Low MA is associated with the inflammatory, as well as the nutritional component of cachexia. Therefore, the clinical value of pre-operative CT could be enhanced by the assessment of MA. PMID:26457674

  6. HDAC4, a prognostic and chromosomal instability marker, refines the predictive value of MGMT promoter methylation.

    PubMed

    Cheng, Wen; Li, Mingyang; Cai, Jinquan; Wang, Kuanyu; Zhang, Chuanbao; Bao, Zhaoshi; Liu, Yanwei; Wu, Anhua

    2015-04-01

    Chromosomal instability is a hallmark of human cancers and is closely linked to tumorigenesis. The prognostic value of molecular signatures of chromosomal instability (CIN) has been validated in various cancers. However, few studies have examined the relationship between CIN and glioma. Histone deacetylases (HDACs) regulate chromosome structure and are linked to the loss of genomic integrity in cancer cells. In this study, the prognostic value of HDAC4 expression and its association with markers of CIN were investigated by analyzing data from our own and four other large sample databases. The results showed that HDAC4 expression is downregulated in high- as compared to low-grade glioma and is associated with a favorable clinical outcome. HDAC4 expression and CIN were closely related in glioma from both functional and statistical standpoints. Moreover, the predictive value of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status-a widely used glioma marker-was refined by HDAC4 expression level, which was significantly related to CIN in our study. In conclusion, we propose that HDAC4 expression, a prognostic and CIN marker, enhances the predictive value of MGMT promoter methylation status for identifying patients who will most benefit from radiochemotherapy.

  7. PD-L2: A prognostic marker in chromophobe renal cell carcinoma?

    PubMed

    Erlmeier, Franziska; Weichert, Wilko; Autenrieth, Michael; Wiedemann, Max; Schrader, Andres Jan; Hartmann, Arndt; Ivanyi, Philipp; Steffens, Sandra

    2017-05-01

    In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma. In contrast, little is known about PD-L2 expression patterns in RCC, especially in rarer subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-L2 expression in chromophobe (ch)RCC. Eighty-one patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for PD-L2 expression by immunohistochemistry. Expression data were associated with clinicopathological parameters and overall survival (OS). Twenty-three (28.4%) patients showed a PD-L2 > median (PD-L2 high) staining intensity. No significant association between clinicopathological parameters and PD-L2 expression was identified. A significant difference between 5- and 10-year OS in dependence of PD-L2 expression was found (PD-L2 low 96.4 and 87.7% vs. PD-L2 high 87.1 and 56%; log rank, p = 0.029). However, in multivariate analysis PD-L2 expression failed to be proofed as an independent prognostic factor. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of PD-L2 in a considerably large cohort of chRCC. Our results showed a significant diminished OS in dependence of PD-L2 expression. This implicates that PD-L2 might play a role as prognostic marker in chRCC demanding further evaluation.

  8. Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone

    PubMed Central

    Webster, Joshua D; Yuzbasiyan-Gurkan, Vilma; Thamm, Douglas H; Hamilton, Elizabeth; Kiupel, Matti

    2008-01-01

    Background Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone. Results Histologic grade 3 MCTs, MCTs with c-KIT mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with c-KIT mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone. Conclusion and clinical importance This study confirms the prognostic value of histologic grade, c-KIT mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs. PMID:18700956

  9. Realizing the Translational Potential of Telomere Length Variation as a Tissue-Based Prognostic Marker for Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer PRINCIPAL INVESTIGATOR: Elizabeth A. Platz CONTRACTING...Translational Potential of Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer 5b. GRANT NUMBER W81XWH-12-1-0545 5c...combination of telomere length variability in prostate cancer cells and short telomere length in cancer -associated stromal cells is an independent

  10. Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers.

    PubMed

    Aradottir, Margret; Reynisdottir, Sigridur T; Stefansson, Olafur A; Jonasson, Jon G; Sverrisdottir, Asgerdur; Tryggvadottir, Laufey; Eyfjord, Jorunn E; Bodvarsdottir, Sigridur K

    2015-01-01

    Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild-type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer-specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23-40.6; p = 0.028). Poor breast cancer-specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19-85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81-51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A

  11. Evaluation of prognostic markers for patients with curatively resected thoracic esophageal squamous cell carcinomas

    PubMed Central

    Ikeguchi, Masahide; Kouno, Yusuke; Kihara, Kyoichi; Suzuki, Kazunori; Endo, Kanenori; Nakamura, Seiichi; Sawada, Takashi; Shimizu, Tetsu; Matsunaga, Tomoyuki; Fukumoto, Yoji; Saito, Hiroaki

    2016-01-01

    The Glasgow Prognostic Score (GPS), neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are prognostic parameters for malignancies. Additionally, serum squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA 21-1) are tumor markers for squamous cell carcinoma. In the present study, the prognostic importance of these markers in patients with resectable thoracic esophageal cancer was investigated. In this retrospective study, 84 enrolled patients diagnosed with resectable clinical stage I–III thoracic esophageal squamous cell carcinomas (ESCCs) underwent thoracic esophageal resection and three-field lymph node dissection at Tottori University Hospital between January 2007 and December 2013. The correlations among preoperative patient markers (GPS, NLR, PNI, SCC-Ag and CYFRA 21-1) and the occurrence of postoperative complications and patient survival were analyzed. The operative mortality was 2.4%, and morbidity was 42.9%. Strong correlations between occurrence of postoperative complications and open thoracotomy (P=0.083) and high-serum CYFRA 21-1 (P=0.007) were observed. In 15 patients with high-serum CYFRA 21-1, postoperative complications were detected in 11 of them (73.3%); on the other hand, complications occurred in 25 of 69 (36.2%) with low-serum CYFRA 21-1. The 5-year disease-free survival rate and 5-year overall survival rate of all the patients were 52.2 and 50.8%, respectively. Among the prognostic parameters, preoperative high NLR was determined to be a poor prognostic factor, independent of the tumor stage in the multivariate analysis. These results may indicate that, in patients with preoperative high-serum CYFRA 21-1, more attention should be paid to the occurrence of postoperative complications. Therefore, in such cases, anastomosis between blood vessels of the substitute esophagus and cervical vessels would be recommended. Furthermore, in patients with high preoperative NLR, effective adjuvant

  12. GERD—Barrett—Adenocarcinoma: Do We Have Suitable Prognostic and Predictive Molecular Markers?

    PubMed Central

    Illig, Romana; Klieser, Eckhard; Kiesslich, Tobias; Neureiter, Daniel

    2013-01-01

    Due to unfavorable lifestyle habits (unhealthy diet and tobacco abuse) the incidence of gastroesophageal reflux disease (GERD) in western countries is increasing. The GERD-Barrett-Adenocarcinoma sequence currently lacks well-defined diagnostic, progressive, predictive, and prognostic biomarkers (i) providing an appropriate screening method identifying the presence of the disease, (ii) estimating the risk of evolving cancer, that is, the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC), (iii) predicting the response to therapy, and (iv) indicating an overall survival—prognosis for EAC patients. Based on histomorphological findings, detailed screening and therapeutic guidelines have been elaborated, although epidemiological studies could not support the postulated increasing progression rates of GERD to BE and EAC. Additionally, proposed predictive and prognostic markers are rather heterogeneous by nature, lack substantial proofs, and currently do not allow stratification of GERD patients for progression, outcome, and therapeutic effectiveness in clinical practice. The aim of this paper is to discuss the current knowledge regarding the GERD-BE-EAC sequence mainly focusing on the disputable and ambiguous status of proposed biomarkers to identify promising and reliable markers in order to provide more detailed insights into pathophysiological mechanisms and thus to improve prognostic and predictive therapeutic approaches. PMID:23573078

  13. Evaluation of Minichromosome Maintenance Protein 7 and c-KIT as Prognostic Markers in Feline Cutaneous Mast Cell Tumours.

    PubMed

    Dobromylskyj, M J; Rasotto, R; Melville, K; Smith, K C; Berlato, D

    2015-11-01

    Mast cell tumours (MCTs) are a common skin tumour in cats, but there is currently no histological grading system or reliable prognostic marker for this species (unlike the situation for dogs). This study utilized a set of 71 feline cutaneous MCTs with known clinical outcomes to assess the potential of various prognostic markers, including the cellular proliferation marker minichromosome maintenance protein (MCM)-7, mitotic index and various KIT labelling characteristics, including KIT positivity, KIT labelling pattern and KIT immunoreactivity score (IS). Of the factors studied, the mitotic index and the KIT labelling pattern were the only features associated significantly with survival times, while the proliferation marker MCM7 and the KIT IS were not. The study also highlights the variability of KIT labelling characteristics between tumours, which may prevent use of this marker as a diagnostic and prognostic tool.

  14. Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker.

    PubMed

    Wreesmann, Volkert B; Sieczka, Elizabeth M; Socci, Nicholas D; Hezel, Michael; Belbin, Thomas J; Childs, Geoffrey; Patel, Snehal G; Patel, Kepal N; Tallini, Giovanni; Prystowsky, Michael; Shaha, Ashok R; Kraus, Dennis; Shah, Jatin P; Rao, Pulivarthi H; Ghossein, Ronald; Singh, Bhuvanesh

    2004-06-01

    Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P = 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34-36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P = 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P = 0

  15. Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma

    PubMed Central

    Lu, Chang-Yi; Chen, Shih-Ya; Peng, Hui-Ling; Kan, Pu-Yeh; Chang, Wan-Chi; Yen, Chia-Jui

    2017-01-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis. Using a whole-genome approach, we identified many hyper-methylated miRNAs in HCC. Furthermore, three abnormally methylated genes and one miRNA were combined to establish a methylation predictive model and tested for its diagnostic and prognostic potential in HCC. Using plasma samples, the predictive model exhibited high sensitivity and specificity (> 80%) for HBV-related HCC. Most importantly, nearly 75% of patients who could not be diagnosed with AFP at 20 ng/mL were detected by this model. Further, the predictive model exhibited an exceedingly high ability to predict 5-year overall survival in HCC patients. These data demonstrate the high diagnostic and prognostic potential of methylation markers in the plasma of HCC patients. PMID:28031532

  16. Insights into Orphan Nuclear Receptors as Prognostic Markers and Novel Therapeutic Targets for Breast Cancer

    PubMed Central

    Aesoy, Reidun; Clyne, Colin D.; Chand, Ashwini L.

    2015-01-01

    There is emerging evidence asserting the importance of orphan nuclear receptors (ONRs) in cancer initiation and progression. In breast cancer, there is a lot unknown about ONRs in terms of their expression profile and their transcriptional targets in the various stages of tumor progression. With the classification of breast tumors into distinct molecular subtypes, we assess ONR expression in the different breast cancer subtypes and with patient outcomes. Complementing this, we review evidence implicating ONR-dependent molecular pathways in breast cancer progression to identify candidate ONRs as potential prognostic markers and/or as therapeutic targets. PMID:26300846

  17. Serum TNF alpha levels: a prognostic marker for assessment of severity of malaria.

    PubMed

    Kinra, P; Dutta, V

    2013-12-01

    Complicated Plasmodium falciparum infection is associated with a 6.4% mortality rate in India, yet its prognostication is incompletely understood. The conventional prognostic markers of falciparum malaria include clinical, haematological and biochemical parameters. However these factors are non-specific. Hence there is a need of an accurate inexpensive objective marker for prognosticating falciparum malaria infection outcomes. Angiopoietins, angiogenic factors, eotaxins, adhesion molecules and inflammatory cytokines have been studied for prognostication of this common disease. Determination of the first four is technically difficult and requires a high level of expertise and equipment. Intermediary cytokines have the most promising role. This study was conducted with the aim to evaluate the serum level of TNF-α in patients with P. falciparum malaria and carry out statistical analysis of levels of serum TNF-α with parasite index, age, severity of anaemia, hypoglycaemia, hepatic and renal dysfunction. In our study the average TNF alpha level in 91healthy controls was 46.42 pg/ml whereas that in mild falciparum malaria was 100.45 pg/ml, in severe malaria - 278.63 pg/ml and in cerebral malaria it was 532.6 pg/ml. The mean TNF alpha level was significantly different in severe malaria and cerebral malaria compared to that in healthy controls (p < 0.02). The difference in levels of TNF alpha was significantly higher in falciparum malaria patients with anaemia, altered liver functions, hyperparasitemia, leucocytosis, hepatosplenomegaly and hypoglycaemia. The TNF levels did not correlate well with haemolysis markers and patients with altered renal function. Hence a raised TNF alpha can predict the likelihood of oncoming anaemia, hypoglycaemia, altered hepatic function and leucocytosis but not the grades of malaria. The duration of stay in hospital and change in parasite index between the 5(th) day and the 1(st) day of admission was used a clinical outcome marker in this

  18. Prognostic factors, predictive markers and cancer biology: the triad for successful oral cancer chemoprevention.

    PubMed

    Monteiro de Oliveira Novaes, Jose Augusto; William, William N

    2016-10-01

    Oral squamous cell carcinomas represent a significant cancer burden worldwide. Unfortunately, chemoprevention strategies investigated to date have failed to produce an agent considered standard of care to prevent oral cancers. Nonetheless, recent advances in clinical trial design may streamline drug development in this setting. In this manuscript, we review some of these improvements, including risk prediction tools based on molecular markers that help select patients most suitable for chemoprevention. We also discuss the opportunities that novel preclinical models and modern molecular profiling techniques will bring to the prevention field in the near future, and propose a clinical trials framework that incorporates molecular prognostic factors, predictive markers and cancer biology as a roadmap to improve chemoprevention strategies for oral cancers.

  19. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

    PubMed

    Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

    2016-11-01

    Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

  20. Assessment of Quantitative and Allelic MGMT Methylation Patterns as a Prognostic Marker in Glioblastoma.

    PubMed

    Kristensen, Lasse S; Michaelsen, Signe R; Dyrbye, Henrik; Aslan, Derya; Grunnet, Kirsten; Christensen, Ib J; Poulsen, Hans S; Grønbæk, Kirsten; Broholm, Helle

    2016-03-01

    Methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a predictive and prognostic marker in newly diagnosed glioblastoma patients treated with temozolomide but how MGMT methylation should be assessed to ensure optimal detection accuracy is debated. We developed a novel quantitative methylation-specific PCR (qMSP) MGMT assay capable of providing allelic methylation data and analyzed 151 glioblastomas from patients receiving standard of care treatment (Stupp protocol). The samples were also analyzed by immunohistochemistry (IHC), standard bisulfite pyrosequencing, and genotyped for the rs1690252 MGMT promoter single nucleotide polymorphism. Monoallelic methylation was observed more frequently than biallelic methylation, and some cases with monoallelic methylation expressed the MGMT protein whereas others did not. The presence of MGMT methylation was associated with better overall survival (p = 0.006; qMSP and p = 0.002; standard pyrosequencing), and the presence of the protein was associated with worse overall survival (p = 0.009). Combined analyses of qMSP and standard pyrosequencing or IHC identified additional patients who benefited from temozolomide treatment. Finally, low methylation levels were also associated with better overall survival (p = 0.061; qMSP and p = 0.02; standard pyrosequencing). These data support the use of both MGMT methylation and MGMT IHC but not allelic methylation data as prognostic markers in patients with temozolomide-treated glioblastoma.

  1. Cerebral venous circulatory disturbance as an informative prognostic marker for neonatal hemorrhagic stroke

    NASA Astrophysics Data System (ADS)

    Semyachkina-Glushkovskaya, Oxana; Pavlov, Alexey; Navolokin, Nikita; Lychagov, Vladislav; Abdurashitov, Arkady; Zinchenko, Ekaterina; Gekaluk, Artemiy; Zhu, Dan; Shi, Rui; Luo, Qingming; Tuchin, Valery

    2016-04-01

    Neonatal hemorrhagic stroke (NHS) is a major problem of future generation's health due to the high rate of death and cognitive disability of newborns after NHS. The incidence of NHS in neonates cannot be predicted by standard diagnostic methods. Therefore, the identification of prognostic markers of NHS is crucial. There is evidence that stress-related alterations of cerebral blood flow (CBF) may contribute to NHS. Here, we assessed the stroke-associated CBF abnormalities for high prognosis of NHS using a new model of NHS induced by sound stress in the pre- and post-stroke state. With this aim, we used interdisciplinary methods such as a histological assay of brain tissues, laser speckle contrast imaging and Doppler coherent tomography to monitor cerebral circulation. Our results suggest that the venous stasis with such symptoms as progressive relaxation of cerebral veins, decrease the velocity of blood flow in them are prognostic markers for a risk of NHS and are an informative platform for a future study of corrections of cerebral venous circulatory disturbance related to NHS.

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

    PubMed Central

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

    2015-01-01

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

  3. Adverse prognostic impact of TGFB1 T869C polymorphism in non-small-cell lung cancer

    PubMed Central

    Sang, Yulan; Bi, Xin; Liu, Yan; Zhang, Wei; Wang, Dongjie

    2017-01-01

    Previously, several polymorphisms in TGFB1 have been identified in non-small-cell lung cancer (NSCLC), and the variants, C-509T, T869C, and G915C, have been demonstrated to associate with higher circulating levels of TGF-β1. However, little is known about the prognostic value of TGF-β1 polymorphisms in cancers. In this study, by genotyping the TGF-β1 T869C polymorphism in a total of 261 patients with NSCLC using DNA from blood lymphocytes, we first found that NSCLC patients, especially those with allele C carriers, had significantly higher serum TGF-β1 levels than healthy individuals. By using chi-square (χ2) test and Fisher’s exact test, we noticed that TC/CC genotypes were positively correlated with smoking, clinical TNM stage, lymph node, and distant metastasis in NSCLC patients. Kaplan–Meier analysis showed that patients with TT genotype had a better overall survival than the allele C carriers (TC + CC). Finally, multivariate analysis confirmed histology, lymph node, and distant metastasis but not T869C polymorphism as independent prognostic factors for NSCLC. Taken together, our data, as a proof of principle, suggest that T869C polymorphism in TGFB1 may act as a genetic modifier in NSCLC progression and a promising prognostic marker of survival in NSCLC patients. PMID:28331344

  4. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    SciTech Connect

    Mestre, Francisco; Gutiérrez, Antonio; Rodriguez, Jose; Ramos, Rafael; Garcia, Juan Fernando; Martinez-Serra, Jordi; Casasus, Marta; Nicolau, Cristina; Bento, Leyre; Herraez, Ines; Lopez-Perezagua, Paloma; Daumal, Jaime; Besalduch, Joan

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  5. Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma

    PubMed Central

    Su, Li; Zhang, Mingwei; Zhang, Weijian; Cai, Chuanshu; Hong, Jinsheng

    2017-01-01

    Abstract Background: Pretreatment hematologic parameters of the inflammatory response, including lymphocyte, neutrophil, and platelet counts, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, have emerged as prognostic factors for patients with cancer. This systematic review and meta-analysis aimed to summarize the association between the hematologic markers and prognosis of nasopharyngeal carcinoma (NPC). Methods: A systematic search of PubMed, Google Scholar, MEDLINE, EMBASE, Web of Science, and the Cochrane Library was conducted up to April 2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and synthesized to examine prognostic outcomes including cancer-specific survival (CSS), overall survival (OS), progression-free survival (PFS), distant metastasis-free survival, and local relapse-free survival (LRFS). Results: Fourteen studies comprising 11,651 NPC patients were ultimately included, and all eligible studies were conducted in East Asia. The OS, CSS, PFS, distant metastasis-free survival, and LRFS risks differed among patients according to hematologic marker levels. All of the parameters were associated with prognostic outcomes in patients with NPC. NLR and lymphocyte counts were most commonly reported. A high NLR was significantly associated with poor NPC prognosis (pooled HR 1.42, 95% CI 1.21–1.67 for CSS; pooled HR 1.77, 95% CI 1.41–2.23 for OS; pooled HR 1.67, 95% CI 1.36–2.06 for PFS; pooled HR 1.64, 95% CI 1.15–2.34 for LRFS). High lymphocyte count indicated favorable NPC prognosis (pooled HR 0.72, 95% CI 0.64–0.81 for OS; pooled HR 0.71, 95% CI 0.56–0.91 for PFS). Conclusions: Meta-analysis indicated that NLR and lymphocyte counts could be prognostic predictors in NPC for East Asian population. Patients with a high NLR or low lymphocyte count had poor prognosis. However, due to the limitation of included population, the conclusion was limited to East Asian

  6. Hypoxia inducible BHLHB2 is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma

    SciTech Connect

    Wang, Weibin; Reiser-Erkan, Carolin; Michalski, Christoph W.; Raggi, Matthias C.; Quan, Liao; Yupei, Zhao; Friess, Helmut; Erkan, Mert; Kleeff, Joerg

    2010-10-22

    cells. Patients with weak/absent nuclear BHLHB2 staining had significantly worse median survival compared to those with strong staining (13 months vs. 27 months, p = 0.03). In a multivariable analysis, BHLHB2 staining was an independent prognostic factor (Hazard-Ratio = 2.348, 95% CI = 1.250-4.411, p = 0.008). Conclusions: Hypoxia-inducible BHLHB2 expression is a novel independent prognostic marker in pancreatic cancer patients and indicates increased chemosensitivity towards gemcitabine.

  7. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  8. Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

    PubMed

    Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-11-25

    Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients.

  9. P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients

    PubMed Central

    Pan, Yunbao; Yuan, Yufen; Liu, Guoshi; Wei, Yongchang

    2017-01-01

    Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC. PMID:28235003

  10. Auto-antibodies as emergent prognostic markers and possible mediators of ischemic cardiovascular diseases.

    PubMed

    Roux-Lombard, P; Pagano, S; Montecucco, F; Satta, N; Vuilleumier, N

    2013-02-01

    During the last 15 years, a growing body of evidence supported the fact that auto-antibodies represent not only emergent markers but also active mediators of cardiovascular disease (CVD), clinically represented mostly by acute coronary syndrome (ACS) and stroke. There is a contrasted relationship between auto-antibodies and CVD, some being protective, while others acting as potential risk factors. Therefore, we performed a review of the literature on the respective cardiovascular prognostic value of the most relevant auto-antibodies in ACS and stroke, and their putative pathophysiological properties in atherogenesis. This review highlights auto-antibodies as active modulators of the innate immune system in atherogenesis (either toward a pro- or anti-inflammatory response), or by affecting basal heart rate regulation (anti-apoA-1 IgG). Given their apparent prognostic independency towards traditional cardiovascular risk factors, the data available in the literature indicates that some of those auto-antibodies could be of valuable help for cardiovascular risk stratification in the future, especially because their deleterious effects have been shown to be potentially abrogated in vivo and in vitro by existing therapeutic modalities. Although evidence in humans is currently lacking, these studies may open innovative therapeutic perspectives for CVD in the future.

  11. GDF 15 as an anti-apoptotic, diagnostic and prognostic marker in oral squamous cell carcinoma.

    PubMed

    Schiegnitz, E; Kämmerer, P W; Koch, F P; Krüger, M; Berres, M; Al-Nawas, B

    2012-07-01

    Growth-differentiation factor 15 (GDF 15) is involved in tumor pathogenesis and its expression is increased in many types of cancers. Functional effects of GDF 15 on oncogenesis of oral squamous cell carcinoma (OSCC) remain unclear. Therefore, the aim of this study was to examine the apoptotic characteristics of GDF 15 in OSCC cell lines in vitro and to analyze serum GDF 15 concentrations as a diagnostic and prognostic tumor marker for OSCC in vivo. Caspase activity was assessed in OSCC cell lines with the Caspase-Glo 3/7 system. Serum GDF 15 concentrations from 64 patients with histopathological proven OSCC and from 30 healthy volunteers were measured using an enzyme-linked immunosorbent assay. In 21 patients, serum GDF 15 was also analyzed postoperatively. In vitro, treatment of OSCC cell lines with GDF 15 reduced Caspase 3/7 activity significantly (p<0.05). In vivo, serum GDF 15 concentrations of the OSCC patients in all stages of OSCC were significantly higher than those of the healthy subjects (p<0.0001). After surgery, GDF 15 concentrations declined significantly from 1545±774pg/ml preoperative to 953±438pg/ml postoperative (p=0.003). The median survival time of OSCC patients with GDF 15 levels below 875pg/ml was significantly higher than of OSCC patients with GDF 15 levels above or equal 875pg/ml (p=0.031). Determination of receiver operating characteristic curves (ROC) showed a respective area under the ROC curve (AUC) of 0.943. The anti-apoptotic effect of GDF 15 in OSCC cell lines was shown in vitro. In vivo, significant elevated serum GDF 15 levels with prognostic value in OSCC-patients were seen for the first time. The results indicate that GDF15 may be used as a potential marker for diagnosis and prognosis of this entity.

  12. Senescence marker protein 30 (SMP30) serves as a potential prognostic indicator in hepatocellular carcinoma

    PubMed Central

    Mo, Zhijing; Zheng, Shunxin; Lv, Zhilue; Zhuang, Yuan; Lan, Xiuwan; Wang, Feng; Lu, Xiaoling; Zhao, Yongxiang; Zhou, Sufang

    2016-01-01

    Senescence marker protein 30 (SMP30) has been identified as a tumor-related molecule of hepatocellular carcinoma (HCC). Its clinical significance and underlying mechanisms in HCC tissues, however, remain largely unexplored. We have demonstrated a preferentially expressed SMP30 in normal liver using a tissue microarray. By employing real-time quantitative PCR, two tissue microarrays and Oncomine database analysis, we have also shown that the SMP30 in HCC tissues has significantly reduced when compared with that in paired adjacent non-tumor tissues (P = 0.0037). The reduced expression of SMP30 is very noticeably related to larger tumor size (P = 0.012), enhanced TNM (P = 0.009) and worse survival (P < 0.0001) in HCC patients. The analyses using Cox regression have indicated that the decreased SMP30 expression is an independent risk to the reduced overall survival rate of HCC patients (P = 0.001), and the down-regulation of SMP30 in HCC might be mediated by DNA methylation. Moreover, genes co-expressed with SMP30 may affect the prognosis through apoptotic process, biological adhesion and blood coagulation by PANTHER analyses. Our studies have indicated that the SMP30 may serve as a candidate of HCC clinical prognostic marker and a potential therapeutic target. PMID:27991558

  13. Combination of meta-analysis and graph clustering to identify prognostic markers of ESCC.

    PubMed

    Gao, Hongyun; Wang, Lishan; Cui, Shitao; Wang, Mingsong

    2012-04-01

    Esophageal squamous cell carcinoma (ESCC) is one of the most malignant gastrointestinal cancers and occurs at a high frequency rate in China and other Asian countries. Recently, several molecular markers were identified for predicting ESCC. Notwithstanding, additional prognostic markers, with a clear understanding of their underlying roles, are still required. Through bioinformatics, a graph-clustering method by DPClus was used to detect co-expressed modules. The aim was to identify a set of discriminating genes that could be used for predicting ESCC through graph-clustering and GO-term analysis. The results showed that CXCL12, CYP2C9, TGM3, MAL, S100A9, EMP-1 and SPRR3 were highly associated with ESCC development. In our study, all their predicted roles were in line with previous reports, whereby the assumption that a combination of meta-analysis, graph-clustering and GO-term analysis is effective for both identifying differentially expressed genes, and reflecting on their functions in ESCC.

  14. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers.

    PubMed

    Pepper, Chris; Lin, Thet Thet; Pratt, Guy; Hewamana, Saman; Brennan, Paul; Hiller, Louise; Hills, Robert; Ward, Rachel; Starczynski, Jane; Austen, Belinda; Hooper, Laura; Stankovic, Tatjana; Fegan, Chris

    2008-11-01

    Bcl-2 family proteins play a critical role in the regulation of apoptosis in chronic lymphocytic leukemia (CLL). However, their association with established prognostic markers is unknown. In this study, we analyzed the expression of Bcl-2, Bax, and Mcl-1 in 185 CLL patients and evaluated their relationship with other prognostic markers, in vitro sensitivity to fludarabine, and clinical outcome. Mcl-1 expression was significantly correlated with stage of disease (P < .001), lymphocyte doubling time (P = .01), V(H) gene mutation status (P < .001), CD38 expression (P < .001), and ZAP-70 expression (P = .003). In addition, Mcl-1 and Mcl-1/Bax ratios showed strong correlations with in vitro resistance to fludarabine (P = .005 and P < .001, respectively). Furthermore, elevated Mcl-1 expression and Mcl-1/Bax ratios were predictive of time to first treatment in the whole cohort (P < .001 and P < .001, respectively) and in stage A patients only (P = .002 and P = .001, respectively). Taken together, our data show that Mcl-1 is a key controller of in vitro drug resistance and is an important regulator of disease progression and outcome in CLL. It therefore represents a promising therapeutic target in this incurable condition. The close correlation between Mcl-1 expression and V(H) gene mutation status, CD38 expression, and ZAP-70 expression offers a biologic explanation for their association with adverse prognosis.

  15. Adverse Effects of Pesticides Residues on Biochemical Markers in Pakistani Tobacco Farmers

    PubMed Central

    Khan, Dilshad A; Bhatti, Mahwish M; Khan, Farooq A; Naqvi, Syed T; Karam, A

    2008-01-01

    Tobacco is an important cash crop of Pakistan and tremendous amount of irrational pesticides are being used to control insect growth. The frequency of plasma pesticide residues above acceptable daily intake (ADI) and its correlation with biochemical markers for assessment of adverse health effects in the tobacco farmers at district Sawabi, Pakistan was determined. Total 109 adult males consisting of 55 tobacco farmers exposed to pesticides and 54 controls were included. Pesticides residues in blood were analyzed on HPLC and GC-NPD. Plasma butyrylcholinesterase (BChE) was analyzed by Ellman's method. Biochemical markers including serum calcium, phosphorus, urea, creatinine, bilirubin and liver enzymes were measured on Selectra-E auto analyzer. The tobacco farmers had multiple pesticides residues above ADI in their blood consisting of 35 (63%) methomyl; 31 (56%) thiodicarb; 34(62%) cypermethrin; 27 (49%) Imidacloprid; 18 (32%) Methamidophos and 15 (27%) endosulfan. BChE activity was significantly decreased in the pesticides exposed farmers as compared to controls (P<0.001). Plasma biochemical markers including ALT, AST, CK, LDH and phosphate were significantly raised in the pesticides exposed farmers as compared to control group (P<0.001). Total pesticides residues revealed a significant positive correlation with AST (r=0.42), LDH(r= 0.47), ALT (r=0.20) and phosphorus (r=0.51). Excessive exposure to pesticide caused cytotoxic changes in the hepatic and renal biochemical markers which were positively correlated with pesticide residue. Hence these biomarkers might be used in addition to BChE activity for monitoring of adverse effects of pesticides on the health of farm workers. PMID:19079663

  16. Alpha-1 Antitrypsin, a Diagnostic and Prognostic Marker of Vernal Keratoconjunctivitis

    PubMed Central

    Salman, Khushtar A; Alam, Sana; Siddiqui, Anwar H; Naeem, Syed Shariq; Ahmad, Aquil; Khan, Iqbal M

    2014-01-01

    Introduction: A major chunk of ocular allergies in humans involve the conjunctiva, of which Vernal Keratoconjunctivitis (VKC) appears to be more common. VKC, a chronic allergic conjunctivitis, frequently affects young males and is characterized by intense inflammation of the limbal and/or tarsal conjunctiva. The etiology and immuno-pathogenesis of VKC still remain unclear. Alpha-1 antitrypsin (AAT), a member of serine proteinase inhibitor (SERPIN) superfamily, is an acute phase protein whose concentration in blood increases in response to inflammation. AAT deficiency is one of the many factors that may be involved in several abnormalities such as liver disease, emphysema, inflammatory joint diseases and inflammatory eye diseases. In the present study, the role played by this protein in VKC was analyzed in a selective case/control study to assess its diagnostic and prognostic value. Materials and Methods: The case control study included 50 patients of VKC reporting to Ophthalmology out patient department (OPD). Age and sex matched 40 healthy subjects served as control. Serum AAT level of both the cases and controls were evaluated and compared. Moreover the serum AAT levels of the patients at presentation were compared with their serum AAT level after three weeks post treatment. Result: Levels of AAT in the serum of VKC patients at presentation (2.80 ± 0.42 mg/ml) were significantly higher as compared to controls (2.31 ± 0.21 mg/ml) whereas no significant difference was observed between the serum level of post treatment VKC patients (2.48 ± 0.26 mg/ml) and controls. Conclusion: AAT is a potent acute phase protein whose concentration rises significantly in VKC, irrespective of the age and sex of the patient. Moreover, the serum level of AAT declined significantly post treatment; therefore it might be used as a prognostic marker. PMID:24995171

  17. The prognostic value of the myeloid-mediated immunosuppression marker Arginase-1 in classic Hodgkin lymphoma

    PubMed Central

    Romano, Alessandra; Parrinello, Nunziatina Laura; Vetro, Calogero; Tibullo, Daniele; Giallongo, Cesarina; La Cava, Piera; Chiarenza, Annalisa; Motta, Giovanna; Caruso, Anastasia L.; Villari, Loredana; Tripodo, Claudio; Cosentino, Sebastiano; Ippolito, Massimo; Consoli, Ugo; Gallamini, Andrea; Pileri, Stefano; Di Raimondo, Francesco

    2016-01-01

    Purpose Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL. Experimental design First, N-HL function was evaluated in vitro, showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training (N = 40) and validation (N = 78) sets. Results s-Arg-1 was higher in patients with advanced stage (p = 0.045), B-symptoms (p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2. Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012). Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% (p = 0.0004). Conclusions We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis. PMID:27637084

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

    SciTech Connect

    Noordhuis, Maartje G.; Eijsink, Jasper J.H.; Roossink, Frank; Graeff, Pauline de; Pras, Elisabeth; Schuuring, Ed; Wisman, G. Bea A.; Bock, Geertruida H. de; Zee, Ate G.J. van der

    2011-02-01

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

  19. Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma

    PubMed Central

    Park, Eunhyang; Park, Soo Young; Sun, Ping-Li; Jin, Yan; Kim, Ji Eun; Jheon, Sanghoon; Kim, Kwhanmien; Lee, Choon Taek

    2016-01-01

    Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma (n = 226) or squamous cell carcinoma (n = 142). We correlated the expression of six CSC markers – CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog – with clinicopathologic and molecular variables and survival outcomes. In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma. CSC markers had no prognostic value in squamous cell carcinoma. These results suggest that Nanog is an independent negative prognostic factor that may be associated with epithelial-mesenchymal transition in lung adenocarcinoma. PMID:27285762

  20. Prognostic markers for canine melanocytic neoplasms: a comparative review of the literature and goals for future investigation.

    PubMed

    Smedley, R C; Spangler, W L; Esplin, D G; Kitchell, B E; Bergman, P J; Ho, H-Y; Bergin, I L; Kiupel, M

    2011-01-01

    Many studies have evaluated various prognostic markers for canine melanocytic neoplasms either as primary or secondary goals; however, design, methodology, and statistical validation vary widely across these studies. The goal of this article was to evaluate and compare published canine melanocytic neoplasm studies in relation to the principals established in the Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology. Based on this evaluation, we determined which parameters currently have the most statistically supported validity for prognostic use in canine melanocytic neoplasia. This information can also be used as part of evidence-based prospective evaluations of treatment regimens. Additionally, we highlight areas in which the current data are incomplete and that warrant further evaluation. This article represents an initiative of the American College of Veterinary Pathologists' Oncology Committee and has been reviewed and endorsed by the World Small Animal Veterinary Association.

  1. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received

    PubMed Central

    Dawson, S-J; Makretsov, N; Blows, F M; Driver, K E; Provenzano, E; Le Quesne, J; Baglietto, L; Severi, G; Giles, G G; McLean, C A; Callagy, G; Green, A R; Ellis, I; Gelmon, K; Turashvili, G; Leung, S; Aparicio, S; Huntsman, D; Caldas, C; Pharoah, P

    2010-01-01

    Background: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker. Methods: Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2. Results: In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66–0.88, P<0.001). BCL2 was a powerful prognostic marker in ER− (HR 0.63, 95% CI 0.54–0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48–0.65, P<0.001), and in HER2− (HR 0.55, 95% CI 0.49–0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57–0.85, P<0.001), irrespective of the type of adjuvant therapy received. Addition of BCL2 to the Adjuvant! Online prognostic model, for a subset of cases with a 10-year follow-up, improved the survival prediction (P=0.0039). Conclusions: BCL2 is an independent indicator of favourable prognosis for all types of early-stage breast cancer. This study establishes the rationale for introduction of BCL2 immunohistochemistry to improve prognostic stratification. Further work

  2. FGFR4 Profile as a Prognostic Marker in Squamous Cell Carcinoma of the Mouth and Oropharynx

    PubMed Central

    Dutra, Roberta Lelis; de Carvalho, Marcos Brasilino; dos Santos, Marcelo; Mercante, Ana Maria da Cunha; Gazito, Diana; de Cicco, Rafael; Group, GENCAPO; Tajara, Eloiza Helena; Louro, Iúri Drumond; da Silva, Adriana Madeira Álvares

    2012-01-01

    Background Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis. Patients and Methods DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays. Results Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death. Conclusion Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx. PMID:23226373

  3. The Eag potassium channel as a new prognostic marker in ovarian cancer

    PubMed Central

    2010-01-01

    Background Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression. Objectives To determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation. Methods The expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3). Results We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014) and presence of residual disease (P = 0.011). Proliferation of SK-OV-3 cells was significantly (P < 0.001) inhibited after treatment with voltage gated K+ channel blockers. Conclusion This novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer. PMID:21138547

  4. Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer.

    PubMed

    Rodrigues, P R S; Maia, L L; Santos, M; Peterle, G T; Alves, L U; Takamori, J T; Souza, R P; Barbosa, W M; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-11-25

    The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies.

  5. Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma.

    PubMed

    Masugi, Yohei; Tanese, Keiji; Emoto, Katsura; Yamazaki, Ken; Effendi, Kathryn; Funakoshi, Takeru; Mori, Mariko; Sakamoto, Michiie

    2015-12-01

    Malignant melanoma is one of the lethal malignant tumors worldwide. Previously we reported that adenylate cyclase-associated protein 2 (CAP2), which is a well-conserved actin regulator, was overexpressed in hepatocellular carcinoma; however, CAP2 expression in other clinical cancers remains unclear. The aim of the current study was to clarify the clinicopathological significance of CAP2 overexpression in malignant melanoma. Immunohistochemical analyses revealed that many melanoma cells exhibited diffuse cytoplasmic expression of CAP2, whereas no normal melanocytes showed detectable immunostaining for CAP2. A high level of CAP2 expression was seen in 14 of 50 melanomas and was significantly correlated with greater tumor thickness and nodular melanoma subtypes. In addition, a high level of CAP2 expression was associated with poor overall survival in univariate and multivariate analyses. For 13 patients, samples of primary and metastatic melanoma tissue were available: four patients exhibited higher levels of CAP2 expression in metastatic tumor compared to the primary site, whereas no patient showed lower levels of CAP2 expression in metastatic melanomas. Our findings show that CAP2 overexpression is a novel prognostic marker in malignant melanoma and that CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma.

  6. TGF-β1 of no avail as prognostic marker in lyme disease.

    PubMed

    Schumann, Julia

    2014-01-01

    Background. Within the present in vivo study using the wild type mouse strains C3H/HeN and FVB/N it was intended to (1) measure TGF-β1 expression in the course of lyme disease, (2) examine the potential correlation of TGF-β1 expression with the clinical outcome of a Borrelia infection (with a focus on lyme arthritis), (3) develop a diagnostic tool based on the endogenous factor TGF-β1 to predict the progressivity of lyme disease. Findings. In the course of lyme disease there was an increase in the serum content of active TGF-β1, which became significant 56 days post infection (p < 0.001). The serum concentration of total TGF-β1 in the course of infection initially decreased then rebounded and subsequently dropped again. Despite considerable individual variations in active TGF-β1 serum concentrations there were no identifiable dissimilarities in the clinical appearance of the mice. Likewise, no correlation could be seen between the serum content of active TGF-β1 and the severity of lyme arthritis of tibiotarsal joints of infected mice. Conclusions. The present study clearly shows that TGF-β1 is of no avail as prognostic marker in lyme disease. Hence, the search for an endogenous predictive factor, which can be determined in an easy and reliable manner, remains open.

  7. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker.

    PubMed

    Chavan, S S; He, J; Tytarenko, R; Deshpande, S; Patel, P; Bailey, M; Stein, C K; Stephens, O; Weinhold, N; Petty, N; Steward, D; Rasche, L; Bauer, M; Ashby, C; Peterson, E; Ali, S; Ross, J; Miller, V A; Stephens, P; Thanendrarajan, S; Schinke, C; Zangari, M; van Rhee, F; Barlogie, B; Mughal, T I; Davies, F E; Morgan, G J; Walker, B A

    2017-02-24

    The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance.

  8. Loss of RUNX3 expression is an independent adverse prognostic factor in diffuse large B-cell lymphoma.

    PubMed

    Duncan, Virginia E; Ping, Zheng; Varambally, Sooryanarayana; Peker, Deniz

    2017-01-01

    Runt-related transcription factor-3 (RUNX3) is an apoptotic factor correlated with tumorigenesis and cancer progression. Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been shown to mediate silencing of RUNX3. We investigated RUNX3 and EZH2 expression in diffuse large B-cell lymphoma (DLBCL). A chart review was conducted and tissue-microarray (TMA) was constructed using archived tissue from 83 DLBCL cases. RUNX3 and EZH2 protein expression was correlated with immunophenotypic subtypes and survival. Loss of RUNX3 was observed in 20 cases; EZH2 expression was observed in 59 cases. RUNX3-negative tumors had significantly lower overall and recurrence-free survival (log-rank test, p < 0.0001 for each). No correlation was found between RUNX3 and EZH2 staining (r = 0.14; p = 0.2). Results suggest a role for the RUNX3 gene in the pathogenesis of DLBCL. Loss of RUNX3 expression strongly correlated with adverse prognosis, independent of subtype. Further studies are warranted to elucidate the biology and prognostic utility of RUNX3 in DLBCL.

  9. The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

    SciTech Connect

    Kong, Christina S.; Narasimhan, Balasubramanian; Cao Hongbin; Kwok, Shirley; Erickson, Julianna P.; Koong, Albert; Pourmand, Nader; Le, Quynh-Thu

    2009-06-01

    Purpose: To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. Methods and Materials: HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16{sup INK4a} staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO{sub 2} and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Results: Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16{sup INK4a} staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16{sup INK4a} staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO{sub 2} or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. Conclusion: HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.

  10. HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker12

    PubMed Central

    Sconocchia, Giuseppe; Eppenberger-Castori, Serenella; Zlobec, Inti; Karamitopoulou, Eva; Arriga, Roberto; Coppola, Andrea; Caratelli, Sara; Spagnoli, Giulio Cesare; Lauro, Davide; Lugli, Alessandro; Han, Junyi; Iezzi, Giandomenica; Ferrone, Cristina; Ferlosio, Amedeo; Tornillo, Luigi; Droeser, Raoul; Rossi, Piero; Attanasio, Antonio; Ferrone, Soldano; Terracciano, Luigi

    2014-01-01

    The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1β (IL-1β) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1β production by monocytes. PMID:24563618

  11. Ki-67 as a prognostic marker according to breast cancer molecular subtype

    PubMed Central

    Soliman, Nahed A.; Yussif, Shaimaa M.

    2016-01-01

    Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed. Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Follow-up ranged from 32 months up to 6 years. Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative (TN), respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in 34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than 15% (P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15% (P = 0.000). Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients. PMID:28154782

  12. Non-invasive urinary metabolomic profiling identifies diagnostic and prognostic markers in lung cancer

    PubMed Central

    Mathé, Ewy A.; Patterson, Andrew D.; Haznadar, Majda; Manna, Soumen K.; Krausz, Kristopher W.; Bowman, Elise D.; Shields, Peter G.; Idle, Jeffrey R.; Smith, Philip B.; Anami, Katsuhiro; Kazandjian, Dickran G.; Hatzakis, Emmanuel; Gonzalez, Frank J.; Harris, Curtis C.

    2014-01-01

    Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1500 Da) were measured in urine collected from 469 lung cancer patients and 536 population controls using unbiased liquid chromatography-mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further validated in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared to the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA), were each significantly (P <0.00001) elevated in non–small cell lung cancer (NSCLC) and associated with worse prognosis (hazard ratio (HR) =1.81 [P =0.0002], and 1.54 [P =0.025], respectively). Creatine riboside was the strongest classifier of lung cancer status in all and stage I–II cases, important for early detection, and also associated with worse prognosis in stage I–II lung cancer (HR =1.71, P =0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 – 0.99. Both metabolites were significantly (P <0.03) enriched in tumor tissue compared to adjacent non-tumor tissue (N =48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis. PMID:24736543

  13. Prognostic Value of a New Marker of Ventricular Repolarization in Cirrhotic Patients

    PubMed Central

    Salgado, Angelo Antunes; Barbosa, Paulo Roberto Benchimol; Ferreira, Alinne Gimenez; Reis, Camila Aparecida de Souza Segrégio; Terra, Carlos

    2016-01-01

    Background There is still debate about the relationship between changes in ventricular repolarization on the surface electrocardiogram and cirrhosis severity. Objective To study the relationship between variables related to ventricular repolarization and the clinical severity of the cirrhotic disease. Methods We selected 79 individuals with hepatic cirrhosis, classified according to the Child-Pugh-Turcotte criteria (Child A, B, and C). We measured the QT and corrected QT (QTc) intervals, and the interval between the peak and the end of the T wave (TpTe), and we identified their minimum, maximum, and mean values in the 12-lead electrocardiogram. We also calculated the dispersion of the QT (DQT) and QTc (DQTc) intervals. Results In 12 months of clinical follow-up, nine subjects underwent hepatic transplantation (Child A: 0 [0%]; Child B: 6 [23.1%]; Child C: 3 [18.8%]; p = 0.04) and 12 died (Child A: 3 [12.0%]; Child B: 4 [15.4%]; Child C: 5 [31.3%]; p = 0.002). No significant differences were observed between the cirrhotic groups related to the minimum, maximum, and mean values for the QT, QTc, TpTe, DQT, and DQTc intervals. A minimum TpTe interval ≤ 50 ms was a predictor for the composite endpoints of death or liver transplantation with a sensitivity of 90% and a specificity of 57% (p = 0.005). In the Cox multivariate analysis, the Child groups and a minimum TpTe of ≤ 50 ms were independent predictors of the composite endpoints. Conclusion The intervals QT, QTc, DQT, DQTc, and TpTe have similar distributions between different severity stages in cirrhotic disease. The TpTe interval proved to be a prognostic marker in subjects with cirrhosis, regardless of disease severity (NCT01433848).

  14. Waterlow score as a surrogate marker for predicting adverse outcome in acute pancreatitis

    PubMed Central

    Gillick, K; Elbeltagi, H; Bhattacharya, S

    2016-01-01

    Introduction Introduced originally to stratify risk for developing decubitus ulcers, the Waterlow scoring system is recorded routinely for surgical admissions. It is a composite score, reflecting patients’ general condition and co-morbidities. The aim of this study was to investigate whether the Waterlow score can be used as an independent surrogate marker to predict severity and adverse outcome in acute pancreatitis. Methods In this retrospective analysis, a consecutive cohort was studied of 250 patients presenting with acute pancreatitis, all of whom had their Waterlow score calculated on admission. Primary outcome measures were length of hospital stay and mortality. Secondary outcome measures included rate of intensive care unit (ICU) admission and development of complications such as peripancreatic free fluid, pancreatic necrosis and pseudocyst formation. Correlation of the Waterlow score with some known markers of disease severity and outcomes was also analysed. Results The Waterlow score correlated strongly with the most commonly used marker of disease severity, the Glasgow score (analysis of variance, p=0.0012). Inpatient mortality, rate of ICU admission and length of hospital stay increased with a higher Waterlow score (Mann–Whitney U test, p=0.0007, p=0.049 and p=0.0002 respectively). There was, however, no significant association between the Waterlow score and the incidence of three known complications of pancreatitis: presence of peripancreatic fluid, pancreatic pseudocyst formation and pancreatic necrosis. Receiver operating characteristic curve analysis demonstrated good predictive power of the Waterlow score for mortality (area under the curve [AUC]: 0.73), ICU admission (AUC: 0.65) and length of stay >7 days (AUC: 0.64). This is comparable with the predictive power of the Glasgow score and C-reactive protein. Conclusions The Waterlow score for patients admitted with acute pancreatitis could provide a useful tool in prospective assessment of

  15. BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

    PubMed Central

    Lee, Y-K; Choi, E; Kim, M A; Park, P-G; Park, N-H; Lee, H

    2009-01-01

    Background: Epithelial ovarian cancer is one of the most lethal malignancies, and has a high recurrence rate. Thus, prognostic markers for recurrence are crucial for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome instability, we aimed at assessing the prognostic significance of two key mitotic kinases, BubR1 and Aurora A. Methods: We analysed paraffin-embedded tissue sections from 160 ovarian cancer patients whose clinical outcomes had been tracked after first-line treatment. Results: The median recurrence-free survival in patients with a positive and negative expression of BubR1 was 27 and 83 months, respectively (P<0.001). A positive BubR1 expression was also associated with advanced stage, serous histology and high grade. In contrast, Aurora A immunostaining did not correlate with any of the clinical parameters analysed. Conclusion: BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers. PMID:19603021

  16. Entropy-based adaptive nuclear texture features are independent prognostic markers in a total population of uterine sarcomas.

    PubMed

    Nielsen, Birgitte; Hveem, Tarjei Sveinsgjerd; Kildal, Wanja; Abeler, Vera M; Kristensen, Gunnar B; Albregtsen, Fritz; Danielsen, Håvard E

    2015-04-01

    Nuclear texture analysis measures the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image and is a promising quantitative tool for prognosis of cancer. The aim of this study was to evaluate the prognostic value of entropy-based adaptive nuclear texture features in a total population of 354 uterine sarcomas. Isolated nuclei (monolayers) were prepared from 50 µm tissue sections and stained with Feulgen-Schiff. Local gray level entropy was measured within small windows of each nuclear image and stored in gray level entropy matrices, and two superior adaptive texture features were calculated from each matrix. The 5-year crude survival was significantly higher (P < 0.001) for patients with high texture feature values (72%) than for patients with low feature values (36%). When combining DNA ploidy classification (diploid/nondiploid) and texture (high/low feature value), the patients could be stratified into three risk groups with 5-year crude survival of 77, 57, and 34% (Hazard Ratios (HR) of 1, 2.3, and 4.1, P < 0.001). Entropy-based adaptive nuclear texture was an independent prognostic marker for crude survival in multivariate analysis including relevant clinicopathological features (HR = 2.1, P = 0.001), and should therefore be considered as a potential prognostic marker in uterine sarcomas.

  17. Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death

    PubMed Central

    Heaphy, Christopher M.; Yoon, Ghil Suk; Peskoe, Sarah B.; Joshu, Corinne E.; Lee, Thomas K.; Giovannucci, Edward; Mucci, Lorelei A.; Kenfield, Stacey A.; Stampfer, Meir J.; Hicks, Jessica L.; De Marzo, Angelo M.; Platz, Elizabeth A.; Meeker, Alan K.

    2013-01-01

    Current prognostic indicators are imperfect predictors of outcome in men with clinicallylocalized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer-associated stromal cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies. PMID:23779129

  18. Tumor Epression of Major Vault Protein is an Adverse Prognostic Factor for Radiotherapy Outcome in Oropharyngeal Carcinoma

    SciTech Connect

    Silva, Priyamal; West, Catharine M.; Slevin, Nick F.R.C.R.; Valentine, Helen; Ryder, W. David J. Grad. I.S.; Hampson, Lynne; Bibi, Rufzan; Sloan, Philip; Thakker, Nalin; Homer, Jarrod; Hampson, Ian

    2007-09-01

    Purpose: Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport, with the major vault protein (MVP or lung resistance-related protein [LRP]) being the main component. The MVP gene is located on chromosome 16 close to the multidrug resistance-associated protein and protein kinase c-{beta} genes. The role of MVP in cancer drug resistance has been demonstrated in various cell lines as well as in ovarian carcinomas and acute myeloid leukemia, but nothing is known about its possible role in radiation resistance. Our aim was to examine this in head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Archived biopsy material was obtained for 78 patients with squamous cell carcinoma of the oropharynx who received primary radiotherapy with curative intent. Immunohistochemistry was used to detect MVP expression. Locoregional failure and cancer-specific survival were estimated using cumulative incidence and Cox multivariate analyses. Results: In a univariate and multivariate analysis, MVP expression was strongly associated with both locoregional failure and cancer-specific survival. After adjustment for disease site, stage, grade, anemia, smoking, alcohol, gender, and age, the estimated hazard ratio for high MVP (2/3) compared with low (0/1) was 4.98 (95% confidence interval, 2.17-11.42; p 0.0002) for locoregional failure and 4.28 (95% confidence interval, 1.85-9.95; p = 0.001) for cancer-specific mortality. Conclusion: These data are the first to show that MVP may be a useful prognostic marker associated with radiotherapy resistance in a subgroup of patients with HNSCC.

  19. HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions.

    PubMed

    Ikeda, Hiroko; Takahashi, Yukitoshi; Yamazaki, Etsuko; Fujiwara, Tateki; Kaniwa, Nahoko; Saito, Yoshiro; Aihara, Michiko; Kashiwagi, Mariko; Muramatsu, Masaaki

    2010-02-01

    Carbamazepine (CBZ) is frequently used for treating epilepsy, but this drug causes cutaneous adverse drug reactions (cADRs) that may range from mild to severe. It is reported recently that the human leukocyte antigen HLA-B*1502 is associated with Stevens-Johnson syndrome (SJS) induced by CBZ in Han Chinese. We examined HLA class I in 15 Japanese patients who fulfilled the diagnostic criteria for CBZ-induced cADRs (mild in 10 and severe = SJS in 5). HLA-B*1518, HLA-B*5901 and HLA-C*0704 alleles showed higher relative risks (above 10.0) for severe cADRs. The haplotype (HLA-A*2402-B*5901-C*0102) had high relative risk (16.09) for severe cADRs. In patients with severe cADRs, frequencies of HLA-A*1101, HLA-A*3303, HLA-B*1501, HLA-B*4403, HLA-B*5101, HLA-B*5201, HLA-C*0702, and HLA-C*1202 alleles are relatively lower than in the Japanese population. These data may suggest that HLA-B*5901 is one of the candidate markers for CBZ-induced SJS in Japanese.

  20. Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders in solid transplant.

    PubMed

    Oton, Ana B; Wang, Hong; Leleu, Xavier; Melhem, Mona F; George, Diane; Lacasce, Ann; Foon, Kenneth; Ghobrial, Irene M

    2008-09-01

    We sought to determine the clinical and immunohistopathological prognostic factors for overall survival (OS) in adult patients with post-transplant lymphoproliferative disorders (PTLDs). Eighty-four patients diagnosed with PTLDs between 1980 and 2004 at the University of Pittsburgh Medical Center were identified. Immunohistochemical staining was performed on tumor tissue at the time of diagnosis for the following proteins: Bcl-2, Bcl-6, c-myc and p53. The median survival for all patients was 20.8 months, 95% CI: (7.4-77.6). On univariate analysis for OS, the following poor prognostic factors were identified: age at transplant >60 years (p = 0.024), multiorgan transplant (p = 0.019), ECOG > 2 (p < 0.0001), grafted organ involvement (p < 0.0001), extranodal disease (p = 0.011), early (<1 year) PTLDs (p < 0.0001), stage IV (p = 0.0017), EBV positive (p = 0.012) and elevated white blood count (p = 0.010). Good prognostic factors included ECOG<2 (p < 0.0001), late (>1 year) PTLDs (p = 0.002), early stage at diagnosis (stages I and II, p = 0.005), nodal disease (p = 0.0053), monomorphic disease (0.0034), initial immunosuppression reduction (p = 0.0015) and use of rituximab (p = 0.045). Bcl-2 but not Bcl-6, c-myc, or p53 correlated with poor survival, p = 0.0036. This study identifies new clinical and pathological markers for poor survival in PTLDs.

  1. FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma.

    PubMed

    Peterle, G T; Santos, M; Mendes, S O; Carvalho-Neto, P B; Maia, L L; Stur, E; Agostini, L P; Silva, C V M; Trivilin, L O; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-09-22

    Currently, the most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of regional lymph node metastases, which correlates with a 50% reduction in life expectancy. We have previously observed that expression of hypoxia genes in the tumor inflammatory infiltrate is statistically related to prognosis in OSCC. FAS and FASL expression levels in OSCC have previously been related to patient survival. The present study analyzed the relationship between FASL expression in the inflammatory infiltrate lymphoid cells and clinical variables, tumor histology, and prognosis of OSCC. Strong FASL expression was significantly associated with lymph node metastases (P = 0.035) and disease-specific death (P = 0.014), but multivariate analysis did not confirm FASL expression as an independent death risk factor (OR = 2.78, 95%CI = 0.81-9.55). Disease-free and disease-specific survival were significantly correlated with FASL expression (P = 0.016 and P = 0.005, respectively). Multivariate analysis revealed that strong FASL expression is an independent marker for earlier disease relapse and disease-specific death, with approximately 2.5-fold increased risk compared with weak expression (HR = 2.24, 95%CI = 1.08-4.65 and HR = 2.49, 95%CI = 1.04-5.99, respectively). Our results suggest a potential role for this expression profile as a tumor prognostic marker in OSCC patients.

  2. C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic.

    PubMed

    Gil da Costa, Rui M

    2015-07-01

    Cutaneous mast cell tumours (MCTs) are some of the most common canine neoplasms and their variable and often aggressive biological behaviour makes them particularly challenging for the veterinary practitioner. Over the years, scientists have accumulated a wealth of knowledge on these tumours and developed better prognostic markers and targeted therapies, mostly focused on inhibiting c-kit, a protein that plays a major role in the biopathology of MCTs. Masitinib and toceranib, targeted inhibitors of c-kit and other receptor tyrosine-kinases (RTKs), offer the promise of improving the outcome of patients with aggressive MCTs. Much of the available knowledge on MCTs is dispersed, making it difficult for practitioners to benefit when consulting a pathologist or making therapeutic decisions. This article seeks to bring together current knowledge on the biopathology of MCTs, reviewing prognostic markers and their applications, and the development of c-kit inhibitors in the context of the basic cellular, molecular and pathological features of MCTs. Future perspectives following recent biopathological data and experimental therapeutic approaches are also addressed.

  3. Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer.

    PubMed

    Chen, Jie; Li, Yan; Zheng, Qiupeng; Bao, Chunyang; He, Jian; Chen, Bin; Lyu, Dongbin; Zheng, Biqiang; Xu, Yu; Long, Ziwen; Zhou, Ye; Zhu, Huiyan; Wang, Yanong; He, Xianghuo; Shi, Yingqiang; Huang, Shenglin

    2017-03-01

    Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. Here we identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in gastric cancer (GC) tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene and termed it as circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in GC.

  4. Expression and Prognostic Significance of a Panel of Tissue Hypoxia Markers in Head-and-Neck Squamous Cell Carcinomas

    SciTech Connect

    Le, Quynh-Thu Kong, Christina; Lavori, Phillip W.; O'Byrne, Ken; Erler, Janine T.; Huang Xin; Chen Yijun; Cao Hongbin; Tibshirani, Robert; Denko, Nic; Giaccia, Amato J.; Koong, Albert C.

    2007-09-01

    Purpose: To investigate the expression pattern of hypoxia-induced proteins identified as being involved in malignant progression of head-and-neck squamous cell carcinoma (HNSCC) and to determine their relationship to tumor pO{sub 2} and prognosis. Methods and Materials: We performed immunohistochemical staining of hypoxia-induced proteins (carbonic anhydrase IX [CA IX], BNIP3L, connective tissue growth factor, osteopontin, ephrin A1, hypoxia inducible gene-2, dihydrofolate reductase, galectin-1, I{kappa}B kinase {beta}, and lysyl oxidase) on tumor tissue arrays of 101 HNSCC patients with pretreatment pO{sub 2} measurements. Analysis of variance and Fisher's exact tests were used to evaluate the relationship between marker expression, tumor pO{sub 2}, and CA IX staining. Cox proportional hazard model and log-rank tests were used to determine the relationship between markers and prognosis. Results: Osteopontin expression correlated with tumor pO{sub 2} (Eppendorf measurements) (p = 0.04). However, there was a strong correlation between lysyl oxidase, ephrin A1, and galectin-1 and CA IX staining. These markers also predicted for cancer-specific survival and overall survival on univariate analysis. A hypoxia score of 0-5 was assigned to each patient, on the basis of the presence of strong staining for these markers, whereby a higher score signifies increased marker expression. On multivariate analysis, increasing hypoxia score was an independent prognostic factor for cancer-specific survival (p = 0.015) and was borderline significant for overall survival (p = 0.057) when adjusted for other independent predictors of outcomes (hemoglobin and age). Conclusions: We identified a panel of hypoxia-related tissue markers that correlates with treatment outcomes in HNSCC. Validation of these markers will be needed to determine their utility in identifying patients for hypoxia-targeted therapy.

  5. Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

    PubMed Central

    Karan-Djurasevic, Teodora; Marjanovic, Irena; Tosic, Natasa; Mitrovic, Mirjana; Djunic, Irena; Colovic, Natasa; Vidovic, Ana; Suvajdzic-Vukovic, Nada; Tomin, Dragica; Pavlovic, Sonja

    2016-01-01

    Abstract Background Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Patients and methods In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. Results IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. Conclusions Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection. PMID:27904446

  6. The adverse prognostic hallmarks in identical twins with Langerhans cell histiocytosis: a clinical report and literature review.

    PubMed

    Chai, Damin; Tao, Yisheng; Bao, Zhengqi; Yang, Li; Feng, Zhenzhong; Ma, Li; Liang, Limei; Zhou, Xinwen

    2013-01-01

    Langerhans cell histiocytosis (LCH) is characterized by uncontrolled proliferation of Langerhans cells accompanying eosinophils. It often attacks children under 10 years of age. LCH in identical twins is very rare and its prognosis is different. Here we report identical-twin sisters with LCH. Computed tomography (CT) revealed osteolytic change in each twin's skull, and the elder exhibited poor eyesight. There were massive histiocyte-like cells surrounded by eosinophils in pathologic specimen of the abnormal lesions, which is typical pathologic finding in LCH. These pathologic cells were positive for S-100 and the cell surface protein CD1 antigen (CD1α), the known markers of LCH. After treating them with surgery, no symptoms were seen in the younger until now. While the older was found another soft mass (about 2.0 cm in diameter) in the left temporal area 18 months later. The same treatment was given to the older after admission, and she is healthy to date. To explore the relationship between hallmarks and the prognosis of identical-twin patients with LCH, we retrieved the 16 literatures (16 identical-twin pairs, 31 patients) listed in PubMed during the past 60 years. The data revealed all those patients who have disseminated to the bone marrow, spleen and liver with symptoms of fever and hepatosplenomegaly exhibited worse prognosis (9 out of the 31 patients). The other identical-twin subjects without infiltration of those organs recovered well. In conclusion, this study reveals the adverse hallmarks of prognosis in identical-twin patients with LCH by reviewing relevant literatures.

  7. Comparison of the prognostic values of inflammation markers in patients with acute pancreatitis: a retrospective cohort study

    PubMed Central

    Li, Yuanyuan; Zhao, Ying; Feng, Limin; Guo, Renyong

    2017-01-01

    Objectives Inflammation-based prognostic markers (neutrophil–lymphocyte ratio (NLR), prognostic nutritional index (PNI), red cell distribution width (RDW) and lymphocyte–monocyte ratio (LMR)) are associated with overall survival in some diseases. This study assessed their prognostic value in mortality and severity in acute pancreatitis (AP). Design A retrospective cohort study. Setting Patients with AP were recruited from the emergency department at our hospital. Participants A total of 359 patients with AP (31 non-survivors) were enrolled. Primary and secondary outcome measures Mortality and severity of AP were the primary and secondary outcome measures, respectively. Biochemistry and haematology results of the first test after admission were collected. Independent relationships between severe AP (SAP) and markers were assessed using multivariate logistic regression models. Mortality prediction ability was evaluated using receiver operating characteristic (ROC) curves. Overall survival was evaluated using the Kaplan-Meier method, with differences compared using the log-rank test. Independent relationships between mortality and each predictor were estimated using the Cox proportional hazard models. Results Compared with survivors of AP, non-survivors had higher RDW (p<0.001), higher NLR (p<0.001), lower LMR (p<0.001) and lower PNI (p<0.001) at baseline. C reactive protein (CRP; OR=8.251, p<0.001), RDW (OR=2.533, p=0.003) and PNI (OR=7.753, p<0.001) were independently associated with the occurrence of SAP. For predicting mortality, NLR had the largest area under the ROC curve (0.804, p<0.001), with a 16.64 cut-off value, 82.4% sensitivity and 75.6% specificity. RDW was a reliable marker for excluding death owing to its lowest negative likelihood ratio (0.11). NLR (HR=4.726, p=0.004), CRP (HR=3.503, p=0.003), RDW (HR=3.139, p=0.013) and PNI (HR=2.641, p=0.011) were independently associated with mortality of AP. Conclusions NLR was the most powerful marker of

  8. Overexpression of Pleomorphic Adenoma Gene-Like 2 Is a Novel Poor Prognostic Marker of Prostate Cancer

    PubMed Central

    Guo, Jia; Wang, Min; Wang, Zhishun; Liu, Xiuheng

    2016-01-01

    Pleomorphic adenoma gene like-2 (PLAGL2) is a member of the PLAG gene family. Previous studies have revealed that overexpression of PLAGL2 is associated with many human cancers. However, it has been reported that PLAGL2 also plays as a tumor suppressor. The precise role of PLAGL2 in prostate cancer (PCa) is still unknown. The aim of this study was to investigate the expression and prognostic value of PLAGL2 in PCa. Data from microarray datasets demonstrated that the DNA copy number and mRNA level of PLAGL2 were significantly increased in PCa compared with normal prostate. qRT-PCR and western blot analysis from paired PCa samples and prostate cell lines confirmed upregulated mRNA and protein expression levels in PCa. Immunohistochemistry analysis showed that staining of PLAGL2 in PCa tissues was significantly higher than that in benign prostatic hyperplasia (BPH) tissues. In addition, the high expression of PLAGL2 was only involved in preoperative PSA, but was not related to age, Gleason score, seminal vesicle invasion, surgical margin status, clinical stage and positive lymph node metastasis. Moreover, our results showed that PLAGL2 was an independent prognostic factor for biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients, and overexpressed PLAGL2 was related to early development of BCR and poor OS. In conclusion, our findings suggest that PLAGL2 is overexpressed in PCa. The increased expression of PLAGL2 correlates to PCa progression following radical prostatectomy and may serve as a novel poor prognostic marker for PCa. PMID:27537362

  9. Role of Stem Cells in Colorectal Cancer Progression and Prognostic and Predictive Characteristics of Stem Cell Markers in Colorectal Cancer.

    PubMed

    Fedyanin, Mikhail; Anna, Popova; Elizaveta, Polyanskaya; Sergei, Tjulandin

    2017-01-01

    In the last decade, an increasing number of studies on tumor stem cell theory stating that there is only a small fraction of tumor cells capable of inducing tumor growth have been published. These cells can not only differentiate into more mature tumor cells, but also can maintain their own pool, that is the capacity for self-renewal. There are distinct subpopulations of cells within a tumor that express different combinations of stem cell markers and have different functions. The following markers are typically considered as markers of colorectal adenocarcinoma stem cells: CD133, CD144, CD24, CD166, CD44, CD29, ALDH1, LGR5, and CXCR4. However, data on the role of cancer stem cells in the process of colorectal cancer progression, their prognostic and predictive role are lacking. Researches on the phenotype, molecular and functional properties of this tumor cell subpopulation in both primary site and metastases of colorectal cancer are of great interest because they can allow developing new diagnostic and therapeutic strategies in the future.

  10. Adverse Pregnancy Outcomes: Opportunity for Analysis of Biospecimens and Co-development of Prognostics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Pregnancy and Perinatology Branch seeks partners interested in collaborative research to: (i) evaluate data and samples taken from women for potential biomarkers indicative for adverse pregnancy outcomes and (ii) co-develop diagnostic kits useful as predictors of adverse pregnancy outcomes.

  11. Wild-type p53-induced phosphatase 1 is a prognostic marker and therapeutic target in bladder transitional cell carcinoma

    PubMed Central

    Wang, Zhi-Peng; Chen, Shu-Yuan; Tian, Ye

    2017-01-01

    Wild-type p53-induced phosphatase (Wip1) is an established oncogene and is associated with development of multiple forms of human cancer. However, the expression and role of Wip1 in human bladder transitional cell carcinoma (TCC) remains to be elucidated. In the present study, immunohistochemistry demonstrated that Wip1 was overexpressed in bladder TCC tissues compared with corresponding normal bladder tissues in 106 bladder TCC cases (P<0.0001). Furthermore, high expression levels of Wip1 were significantly associated with increasing tumor size (P=0.002), pathological grade (P=0.025), clinical T stage (P=0.001) and lymph nodal metastasis (P=0.003). Kaplan-Meier survival analysis identified that patients with high Wip1 expression levels exhibited a lower overall survival time (P<0.0001), and Cox proportional hazards regression model analysis demonstrated that Wip1 expression was an independent prognostic factor in patients with bladder TCC (P=0.025). In addition, downregulation of Wip1 expression by transfection with small interfering RNA in bladder cancer cells inhibited cell proliferation, invasion and migration (P<0.05), along with the upregulation of p53 protein levels (P<0.05). These findings suggest that Wip1 may function as a potential prognostic marker and therapeutic target in bladder cancer. PMID:28356972

  12. Serum Soluble TACI, a BLyS Receptor, Is a Powerful Prognostic Marker of Outcome in Chronic Lymphocytic Leukemia

    PubMed Central

    Kyrtsonis, Marie-Christine; Sarris, Katerina; Koulieris, Efstathios; Maltezas, Dimitrios; Nikolaou, Eftychia; Angelopoulou, Maria K.; Bartzis, Vassiliki; Tzenou, Tatiana; Dimou, Maria; Siakandaris, Mariana P.; Viniou, Nora A.; Sachanas, Sotirios; Kalpadakis, Christina; Sfikakis, Petros P.; Pangalis, Gerassimos A.; Panayiotidis, Panayiotis

    2014-01-01

    BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells' surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients' outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS (P = −0.000021), b2-microglobulin (P = 0.005), anemia (P = −0.03), thrombocytopenia (P = 0.04), Binet stage (P = 0.02), and free light chains ratio (P = 0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT (P = 0.0003 and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival (P = 0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS. PMID:25162001

  13. Prognostic significance of selected histochemical and immunohistochemical markers in breast cancer.

    PubMed

    Petrková, J; Kolár, Z

    1989-01-01

    The bioptic materials from patients with breast carcinoma operated in the period of 1976 to 1977 were studied for expression of binding sites for monoclonal antibodies HMFG.06 (detecting mucine-like molecules of membranes of milk fat globules) and 2FD4 (detecting the protein epitope of CEA), and for lectin Con A (detecting free residua of alpha-D-mannose). The results obtained were compared with survival rate of patients and with histological type of carcinoma. The interpretation of the results can help to specify the prognostic validity of histopathological diagnosis.

  14. Prognostic nutritional index serves as a predictive marker of survival and associates with systemic inflammatory response in metastatic intrahepatic cholangiocarcinoma

    PubMed Central

    Zhang, Chenyue; Wang, Haiyong; Ning, Zhouyu; Xu, Litao; Zhuang, Liping; Wang, Peng; Meng, Zhiqiang

    2016-01-01

    Objective The significance of the prognostic nutritional index (PNI) has been widely reported and confirmed in many types of cancers. However, few studies are available indicating its prognostic power in patients with intrahepatic cholangiocarcinoma (ICC). Thus, we investigated its relationship with overall survival (OS) to evaluate its role in predicting survival in patients with ICC. Patients and methods Between October 2011 and October 2015, 173 consecutive patients with pathologically confirmed locally advanced or metastatic ICC were enrolled. First, the correlations between PNI and clinical factors were analyzed among these patients. Next, univariate and multivariate analyses were conducted to evaluate the association between PNI and OS among these patients with ICC. In addition, the relationships between PNI and three typical systemic inflammatory response (SIR) markers – the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), and the lymphocyte/monocyte ratio (LMR) – were also assessed. Results A lower PNI was linked with a shorter OS in patients with ICC, as reflected obviously in the Kaplan–Meier analyses. The patients with ICC were divided into the locally advanced group and the metastatic group. Further analyses revealed that PNI is not associated with OS in the locally advanced group. However, in the subgroup of patients with metastatic ICC, a lower PNI significantly correlated with a worsened OS. The OS for patients with a low PNI is 5 months, whereas the OS is 10.17 months for patients with a high PNI. Multivariate analyses revealed that PNI is independently correlated with OS. We finally proved that PNI is negatively proportional to NLR and PLR and positively proportional to LMR. Conclusion Our results demonstrate that decreased PNI signifies a poor OS and is associated with SIR in patients with metastatic ICC. Therefore, it may serve as a valuable predictive marker in patients with metastatic ICC. PMID:27799789

  15. Ascitic Fluid High Sensitive C-Reactive Protein (hs-CRP). A Prognostic Marker in Cirrhosis with Spontaneous Bacterial Peritonitis

    PubMed Central

    Kadam, Nakul; Shukla, Samarth; Gupta, Kriti

    2016-01-01

    Introduction C-Reactive Protein (CRP) is an acute phase reactant. Its level increases in the presence of acute or chronic inflammation and infections. High sensitive CRP (hs-CRP) is more sensitive than CRP as an inflammatory marker. High sensitive CRP has been known to be elevated in chronic liver diseases and Spontaneous Bacterial Peritonitis (SBP). Aim The aim of the study was to establish the role of ascitic fluid high sensitive C-reactive protein (hs –CRP) as a prognostic indicator in patients with SBP. Materials and Methods A total of 100 patients with decompensated cirrhosis admitted in medicine ward and ICU were included, of which 50 patients of acute bacterial peritonitis were used as study group and 50 patients of sterile ascites were used as control group. Hs-CRP level of cases and controls were estimated. SBP cases were treated with its standard recommended antibiotic therapy and hs-CRP level was again estimated after 5 days of antibiotic therapy or at the time of discharge. Results The mean level of hs-CRP before antibiotic therapy of the patients with SBP was significantly higher than that of the patients without spontaneous bacterial peritonitis (t98=17.72; p=0.0001). The mean level of hs-CRP at 5th day or discharge after initiation of antibiotic therapy was significantly lower than that of level of hs-CRP before initiation of antibiotic therapy (p<0.05). The mean hs-CRP of the cases with poor outcome (death and prolonged hospital stay) was significantly higher than others. Conclusion Ascitic fluid hs-CRP level can be considered as a surrogate prognostic marker in cases of Cirrhosis with SBP. PMID:27190862

  16. Genome-Wide Gene Expression Profile Analyses Identify CTTN as a Potential Prognostic Marker in Esophageal Cancer

    PubMed Central

    He, Wei; Wang, Jin; Jia, Yongxu; Sun, Yan; Tang, Senwei; Fu, Li; Qin, Yanru

    2014-01-01

    Aim Esophageal squamous cell carcinoma (ESCC) is one of the most common fatal malignances of the digestive tract. Its prognosis is poor mainly due to the lack of reliable markers for early detection and prognostic prediction. Here we aim to identify the molecules involved in ESCC carcinogenesis and those as potential markers for prognosis and as new molecular therapeutic targets. Methods We performed genome-wide gene expression profile analyses of 10 primary ESCCs and their adjacent normal tissues by cDNA microarrays representing 47,000 transcripts and variants. Candidate genes were then validated by semi quantitative reverse transcription-PCR (RT-PCR), tissue microarrays (TMAs) and immunohistochemistry (IHC) staining. Results Using an arbitrary cutoff line of signal log ratio of ≥1.5 or ≤−1.5, we observed 549 up-regulated genes and 766 down-regulated genes in ESCCs compared with normal esophageal tissues. The functions of 302 differentially expressed genes were associated with cell metabolism, cell adhesion and immune response. Several candidate deregulated genes including four overexpressed (CTTN, DMRT2, MCM10 and SCYA26) and two underexpressed (HMGCS2 and SORBS2) were subsequently verified, which can be served as biomarkers for ESCC. Moreover, overexpression of cortactin (CTTN) was observed in 126/198 (63.6%) of ESCC cases and was significantly associated with lymph node metastasis (P = 0.000), pathologic stage (P = 0.000) and poor survival (P<0.001) of ESCC patients. Furthermore, a significant correlation between CTTN overexpression and shorter disease-specific survival rate was found in different subgroups of ESCC patient stratified by the pathologic stage (P<0.05). Conclusion Our data provide valuable information for establishing molecules as candidates for prognostic and/or as therapeutic targets. PMID:24551190

  17. Association between Mutation and Expression of TP53 as a Potential Prognostic Marker of Triple-Negative Breast Cancer

    PubMed Central

    Kim, Ji-Yeon; Park, Kyunghee; Jung, Hae Hyun; Lee, Eunjin; Cho, Eun Yoon; Lee, Kwang Hee; Bae, Soo Youn; Lee, Se Kyung; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    Purpose TP53, the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of TP53 status as a prognostic and predictive marker of triple-negative breast cancer (TNBC). Materials and Methods We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between TP53 alteration and clinical outcomes of TNBC patients. Results Seventy-seven of 174 TNBC patients were found to harbor a TP53 mutation. Patients with missense mutations showed high protein expression in contrast to patients with deletion mutations (positivity of IHC: wild type vs. missense vs. deletion mutation, 53.6% vs. 89.8% vs. 25.0%, respectively; p < 0.001). TP53 mRNA expression was influenced by mutation status (mRNA expression [median]: wild type vs. missense vs. deletion mutation, 207.36± 132.73 vs. 339.61±143.21 vs. 99.53±99.57, respectively; p < 0.001). According to survival analysis, neither class of mutation nor protein or mRNA expression status had any impact on patient prognosis. In subgroup analysis, low mRNA expression was associated with poor prognosis in patients with a TP53 missense mutation (5-year distant recurrence-free survival [5Y DRFS]: low vs. high, 50.0% vs. 87.8%; p=0.009), while high mRNA expression with a TP53 deletion mutation indicated poor prognosis (5Y DRFS: low vs. high, 91.7% vs. 75.0%; p=0.316). Conclusion Association between TP53 mutation and expression indicates a potential prognostic marker of TNBC; hence both DNA sequencing and mRNA expression analysis may be required to predict the prognosis of TNBC patients. PMID:26910472

  18. Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

    PubMed Central

    Vucicevic, Ksenija; Jakovljevic, Vladimir; Colovic, Natasa; Tosic, Natasa; Kostic, Tatjana; Glumac, Irena; Pavlovic, Sonja; Colovic, Milica

    2016-01-01

    Summary Background In chronic lymphocytic leukemia (CLL), in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role. Aim The aim of this study was to investigate the association of pro-apoptotic Bax gene expression and Bcl2/Bax ratio with the clinical features of CLL patients as well as with molecular prognostic markers, namely the mutational status of rearranged immunoglobulin heavy variable (IGHV) genes and lipoprotein lipase (LPL) gene expression. Methods We analyzed the expression of Bax mRNA and Bcl2/Bax mRNA ratio in the peripheral blood mononuclear cells of 58 unselected CLL patients and 10 healthy controls by the quantitative reverse-transcriptase polymerase chain reaction. Results We detected significant Bax gene overexpression in CLL samples compared to non-leukemic samples (p=0.003), as well as an elevated Bcl2/Bax ratio (p=<0.001). Regarding the association with prognostic markers, the Bcl2/Bax ratio showed a negative correlation to lymphocyte doubling time (r=-0.307; p=0.0451), while high-level Bax expression was associated with LPL-positive status (p=0.035). Both the expression of Bax and Bcl2/Bax ratio were higher in patients with unmutated vs. mutated IGHV rearrangements, but this difference did not reach statistical significance. Conclusions Our results suggest that dysregulated expression of Bcl2 and Bax, which leads to a high Bcl2/Bax ratio in leukemic cells, contributes to the pathogenesis and clinical course of CLL. PMID:28356875

  19. Computerized three-class classification of MRI-based prognostic markers for breast cancer

    NASA Astrophysics Data System (ADS)

    Bhooshan, Neha; Giger, Maryellen; Edwards, Darrin; Yuan, Yading; Jansen, Sanaz; Li, Hui; Lan, Li; Sattar, Husain; Newstead, Gillian

    2011-09-01

    The purpose of this study is to investigate whether computerized analysis using three-class Bayesian artificial neural network (BANN) feature selection and classification can characterize tumor grades (grade 1, grade 2 and grade 3) of breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected. The computer automatically segmented the lesions, and kinetic and morphological lesion features were automatically extracted. The discrimination tasks—grade 1 versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions—were investigated. Step-wise feature selection was conducted by three-class BANNs. Classification was performed with three-class BANNs using leave-one-lesion-out cross-validation to yield computer-estimated probabilities of being grade 3 lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to evaluate the performances. We achieved AUC values of 0.80 ± 0.05, 0.78 ± 0.05 and 0.62 ± 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2 versus grade 3, respectively. This study shows the potential for (1) applying three-class BANN feature selection and classification to CADx and (2) expanding the role of DCE-MRI CADx from diagnostic to prognostic classification in distinguishing tumor grades.

  20. DEK: A novel early screening and prognostic marker for breast cancer.

    PubMed

    Ying, Guo; Wu, Yonghui

    2015-11-01

    The present study aimed to investigate the expression status and clinical implications of DEK in breast cancer, in order to contribute to developments in breast cancer management. DEK expression status was detected in 628 breast cancer specimens by western blot analysis and immunohistochemistry staining, and the correlation between DEK protein and clinico‑pathological parameters and prognosis of breast cancer was subsequently determined. In comparison to para-carcinoma tissues, DEK protein was highly expressed in breast cancer specimens and was correlated with chemotherapy resistance. In total, 61.94% (389/628) of breast cancer cases exhibited high expression of DEK. According to universal analysis, it was observed that age, tumor size, histological grade, metastatic nodes and distant metastasis (P=0.024, 0.001, 0.001, 0.001 and 0.001 respectively) are key factors associated with DEK. Furthermore, compared with samples with no or low DEK protein expression, high DEK expression resulted in a significantly increased distant metastasis rate and poor disease‑specific survival (P=0.001). In addition, DEK protein was detected as an independent prognostic factor (P=0.001) in the Cox regression analysis. DEK was correlated with chemotherapy resistance and may be an independent prognostic factor for breast cancer, as well as a potential therapeutic target.

  1. Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker.

    PubMed

    Lei, Bo; Zhang, Xian-Yu; Zhou, Jia-Peng; Mu, Guan-Nan; Li, Yi-Wen; Zhang, You-Xue; Pang, Da

    2016-11-01

    In cancer stem cell theory, breast cancer stem cells (BCSCs) are postulated to be the root cause of recurrence and metastasis in breast cancer. Discovery of new biomarkers and development of BCSC-targeted therapy are practical issues that urgently need to be addressed in the clinic. However, few breast cancer stem cell targets are known. Given that there are few BCSCs, performing transcriptome sequencing on them thus far has not been possible. With the emergence of single-cell sequencing technology, we have now undertaken such a study. We prepared single-cell suspensions, which were sorted using flow cytometry from breast tumor tissue and adjacent normal breast tissue from two HER2-positive patients. We obtained BCSCs, breast cancer cells, mammary cells, and CD44(+) mammary cells. Transcriptome sequencing was then performed on these four cell types. Using bioinformatics, we identified 404 differentially expressed BCSC genes from the HER2-positive tumors and preliminary explored transcriptome characteristics of BCSCs. Finally, by querying a public database, we found that CA12 was a novel prognostic biomarker in HER2-positive breast cancer, which also had prognostic value in all breast cancer types. In conclusion, our results suggest that CA12 may be associated with BCSCs, especially HER2-positive BCSCs, and is a potential novel therapeutic target and biomarker.

  2. Prognostic Value of Cancer Stem Cell Markers in Head and Neck Squamous Cell Carcinoma: a Meta-analysis

    PubMed Central

    Fan, Zhaona; Li, Mianxiang; Chen, Xiaobing; Wang, Juan; Liang, Xueyi; Wang, Hongfei; Wang, Zhi; Cheng, Bin; Xia, Juan

    2017-01-01

    Bmi-1, CD133, Nanog and Oct-4 have been reported as cancer stem cell (CSC) markers in head and neck squamous cell carcinoma (HNSCC). However, the prognostic value of them in HNSCC remains controversial. Hence, this meta-analysis was conducted to access the association between the four CSC markers and survival outcome of HNSCC patients. A total of 22 articles with 27 studies met the inclusion criteria and the combined hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated. Data analysis showed that high expression of CSC markers was associated with poor overall survival (OS) (HR = 1.93; 95% CI: 1.46–2.55, P < 0.001) and disease free survival (DFS) (HR = 4.78; 95% CI: 2.95–7.75, P < 0.001) but not disease specific survival (DSS) (HR = 1.17; 95% CI: 0.74–1.84, P = 0.50) of HNSCC patients. Subgroup analysis indicted that high expression of CD133 (HR = 2.33, 95%CI: 1.42–3.83, P < 0.001), Oct-4(HR = 2.10, 95%CI: 1.36–3.22, P = 0.007) and Nanog (HR = 2.49, 95%CI: 1.66–3.72, P < 0.001) could predict poor OS in HNSCC patients respectively whereas overexpression of Bmi-1 was not related to the reduced OS in HNSCC patients (HR = 1.32, 95%CI: 0.66–2.65, P = 0.43). Therefore, we concluded that CSC markers, especially CD133, Nanog and Oct-4, might be predictive factors in HNSCC patients. PMID:28220856

  3. Expression status of cyclase‑associated protein 2 as a prognostic marker for human breast cancer.

    PubMed

    Xu, Lihua; Peng, Sida; Huang, Qunai; Liu, Yu; Jiang, Hua; Li, Xi; Wang, Jiani

    2016-10-01

    Cyclase-associated protein 2 (CAP2) protein is reported to be upregulated in hepatocellular carcinoma (HCC). However, data regarding its expression pattern and clinical relevance in breast cancer are unknown. The aim of this study was to investigate CAP2 expression and its prognostic significance in breast cancer. CAP2 expression at the mRNA and protein levels was examined by real‑time quantitative-polymerase chain reaction and western blotting in 10 paired breast cancer tissues and adjacent normal tissues. The expression level of CAP2 protein in normal breast epithelial cells and breast cancer cell lines was quantified by western blotting. CAP2 protein expression was analyzed in paraffin‑embedded breast cancer samples, paired adjacent non‑tumor and normal breast tissues by immunohistochemical analysis. Statistical analyses were also performed to evaluate the clinicopathological significance of CAP2 expression. The results showed that the expression of CAP2 mRNA and protein was higher in breast cancer than that noted in the adjacent normal tissues in 10 paired samples. The expression level of CAP2 protein in breast cancer cell lines was higher than that in normal breast epithelial cells. In paraffin‑embedded tissue samples, the expression of CAP2 was higher in breast cancer than that found in the adjacent non‑cancerous tissues and normal breast tissues. Compared with the adjacent non‑cancerous tissues, overexpression of CAP2 was detected in 29.4% (37/126) of the patients. Overexpression of CAP2 was significantly associated with progesterone receptor (PR) expression (p<0.05), and decreased overall survival (OS) (p<0.05). In multivariate analysis, expression of CAP2 was an independent prognostic factor for OS [hazard ratio (HR), 4.821; 95% confidence interval (CI), 2.442‑9.518; p<0.001]. CAP2 is upregulated in breast cancer and is associated with the expression of PR and patient survival. CAP2 may serve as a prognostic indicator for patients

  4. Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Soumya, M; D'mello, Sarah; Kuriakose, Moni Abraham; Govindan, Sindhu

    2016-01-01

    Background and Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common head and neck carcinomas and corresponds to 95% of all oral cancers with an increasing morbidity and mortality. Its prognosis is affected by several clinicopathologic factors, one of which is pattern of invasion (POI). The histological features of OSCC may differ widely, but there is general agreement that the most useful prognostic information can be deduced from the invasive front of the tumor. In this retrospective study, our aim was to compare the POI, the status of connective tissue and the status of inflammation at the tumor–host interface in primary and recurrent (secondary) OSCC and test the validity of POI, to serve as a potential marker to assess the prognosis of the patient. Materials and Methods: Differentiation of tumors, POI, status of connective tissue and inflammation was assessed in 168 cases of primary and recurrent cases of OSCC. Statistical Analysis: Fisher's exact test was used to determine the statistical significance and P < 0.05 was considered to be statistically significant. Results: Our study showed that majority of the primary and secondary tumors were well differentiated, 117 [95.9%] and 34 [73.9%], respectively. Predominant POI in the primary and secondary tumor group was Pattern II and least was Pattern V. Worst pattern in primary tumor and highest distribution was seen for Pattern III (53.3%), and least for Pattern V (0.00%). In secondary tumors, the predominant worst pattern was Pattern IV (50.0%) and least distribution was seen for Pattern I (0.00%). Connective tissue status for both primary and secondary tumors showed the predominance of loose type (85.2% and 79.2%) and least was variable type (0.8% and 0.6%), respectively. Status of inflammation in the primary tumor group showed a predominance of moderate grade of inflammation (50.0%) and very mild grade of inflammation (6.6%) was the least type. In the secondary tumor group, moderate grade

  5. Vein of Galen Aneurysmal Malformation: Prognostic Markers Depicted on Fetal MRI

    PubMed Central

    Wagner, Matthias W; Vaught, Arthur J; Poretti, Andrea; Blakemore, Karin J

    2015-01-01

    Fetal magnetic resonance imaging (MRI) serves a dual role in the prenatal diagnostic work up of a vein of Galen aneurysmal malformation (VGAM). First, it may confirm the prenatal ultrasound findings and secondly it may identify prognostically important secondary complications of the VGAM. Progressive heart failure with development of fetal hydrops and hemispheric white matter injuries are associated with a poor outcome in children with a VGAM. We present the prenatal findings using both ultrasound and MRI of a fetus with VGAM including bilateral injury of the cerebral hemispheres, severe dilatation of the jugular veins, cardiomegaly, and hydrops fetalis. The neonate died within 30 minutes after delivery. Moreover, fetal MRI revealed complete placenta praevia, uterine fibroids, and wrapping of the umbilical cord around the fetal neck. This additional information is unrelated to the fetal pathology, but could have been of importance to plan the delivery. PMID:25924177

  6. Circulating Cytokine Levels as Markers of Inflammation in Philadelphia Negative Myeloproliferative Neoplasms: Diagnostic and Prognostic Interest

    PubMed Central

    Mondet, Julie; Hussein, Kais; Mossuz, Pascal

    2015-01-01

    Cytokines are well known mediators of numerous physiological and pathological processes. They contribute to the regulation of normal hematopoiesis but increasing data suggest that they also have a clinical impact in some hematopoietic malignancies. In particular, there is evidence that cytokines are implicated in the functional symptoms of Philadelphia negative myeloproliferative neoplasms (Ph− MPNs), suggesting that evaluation of circulating levels of cytokines could be of clinical interest for the characterization of patients at the time of diagnosis and for disease prognosis. In this review, we present the current knowledge on alteration of circulating cytokine profiles in MPNs and their role in myelofibrosis pathogenesis. Phenotypic correlation, prognostic value of cytokines, and impact of JAK inhibitors are also discussed. PMID:26525644

  7. 25-Hydroxyvitamin D and TSH as Risk Factors or Prognostic Markers in Thyroid Carcinoma

    PubMed Central

    Danilovic, Debora Lucia Seguro; Ferraz-de-Souza, Bruno; Fabri, Amanda Wictky; Santana, Nathalie Oliveira; Kulcsar, Marco Aurelio; Cernea, Claudio Roberto; Marui, Suemi; Hoff, Ana Oliveira

    2016-01-01

    Objective The increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC). Methods We retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed. Results Subjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36–4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC. Conclusions In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules. PMID:27737011

  8. Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma.

    PubMed

    Malandrino, Pasqualino; Al Ghuzlan, Abir; Castaing, Marine; Young, Jacques; Caillou, Bernard; Travagli, Jean-Paul; Elias, Dominique; de Baere, Thierry; Dromain, Clarisse; Paci, Angelo; Chanson, Philippe; Schlumberger, Martin; Leboulleux, Sophie; Baudin, Eric

    2010-09-01

    To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level > or =14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.

  9. Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker.

    PubMed

    Stengel, Anna; Kern, Wolfgang; Zenger, Melanie; Perglerová, Karolína; Schnittger, Susanne; Haferlach, Torsten; Haferlach, Claudia

    2016-01-01

    T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm with aggressive clinical course and short overall survival. So far, due to the rareness of this disease, genetic data are available only from individual cases or small cohorts. In our study, we aimed at performing a comprehensive cytogenetic and molecular genetic characterization of T-PLL comprising the largest cohort of patients with T-PLL analyzed so far, including correlations between the respective markers and their impact on prognosis. Genetic abnormalities were found in all 51 cases with T-PLL, most frequently involving the TCRA/D locus (86%). Deletions were detected for ATM (69%) and TP53 (31%), whereas i(8)(q10) was observed in 61% of cases. Mutations in ATM, TP53, JAK1, and JAK3 were detected in 73, 14, 6, and 21% of patients, respectively. Additionally, BCOR mutations were observed for the first time in a lymphoid malignancy (8%). Two distinct genetic subgroups of T-PLL were identified: A large subset (86% of patients) showed abnormalities involving the TCRA/D locus activating the proto-oncogenes TCL1 or MTCP1, while the second group was characterized by a high frequency of TP53 mutations (4/7 cases). Further, analyses of overall survival identified JAK3 mutations as important prognostic marker, showing a significant negative impact.

  10. Evaluation of EGFR as a prognostic and diagnostic marker for head and neck squamous cell carcinoma patients

    PubMed Central

    Polanska, Hana; Raudenska, Martina; Hudcová, Kristyna; Gumulec, Jaromir; Svobodova, Marketa; Heger, Zbynek; Fojtu, Michaela; Binkova, Hana; Horakova, Zuzana; Kostrica, Rom; Adam, Vojtech; Kizek, Rene; Masarik, Michal

    2016-01-01

    Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival of patients with head and neck squamous cell carcinoma (HNSCC) is low (≤50%). A non-invasive marker of disease progression is sorely required. The present study focused on the plasmatic levels of epidermal growth factor receptor (EGFR) in HNSCC patients (N=92) compared with healthy (N=29) and diabetic [type 2 diabetes mellitus (T2DM); N=26] controls. Enzyme-linked immunosorbent assay using antibodies against the extracellular region of EGFR (L25-S645) was performed. No significant changes were observed between diabetic and healthy controls. However, there were significantly higher EGFR plasma levels in HNSCC patients compared with both control groups (P=0.001 and 0.005, respectively). Receiver operating characteristic curve analysis identified a sensitivity of 76.09%, a specificity of 67.27% and an area under curve of 0.727 for this comparison. No significant association was observed between EGFR plasma levels and tumor stage, tumor grade, lymph node or distant metastasis occurrence, smoking habit or hypertension. However, the presence of human papillomavirus infection and T2DM in HNSCC patients had borderline effect on the plasma EGFR levels. Survival analysis revealed no significant influence of plasmatic EGFR levels on the overall and disease-specific survival of HNSCC patients. In conclusion, EGFR plasma levels appear to be a relatively promising diagnostic, but poor prognostic, HNSCC marker. PMID:27602151

  11. Usefulness of thrombocytopenia at admission as a prognostic marker in native valve left-sided infective endocarditis.

    PubMed

    Ferrera, Carlos; Vilacosta, Isidre; Fernández, Cristina; López, Javier; Sarriá, Cristina; Olmos, Carmen; Vivas, David; Sáez, Carmen; Sánchez-Enrique, Cristina; Ortiz, Carlos; San Román, José Alberto

    2015-04-01

    In-hospital mortality of patients with infective endocarditis (IE) remains exceedingly high. Quick recognition of parameters accurately identifying high-risk patients is of paramount importance. The objective of this study was to analyze the incidence and severity of thrombocytopenia at presentation and its prognostic impact in patients with native valve left-sided IE. We studied a cohort of 533 consecutive episodes of native valve left-sided IE prospectively recruited. We distinguished 2 groups: group I (n = 175), episodes who had thrombocytopenia at admission, and group II (n = 358) gathered all the episodes who did not. Thrombocytopenia at admission was defined as a platelet count of <150,000/μl. No differences were found in the need for surgery, but in-hospital mortality was significantly higher in patients with thrombocytopenia (p <0.001). Mortality rate was associated with the degree of thrombocytopenia (p <0.001). In the multivariable analysis, thrombocytopenia at admission was an independent predictor of higher mortality (p = 0.002). A synergistic interaction between thrombocytopenia and Staphylococcus aureus on mortality risk was also observed (p = 0.04). In conclusion, thrombocytopenia at admission is an early risk marker of increased mortality in patients with native valve left-sided IE. Mortality rates increased with increasing severity of thrombocytopenia. Thrombocytopenia at admission should be used as an early marker for risk stratification in patients with native valve IE to identify those at risk of complicated in-hospital evolution and increased mortality.

  12. SLC6A4 methylation as an epigenetic marker of life adversity exposures in humans: A systematic review of literature.

    PubMed

    Provenzi, Livio; Giorda, Roberto; Beri, Silvana; Montirosso, Rosario

    2016-12-01

    The application of epigenetics to the study of behavioral and socio-emotional development in humans has revealed that DNA methylation could be a potential marker of adversity exposure and long-lasting programming of health and disease. The serotonin transporter gene (SLC6A4) is a stress-related gene which has well-documented implications for behavioral and socio-emotional development and which has been shown to be susceptible to transcriptional regulation via epigenetic mechanisms. In the present paper, a systematic review of papers assessing the association among adversity exposures, SLC6A4 methylation and developmental outcomes is reported. Nineteen studies were included. Findings revealed that SLC6A4 methylation has been investigated in humans in association with a number of prenatal and postnatal adverse exposures, encompassing maternal depression during pregnancy, perinatal stress exposure, childhood trauma and abuse, and environmental stress. SLC6A4 is confirmed as a relevant biomarker of early adversity exposures, and epigenetic mechanisms occurring at this gene appear to play a critical role for programming. Nonetheless, specific methodological issues still need to be addressed in future human behavioral epigenetic research.

  13. Prognostic Significance of the Metabolic Marker Hexokinase-2 in Various Solid Tumors: A Meta-Analysis

    PubMed Central

    Liu, Yulin; Wu, Ke; Shi, Liang; Xiang, Fan; Tao, Kaixiong; Wang, Guobin

    2016-01-01

    Objective Recently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor. Methods Eligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients’ ethnicities, tumor types, detection methods, and analysis types. Results Data from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51–2.38, p < 0.001) and PFS (pooled HR = 2.91, 95% CI = 2.02–4.22, p < 0.001) in solid tumor. As to a specific form of cancer, the negative effect of HK2 on OS was observed in hepatocellular carcinoma (pooled HR = 2.06, 95% CI = 1.67–2.54, p < 0.001), gastric cancer (pooled HR = 1.72, 95% CI = 1.09–2.71, p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62–5.16, p < 0.001), but not in pancreatic cancer (pooled HR = 1.13, 95% CI = 0.28–4.66, p = 0.864). No publication bias was found in the included studies for OS (Begg’s test, p = 0.325; Egger’s test, p = 0.441). Conclusion In this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type. PMID:27824926

  14. Histone demethylase GASC1 - a potential prognostic and predictive marker in invasive breast cancer

    PubMed Central

    2012-01-01

    Background The histone demethylase GASC1 (JMJD2C) is an epigenetic factor suspected of involvement in development of different cancers, including breast cancer. It is thought to be overexpressed in the more aggressive breast cancer types based on mRNA expression studies on cell lines and meta analysis of human breast cancer sets. This study aimed to evaluate the prognostic and predictive value of GASC1 for women with invasive breast cancer. Methods All the 355 cases were selected from a cohort enrolled in the Kuopio Breast Cancer Project between April 1990 and December 1995. The expression of GASC1 was studied by immunohistochemistry (IHC) on tissue microarrays. Additionally relative GASC1 mRNA expression was measured from available 57 cases. Results In our material, 56% of the cases were GASC1 negative and 44% positive in IHC staining. Women with GASC1 negative tumors had two years shorter breast cancer specific survival and time to relapse than the women with GASC1 positive tumors (p=0.017 and p=0.034 respectively). The majority of GASC1 negative tumors were ductal cases (72%) of higher histological grade (84% of grade II and III altogether). When we evaluated estrogen receptor negative and progesterone receptor negative cases separately, there was 2 times more GASC1 negative than GASC1 positive tumors in each group (chi2, p= 0.033 and 0.001 respectively). In the HER2 positive cases, there was 3 times more GASC1 negative cases than GASC1 positives (chi2, p= 0.029). Patients treated with radiotherapy (n=206) and hormonal treatment (n=62) had better breast cancer specific survival, when they were GASC1 positive (Cox regression: HR=0.49, p=0.007 and HR=0.33, p=0.015, respectively). The expression of GASC1 mRNA was in agreement with the protein analysis. Conclusions This study indicates that the GASC1 is both a prognostic and a predictive factor for women with invasive breast cancer. GASC1 negativity is associated with tumors of more aggressive histopathological

  15. Building associations between markers of environmental stressors and adverse human health impacts using frequent itemset mining

    EPA Science Inventory

    Building associations between markers of exposure and effect using frequent itemset mining The human-health impact of environmental contaminant exposures is unclear. While some exposure-effect relationships are well studied, health effects are unknown for the vast majority of the...

  16. CD38+ CD58- is an independent adverse prognostic factor in paediatric Philadelphia chromosome negative B cell acute lymphoblastic leukaemia patients.

    PubMed

    Li, Xu-Mian; Zhang, Le-Ping; Wang, Ya-Zhe; Lu, Ai-Dong; Chang, Yan; Zhu, Hong-Hu; Qin, Ya-Zhen; Lai, Yue-Yun; Kong, Yuan; Huang, Xiao-Jun; Liu, Yan-Rong

    2016-04-01

    To explore new risk predictors for a high risk of relapse in Philadelphia chromosome negative (Ph-) B cell acute lymphoblastic leukaemia (B-ALL) patients, 196 paediatric Ph- B-ALL patients (≤ 18 years) were retrospectively analysed. We mainly focus on investigating the prognostic value of CD38 and CD58 expression in leukemic blasts in these patients by four colour flow cytometry. The CD38+ CD58- group (n=16) had a higher relapse rate, a shorter 3-year event-free survival (EFS) and overall survival (OS) than the CD38+ CD58+ group (n=157; 31.3% vs 10.2%, P=0.04; 52.4% vs 92.3%, P<0.01; 32.5% vs 91.0%, P=0.01); CD38+ CD58- was an independent adverse prognostic predictor for relapse (hazard ratio [HR], 0.203; 95%CI, 0.063-0.656; P=0.01), 3-year EFS (HR, 0.091; 95%CI, 0.023-0.355; P<0.01) and OS (HR, 0.102; 95%CI, 0.026-0.3971; P<0.01) in this cohort, as determined by Cox multivariate analysis. We identified, for the first time, a higher risk population of paediatric Ph- B-ALL patients with CD38+ CD58- who had a higher relapse risk and a shorter survival. Our results may allow better risk stratification and individualized treatment.

  17. Cerebral Arterial Calcification Is an Imaging Prognostic Marker for Revascularization Treatment of Acute Middle Cerebral Arterial Occlusion

    PubMed Central

    Lee, Seong-Joon; Hong, Ji Man; Lee, Manyong; Huh, Kyoon; Choi, Jin Wook

    2015-01-01

    Background and Purpose To study the significance of intracranial artery calcification as a prognostic marker for acute ischemic stroke patients undergoing revascularization treatment after middle cerebral artery (MCA) trunk occlusion. Methods Patients with acute MCA trunk occlusion, who underwent intravenous and/or intra-arterial revascularization treatment, were enrolled. Intracranial artery calcification scores were calculated by counting calcified intracranial arteries among major seven arteries on computed tomographic angiography. Patients were divided into high (HCB; score ≥3) or low calcification burden (LCB; score <3) groups. Demographic, imaging, and outcome data were compared, and whether HCB is a prognostic factor was evaluated. Grave prognosis was defined as modified Rankin Scale 5-6 for this study. Results Of 80 enrolled patients, the HCB group comprised 15 patients, who were older, and more commonly had diabetes than patients in the LCB group. Initial National Institutes of Health Stroke Scale (NIHSS) scores did not differ (HCB 13.3±2.7 vs. LCB 14.6±3.8) between groups. The final good reperfusion after revascularization treatment (thrombolysis in cerebral infarction score 2b-3, HCB 66.7% vs. LCB 69.2%) was similarly achieved in both groups. However, the HCB group had significantly higher NIHSS scores at discharge (16.0±12.3 vs. 7.9±8.3), and more frequent grave outcome at 3 months (57.1% vs. 22.0%) than the LCB group. HCB was proven as an independent predictor for grave outcome at 3 months when several confounding factors were adjusted (odds ratio 4.135, 95% confidence interval, 1.045-16.359, P=0.043). Conclusions Intracranial HCB was associated with grave prognosis in patients who have undergone revascularization for acute MCA trunk occlusion. PMID:25692109

  18. Sickness absence as a prognostic marker for common chronic conditions: analysis of mortality in the GAZEL study

    PubMed Central

    Kivimaki, Mika; Head, Jenny; Ferrie, Jane E.; Singh-Manoux, Archana; Westerlund, Hugo; Vahtera, Jussi; Leclerc, Annette; Melchior, Maria; Chevalier, Anne; Alexanderson, Kristina; Zins, Marie; Goldberg, Marcel

    2008-01-01

    Objectives To determine whether sickness absence is a prognostic marker in terms of mortality among people with common chronic conditions. Methods Prospective occupational cohort study of 13 077 men and 4871 women aged 37 to 51 from the National Gas and Electricity Company, France. Records of physician-certified sickness absences over a 3-year period were obtained from employers’ registers. Chronic conditions were assessed in annual surveys over the same period. The main outcome measure was all-cause mortality (803 deaths, mean follow-up after assessment of sickness absence, 13.9 years) Results In Cox proportional-hazard models adjusted for age, sex, socioeconomic position and co-morbidity, >28 annual sickness absence days vs no absence days was associated with an excess mortality risk among those with cancer (hazard ratio 5.4, 95% CI 2.2 to 13.1), depression (1.7, 1.1 to 2.8), chronic bronchitis/asthma (2.7, 1.6 to 4.6), and hypertension (1.6, 1.0 to 2.6). The corresponding hazard ratios for more than 5 long (>14 days) sickness absence episodes per 10 person-years vs no such episodes were 5.4 (2.2 to 13.1), 1.8 (1.3 to 2.7), 2.0 (1.3 to 3.2) and 1.8 (1.2 to 2.7), respectively. Areas under receiver-operating-characteristics curves for these absence measures varied between 0.56 and 0.73 indicating the potential of these measures to distinguish groups at high risk of mortality. The findings were consistent across sex, age and socioeconomic groups and in those with and without co-morbid conditions. Conclusion Data on sickness absence may provide useful prognostic information for common chronic conditions at the population level. PMID:18611969

  19. MALDI-imaging reveals thymosin beta-4 as an independent prognostic marker for colorectal cancer

    PubMed Central

    Gemoll, Timo; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Habermann, Jens K.

    2015-01-01

    DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for direct analysis of multiple proteins in tissue sections while maintaining the cellular and molecular integrity. We compared diploid and aneuploid colon cancer tissues against normal mucosa of the colon by means of IMS. DNA image cytometry determined the ploidy status of tissue samples that were subsequently subjected to MALDI-IMS. After obtaining protein profiles through direct analysis of tissue sections, a discovery and independent validation set were used to predict ploidy status by applying proteomic classification algorithms [Supervised Neural Network (SNN) and Receiver Operating Characteristic (ROC)]. Five peaks (m/z 2,395 and 4,977 for diploid vs. aneuploid comparison as well as m/z 3,376, 6,663, and 8,581 for normal mucosa vs. carcinoma comparison) were significant in both SNN and ROC analysis. Among these, m/z 4,977 was identified as thymosin beta 4 (Tβ-4). Tβ-4 was subsequently validated in clinical samples using a tissue microarray to predict overall survival in colon cancer patients. PMID:26556858

  20. ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer

    PubMed Central

    Hou, Pingfu; Zhang, Zhe; Zhang, Yafei; Wang, Weimin; Sun, Guixiang; Xu, Lichun; Zhou, Jianwei; Bai, Jin; Zheng, Junnian

    2016-01-01

    ING4, a potential tumor suppressor, is implicated in cell cycle arrest, apoptosis, cell migration and angiogenesis. Here, we investigated the clinical value of ING4 and its impact on angiogenesis in colorectal cancer (CRC). In this study, we found that ING4 expression was significantly reduced in CRC tissues versus paired normal colon tissues. Moreover, low ING4 expression was significantly associated with increased lymph node metastasis, advanced TNM stage and poor overall survival. Multivariate Cox regression analysis showed that ING4 expression was an independent favourable prognostic factor for CRC (hazard ratio = 0.45, P = 0.001). In addition, we found that ING4 strongly inhibited CRC angiogenesis by suppressing Sp1 expression and transcriptional activity through ubiquitin degradation and down-regulating the expressions of Sp1 downstream pro-angiogenic genes, MMP-2 and COX-2. Moreover, ING4 might inhibit phosphorylation activity of cyclin/CDK2 complexes to trigger Sp1 degradation by inducing p21 expression in despite of p53 status. Our findings imply that reduced ING4 expression in CRC resulted in increased angiogenesis and contributed to CRC metastasis and poor prognosis. Restoration of ING4 may be a novel strategy for the treatment of metastatic CRC. PMID:27806345

  1. MLL2 protein is a prognostic marker for gastrointestinal diffuse large B-cell lymphoma

    PubMed Central

    Ye, Haige; Lu, Lu; Ge, Bei; Gao, Shenmeng; Ma, Yongyong; Liang, Bin; Yu, Kang; Yang, Kaiyan

    2015-01-01

    Mixed linage leukemia gene 2 (MLL2) is identified as a novel mutation gene in diffuse large B cell lymphoma (DLBCL). However, the significance of MLL2 protein expression for the prognosis of DLBCL is unclear. In this study, we detected MLL2 protein expression in primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL) samples by using tissue microarray immunohistochemistry, and analyzed the correlation between MLL2 protein expression and tumor proliferation activity. In addition, we investigated clinical significance of MLL2 protein expression for PGI-DLBCL prognosis. We found that there was significant difference in MLL2 protein expression between PGI-DLBCL and reactive hyperplasia of lymph node. High expression of MLL2 protein indicated higher clinical stage. In older patients (>60 years) with PGI-DLBCL, MLL2 protein expression was positively correlated with Ki-67 expression and negatively correlated with patient survival. Our data suggest that MLL2 protein is overexpressed in PGI-DLBCL and appears as a prognostic factor for patients of PGI-DLBCL, especially for those older than 60 years old. PMID:26722499

  2. MAP17 and SGLT1 Protein Expression Levels as Prognostic Markers for Cervical Tumor Patient Survival

    PubMed Central

    Perez, Marco; Praena-Fernandez, Juan M.; Felipe-Abrio, Blanca; Lopez-Garcia, Maria A.; Lucena-Cacace, Antonio; Garcia, Angel; Lleonart, Matilde; Roncador, Guiovanna; Marin, Juan J.; Carnero, Amancio

    2013-01-01

    MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS) generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types. PMID:23418532

  3. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

    PubMed Central

    Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

    2015-01-01

    Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

  4. Molecular Markers as Prognostic Factors in DCIS and Small Invasive Breast Cancers.

    PubMed

    Sänger, N; Engels, K; Graf, A; Ruckhäberle, E; Effenberger, K E; Fehm, T; Holtrich, U; Becker, S; Karn, T

    2014-11-01

    Ductal carcinoma in situ (DCIS) accounts for up to half of screen-detected breast cancers and thus constitutes a major public health problem. Despite effective current treatment many patients with DCIS are either over- or undertreated because of the paucity of precise models to predict recurrence or progression. The combination of clinical and molecular factors as already applied for invasive disease may help to build such models also for DCIS. We compared 53 DCIS (36.6 %) and 92 (63.4 %) invasive breast cancer cases and found no significant differences in age, receptor status of ER, PR, and HER2, and the use of radiotherapy. Interestingly, the proportion of disseminated tumor cells (DTC) did also not significantly differ between DCIS and invasive cases (p = 0.57). A negative PR status was associated with the detection of DTCs (p = 0.026). We then compared relationships of clinical parameters and biomarkers with patients' prognosis in 43 DCIS and 40 small invasive tumors ≤ 5 mm (T1a). ER negativity was associated with shorter relapse free survival in the complete cohort (p = 0.004) and showed a trend in both subgroups (p = 0.053 for DCIS and p = 0.046 for T1a, respectively). In conclusion, we found markedly similar properties of both DCIS and small invasive breast cancers with respect to the distribution of several parameters as well as to the prognostic value of biomarkers. DCIS with a luminal phenotype seem to be characterized by a favourable prognosis.

  5. Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction

    PubMed Central

    Cruz-Gonzalez, Ignacio; Pabón, Pedro; Rodríguez-Barbero, Alicia; Martín-Moreiras, Javier; Pericacho, Miguel; Sánchez, Pedro L; Ramirez, Victor; Sánchez-Ledesma, María; Martín-Herrero, Francisco; Jiménez-Candil, Javier; Maree, Andrew O; Sánchez-Rodríguez, Angel; Martín-Luengo, Cándido; López-Novoa, José M

    2008-01-01

    Abstract Endoglin is a proliferation-associated and hypoxia-inducible protein expressed in endothelial cells. The levels of soluble circulating endoglin and their prognostic significance in patients with acute myocardial infarction (AMI) are not known. In this observational prospective study serum endoglin levels were measured by ELISA in 183 AMI patients upon admission to hospital and 48 hrs later and in 72 healthy controls. Endoglin levels in AMI patients on admission were significantly lower than in healthy controls (4.25 ± 0.99 ng/ml versus 4.59 ± 0.87 ng/ml; P= 0.013), and decreased further in the first 48 hours (3.65 ± 0.76 ng/ml, P < 0.001). Upon follow-up (median 319 days), patients who died had a significantly greater decrease in serum endoglin level over the first 48 hrs than those who survived (1.03 ± 0.91 versus 0.54 ± 0.55 ng/ml; P= 0.025). Endoglin decrease was an independent predictor of short-term (30 days) (hazard ratio 2.33;95% CI = 1.27–4.23; P= 0.006) cardiovascular mortality, and also predicts overall cardiovascular mortality during the follow-up (median 319 days) in AMI patients (hazard ratio 2.13;95% CI = 1.20–3.78; P= 0.01). In conclusion, early changes in serum endoglin may predict mortality after AMI. PMID:18494936

  6. Identification of androgen-responsive lncRNAs as diagnostic and prognostic markers for prostate cancer

    PubMed Central

    Yang, Shu; Zhang, Yalong; Pu, Honglei; Fu, Fangqiu; Huang, Yan; Wu, Hai; Li, Tao; Li, Yao

    2016-01-01

    Prostate cancer (PCa) is a leading cause of mortality among males. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that may act as biomarkers and therapeutic targets. In this study, we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909. Next, we performed microarray to observe genome-wide lncRNAs' expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE. Combined the two results, a total of 44 androgen-responsive lncRNAs with ARE were found to be over-expressed in PCa samples. Ten lncRNAs were selected for further validation by examining their expressions in LNCaP cells under DHT stimulation, and in PCa samples and cell lines. Among them, RP1-4514.2, LINC01138, SUZ12P1 and KLKP1 were validated as directly AR-targeted lncRNAs by ChIP-PCR. Then we conducted a bioinformatic analysis to identify lncRNAs as putative prognostic and therapeutic targets by using TCGA data. Three androgen-responsive lncRNAs, LINC01138, SUZ12P1 and SNHG1 showed association with gleason score and pT-stage. The biological functions of LINC01138 and SUZ12P1 were also evaluated, both lncRNAs promoted the proliferation and inhibited apoptosis of PCa. These results provide potent information for exploring potential biomarkers and therapeutic targets for prostate cancer, especially for castration-resistant PCa. PMID:27556357

  7. Serum Levels of Vasoactive Intestinal Peptide as a Prognostic Marker in Early Arthritis

    PubMed Central

    Martínez, Carmen; Ortiz, Ana M.; Juarranz, Yasmina; Lamana, Amalia; Seoane, Iria V.; Leceta, Javier; García-Vicuña, Rosario

    2014-01-01

    Objective Suitable biomarkers are essential for the design of therapeutic strategies in personalized medicine. Vasoactive intestinal peptide (VIP) has demonstrated immunomodulatory properties in autoimmune murine and ex vivo human models. Our aim was to study serum levels of VIP during the follow-up of an early arthritis (EA) cohort and to analyze its value as a biomarker predicting severity and therapeutic requirements. Methods Data from 91 patients on an EA register were analyzed (76% rheumatoid arthritis (RA), 24% undifferentiated arthritis, 73% women, and median age 54 years; median disease duration at entry, 5.4 months). We collected per protocol sociodemographic, clinical, and therapeutic data. VIP levels were determined by enzyme immunoassay in sera harvested from the 91 patients (353 visits; 3.9 visit/patient) and from 100 healthy controls. VIP values below the 25th percentile of those assessed in healthy population were considered low. To determine the effect of independent variables on VIP levels, we performed a longitudinal multivariate analysis nested by patient and visit. A multivariate ordered logistic regression was modeled to determine the effect of low VIP serum levels on disease activity at the end of follow-up. Results VIP concentrations varied considerably across EA patients. Those fulfilling the criteria for RA had the lowest values in the whole sample, although no significant differences were observed compared with healthy donors. Disease activity, which was assessed using DAS28, inversely correlated with VIP levels. After a two-year follow-up, those patients with low baseline levels of VIP displayed higher disease activity and received more intensive treatment. Conclusion Patients who are unable to up-regulate VIP seem to have a worse clinical course despite receiving more intense treatment. Therefore, measurement of VIP levels may be suitable as a prognostic biomarker. PMID:24409325

  8. Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.

    PubMed

    Fonseca, Felipe Paiva; Sena Filho, Marcondes; Altemani, Albina; Speight, Paul M; Vargas, Pablo Agustin

    2016-02-01

    Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers.

  9. MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer

    PubMed Central

    Ren, Fei; Wang, Lisha; Shen, Xiaohan; Xiao, Xiuying; Liu, Zebing; Wei, Ping; Wang, Yiqin; Qi, Peng; Shen, Chen; Sheng, Weiqi; Du, Xiang

    2015-01-01

    The MYBL2 gene plays an important role in the genesis and progression of tumors; however, few studies to date have defined the role of this gene in colorectal cancer (CRC). The aim of this study was to determine the relationship between MYBL2 and the prognosis of patients with CRC and to determine the possible effect of MYBL2 on colorectal carcinogenesis. Solid CRC tissues (n=180) preserved with RNAlater were collected to examine the mRNA levels of MYBL2 by real-time quantitative PCR (RT-qPCR). Formalin-fixed, paraffin-embedded (FFPE) blocks of CRC tissues (n=97) and adjacent noncancerous tissues (ANCTs, n=104) were obtained to detect MYBL2 protein levels by immunohistochemistry (IHC). siRNA was used to downregulate MYBL2 expression in the SW480 cell line to detect changes in proliferation, cell cycle progression, apoptosis, migration and invasion. The protein levels of MYBL2 were significantly higher in CRC tissues compared with ANCTs (P<0.05). Kaplan-Meier survival curves indicated that disease-free survival (DFS) was significantly worse in CRC patients in whom MYBL2 was overexpressed (at both the mRNA and protein levels) compared with patients not overexpressing MYBL2. Cox multivariate analysis revealed MYBL2 overexpression as an independent prognostic factor for poor patient survival. In addition, siRNA downregulation of MYBL2 suppressed SW480 cell proliferation, delayed cell cycle progression and induced apoptosis; however, changes in cell migration were minor. Western blot analysis demonstrated an association between MYBL2 expression and that of MMP9, Vimentin, and E-cadherin. MYBL2 is overexpressed in CRC and may therefore play an important role in tumourigenesis. PMID:26101717

  10. Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer

    PubMed Central

    Wang, Peng; Ning, Shangwei; Zhang, Yunpeng; Li, Ronghong; Ye, Jingrun; Zhao, Zuxianglan; Zhi, Hui; Wang, Tingting; Guo, Zheng; Li, Xia

    2015-01-01

    Recent studies have suggested that long non-coding RNAs (lncRNAs) can interact with microRNAs (miRNAs) and indirectly regulate miRNA targets though competing interactions. However, the molecular mechanisms underlying these interactions are still largely unknown. In this study, these lncRNA–miRNA–gene interactions were defined as lncRNA-associated competing triplets (LncACTs), and an integrated pipeline was developed to identify lncACTs that are active in cancer. Competing lncRNAs had sponge features distinct from non-competing lncRNAs. In the lncACT cross-talk network, disease-associated lncRNAs, miRNAs and coding-genes showed specific topological patterns indicative of their competence and control of communication within the network. The construction of global competing activity profiles revealed that lncACTs had high activity specific to cancers. Analyses of clustered lncACTs revealed that they were enriched in various cancer-related biological processes. Based on the global cross-talk network and cluster analyses, nine cancer-specific sub-networks were constructed. H19- and BRCA1/2-associated lncACTs were able to discriminate between two groups of patients with different clinical outcomes. Disease-associated lncACTs also showed variable competing patterns across normal and cancer patient samples. In summary, this study uncovered and systematically characterized global properties of human lncACTs that may have prognostic value for predicting clinical outcome in cancer patients. PMID:25800746

  11. Troponin I as a prognostic marker of cardiac events in asymptomatic hemodialysis patients using a sensitive troponin I assay.

    PubMed

    Gaiki, Meghana R; DeVita, Maria V; Michelis, Michael F; Panagopoulos, Georgia; Rosenstock, Jordan L

    2012-12-01

    Elevated troponin T is known to be a prognostic marker for long-term cardiac events and mortality in asymptomatic end-stage renal disease patients. There are conflicting data in this regard with respect to troponin I (TnI). We recently showed a high incidence of elevated TnI levels in asymptomatic hemodialysis (HD) patients using a new generation sensitive TnI assay. The aim of this pilot study was to explore the prognostic value of TnI, as measured with this new assay, as a marker for outcomes in HD patients over a 2-year follow-up period. Fifty-one asymptomatic HD patients were enrolled, and pre-dialysis TnI levels were checked once monthly over 3 consecutive months. Patients were considered to be in the TnI positive group if TnI level on any of the three draws was ≥0.035 ng/ml. All patients were followed for a period of 2 years. The primary end points were acute coronary syndrome, coronary revascularization, sudden death, or cardiac arrest. The secondary end point was all-cause mortality. Elevated TnI levels were found in 51% (26/51) of patients in our cohort. One TnI positive patient was subsequently lost to follow up. There were 6 cardiac events over 2 years, all of which were in the troponin positive group (6/25 or 24%). The presence of a positive TnI at baseline was significantly associated with future cardiac events (p=0.022). A prior history of coronary artery disease (CAD) was also significantly related to future cardiac events (p=0.010). No patient with negative TnI at baseline developed a cardiac event, while 45.5% of those with both a positive TnI and a history of CAD had an event. Fourteen deaths occurred over 2 years, 8 in TnI positive and 6 in the negative group. All-cause mortality was not associated with elevated TnI levels at baseline. We found a significant association between positive TnI and subsequent cardiac events in asymptomatic HD patients followed for 2 years. TnI levels, as measured with a sensitive assay, may be useful in assessing

  12. Clinicopathological and prognostic significance of cancer stem cell markers CD44 and CD133 in patients with gastric cancer

    PubMed Central

    Lu, Li; Wu, Menglin; Sun, Longhao; Li, Weidong; Fu, Weihua; Zhang, Xuening; Liu, Tong

    2016-01-01

    Abstract Background: In recent years, CD44 and CD133 have been identified as 2 common used cancer stem cell (CSC) markers in gastric cancer. However, the clinicopathological and prognostic value of these markers in gastric cancer remains controversial; moreover, there is lack of comparison of these 2 markers’ roles in clinical applications. A systematic review and meta-analysis was conducted to elucidate these markers’ clinicopathological features and association with prognosis in patients with gastric cancer. Methods: Eligible studies were identified and odds ratios (ORs), hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Heterogeneity and sensitivity were analyzed as well. Publication bias was assessed using funnel plots and Egger tests. Results: The meta-analysis included 26 studies involving 4729 patients. High expression of CD44 was associated with Lauren type (intestinal type) (OR, 1.53 [95% CI, 1.02–2.30]; P = 0.038) and lymphatic vessel invasion (OR, 1.36 [95% CI, 1.06–1.76]; P = 0.021). CD133 overexpression was related to high TNM stage (III/IV) (OR, 3.18 [95% CI, 2.48–4.07]; P = 0.000), high depth of invasion (T3/T4) (OR, 2.97 [95% CI, 2.20–4.03]; P = 0.000), lymph node metastasis (OR, 2.82 [95% CI, 2.16–3.69]; P = 0.000), vascular invasion (OR, 6.71 [95% CI, 1.63–27.63]; P = 0.008), and distant metastasis (OR, 2.32 [95% CI, 1.64–3.29]; P = 0.000). In addition, survival analysis demonstrated a significant association between CD44, as well as CD133 and poor 5-year overall survival (HR, 1.87 [95% CI, 1.55–2.26]; P = 0.000; HR, 2.07 [95% CI, 1.76–2.44]; P = 0.000, respectively). Conclusion: These data suggest that upregulated expression of CD44 and CD133 correlates with several clinicopathological features and poor prognosis. Since the related features do not overlap, combined detection of CD44 and CD133 expression can be an especially effective tool for pathological diagnosis

  13. Diagnostic/prognostic molecular cytogenetic follow-up applied in satellited marker cases

    SciTech Connect

    Papenhausen, P.R.; Anderson, S.

    1994-09-01

    Special caution needs to be exercised in offering a good prognosis in Prader-Willi probe negative 15-derived marker cases, since it is clear that phenotypic effects can still be associated with the apparent presence of proximal sequences. We have had two postnatal cases in this category, one which was inherited from an unaffected paternal (non-mosaic) carrier, possibly demonstrating imprinting effects. Familial studies are continuing in this case. Although the D22/S9 locus appears diagnostic of cateye syndrome (CES), the dual specificity of the 14/22 centromeric probe leaves the possibility of a poor prognosis 14 derivation when the CES probe is negative. Therefore, it is imperative that proximal long arm 13, 14, 21 and more proximal 15 FISH probes be implemented so that a phenotypically correlated database may indicate the proper FISH probes necessary for accurate prognosis. Bisatellited markers is which a bipartite centromeric probe signal was found were considered to be higher risk than those with the single signal in counseling.

  14. Association of FOXM1 expression with tumor histology and prognosis in Wilms tumor: Potential for a new prognostic marker

    PubMed Central

    Apelt, Nadja; Hubertus, Jochen; Mayr, Doris; Graf, Norbert; Furtwängler, Rhoikos; Von Schweinitz, Dietrich; Kappler, Roland

    2016-01-01

    Wilms tumor (WT) is the most common pediatric renal malignancy. A recent ontogenic model suggests that undifferentiated tumor state, and hence poor prognosis, in WT is determined by stabilization of β-catenin in the nucleus. Forkhead box M1 (FOXM1) is a downstream component of the Wnt pathway and promotes nuclear localization of β-catenin. As elevation of FOXM1 gene expression is prognostic in various types of malignancy, we hypothesized that high FOXM1 expression in WT is associated with undifferentiated histology and thus poor prognosis. In the current study, the expression of FOXM1 mRNA was determined in 46 WT specimens and 11 renal tissue controls from patients undergoing tumor nephrectomy, and these data were assessed with regard to clinicopathological parameters. The results demonstrated an upregulation of FOXM1 in WT by 10-fold compared to normal tissue. Expression differed significantly between controls and tumors of intermediate- and high-risk histopathology (P<0.001, Kruskal-Wallis), and distinguished normal tissue from tumors of good and adverse clinical outcome (P<0.001, Kruskal-Wallis). Notably, FOXM1 expression was significantly lower (P=0.009) in patients that received preoperative doxorubicin. These results suggest that FOXM1 may serve as a companion diagnostic factor for doxorubicin-based therapies in WT. PMID:27698870

  15. Single nucleotide polymorphisms as susceptibility, prognostic, and therapeutic markers of nonsmall cell lung cancer

    PubMed Central

    Zienolddiny, Shanbeh; Skaug, Vidar

    2012-01-01

    Lung cancer is a major public health problem throughout the world. Among the most frequent cancer types (prostate, breast, colorectal, stomach, lung), lung cancer is the leading cause of cancer-related deaths worldwide. Among the two major subtypes of small cell lung cancer and nonsmall cell lung cancer (NSCLC), 85% of tumors belong to the NSCLC histological types. Small cell lung cancer is associated with the shortest survival time. Although tobacco smoking has been recognized as the major risk factor for lung cancer, there is a great interindividual and interethnic difference in risk of developing lung cancer given exposure to similar environmental and lifestyle factors. This may indicate that in addition to chemical and environmental factors, genetic variations in the genome may contribute to risk modification. A common type of genetic variation in the genome, known as single nucleotide polymorphism, has been found to be associated with susceptibility to lung cancer. Interestingly, many of these polymorphisms are found in the genes that regulate major pathways of carcinogen metabolism (cytochrome P450 genes), detoxification (glutathione S-transferases), adduct removal (DNA repair genes), cell growth/apoptosis (TP53/MDM2), the immune system (cytokines/chemokines), and membrane receptors (nicotinic acetylcholine and dopaminergic receptors). Some of these polymorphisms have been shown to alter the level of mRNA, and protein structure and function. In addition to being susceptibility markers, several of these polymorphisms are emerging to be important for response to chemotherapy/radiotherapy and survival of patients. Therefore, it is hypothesized that single nucleotide polymorphisms will be valuable genetic markers in individual-based prognosis and therapy in future. Here we will review some of the most important single nucleotide polymorphisms in the metabolic pathways that may modulate susceptibility, prognosis, and therapy in NSCLC. PMID:28210120

  16. Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer

    PubMed Central

    Lu, Wei; Cao, Yang; Zhang, Yijian; Li, Sheng; Gao, Jian; Wang, Xu-An; Mu, Jiasheng; Hu, Yun-Ping; Jiang, Lin; Dong, Ping; Gong, Wei; Liu, Yingbin

    2016-01-01

    Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression. PMID:27283076

  17. Serum Golgi Protein 73 (GP73) is a Diagnostic and Prognostic Marker of Chronic HBV Liver Disease

    PubMed Central

    Xu, Zhengju; Liu, Liguan; Pan, Xingnan; Wei, Kaipeng; Wei, Meijuan; Liu, Lifei; Yang, Huanwen; Liu, Qian

    2015-01-01

    Abstract Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections. This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay. Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy. Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels. PMID:25816035

  18. Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

    PubMed Central

    Kwak, Yoonjin; Koh, Jiwon; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Woo Ho; Lee, Hye Seung

    2016-01-01

    Background The immunoscore (IS), an index based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumor-associated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases. Methods The density of CD3+, CD4+, CD8+, FOXP3+, CD68+, and CD163+ immune cells within CRC tissue procured from three sites–the primary CT, IM, and distant metastasis (DM)–was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3+ and CD8+ TILs in the CT and IM. IS-metastatic and IS-macrophage–additional IS models designed in this study–were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS. Result Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status. Conclusion IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3+ and CD8+ TIL densities at DM could be a strong prognostic marker for advanced CRC. PMID:27835889

  19. Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

    PubMed Central

    Martins, Gustavo Rodrigues; Gelaleti, Gabriela Bottaro; Moschetta, Marina Gobbe; Maschio-Signorini, Larissa Bazela; Zuccari, Debora Ap. Pires de Campos

    2016-01-01

    Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-α with procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-α were found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-α protein expression and survival time was observed (p < 0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p < 0.05). In addition, there was a positive correlation between TNF-α and IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer. PMID:26989335

  20. Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11

    PubMed Central

    Liao, Yunfei; Sassi, Slim; Halvorsen, Stefan; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

    2017-01-01

    Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment. PMID:28262798

  1. Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer?

    PubMed Central

    Khodapasand, Ehsan; Jafarzadeh, Narges; Farrokhi, Farid; Kamalidehghan, Behnam; Houshmand, Massoud

    2015-01-01

    Background: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate. Methods: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer. Results: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors. Conclusion: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer. PMID:25864810

  2. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters.

    PubMed

    Catasus, Lluis; Gallardo, Alberto; Cuatrecasas, Miriam; Prat, Jaime

    2008-02-01

    Mutations of the oncogene PIK3CA occur frequently in endometrial carcinomas, but their prognostic significance is unclear. To determine the clinicopathological and molecular implications of these mutations, PIK3CA status was investigated in 109 endometrial (102 endometrioid and 7 mixed) carcinomas and the results were compared with clinicopathological parameters associated with prognosis. Tumors were also investigated for microsatellite instability and PTEN, beta-catenin gene (CTNNB1), K-RAS, and B-RAF mutations. We found 35 PIK3CA somatic missense mutations in 32 (29%) endometrial carcinomas. Eighteen mutations occurred in exon 20 (kinase domain), and 17 in exon 9 (helical domain). Almost all mutated tumors were pure endometrioid adenocarcinomas. All tumors with PIK3CA mutations exhibited myometrial invasion (P=0.032). Lymphovascular invasion was found more frequently in mutated (28%) than nonmutated carcinomas (18%). Histological grade varied significantly according to the location of the PIK3CA mutations whether in exon 9 or exon 20 (P=0.033). The frequency of exon 9 mutations was higher in grade 1 carcinomas (57%) than in grade 2 (29%) or grade 3 (14%) tumors. Conversely, mutations in exon 20 were more common in grade 3 (60%) than in grade 2 (20%) or grade 1 (20%) carcinomas. None of the tumors confined to the endometrium (stage IA) had PIK3CA mutations. Furthermore, whereas 64% of adenocarcinomas with exon 9 mutations had invaded < or =(1/2) of the myometrial thickness (stage IB), 73% of tumors with exon 20 mutations had either deeper myometrial invasion (stage IC) or cervical involvement (stage II) (P=0.045). PIK3CA mutations coexisted with microsatellite instability and mutations in PTEN, CTNNB1, K-RAS, and B-RAF genes. These results favor that PIK3CA mutations are associated with myometrial invasion and, moreover, that tumors harboring PIK3CA mutations in exon 20 are frequently high-grade, deeply invasive endometrial carcinomas that tend to exhibit

  3. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion

    PubMed Central

    Verma, Akash; Phua, Chee Kiang; Sim, Wen Yuan; Algoso, Reyes Elmer; Tee, Kuan Sen; Lew, Sennen J. W.; Lim, Albert Y. H.; Goh, Soon Keng; Tai, Dessmon Y. H.; Kor, Ai Ching; Ho, Benjamin; Abisheganaden, John

    2016-01-01

    Abstract To study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis. Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012. Univariate analyses showed lower pleural fluid LDH 667 (313–967) versus 971 (214–3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 (100%) versus 36 (55.3%), P = 0.009, and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy 8 (89%) versus 26 (40%), P = 0.009 to correlate with survival of more than 1.7 year versus less than 1.7 year. In multivariate analysis, low pleural fluid LDH and female gender maintained significance. The pleural LDH level of ≤1500 and >1500 U/L discriminated significantly (P = 0.009) between survival. High pleural LDH (>1500 IU/L) predicts shorter survival (less than a year) in patients with adenocarcinoma lung presenting with MPE at the time of initial diagnosis. This marker may be clinically applied for selecting therapeutic modality directed at prevention of reaccumulation of MPE. Patients with low pleural LDH may be considered suitable for measures that provide more sustained effect on prevention of reaccumulation such as chemical pleurodesis or tunneled pleural catheter. PMID:27368006

  4. Serum YKL-40: a new independent prognostic marker for skeletal complications in patients with multiple myeloma.

    PubMed

    Mylin, Anne K; Abildgaard, Niels; Johansen, Julia S; Heickendorff, Lene; Kreiner, Svend; Waage, Anders; Turesson, Ingemar; Gimsing, Peter

    2015-01-01

    In a time of increasing treatment options for multiple myeloma bone disease, risk factors predicting progression need to be elucidated. This study investigated the value of serum YKL-40, previously shown to be associated with radiographic progression of bone destruction, as a predictor for time to clinical progression, i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with multiple myeloma receiving intravenous bisphosphonates. Serum concentrations of YKL-40 and biochemical bone markers (CTX-MMP, CTX-I, PINP) were measured at diagnosis. Patients were evaluated every third month for SRE and at 9 and 24 months for radiographic progression. Elevated serum YKL-40 was seen in 47% of patients and associated with high-risk disease (International Staging System stage III; p < 0.001), increased bone resorption (serum CTX/MMP; p < 0.001) and early radiographic progression at 9 months (p = 0.01). Serum YKL-40 together with serum CTX-MMP/PINP ratio and World Health Organization status were independent predictors of time to first SRE.

  5. The Expression and Prognostic Impact of CD95 Death Receptor and CD20, CD34 and CD44 Differentiation Markers in Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    M. Kamazani, Fatemeh; Bahoush-Mehdiabadi, Gholamreza; Aghaeipour, Mahnaz; Vaeli, Shahram; Amirghofran, Zahra

    2014-01-01

    Objective: This study investigated the expression and prognostic significance of the CD95 death receptor and CD20, a B cell-lineage associated marker, along with CD34 and CD44 non-lineage associated molecules in Iranian children with acute lymphoblastic leukemia (ALL). Methods: We performed immunophenotyping for expressions of the molecules in blood samples from children diagnosed with ALL by using a panel of monoclonal antibodies for flow cytometry analysis. The expression of markers was evaluated in relation to clinical and paraclinical features as well as response to treatment in the patients. Findings : CD95 showed a higher expression in T-ALL compared to B-ALL (P<0.001). Analysis of the clinical and laboratory findings at diagnosis in the group of B-ALL patients revealed an association between CD95 expression with lower white blood cell (WBC) numbers and bone marrow blasts (P<0.05). We detected a positive correlation between the expressions of CD95 and CD44 (r=0.445, P<0.01) in B-ALL patients. There was an association between CD20 expression and several poor prognostic factors that included increased extramedullary involvement (EMI) and decreased platelet numbers (P<0.008). The mean expression of CD34 in B-ALL was higher than T-ALL (P=0.004). At follow-up, complete remission duration (CRD) and survival duration did not significantly differ between patients who were positive or negative for each marker. Conclusion: Association of the studied molecules with several prognostic factors implies the significance of CD95 molecule as favorable and CD20 as unfavorable prognostic markers for childhood ALL. PMID:25755857

  6. Methylation of S100A8 is a promising diagnosis and prognostic marker in hepatocellular carcinoma

    PubMed Central

    Xiao, Feifan; Li, Yingfang; Zhang, Ruoheng; Dou, Dongwei; Liang, Jiezhen; Qin, Jian; Lin, Zhidi; Zhao, Dong; Jiang, Min; Liang, Zhenxin; Su, Jie; Gupta, Vanaparthy Pranay; He, Min; Yang, Xiaoli

    2016-01-01

    The abnormality of DNA methylation is one of the major epigenetic alterations in the human hepatocellular carcinoma (HCC). We have assessed the global genomic DNA methylation profiles in human HCC patients by using the Infinium Human Methylation27 BeadChip. A CpG loci of S100A8 was found to be significantly hypomethylated in HCC. Pooled meta-analysis of five validation public datasets demonstrated its methylation level was significantly lower for HCC compared to paired adjacent normal tissues. Quantitative pyrosequencing analysis also showed that the S100A8 methylation level was decreased in cancer tissues (31.90%±13.31%) than that in the paired adjacent normal tissues (65.33%±3.64%, p<0.01). The area under the ROC curve (AUC) value was 0.950 (p<0.01). Kaplan-Meier survival curves revealed that hypomethylation of S100A8 was associated with shortened overall survival (OS) and progression-free survival (PFS) (log rank p<0.05). Multivariate Cox proportional hazards model also indicated significantly shorter OS (HR, 1.709; 95 % CI, 1.127–2.591) and PFS (HR, 1.767; 95 % CI, 1.168–2.974) were observed in the low-methylation-level group compared to the high-methylation-level group. Furthermore, S100A8 overexpression in Huh7 and MHCC-97H hepatoma cell lines led to increased cell proliferation, migration, invasion, and tumor growth. These findings suggested S100A8 methylation to be served as potential diagnosis and prognosis marker for HCC. S100A8 also may play as a tumor promoter in HCC. PMID:27462864

  7. Prognostic value of depression, anxiety, and anger in hospitalized cardiovascular disease patients for predicting adverse cardiac outcomes.

    PubMed

    Nakamura, Shunichi; Kato, Koji; Yoshida, Asuka; Fukuma, Nagaharu; Okumura, Yasuyuki; Ito, Hiroto; Mizuno, Kyoichi

    2013-05-15

    Although attention has recently been focused on the role of psychosocial factors in patients with cardiovascular disease (CVD), the factors that have the greatest influence on prognosis have not yet been elucidated. The aim of this study was to evaluate the effects of depression, anxiety, and anger on the prognosis of patients with CVD. Four hundred fourteen consecutive patients hospitalized with CVD were prospectively enrolled. Depression was evaluated using the Patient Health Questionnaire, anxiety using the Generalized Anxiety Disorder Questionnaire, and anger using the Spielberger Trait Anger Scale. Cox proportional-hazards regression was used to examine the individual effects of depression, anxiety, and anger on a combined primary end point of cardiac death or cardiac hospitalization and on a combined secondary end point of all-cause death or hospitalization during follow-up (median 14.2 months). Multivariate analysis showed that depression was a significant risk factor for cardiovascular hospitalization or death after adjusting for cardiac risk factors and other psychosocial factors (hazard ratio 2.62, p = 0.02), whereas anxiety was not significantly associated with cardiovascular hospitalization or death after adjustment (hazard ratio 2.35, p = 0.10). Anger was associated with a low rate of cardiovascular hospitalization or death (hazard ratio 0.34, p <0.01). In conclusion, depression in hospitalized patients with CVD is a stronger independent risk factor for adverse cardiac events than either anxiety or anger. Anger may help prevent adverse outcomes. Routine screening for depression should therefore be performed in patients with CVD, and the potential effects of anger in clinical practice should be reconsidered.

  8. Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

    NASA Astrophysics Data System (ADS)

    Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

    2016-04-01

    Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

  9. Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients.

    PubMed

    Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai, Jr-Ming; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

    2016-04-14

    Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

  10. A study for proposal of use of regulatory T cells as a prognostic marker and establishing an optimal threshold level for their expression in chronic lymphocytic leukemia.

    PubMed

    Dasgupta, Alakananda; Mahapatra, Manoranjan; Saxena, Renu

    2015-06-01

    Although regulatory T cells (Tregs) have been extensively studied in chronic lymphocytic leukemia, there is no uniform guideline or consensus regarding their use as a prognostic marker. This study describes the methodology used to develop an optimal threshold level for Tregs in these patients. Treg levels were assessed in the peripheral blood of 130 patients and 150 controls. Treg frequencies were linked to established prognostic markers as well as overall survival and time to first treatment. The cut-offs for Treg positivity were assessed by receiver operating characteristic (ROC) analysis. A cut-off of 5.7% for Treg cell percentage and of 35 cells/μL for absolute Treg cell count were determined as optimal in patients with CLL along with a median Treg percentage of 15.5% used to separate patients with low- and high-risk disease. The experiments presented here will possibly aid in the use of Treg frequencies as a potential prognostic marker in CLL.

  11. Exploration and Validation of C-Reactive Protein/Albumin Ratio as a Novel Inflammation-Based Prognostic Marker in Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Yuan; Zhou, Guan-Qun; Liu, Xu; Chen, Lei; Li, Wen-Fei; Tang, Ling-Long; Liu, Qing; Sun, Ying; Ma, Jun

    2016-01-01

    Background: The prognostic value of C-reactive protein/albumin ratio (CRP/Alb), a novel inflammation-based marker, remains unknown in nasopharyngeal carcinoma (NPC). Methods: We conducted a retrospective review of 1572 consecutive patients with non-metastatic NPC. Patients were randomly divided into a training set (n = 514) and validation set (n = 1058). The prognostic value of the CRP/Alb ratio and the modified Glasgow prognostic score (mGPS; a well-recognized inflammation-based score) was assessed. Results: Receiver-operating characteristic analysis identified 0.05 as the optimal CRP/Alb cut-off value for disease failure in the training set. Patients with a CRP/Alb > 0.05 had poorer overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the training set (all P < 0.05). These results were confirmed in the validation set (all P < 0.05) and the whole cohort (all P < 0.001). In multivariate analysis of the entire cohort, the pretreatment CRP/Alb ratio was an independent prognostic factor for OS (HR, 1.394; 95% CI, 1.004-1.937; P = 0.048) and DMFS (HR, 1.545; 95% CI, 1.124-2.122; P = 0.007), but not for DFS (P = 0.083). The mGPS had no significant independent prognostic value for any end-point. Conclusion: CRP/Alb ratio is an useful prognostic indicator in patients with NPC, independent of disease stage. PMID:27471556

  12. MT-2 cell tropism as prognostic marker for disease progression in human immunodeficiency virus type 1 infection.

    PubMed Central

    Karlsson, A; Parsmyr, K; Sandström, E; Fenyö, E M; Albert, J

    1994-01-01

    The ability of human immunodeficiency virus type 1 (HIV-1) isolates to replicate in MT-2 cells was investigated as a prognostic marker for disease progression and CD4+ lymphocyte depletion in 53 HIV-1-infected, asymptomatic individuals. MT-2-negative viruses were isolated from 49% of the patients both early and late during the follow-up period; 38% converted from being MT-2 negative to MT-2 positive, while 11% were MT-2 positive throughout the study. One individual showed a fluctuating virus phenotype. The loss of CD4+ lymphocytes was significantly more rapid in MT-2-positive patients. We found a broad spectrum of CD4+ lymphocyte changes in patients whose virus changed its MT-2 tropism. Our data suggest that the changes could be divided into three general patterns. A stable or slowly decreasing CD4+ lymphocyte count changed into a more rapid fall in 44% of the patients, no significant change in rate of decline could be noted in 44% of the patients, while a stable CD4+ lymphocyte level after a change in MT-2 tropism was noted in 12% of the patients. A correlation between MT-2 tropism and clinical symptoms was also noted. Half of the patients with MT-2-negative virus throughout the study were still asymptomatic after a mean follow-up time of 80 months, while only 15% of those who converted remained asymptomatic. All patients with MT-2-positive viruses at the time of inclusion in the study developed HIV-1-related symptoms, and half of them died during the study. The MT-2 status of 16 patients, could be determined at the time of AIDS diagnosis; 50% were Mt-2 positive, while 50% were MT-2 negative. No difference in AIDS-defining diagnoses or CD4+ lymphocyte counts at the time of diagnosis was noted. Knowledge of the HIV-1 phenotype may improve the early recognition of progressive disease. PMID:7908672

  13. The expressions of MIF and CXCR4 protein in tumor microenvironment are adverse prognostic factors in patients with esophageal squamous cell carcinoma

    PubMed Central

    2013-01-01

    Background Tumor-derived cytokines and their receptors usually take important roles in the disease progression and prognosis of cancer patients. In this survey, we aimed to detect the expression levels of MIF and CXCR4 in different cell populations of tumor microenvironments and their association with survivals of patients with esophageal squamous cell carcinoma (ESCC). Methods MIF and CXCR4 levels were measured by immunochemistry in tumor specimens from 136 resected ESCC. Correlation analyses and independent prognostic outcomes were determined using Pearson’s chi-square test and Cox regression analysis. Results The expression of CXCR4 in tumor cells was positively associated with tumor status (P = 0.045) and clinical stage (P = 0.044); whereas the expression of CXCR4 in tumor-infiltrating lymphocytes (TILs) and the expression of MIF in tumor cells and in TILs were not associated with clinical parameters of ESCC patients. High MIF expression in tumor cells or in TILs or high CXCR4 expression in tumor cells was significantly related to poor survival of ESCC patients (P < 0.05). Multivariate analysis showed that the expression of MIF or CXCR4 in tumor cells and the expression of MIF in TILs were adverse independent factors for disease-free survival (DFS) and overall survival (OS) in the whole cohort of patients (P < 0.05). Furthermore, the expression of MIF and CXCR4 in tumor cells were independent factors for reduced DFS and OS in metastatic/recurrent ESCC patients (P < 0.05). Interestingly, the expressions of MIF and CXCR4 in tumor cells and in TILs were significantly positively correlated (P < 0.05), and the combined MIF and CXCR4 expression in tumor cells was an independent adverse predictive factor for DFS and OS (P < 0.05). Conclusion The expressions of MIF and CXCR4 proteins in tumor cells and TILs have different clinically predictive values in ESCC. PMID:23497377

  14. Wisteria floribunda Agglutinin and Its Reactive-Glycan-Carrying Prostate-Specific Antigen as a Novel Diagnostic and Prognostic Marker of Prostate Cancer

    PubMed Central

    Hagiwara, Kazuhisa; Tobisawa, Yuki; Kaya, Takatoshi; Kaneko, Tomonori; Hatakeyama, Shingo; Mori, Kazuyuki; Hashimoto, Yasuhiro; Koie, Takuya; Suda, Yoshihiko; Ohyama, Chikara; Yoneyama, Tohru

    2017-01-01

    Wisteria floribunda agglutinin (WFA) preferably binds to LacdiNAc glycans, and its reactivity is associated with tumor progression. The aim of this study to examine whether the serum LacdiNAc carrying prostate-specific antigen–glycosylation isomer (PSA-Gi) and WFA-reactivity of tumor tissue can be applied as a diagnostic and prognostic marker of prostate cancer (PCa). Between 2007 and 2016, serum PSA-Gi levels before prostate biopsy (Pbx) were measured in 184 biopsy-proven benign prostatic hyperplasia patients and 244 PCa patients using an automated lectin-antibody immunoassay. WFA-reactivity on tumor was analyzed in 260 radical prostatectomy (RP) patients. Diagnostic and prognostic performance of serum PSA-Gi was evaluated using area under the receiver-operator characteristic curve (AUC). Prognostic performance of WFA-reactivity on tumor was evaluated via Cox proportional hazards regression analysis and nomogram. The AUC of serum PSA-Gi detecting PCa and predicting Pbx Grade Group (GG) 3 and GG ≥ 3 after RP was much higher than those of conventional PSA. Multivariate analysis showed that WFA-reactivity on prostate tumor was an independent risk factor of PSA recurrence. The nomogram was a strong model for predicting PSA-free survival provability with a c-index ≥0.7. Serum PSA-Gi levels and WFA-reactivity on prostate tumor may be a novel diagnostic and pre- and post-operative prognostic biomarkers of PCa, respectively. PMID:28134773

  15. Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy

    PubMed Central

    Nieder, Carsten; Dalhaug, Astrid; Haukland, Ellinor; Mannsaker, Bard; Pawinski, Adam

    2017-01-01

    Background The aim of the study was to explore the prognostic impact of different abnormal blood tests and the tumor marker CA 15-3 as well as established parameters such as disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in addition to contemporary systemic treatment. Methods This was a retrospective uni- and multivariate analysis of 118 female patients treated in the time period from 2007 to 2014 (median follow-up 28 months). Results The median age was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was 7 months). Only 16% of patients had normal serum CA 15-3. HER2 receptor status correlated with CA 15-3. The median survival was 17.6 months (lowest CA 15-3 quartile), 14.7 months (intermediate), and 6.9 months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive protein, and anemia with need for blood transfusion (all P < 0.05) rather than CA 15-3. Conclusions Survival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate prognostic model. PMID:28179964

  16. Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR.

    PubMed

    Poremba, Christopher; Heine, Bernhard; Diallo, Raihanatou; Heinecke, Achim; Wai, Daniel; Schaefer, Karl-Ludwig; Braun, Yvonne; Schuck, Andreas; Lanvers, Claudia; Bànkfalvi, Agnes; Kneif, Sören; Torhorst, Joachim; Zuber, Markus; Köchli, Ossi R; Mross, Frank; Dieterich, Holger; Sauter, Guido; Stein, Harald; Fogt, Franz; Boecker, Werner

    2002-10-01

    Telomerase activity (TA) has been shown to correlate with poor clinical outcome in various tumour entities, indicating that tumours expressing this enzyme may be more aggressive and that TA may be a useful prognostic marker. For breast cancer, however, TA is a controversial prognostic marker; whereas some studies suggest an association between TA and disease outcome, others do not find this association. This study used tissue microarrays (breast carcinoma prognosis arrays) containing 611 samples (each 0.6 mm in diameter) from the tumour centre of paraffin-embedded breast carcinomas to analyse the catalytic subunit of telomerase, human telomerase reverse-transcriptase (hTERT), and the internal RNA component (hTR), which are the core components of the telomerase holoenzyme complex. hTERT protein expression was obtained by immunohistochemistry (human anti-telomerase antibody Ab-2, Calbiochem), and hTR RNA was measured by radioactive in situ hybridization. hTERT and hTR expression were determined semi-quantitatively and graded (scores 1-4). Clinical data, such as histological subtype, pT stage, tumour diameter, pN stage, BRE grade, tumour-specific survival (in months), patient's age and others, were available for statistical analysis. A statistically significant correlation was found between tumour-specific survival (overall survival) and hTERT expression (p < 0.0001) or hTR expression (p = 0.00110). Tumours with higher scores (scores 3, 4) for hTR and/or hTERT were associated with a worse prognosis. In multivariate analysis, hTERT expression was an independent prognostic factor. Previous studies, focusing on analysis of TA in smaller numbers of fresh-frozen breast carcinomas by the TRAP assay, gave controversial results with respect to TA as a prognostic marker. Using tissue microarrays from 611 breast carcinomas, this study has demonstrated that increased expression levels of the telomerase core components, hTERT and hTR, are associated with lower overall survival

  17. Greater Age-Related Decline in Markers of Physical, Mental and Cognitive Health among Israeli Older Adults Exposed to Lifetime Cumulative Adversity

    PubMed Central

    Shrira, Amit

    2013-01-01

    Objectives This longitudinal investigation addressed whether and how lifetime cumulative adversity and depressive symptoms moderated age-related decline in markers of physical, mental and cognitive health. Method 1,248 older adults (mean age = 62 at Wave 1) who completed the first two waves of the Israeli component of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel) reported on exposure to potentially traumatic life events, depressive symptoms, and three outcomes – disability, quality of life and cognitive markers. Results Age was related to greater functional decline in outcome measures across the two waves (i.e., increase in disability and decrease in quality of life and cognitive functioning). This age-related decline became stronger as lifetime adversity increased. A three-way interaction showed that the greatest age-related functional decline in outcome measures was especially salient among those with high level of lifetime adversity and high level of depressive symptoms. Conclusion Lifetime cumulative adversity is associated with a more noticeable process of age-related dysfunction across various markers of health. Although the majority of older adults are resilient to lifetime adversity, prevention and intervention programs should be aimed at mitigating the pronounced senescence observed when adversity accumulated to a large degree, and especially when it is accompanied with high level of distress. PMID:24328416

  18. t-10, c-12 CLA dietary supplementation inhibits atherosclerotic lesion development despite adverse cardiovascular and hepatic metabolic marker profiles.

    PubMed

    Mitchell, Patricia L; Karakach, Tobias K; Currie, Deborah L; McLeod, Roger S

    2012-01-01

    Animal and human studies have indicated that fatty acids such as the conjugated linoleic acids (CLA) found in milk could potentially alter the risk of developing metabolic disorders including diabetes and cardiovascular disease (CVD). Using susceptible rodent models (apoE(-/-) and LDLr(-/-) mice) we investigated the interrelationship between mouse strain, dietary conjugated linoleic acids and metabolic markers of CVD. Despite an adverse metabolic risk profile, atherosclerosis (measured directly by lesion area), was significantly reduced with t-10, c-12 CLA and mixed isomer CLA (Mix) supplementation in both apoE(-/-) (p<0.05, n = 11) and LDLr(-/-) mice (p<0.01, n = 10). Principal component analysis was utilized to delineate the influence of multiple plasma and tissue metabolites on the development of atherosclerosis. Group clustering by dietary supplementation was evident, with the t-10, c-12 CLA supplemented animals having distinct patterns, suggestive of hepatic insulin resistance, regardless of mouse strain. The effect of CLA supplementation on hepatic lipid and fatty acid composition was explored in the LDLr(-/-) strain. Dietary supplementation with t-10, c-12 CLA significantly increased liver weight (p<0.05, n = 10), triglyceride (p<0.01, n = 10) and cholesterol ester content (p<0.01, n = 10). Furthermore, t-10, c-12 CLA also increased the ratio of 18∶1 to 18∶0 fatty acid in the liver suggesting an increase in the activity of stearoyl-CoA desaturase. Changes in plasma adiponectin and liver weight with t-10, c-12 CLA supplementation were evident within 3 weeks of initiation of the diet. These observations provide evidence that the individual CLA isomers have divergent mechanisms of action and that t-10, c-12 CLA rapidly changes plasma and liver markers of metabolic syndrome, despite evidence of reduction in atherosclerosis.

  19. Topoisomerase II alpha: prognostic predictor and cell cycle marker in surface epithelial neoplasms of the ovary and peritoneum.

    PubMed

    Costa, M J; Hansen, C L; Holden, J A; Guinee, D

    2000-07-01

    Immunohistochemistry for Topoisomerase II alpha (TopoIIa), a nuclear protein important for the separation of chromosomes and deoxyribonucleic acid replication, provides insight into the molecular events in the cell cycle and the response to chemotherapeutic agents, which target TopoIIa. We test the hypothesis that the percentage of TopoIIa immunoreactive nuclei (TopoIIaI) aids in the treatment and prognostic evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs) and correlates with established cell cycle control markers: p53, p21WAF1/CIP1 (p21), and Ki67. Paraffin sections from a retrospective surgical series of 108 SENs were immunostained with anti-TopoIIa, anti-p53, anti-p21, and anti-Ki67. The TopoIIaI, the Ki67 proliferation index (Ki67PI), and the immunoreactivity score for p53 and p21 (IMS: S1, S2, S3 < 10%, 10 to 50%, > 50% of strong staining cells, respectively) were evaluated manually. TopoIIaI and Ki67PI ranged from 5 to 84% and 4 to 88% (mean/median: 31/30 and 44/46%), respectively, and were correlated (coefficient 0.62, p < 10(-11)). IMS of 108 SENs was as follows: p53 50% + (2S1, 52S3) and p21 66% + (38S1, 12S2, 21S3). The TopoIIaI associated directly with p53 (p < 10(-5) and inversely with p21 (p < 0.005) IMS. TopoIIaI correlated with SEN architectural/nuclear grade (p < 10(-5)/10(-7)), but not histologic type. Sixty-seven patients had disease at last follow-up, 55 were dead from disease at 2 to 67 months (mean/median 24/21), and 14 were alive with disease at 31 to 230 months (mean/median 73/59). Forty-one patients were disease free at 5 to 228 months (mean/median 75/54). TopoIIaI correlated with presence of disease (p < 0.01) and poor survival (p < 1 x 10(-9), even when only 93 invasive SEN cases are considered (p < 0.005). TopoIIaI correlates with poor prognosis and other cell cycle control markers. The patients in this retrospective series of SEN were treated primarily with platinum-based chemotherapy. These data may

  20. Upregulation of Trefoil Factor 3 (TFF3) After Rectal Cancer Chemoradiotherapy Is an Adverse Prognostic Factor and a Potential Therapeutic Target

    SciTech Connect

    Casado, Enrique; Moreno Garcia, Victor; Sanchez, Jose Javier; Gomez del Pulgar, Maria Teresa; Feliu, Jaime; Maurel, Joan; Castelo, Beatriz; Moreno Rubio, Juan; Lopez, Rocio A.B.; Garcia-Cabezas, Miguel Angel; Burgos, Emilio; and others

    2012-12-01

    Purpose: Management of locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiotherapy (CRT) with fluoropyrimidines, followed by total mesorectal excision. We sought to evaluate the expression of selected genes, some of which were derived from a previous undirected SAGE (serial analysis of gene expression)-based approach, before and after CRT, to identify mechanisms of resistance. Methods: This retrospective cohort study included 129 consecutive patients. Quantitative polymerase chain reaction of 53 candidate genes was performed on the biopsy specimen before treatment and on the surgical specimen after CRT. A paired-samples t test was performed to determine genes that were significantly changed after CRT. The result was correlated with patients' disease-free survival. Results: Twenty-two genes were significantly upregulated, and two were significantly downregulated. Several of the upregulated genes have roles in cell cycle control; these include CCNB1IP1, RCC1, EEF2, CDKN1, TFF3, and BCL2. The upregulation of TFF3 was associated with worse disease-free survival on multivariate analyses (hazard ratio, 2.64; P=.027). Patients whose surgical specimens immunohistochemically showed secretion of TFF3 into the lumen of the tumoral microglands had a higher risk of relapse (hazard ratio, 2.51; P=.014). In vitro experiments showed that DLD-1 cells stably transfected with TFF3 were significantly less sensitive to 5-fluorouracil and showed upregulation of genes involved in the transcriptional machinery and in resistance to apoptosis. Conclusion: Upregulation of TFF3 after CRT for RC is associated with a higher risk of relapse. The physiological role of TFF3 in restoring the mucosa during CRT could be interfering with treatment efficacy. Our results could reveal not only a novel RC prognostic marker but also a therapeutic target.

  1. Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas.

    PubMed

    Tsuyama, Naoko; Ennishi, Daisuke; Yokoyama, Masahiro; Baba, Satoko; Asaka, Reimi; Mishima, Yuko; Terui, Yasuhito; Hatake, Kiyohiko; Takeuchi, Kengo

    2017-03-23

    Expression of T-cell markers, generally investigated for immunophenotyping of T-cell lymphomas, is also observed in several types of B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We previously reported that CD5 expression in DLBCL is an inferior prognostic factor in the era of rituximab. However, data regarding the frequencies, histological relevance, and prognostic importance of T-cell markers other than CD5 are currently unavailable. In the present study, we comprehensively evaluated the expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) in 501 B-cell lymphomas, including 225 DLBCLs, by flow cytometry and subsequent immunohistochemistry. T-cell markers other than CD5, such as CD2, CD4, CD7, and CD8, were expressed in 27 (5%) patients, and notably, all of these cases were classified as large B-cell lymphoma subtypes: 25 DLBCLs and 2 intravascular large B-cell lymphomas. CD5 and other T-cell markers were expressed in 15% (31/225) and 10% (25/225) of DLBCL cases, respectively. Five of them co-expressed CD5 and other T-cell markers. Retrospectively analyzing the prognostic relevance of T-cell markers in 169 patients with primary DLBCL treated with rituximab-based chemotherapy, we showed that only CD5 was a strong predictor of poor survival. This study provides information about the occurrence of T-cell markers other than CD5 in B-cell lymphomas, their frequent histological subtypes, and their prognostic significance in DLBCL. CD5 was reconfirmed as a negative prognostic marker in DLBCL patients receiving rituximab-inclusive chemotherapy, whereas T-cell markers other than CD5 were found to have no impact on clinicopathological and survival analyses.

  2. Isolated tumor cells are frequently detectable in the peritoneal cavity of gastric and colorectal cancer patients and serve as a new prognostic marker.

    PubMed Central

    Schott, A; Vogel, I; Krueger, U; Kalthoff, H; Schreiber, H W; Schmiegel, W; Henne-Bruns, D; Kremer, B; Juhl, H

    1998-01-01

    OBJECTIVE: To evaluate the prognostic significance of isolated tumor cells detected by a panel of various monoclonal antibodies. SUMMARY BACKGROUND DATA: Previously, we showed by using immunocytology that cancer cells are frequently found in bone marrow and peritoneal cavity samples of gastrointestinal cancer patients. METHODS: Findings in bone marrow and peritoneal cavity samples were compared and correlated with the 4-year survival rate of 84 gastric and 109 colorectal patients with cancer. RESULTS: Although positive results in the bone marrow showed little prognostic significance, the peritoneal cavity results correlated with the 4-year survival rate (gastric cancer: p = 0.0038; colorectal cancer: p = 0.0079). Additionally, in subgroups of patients with early (gastric cancer: p = 0.02, colorectal cancer: p = 0.48) and advanced (gastric cancer: p = 0.02, colorectal cancer: p < 0.0001) tumor stages, a correlation of immunocytologic findings and the survival rate was seen. CONCLUSIONS: The detection of minimal residual disease in the peritoneal cavity serves as a new prognostic marker. Images Figure 5. PMID:9527060

  3. p16 expression as a prognostic and predictive marker in high-grade localized osteosarcoma of the extremities: an analysis of 357 cases.

    PubMed

    Righi, Alberto; Gambarotti, Marco; Sbaraglia, Marta; Sisto, Andrea; Ferrari, Stefano; Dei Tos, Angelo P; Picci, Piero

    2016-12-01

    The potential prognostic and predictive value of p16 in high-grade localized osteosarcoma of the extremities has been recently investigated in small series of cases, and the results from different studies were somewhat controversial. A retrospective immunohistochemical analysis of p16 expression was performed in a series of 357 patients, included in different neoadjuvant chemotherapy protocols from 1986 to 2010, to explore its potential prognostic and predictive value. Immunohistochemistry was performed with a commercially available p16 monoclonal mouse antibody. Follow-up data were available in all cases with a median of 120 months. Positivity for p16 was detected in 70.6% (252/357) of cases. The p16 expression did not differ by age, sex, tumor site, histologic subtype, tumor volume, surgical margin, serum alkaline phosphatase levels, and lactate dehydrogenase levels. In the different chemotherapy protocols included, the incidence of p16 expression was similar. The absence of p16 expression was significantly associated with an adverse disease-free survival (P=.04) and overall survival (P=.05) when compared with the presence of p16 expression. At the multivariate Cox regression analysis, p16 expression lost its prognostic significance. Multivariate logistic regression analysis showed that as p16 expression was the only statistically significant parameter to predict the pathological response to neoadjuvant chemotherapy treatment with an odds ratio of 3.025 (P<.001) for "good" chemotherapy response. Our data indicate that the negative expression of p16 is associated with a reduced rate of good response to primary chemotherapy and to a worse probability of survival, although it was not confirmed as an independent prognostic biomarker after multivariate analysis.

  4. Macrophage migration inhibitory factor and stearoyl-CoA desaturase 1: potential prognostic markers for soft tissue sarcomas based on bioinformatics analyses.

    PubMed

    Takahashi, Hiro; Nakayama, Robert; Hayashi, Shuhei; Nemoto, Takeshi; Murase, Yasuyuki; Nomura, Koji; Takahashi, Teruyoshi; Kubo, Kenji; Marui, Shigetaka; Yasuhara, Koji; Nakamura, Tetsuro; Sueo, Takuya; Takahashi, Anna; Tsutsumiuchi, Kaname; Ohta, Tsutomu; Kawai, Akira; Sugita, Shintaro; Yamamoto, Shinjiro; Kobayashi, Takeshi; Honda, Hiroyuki; Yoshida, Teruhiko; Hasegawa, Tadashi

    2013-01-01

    The diagnosis and treatment of soft tissue sarcomas (STSs) has been particularly difficult, because STSs are a group of highly heterogeneous tumors in terms of histopathology, histological grade, and primary site. Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis, treatment selection, and investigation of therapeutic targets. We had previously developed a novel bioinformatics method for marker gene selection and applied this method to gene expression data from STS patients. This previous analysis revealed that the extracted gene combination of macrophage migration inhibitory factor (MIF) and stearoyl-CoA desaturase 1 (SCD1) is an effective diagnostic marker to discriminate between subtypes of STSs with highly different outcomes. In the present study, we hypothesize that the combination of MIF and SCD1 is also a prognostic marker for the overall outcome of STSs. To prove this hypothesis, we first analyzed microarray data from 88 STS patients and their outcomes. Our results show that the survival rates for MIF- and SCD1-positive groups were lower than those for negative groups, and the p values of the log-rank test are 0.0146 and 0.00606, respectively. In addition, survival rates are more significantly different (p = 0.000116) between groups that are double-positive and double-negative for MIF and SCD1. Furthermore, in vitro cell growth inhibition experiments by MIF and SCD1 inhibitors support the hypothesis. These results suggest that the gene set is useful as a prognostic marker associated with tumor progression.

  5. Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence

    PubMed Central

    Squillaro, Tiziana; Pistilli, Barbara; Marcellusi, Andrea; Mariani, Paola; Santinelli, Alfredo; Latini, Luciano; Galderisi, Umberto; Giordano, Antonio

    2014-01-01

    The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features. PMID:25127259

  6. Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence.

    PubMed

    Finicelli, Mauro; Benedetti, Giovanni; Squillaro, Tiziana; Pistilli, Barbara; Marcellusi, Andrea; Mariani, Paola; Santinelli, Alfredo; Latini, Luciano; Galderisi, Umberto; Giordano, Antonio

    2014-10-30

    The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk-patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT-PCR were analyzed and any correlation between their expression and the BC clinic-pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features.

  7. CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

    PubMed Central

    Palmi, Chiara; Savino, Angela M.; Silvestri, Daniela; Bronzini, Ilaria; Cario, Gunnar; Paganin, Maddalena; Buldini, Barbara; Galbiati, Marta; Muckenthaler, Martina U.; Bugarin, Cristina; Mina, Pamela Della; Nagel, Stefan; Barisone, Elena; Casale, Fiorina; Locatelli, Franco; Nigro, Luca Lo; Micalizzi, Concetta; Parasole, Rosanna; Pession, Andrea; Putti, Maria C.; Santoro, Nicola; Testi, Anna M.; Ziino, Ottavio; Kulozik, Andreas E.; Zimmermann, Martin; Schrappe, Martin; Villa, Antonello; Gaipa, Giuseppe; Basso, Giuseppe; Biondi, Andrea; Valsecchi, Maria G.; Stanulla, Martin; Conter, Valentino; te Kronnie, Geertruy; Cazzaniga, Giovanni

    2016-01-01

    Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway. PMID:27449287

  8. Aerobic exercise effect on prognostic markers for systolic heart failure patients: a systematic review and meta-analysis.

    PubMed

    Cipriano, Gerson; Cipriano, Vivian T F; da Silva, Vinicius Z Maldaner; Cipriano, Graziella F B; Chiappa, Gaspar R; de Lima, Alexandra C G B; Cahalin, Lawrence P; Arena, Ross

    2014-09-01

    From previous systematic reviews and meta-analyses, there is consensus about the positive effect of exercise training on exercise capacity for systolic heart failure (HF); however, the effect on actual prognostic markers such as NTproBNP and minute ventilation/carbon dioxide production (VE/VCO2) slope has not been evaluated. The primary aim of the proposed study is to determine the effect of aerobic exercise training (AEX) on the VE/VCO2 slope and NTproBNP. The following databases (up to February 30, 2013) were searched with no language limitations: CENTRAL (The Cochrane Library 2013, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), and Physiotherapy Evidence Database (PEDro) (from January 1929). We screened reference lists of articles and also conducted an extensive hand search of the literature. Randomized controlled trials of exercise-based interventions with 2-month follow-up or longer compared to usual medical care or placebo were included. The study population comprised adults aged between 18 and 65 years, with evidence of chronic systolic heart failure (LVEF < 45 % and baseline NTproBNP > 300 pg/ml). Two review authors independently extracted data on study design, participants, interventions, and outcomes. We assessed the risk of bias using PEDro scale. We calculated mean differences (MD) or standardized mean differences between intervention and control groups for outcomes with sufficient data; for other outcomes, we described findings from individual studies. Eight studies involving a total of 408 participants met the inclusion criteria across the NTproBNP (5 studies with 191 patients) and VE/VCO2 slope (4 studies with 217 patients). Aerobic exercise significantly improved NTproBNP by a MD of -817.75 [95 % confidence interval (CI) -929.31 to -706.19]. Mean differences across VE/VCO2 slope were -6.55 (95 % CI -7.24 to -5.87). Those patients' characteristics and exercise were similar (frequency = 3-5 times/week; duration = 20

  9. Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

    PubMed Central

    Viale, G.; Giobbie-Hurder, A.; Gusterson, B. A.; Maiorano, E.; Mastropasqua, M. G.; Sonzogni, A.; Mallon, E.; Colleoni, M.; Castiglione-Gertsch, M.; Regan, M. M.; Brown, R. W.; Golouh, R.; Crivellari, D.; Karlsson, P.; Öhlschlegel, C.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2010-01-01

    Background: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methods: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). Results: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. Conclusion: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy. PMID:19633051

  10. microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma

    PubMed Central

    Zhao, Jian-Jun; Lin, Jianhong; Lwin, Tint; Yang, Hua; Guo, Jianping; Kong, William; Dessureault, Sophie; Moscinski, Lynn C.; Rezania, Dorna; Dalton, William S.; Sotomayor, Eduardo

    2010-01-01

    Mantle cell lymphoma (MCL) is one of the most aggressive B-cell lymphomas. Although several protein-coding genes are altered, expression signature and importance of microRNA (miRNA) have not been well documented in this malignancy. Here, we performed miRNA expression profile in 30 patients with MCL using a platform containing 515 human miRNAs. Eighteen miRNAs were down-regulated and 21 were up-regulated in MCL compared with normal B lymphocytes. The most frequently altered miRNAs are decrease of miR-29a/b/c, miR-142-3p/5p, and miR-150 and increase of miR-124a and miR-155. Notably, expression levels of miR-29 family are associated with prognosis. The patients with significant down-regulated miR-29 had short survival compared with those who express relatively high levels of miR-29. The prognostic value of miR-29 is comparable with the Mantle Cell Lymphoma International Prognostic Index. Furthermore, we demonstrate miR-29 inhibition of CDK6 protein and mRNA levels by direct binding to 3′-untranslated region. Inverse correlation between miR-29 and CDK6 was observed in MCL. Because cyclin D1 overexpression is a primary event and exerts its function through activation of CDK4/CDK6, our results in primary MCL cells indicate that down-regulation of miR-29 could cooperate with cyclin D1 in MCL pathogenesis. Thus, our findings provide not only miRNA expression signature but also a novel prognostic marker and pathogenetic factor for this malignancy. PMID:20086245

  11. Human Epidermal Growth Factor Receptor-3 mRNA Expression as a Prognostic Marker for Invasive Duct Carcinoma not Otherwise Specified

    PubMed Central

    Hammoda, Ghada Ezat; El-Hefnawy, Sally Mohammed; Abdallah, Rania Abdallah

    2017-01-01

    Introduction Breast cancer is the most common cancer in women and the Erythroblastosis Oncogene B(ErbB) receptor family holds crucial role in its pathogenesis. Human Epidermal Growth Factor Receptor 3 (HER-3) gene over expression in breast tissue has been associated with aggressive clinical behaviour and bad prognosis. Aim To evaluate HER-3 mRNA expression level as a prognostic marker for breast cancer and to correlate its level with other established prognostic parameters. Materials and Methods This study was carried out on specimens of 100 cases that were divided into 40 patients presented with fibroadenoma and 60 patients presented with Invasive Ductal Carcinoma (IDC) not otherwise specified and underwent modified radical mastectomy. All specimens were investigated for HER-2/neu, ER and PR expression by Immunohistochemistry (IHC) and quantitative assay of HER-3 mRNA expression using real time PCR technique. Results There was a significant high HER3 mRNA level in carcinoma cases compared to fibroadenoma. In malignant cases, HER3 mRNA level was significantly associated with advanced T stage, advanced N stage, number of positive lymph nodes, large tumour size and cases associated with an adjacent in situ component. Moreover, HER-3 mRNA level was of highest values in Her-2/neu positive group followed by triple negative cases with the lowest level in luminal group (p<0.05). Conclusion HER-3 gene is upregulated in IDC especially those carrying poor prognostic features. HER-3 mRNA level may identify a subset of patients with a poor prognosis, and who could undergo further evaluation for the efficacy of HER3 targeted anticancer therapy. PMID:28384967

  12. Frequency and pattern of expression of the stem cell marker CD133 have strong prognostic effect on the surgical outcome of colorectal cancer patients.

    PubMed

    Takahashi, Shusaku; Kamiyama, Toshiya; Tomaru, Utano; Ishizu, Akihiro; Shida, Toshiyuki; Osaka, Mineji; Sato, Yutaka; Saji, Yutaka; Ozaki, Michitaka; Todo, Satoru

    2010-11-01

    CD133 has been reported to be a cancer stem cell marker in colorectal cancer (CRC). The aim of this study was to examine the frequency and pattern of CD133 expression by immunohistochemical methods and evaluate their correlation with clinicopathological features, including patient survival (PS) and recurrence. Tissue specimens of 151 CRC patients who underwent surgical treatment for well-differentiated/moderately differentiated adenocarcinoma and stage I-IV tumors (TNM classification) were immunostained for analyzing CD133 expression. The frequency of CD133 expression was 91.4% (138/151), and the pattern of expression was divided into membranous and cytoplasmic expression. Of the 151 patients, 136 (90.1%) showed membranous expression, whereas 44 (29.1%) showed cytoplasmic expression. Both expression patterns were seen in 42 (27.8%) patients. The frequency of CD133 overexpression (>50% of stained cells) was 27.2% (41/151); univariate analysis showed CD133 overexpression to be significantly associated with PS, but not recurrence, and multivariate analysis indicated it to be an independent prognostic factor. Multivariate analysis showed membranous overexpression (>50% of stained tumor cells on the membrane), which significantly correlated with histology and chemoresistance of recurrent and stage IV tumors, to be an independent prognostic factor for PS and recurrence. However, multivariate analysis did not indicate cytoplasmic expression, which significantly correlated with histology, lymph node metastasis, TNM stage and lymphatic invasion, as an independent prognostic factor for PS and recurrence. Our results demonstrated that evaluation of the frequency and pattern of CD133 expression is useful for predicting prognosis, recurrence, and chemosensitivity in CRC patients.

  13. Circulating plasma cells in newly diagnosed symptomatic multiple myeloma as a possible prognostic marker for patients with standard-risk cytogenetics.

    PubMed

    Vagnoni, Davide; Travaglini, Fosco; Pezzoni, Valerio; Ruggieri, Miriana; Bigazzi, Catia; Dalsass, Alessia; Mestichelli, Francesca; Troiani, Emanuela; Falcioni, Sadia; Mazzotta, Serena; Natale, Annalisa; Angelini, Mario; Ferretti, Silvia; Angelini, Stefano; Galieni, Piero

    2015-08-01

    Detection of circulating plasma cells (PCs) in multiple myeloma (MM) patients is a well-known prognostic factor. We evaluated circulating PCs by flow cytometry (FC) in 104 patients with active MM at diagnosis by gating on CD38(+)  CD45(-) cells and examined their relationship with cytogenetic risk. Patients had an average follow-up of 36 months. By using a receiver operating characteristics analysis, we estimated the optimal cut-off of circulating PCs for defining poor prognosis to be 41. Patients with high-risk cytogenetics (n = 24) had poor prognosis, independently of circulating PC levels [PC < 41 vs. PC ≥ 41: overall survival (OS) = 0% vs. OS = 17%, P = not significant (n.s.); progression-free survival (PFS) = 0% vs. 17%, P = n.s.]. Patients with standard-risk cytogenetics (n = 65) showed a better prognosis when associated with a lower number of circulating PCs (PC < 41 vs. PC ≥ 41: OS = 62% vs. 24%, P = 0·008; PFS = 48% vs. 21%, P = 0·001). Multivariate analysis on the subgroup with standard-risk cytogenetics confirmed that the co-presence of circulating PCs ≥ 41, older age, Durie-Salmon stage >I and lack of maintenance adversely affected PFS, while OS was adversely affected only by lactate dehydrogenase, older age and lack of maintenance. Our results indicate that the quantification of circulating PCs by a simple two-colour FC analysis can provide useful prognostic information in newly diagnosed MM patients with standard-risk cytogenetics.

  14. The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers.

    PubMed

    Jiao, Qingli; Wu, Aiguo; Shao, Guoli; Peng, Haoyu; Wang, Mengchuan; Ji, Shufeng; Liu, Peng; Zhang, Jian

    2014-09-01

    Triple negative breast cancer (TNBC) is one type of breast cancer (BC), which is defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her2). Its origins and development seem to be elusive. And for now, drugs like tamoxifen or trastuzumab which specifically apply to ER, PR or Her2 positive BC seem unforeseeable in TNBC clinical treatment. Due to its extreme malignancy, high recurrence rate and poor prognosis, a lot of work on the research of TNBC is needed. This review aims to summarize the latest findings in TNBC in risk factors, possible therapeutic targets and possible prognostic makers.

  15. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  16. Prognostic value of changes in the expression of stem cell markers in the peripheral blood of patients with colon cancer.

    PubMed

    Padín-Iruegas, Maria-Elena; Herranz-Carnero, Michel; Aguin-Losada, Santiago; Brozos-Vazquez, Elena; Anido-Herranz, U; Antunez-Lopez, Jose-Ramon; Ruibal-Morell, Alvaro; López-López, Rafael

    2013-06-01

    Cancer stem cells play an important role in carcinogenesis and resistance to treatment and may lead to metastasis. The isolation of circulating stem cells involves cell sorting based on the presence of cell surface markers. Many surface markers such as CD133, c-Kit, SOX, OCT4 and TWIST have been reported. In the present study, we determined the expression of different stem cell markers and their variation in expression at different stages of the treatment process. Samples of EDTA blood were collected from metastatic colorectal cancer patients, and circulating cancer stem cells were isolated for the analysis of the expression of stem cell markers using RT-PCR. These findings were correlated with the response to therapy. All statistical analyses were performed using the GraphPad Prism 5.03 software. Significant differences were found in the expression levels of the markers CD133, SOX2, OCT4 and TWIST1. No differences were found in c-Kit expression. Correlation in the expression levels of most of the markers was observed. Expression of CD133, OCT4, SOX2 and TWIST1 had a predictive value for colon cancer behavior. Evaluation of this stem cell gene expression panel may be useful for predicting the response during the process of treatment, and the relative easy access to samples facilitates this method. Moreover the correlation between CD133 and TWIST1 expression may be associated with tumor regrowth and metastatic relapse.

  17. Prognostic value of inflammation-based markers in patients with recurrent malignant obstructive jaundice treated by reimplantation of biliary metal stents

    PubMed Central

    Jin, Hao; Pang, Qing; Liu, Huichun; Li, Zongkuang; Wang, Yong; Lu, Yimin; Zhou, Lei; Pan, Hongtao; Huang, Wei

    2017-01-01

    Abstract We aimed to assess the therapeutic effect of reimplantation of biliary metal stents by percutaneous transhepatic cholangial drainage (PTCD) in patients with recurrent malignant obstructive jaundice (MOJ). Furthermore, we explored the prognostic value of inflammation-based markers in these patients. We reviewed 33 cases of recurrent MOJ after implantation of biliary metal stents by PTCD, all of which underwent reimplantation of stents under digital subtraction angiography guidance. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin were compared between before and after reimplantation (1 week, 1 month, and 3 months postoperatively). Preoperative clinical data were collected to calculate the inflammation-based markers, including systemic immune-inflammation index (SII, neutrophil × platelets/ lymphocyte), platelets-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). The primary outcome was overall survival (OS), which was estimated by the Kaplan–Meier method and Cox regression analysis. The levels of ALT, AST, total bilirubin, and direct bilirubin significantly reduced after the reimplantation operation. During a median follow-up time of 10 months, 18 (54.5%) patients died. Gender, albumin, SII, PLR, NLR, and MLR were found to be associated with OS by the log-rank test and univariate analysis. Multivariate Cox analysis identified elevated levels of SII and PLR as significant factors for predicting poor OS. Reimplantation is clinically feasible in patients with recurrent MOJ after implantation of biliary metal stents. SII and PLR are independent, useful inflammation-based prognostic models for predicting outcomes in these patients. PMID:28099348

  18. Down-regulation of microRNA-181b is a potential prognostic marker of non-small cell lung cancer.

    PubMed

    Yang, Junquan; Liu, Hongxia; Wang, Hongbin; Sun, Yuman

    2013-08-01

    The aim of this study was to investigate the clinical significance of microRNA-181b (miR-181b) expression in non-small cell lung cancer (NSCLC). MiR-181b expression in 126 pairs of surgically removed NSCLC tissues and their corresponding normal lung tissues was measured by real-time quantitative RT-PCR assay. Additionally, the correlation of miR-181b expression with clinicopathological factors or prognosis of patients was analyzed. At first, miR-181b expression was significantly down-regulated in NSCLC tissues as compared with their normal counterparts (P<0.001). Then, the low miR-181b expression was found to be closely correlated with larger tumor size (P=0.02), higher p-TNM stage (P=0.008) and positive lymph node metastasis (P=0.03) of NSCLC patients. After that, survival analysis found that the overall survival (P=0.001) and disease-free survival (P=0.008) of NSCLC patients with low miR-181b expression were both significantly poorer compared to those patients with high miR-181b expression. Finally, both univariate and multivariate analyses demonstrated that low miR-181b expression may be a poor prognostic marker of NSCLC patients. This is the first study to indicate that down-regulation of miR-181b may be correlated with aggressive disease progression and poor prognosis of NSCLC patients, suggesting that miR-181b might be involved in lung carcinogenesis and become a potential prognostic marker for NSCLC.

  19. EphA2 expression is a key driver of migration and invasion and a poor prognostic marker in colorectal cancer

    PubMed Central

    Blayney, Jaine K.; McArt, Darragh G.; Redmond, Keara L.; Weir, Jessica-Anne; Bradley, Conor A.; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H.

    2015-01-01

    Purpose EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumour initiation, neo-vascularization and metastasis in a wide range of epithelial and mesenchymal cancers, however its role in colorectal cancer (CRC) recurrence and progression is unclear. Experimental Design EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumours (N=338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive CRC cell line models. Results Colorectal tumours displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III CRC tissues, in both univariate and multivariate analyses. Pre-clinically, we found that EphA2 was highly expressed in KRASMT CRC cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines and down-regulation of EphA2 using RNAi or recombinant EFNA1, suppressed migration and invasion of KRASMT CRC cells. Conclusions These data show that EpHA2 is a poor prognostic marker in stage II/III CRC, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. PMID:26283684

  20. SIRT1 induces tumor invasion by targeting epithelial mesenchymal transition-related pathway and is a prognostic marker in triple negative breast cancer.

    PubMed

    Jin, Min-Sun; Hyun, Chang Lim; Park, In Ae; Kim, Ji Young; Chung, Yul Ri; Im, Seock-Ah; Lee, Kyung-Hun; Moon, Hyeong-Gon; Ryu, Han Suk

    2016-04-01

    Absence of therapeutic targets poses a critical hurdle in improving prognosis for patients with triple negative breast cancer (TNBC). We evaluated interaction between SIRT1 and epithelial mesenchymal transition (EMT)-associated proteins as well as the role of combined protein expression as a predictor of lymph node metastasis and clinical outcome in TNBC through in vivo and vitro studies. Three hundred nineteen patients diagnosed with TNBC were chosen, immunohistochemical staining for SIRT1 and EMT-related markers' expression was performed on tissue microarrays, and in vitro experiments with each of the three human TNBC cell lines were carried out. The cohort was reclassified according to the use of adjuvant chemotherapy, tumor size, and AJCC stage to analyze the prognostic role of SIRT1 and EMT-related proteins' expression considering different therapeutic modalities and AJCC stages. Combination of four proteins including SIRT1 and three EMT-related proteins was revealed to be a statistically significant independent predictor of lymph node metastasis in the tumor size cohort as well as in the total patient population. Upon Cox regression analysis, increased expression level of the combined proteins correlated with decreased disease-free survival in the total patients as well as those who received adjuvant chemotherapy and those who had early stage breast cancer. In additional in vitro experiments, inhibition of SIRT1 expression with small interfering RNA (siRNA) suppressed tumor invasion in three different TNBC cell lines, and altered expression levels of EMT-related proteins following SIRT1 gene inhibition were identified on western blotting and fluorescence activated cell sorting (FACS) analysis; on the other hand, no change in expression levels of the cell cycle-related factors was observed. Our analysis showed the potential role of SIRT1 in association with EMT-related factors on tumor invasion, metastasis, and disease-free survival in TNBC, SIRT1, and

  1. Preoperative computed tomography measurements of pancreatic steatosis and visceral fat: prognostic markers for dissemination and lethality of pancreatic adenocarcinoma

    PubMed Central

    Mathur, Abhishek; Hernandez, Jonathan; Shaheen, Fawad; Shroff, Miloni; Dahal, Sujat; Morton, Connor; Farrior, Thomas; Kedar, Raj; Rosemurgy, Alexander

    2011-01-01

    Background Increased visceral fat and pancreatic steatosis promote lymphatic metastases and decreased survival in patients with pancreatic adenocarcinoma after pancreatoduodenectomy (PD). Objectives We aim to determine the utility of preoperative computed tomography (CT) measurements of pancreatic steatosis and visceral fat as prognostic indicators in patients with pancreatic adenocarcinoma. Methods High-resolution CT scans of 42 patients undergoing PD for pancreatic adenocarcinoma were reviewed. Attenuation in CT of the pancreas, liver and spleen were measured in Hounsfield units and scored by two blinded investigators. Perirenal adipose tissue was measured in mm. Results Lymphatic metastases were present in 57% of patients. Age, gender, tumour size and margin status were similar in patients with and without nodal metastases. Node-positive patients had increased visceral but not subcutaneous fat pads compared with node-negative patients and decreased CT attenuation of the pancreatic body and tail and liver. Node-positive patients stratified by visceral adiposity (≥10 mm vs. <10 mm) demonstrated poorer survival (7 ± 1 months vs. 16 ± 2 months; P < 0.01). Conclusions In resected pancreatic adenocarcinoma, increased pancreatic steatosis and increased visceral fat stores are associated with lymphatic metastases. Furthermore, increased visceral fat is associated with abbreviated survival in patients with lymphatic metastases. Hence, increased visceral fat may be a causative factor of abbreviated survival and serves a prognostic role in patients with pancreatic malignancies. PMID:21609373

  2. Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy

    SciTech Connect

    Fraunholz, Ingeborg; Falk, Stefan

    2013-08-01

    Purpose: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Methods and Materials: Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Results: EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients’ sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). Conclusion: Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT.

  3. Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas.

    PubMed

    Kim, Yoo-Jin; Ketter, Ralf; Steudel, Wolf-Ingo; Feiden, Wolfgang

    2007-07-01

    Mitotic activity is one of the most reliable prognostic factors in meningiomas. The identification of mitotic figures (MFs) and the areas of highest mitotic activity in H&E-stained slides is a tedious and subjective task. Therefore, we compared the results from immunostaining for the mitosis-specific antibody anti-phosphohistone H3 (PHH3 mitotic index [MI]) with standard MF counts (H&E MI) and the Ki-67 labeling index (LI). The relationship between these proliferation indices and prognosis was investigated in a retrospective series of 265 meningiomas. The PHH3 staining method yielded greater sensitivity in the detection of MFs and facilitated MF counting. Mitotic thresholds of H&E MI of 4 or more per 10 high-power fields (HPF) and PHH3 MI of 6 or more per 10 HPF were found as the most appropriate prognostic cutoff values for the prediction of recurrence-free survival. All 3 proliferation indices were univariately associated with recurrences and deaths. In contrast with the Ki-67 LI, H&E MI and PHH3 MI also remained as independent predictors in the multivariate Cox hazards modeling (P = .0007 and P = .0004, respectively).

  4. A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker

    PubMed Central

    HEINZELMANN-SCHWARZ, VIOLA A.; NIXDORF, SHERI; VALADAN, MEHRNAZ; DICZBALIS, MONICA; OLIVIER, JAKE; OTTON, GEOFF; FEDIER, ANDRÉ; HACKER, NEVILLE F.; SCURRY, JAMES P.

    2014-01-01

    Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The prognostic predictors reported in the literature are not unequivocal and the role of lichen sclerosus and c-KIT mutations in the aetiology of vulvar melanoma is unclear. Breslow staging currently seems to be the most adequate predictor of prognosis. We thus performed a clinicopathological and literature review to identify suitable predictors of prognosis and survival and investigated the expression of c-KIT (by immunohistochemistry) in patients with vulvar melanoma (n=33) from the Gynaecological Cancer Centres of the Royal Hospital for Women (Sydney, Australia) and John Hunter Hospital (Newcastle, Australia). Our series of 33 patients fitted the expected clinical profile of older women: delayed presentation, high stage, limited response to treatment and poor prognosis. We identified 3 patients (9.1%) with lichen sclerosus associated with melanoma in situ, although no lichen sclerosus was found in the areas of invasive melanoma. No patient had vulvar nevi. We identified a) Breslow’s depth, b) an absence of any of the pathological risk factors, such as satellitosis, in-transit metastasis, lymphovascular space invasion (LVSI) and dermal mitosis, c) removal of inguino-femoral lymph nodes, d) lateral margin of >1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow’s depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma. PMID:24535703

  5. Pretreatment whole blood Epstein-Barr virus-DNA is a significant prognostic marker in patients with Hodgkin lymphoma.

    PubMed

    Park, Ji Hyun; Yoon, Dok Hyun; Kim, Shin; Park, Jung Sun; Park, Chan-Sik; Sung, Heungsup; Lee, Sang-Wook; Huh, Jooryung; Suh, Cheolwon

    2016-04-01

    Epstein-Barr virus (EBV) in the peripheral blood has become a significant predictor of clinical outcomes in EBV-associated Hodgkin lymphoma (HL). However, due to its relative rarity, prevalence and prognostic role of circulating EBV-DNA has not been well established in Asian patients. Seventy patients with newly diagnosed HL were prospectively registered between October 2007 and January 2013, and underwent pretreatment whole blood (WB) EBV-DNA quantitation using real-time polymerase chain reaction (RT-PCR). WB EBV-DNA in baseline and serial RT-PCR within 1 year were investigated. Clinicopathologic parameters of the patients according to pretreatment WB EBV-DNA were also explored. Twelve patients (17.1 %) demonstrated WB EBV-DNA(+), which was significantly associated to older age, advanced stages, frequent involvements of extranodal sites, low serum albumin and hemoglobin levels, and high international prognostic scores ≥2. Three-year event-free survival (EFS) and overall survival (OS) were significantly inferior in patients with pretreatment WB EBV-DNA(+) (53.5 vs 67.0 and 65.6 vs 90.2 %) (p < 0.032 and <0.01). Negatively conversed EBV-DNA within 1 year after chemotherapy also significantly affected favorable EFS (p < 0.01). Taken together, pretreatment WB EBV-DNA(+) may be a significant predictor of inferior EFS and OS over EBV-encoded RNA in situ hybridization (EBER-ISH)(+) in Korean patients with HL. Serial EBV-DNA monitoring following chemotherapy also seems helpful to predict survival outcomes.

  6. The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease

    PubMed Central

    Jeong, Phildu; Kim, Seon-Kyu; Kim, Seon-Young; Yan, Chunri; Seo, Sung Phil; Lee, Sang Keun; Kim, Jayoung; Kim, Wun-Jae

    2015-01-01

    Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients. PMID:26225770

  7. TERT promoter mutations and Ki-67 labeling index as a prognostic marker of papillary thyroid carcinomas: combination of two independent factors

    PubMed Central

    Matsuse, Michiko; Yabuta, Tomonori; Saenko, Vladimir; Hirokawa, Mitsuyoshi; Nishihara, Eijun; Suzuki, Keiji; Yamashita, Shunichi; Miyauchi, Akira; Mitsutake, Norisato

    2017-01-01

    Although most papillary thyroid carcinomas (PTCs) have a good prognosis, a small but certain fraction shows aggressive behavior. Therefore, a novel and well-performing molecular marker is needed. In the present study, we assessed the impact of the combination of the TERT promoter/BRAF mutations and Ki-67 labeling index (LI) as a prognostic marker in PTC patients. Of 400 PTC samples, 354 were successfully genotyped for both TERT promoter/BRAF and analyzed for Ki-67 LI. Based on the combination of the mutational status and Ki-67 LI, the cases were categorized into three groups: high-, middle-, and low-risk. The recurrence rates of low-, middle-, and high-risk group were 1.9% (6 of 323), 18.2% (4 of 22), and 44.4% (4 of 9), respectively. The Kaplan-Meier curve and log-rank analyses demonstrated that there were statistical differences between any two groups. The hazard ratios for recurrence remained significant after adjustment for age, sex, tumor size, and extrathyroidal extension (low vs. middle: 8.80, 95% CI: 2.35–32.92, p = 0.001; middle vs. high: 6.255, 95% CI: 1.13–34.51, p = 0.035). In conclusion, the combination of the TERT promoter/BRAFV600E mutations and Ki-67 LI performed excellent in predicting PTC recurrence and may be clinically useful. PMID:28150740

  8. Expression of VEGF-A, HIF-1 A, CD34 and Ki67 in clear cell renal cell carcinomas and their relationship with conventional prognostic markers.

    PubMed

    Bürgesser, María Virginia; Riva, Verónica; Ojeda, Silvia María; Muñoz Morales, Duberney; Calafat, Patricia; Diller, Ana

    2014-01-01

    Clear cell renal carcinoma is the most frequent type of renal carcinoma. Recently, attention has been focused in the expression of angiogenic factors by these tumors, which would justify in part their capacity to grow, invade and disseminate, stating a worse evolution of those patients with an unfavorable angiogenic profile. 83 samples of nephrectomy with a diagnosis of clear cell renal cell carcinoma were studied. Clinical and pathological data were collected. Tumors were studied to assess immunohistochemical expression of the following markers: VEGF-A, HIF-1α, CD34 and Ki67. Results indicated a direct linear relationship between expressions of these four markers. Besides, the expression of HIF-1α was directly related to Furhman grade, invasion of the renal vein and tumor stage. Likewise, tumor proliferation index, assessed with Ki67, was directly related to the presence of necrosis, capsular invasion and advanced tumor stage. Regarding the expression of CD34, vascular density was inversely related to tumor necrosis and overall survival. These findings are controversial compared with the available literature. Then, a research scenery would be open, where the importance of generating prospective and more standardized studies are highlighted to determine the role of these angiogenic factors in tumor evolution and prognostic evaluation of these tumors.

  9. The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

    PubMed

    Kim, Young-Won; Yun, Seok Joong; Jeong, Phildu; Kim, Seon-Kyu; Kim, Seon-Young; Yan, Chunri; Seo, Sung Phil; Lee, Sang Keun; Kim, Jayoung; Kim, Wun-Jae

    2015-01-01

    Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

  10. Prognostic Value of Cancer Stem Cell Marker ALDH1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Jiang, Bin; Chang, Weilong; Yuan, Wenzheng; Ma, Zhijun; Liu, Zhengyi; Shu, Xiaogang

    2015-01-01

    Objective Many studies have indicated the prognostic and clinicopathological value of aldehyde dehydrogenase 1 (ALDH1) in colorectal cancer (CRC) patients still remains controversial. Thus we performed this study to clarify the relationship between high ALDH1 expression in CRC and its impact on survival and clinicopathological features. Methods Publications for relevant studies in Pubmed, the Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) through April 2015 were identified. Only articles describing ALDH1 antigen with immunohistochemistry in CRC were included. The software RevMan 5.1 was used to analyze the outcomes, including 5-year overall survival (OS), disease-free survival (DFS) and clinicopathological features. Results 9 studies with 1203 patients satisfying the criteria were included. The overall rate of high ALDH1 expression was 46.5% by immunohistochemical staining. High ALDH1 expression as an independent prognostic factor was significantly associated with the 5-year OS and DFS (OR = 0.42, 95%CI: 0.26–0.68, P = 0.0004; OR = 0.38, 95%CI: 0.24–0.59, P < 0.0001, respectively). High ALDH1 expression was highly correlated with the tumor (T) stage (T3 + T4 vs. T1 + T2; OR = 2.16, 95%CI: 1.09–4.28, P = 0.03), lymph node (N) stage (N1 + N2 vs. N0; OR = 1.8; 95%CI: 1.17–2.79, P = 0.008), and tumor differentiation (G3 vs. G1 + G2; OR = 1.88; 95%CI: 1.07–3.30, P = 0.03). However, high ALDH1 expression was not significantly correlated with the patient age (>60 years old vs. <60 years old; OR = 1.11, 95%CI: 0.63–1.94, P = 0.72). Conclusions High ALDH1 expression indicates a poor prognosis in CRC patients. Moreover, high ALDH1 expression correlates with the T stage, N stage, and tumor differentiation, but not with age. PMID:26682730

  11. Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer

    PubMed Central

    Beyer, Susanne; Zhu, Junyan; Mayr, Doris; Kuhn, Christina; Schulze, Sandra; Hofmann, Simone; Dannecker, Christian; Jeschke, Udo; Kost, Bernd P.

    2017-01-01

    Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival) was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics) status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology. PMID:28241481

  12. Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer.

    PubMed

    Beyer, Susanne; Zhu, Junyan; Mayr, Doris; Kuhn, Christina; Schulze, Sandra; Hofmann, Simone; Dannecker, Christian; Jeschke, Udo; Kost, Bernd P

    2017-02-23

    Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival) was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics) status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology.

  13. Phospho-histone H3 (pHH3) immuno-reactivity as a prognostic marker in non-functioning pituitary adenomas

    PubMed Central

    Hightower, Erica; Cabanillas, Maria E.; Fuller, Greg N.; McCutcheon, Ian E.; Hess, Kenneth R.; Shah, Komal; Waguespack, Steven G.; Corley, Lynda J.

    2013-01-01

    Nonfunctioning pituitary adenomas (NFPA) are typically benign neoplasms that can cause significant morbidity through local mass effects. MIB-1/Ki-67 and p53 immuno-reactivity are used to predict aggressive behavior but have known limitations. No marker to date is widely used to reliably predict tumor progression. Phospho-histone H3 (pHH3) is a protein phosphorylated during chromatin condensation in mitosis, and thus anti-pHH3 immunocyto-chemistry is able to assess mitotic activity. Study objectives were to determine the relationship among pHH3, MIB-1/Ki-67, and p53 in NFPA, and to evaluate the relationship between these indices and time to progression (TTP). Seventy-six patients with NFPA operated on by a single neuro-surgeon at University of Texas M. D. Anderson Cancer Center from 1992 to 2006 were identified from a database and met all criteria for inclusion in this clinicopathology study. PHH3, MIB-1/Ki-67, and p53 immuno-reactivity was evaluated in each case. Retrospective review was used to determine TTP. With 282 person-years of follow-up, 19 progression events were observed. A correlation was found between MIB-1/Ki-67 and p53 immuno-reactivity (r = 0.25, p = 0.031). PHH3 did not correlate with either. When markers were dichotomized at the median, only MIB-1/Ki-67 correlated with TPP (log rank p = 0.018). Rank correlation analysis confirmed a significant inverse correlation between both MIB-1/Ki-67 (Dxy = −0.33, p = 0.036) and p53 (Dxy = −0.40, 0.016) immuno-reactivity and TTP. Our results support previous data suggesting that MIB-1/Ki-67 and p53 have clinical utility as prognostic markers for tumor progression. PHH3 did not prove to be associated with TTP in this retrospective study limited by few progression events. PMID:22120760

  14. IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas.

    PubMed

    Riener, Marc-Oliver; Fritzsche, Florian R; Clavien, Pierre-Alain; Pestalozzi, Bernhard C; Probst-Hensch, Nicole; Jochum, Wolfram; Kristiansen, Glen

    2009-10-01

    The oncofetal protein IMP3 (insulin-like growth factor II mRNA binding protein 3) is expressed during embryogenesis and carcinogenesis. Various tumor types have been analyzed for IMP3 expression, which was exclusively found in tumor cells and correlated with increased tumor aggressiveness and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in bile duct carcinomas. Using large tissue sections from resection specimens of the extrahepatic biliary tract, we analyzed IMP3 in normal bile ducts (n = 36), bile ducts with acute inflammation and reactive epithelial changes (n = 26), low-grade dysplasia (n = 9), and high-grade dysplasia (n = 11). Furthermore, IMP3 expression was assessed in bile duct carcinoma (n = 115) using clinically well-characterized tissue microarrays. The findings were correlated with clinical-pathologic parameters including survival. High-grade dysplasia was strongly positive for IMP3 in all cases studied compared with no or weak expression in normal, inflamed, and low-grade dysplastic bile ducts. Of the bile duct carcinomas 58.3% (67/115) were strongly positive for IMP3, which was associated with a higher proliferation rate (P = .004) and p53 positivity (P = .022). Patients with strong IMP3 expression had significantly reduced overall survival (P = .037) similarly to the subgroup of pT3 carcinomas (P = .007). In multivariate analysis, IMP3 expression was an independent prognostic factor for overall survival (P = .040, RR = 1.809). This comprehensive study shows that IMP3 is an independent prognostic biomarker in bile duct carcinoma. In addition, it may be a marker for high-grade dysplasia in the extrahepatic biliary tract.

  15. Assessment of combined expression of B7-H3 and B7-H4 as prognostic marker in esophageal cancer patients

    PubMed Central

    Shi, Liangrong; Wu, Changping; Jiang, Jingting

    2016-01-01

    The co-stimulatory ligands of B7-family have been confirmed to play an important role in negatively regulating the T-cell mediated anti-tumor immunity. In addition, these inhibitory molecules are also aberrantly expressed on various human cancers tissues, and significantly associated with cancer progression and patients' poor prognoses. We have previously reported that B7-H3 and B7-H4 ligands are highly expressed in human esophageal cancer tissues. Herein, we tried to further analyze the value of their combined expression on prognostic prediction for esophageal cancer patients. We found that the combined expression of both B7-H3 and B7-H4 could be used as a valuable risk factor for predicting the prognosis of esophageal cancer patients (P=0.003). Moreover the status of these patients with high expression of both B7-H3 and B7-H4, was positively and significantly associated with the tumor invasion depth (P=0.0414) and TNM stage (P=0.0414). The Cox multivariate proportional hazards regression analysis revealed that the tumor size (P=0.007), the TNM stage (P=0.024) and the status of both B7-H3 and B7-H4 high expression (P=0.011), could be used as an independent risk factor for predicting patients' postoperative prognosis, respectively. In conclusion, our data indicated that the combined application of B7-H3 and B7-H4 expression can be effectively used as a prognostic marker in esophageal cancer patients. PMID:27764786

  16. Human epidermal growth factor receptor 4 (HER4) is a favorable prognostic marker of breast cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Jue; Yin, Jun; Yang, Qing; Ding, Feng; Chen, Xiao; Li, Bingjie; Tian, Xingsong

    2016-01-01

    Based on a large cohort of clinical studies involving a total of 8024 patients and reporting the effects of HER4 on breast cancer prognosis, we conducted the first meta-analysis and review of this type. We identified 26 studies published between 1985 and 2016 and assessed the prognostic value of HER4 in breast cancer by either real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR, for mRNA levels) or immunohistochemistry (IHC, for protein levels). Elevated expression of HER4 was significantly associated with longer relapse-free survival (RFS) (HR = 0.63; CI: 0.48−0.83; P = 0.001, random effects). Further subgroup analysis showed that our results were stable irrespective of subtype [Luminal: HR = 0.40, CI: 0.30−0.53, P < 0.001, fixed effects; triple negative breast cancer (TNBC): HR = 0.49, CI: 0.26−0.90, P = 0.02, fixed effects; and HER2-positive: HR = 0.53, CI: 0.40−0.71, P < 0.001, fixed effects]. Cytoplasmic HER4 was more effective than nuclear HER4 (HR = 0.74, CI: 0.60−0.92, P = 0.007, fixed effects) for predicting RFS. HER4 was also found to be a favorable prognostic marker for overall survival (OS) among patients with non-TNBC in the subgroup analysis (Luminal: HR = 0.71, CI: 0.52−0.95, P = 0.023, fixed effects; HER2-positive: HR = 0.48, CI: 0.26−0.89, P = 0.020, fixed effects). PMID:27736797

  17. Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review.

    PubMed

    Brownrigg, J R W; Hinchliffe, R J; Apelqvist, J; Boyko, E J; Fitridge, R; Mills, J L; Reekers, J; Shearman, C P; Zierler, R E; Schaper, N C

    2016-01-01

    Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation.

  18. ERp57 modulates STAT3 activity in radioresistant laryngeal cancer cells and serves as a prognostic marker for laryngeal cancer.

    PubMed

    Choe, Min Ho; Min, Joong Won; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Lee, Hyun Gyu; Hwang, Sang-Gu; An, Sungkwan; Han, Young-Hoon; Kim, Jae-Sung

    2015-02-20

    Although targeting radioresistant tumor cells is essential for enhancing the efficacy of radiotherapy, the signals activated in resistant tumors are still unclear. This study shows that ERp57 contributes to radioresistance of laryngeal cancer by activating STAT3. Increased ERp57 was associated with the radioresistant phenotype of laryngeal cancer cells. Interestingly, increased interaction between ERp57 and STAT3 was observed in radioresistant cells, compared to the control cells. This physical complex is required for the activation of STAT3 in the radioresistant cells. Among STAT3-regulatory genes, Mcl-1 was predominantly regulated by ERp57. Inhibition of STAT3 activity with a chemical inhibitor or siRNA-mediated depletion of Mcl-1 sensitized radioresistant cells to irradiation, suggesting that the ERp57-STAT3-Mcl-1 axis regulates radioresistance of laryngeal cancer cells. Furthermore, we observed a positive correlation between ERp57 and phosphorylated STAT3 or Mcl-1 and in vivo interactions between ERp57 and STAT3 in human laryngeal cancer. Importantly, we also found that increased ERp57-STAT3 complex was associated with poor prognosis in human laryngeal cancer, indicating the prognostic role of ERp57-STAT3 regulation. Overall, our data suggest that ERp57-STAT3 regulation functions in radioresistance of laryngeal cancer, and targeting the ERp57-STAT3 pathway might be important for enhancing the efficacy of radiotherapy in human laryngeal cancer.

  19. The Diagnostic and Prognostic Accuracy of Five Markers of Serious Bacterial Infection in Malawian Children with Signs of Severe Infection

    PubMed Central

    Carrol, Enitan D.; Mankhambo, Limangeni A.; Jeffers, Graham; Parker, Deborah; Guiver, Malcolm; Newland, Paul; Banda, Daniel L.; Molyneux, Elizabeth M.; Heyderman, Robert S.

    2009-01-01

    Background Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children. Methodology and Principal Findings Children presenting with a signs of meningitis (n = 282) or pneumonia (n = 95), were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74%) had SBI and 83 (22%) died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01). In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively). In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and CD163 was higher in non-survivors (p = 0.05). The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs) were 0.81 (95% CI 0.73–0.89) and 0.86 (95% CI 0.79–0.92) respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50–0.71). Conclusions Admission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting. PMID:19675669

  20. Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: A retrospective multicentre study.

    PubMed

    Schroeder, Lea; Boscolo-Rizzo, Paolo; Dal Cin, Elisa; Romeo, Salvatore; Baboci, Lorena; Dyckhoff, Gerhard; Hess, Jochen; Lucena-Porcel, Carlota; Byl, Anne; Becker, Nikolaus; Alemany, Laia; Castellsagué, Xavier; Quer, Miquel; León, Xavier; Wiesenfarth, Manuel; Pawlita, Michael; Holzinger, Dana

    2017-03-01

    Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers for HPV transformation in NSCCUP could allow focussing on the oropharynx in primary tumour search and could be of value for choice and extent of treatment. In a retrospective multicentre study (Germany, Italy and Spain), we analysed metastatic lymph nodes from 180 NSCCUP patients for the presence of HPV DNA, HPV E6*I mRNA and cellular p16(INK4a) overexpression, a surrogate marker for HPV-induced transformation. HPV status, defined as positivity for viral mRNA with at least one additional marker, was correlated with clinical parameters and survival outcome. A substantial proportion (16%) of NSCCUP were HPV-driven, mainly by HPV16 (89%). HPV prevalence increased with year of diagnosis from 9% during 1998-2004 to 23% during 2005-2014 (p = 0.007). HPV-driven NSCCUP had significantly better overall and progression-free survival rates (p ≤ 0.008). Based on this survival benefit, it is contended that HPV RNA status should be included in NSCCUP diagnosis and in therapeutic decision-making. Deintensification of radiation in patients with HPV-driven NSCCUP, while concurrently concentrating on the oropharynx appears to be a promising therapeutic strategy, the efficacy of which should be assessed in prospective trials. To our knowledge, this is the largest study on HPV in NSCCUP.

  1. Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy

    PubMed Central

    Lapa, Constantin; Hänscheid, Heribert; Wild, Vanessa; Pelzer, Theo; Schirbel, Andreas; Werner, Rudolf A.; Droll, Sabine; Herrmann, Ken; Buck, Andreas K.; Lückerath, Katharina

    2016-01-01

    Despite initial responsiveness to both chemotherapy and radiotherapy, small cell lung cancer (SCLC) commonly relapses within months. Although neuroendocrine characteristics may be difficult to demonstrate in individual cases, a relevant expression of somatostatin receptors (SSTR) on the cell surface has been described. We aimed to evaluate the prognostic value of SSTR-expression in advanced SCLC. We further examined pre-requisites for successful peptide receptor radionuclide therapy (PRRT). 21 patients with extensive stage SCLC were enrolled. All patients underwent positron emission tomography/computed tomography (PET/CT) with 68Ga-DOTATATE to select patients for SSTR-directed therapy. PET scans were visually and semi-quantitatively assessed and compared to SSTR2a and SSTR5 expression in biopsy samples. Peak standardized uptake values (SUVpeak) of tumors as well as tumor-to-liver ratios were correlated to progression-free (PFS) and overall survival (OS). In 4/21 patients all SCLC lesions were PET-positive. 6/21 subjects were rated “intermediate” with the majority of lesions positive, the remaining 11/21 patients were PET-negative. PET-positivity correlated well with histologic SSTR2a, but not with SSTR5 expression. Neither PET-positivity nor SUVpeak were predictors of PFS or OS. In 4 patients with intensive SSTR2a-receptor expression, PRRT was performed with one partial response and one stable disease, respectively. SSTR-expression as detected by 68Ga-DOTATATE-PET and/or histology is not predictive of PFS or OS in patients with advanced SCLC. However, in patients exhibiting sufficient tracer uptake, PRRT might be a treatment option given its low toxicity and the absence of effective alternatives. PMID:26936994

  2. Role of Soluble ST2 as a Prognostic Marker in Patients with Acute Heart Failure and Renal Insufficiency.

    PubMed

    Kim, Min-Seok; Jeong, Tae-Dong; Han, Seung-Bong; Min, Won-Ki; Kim, Jae-Joong

    2015-05-01

    This study sought to assess the relationship between serum concentrations of the soluble ST2 (sST2) and B-type natriuretic peptide (BNP) and investigate the role of sST2 as a prognosticator in patients hospitalized with acute heart failure (HF) and renal insufficiency. sST2 was measured at admission and discharge in 66 patients hospitalized with acute decompensated HF and renal insufficiency (estimated glomerular filtration rate [eGFR] < 90 mL/min/1.73 m(2)) using a high sensitivity immunoassay. BNP was sampled at the same time and compared to sST2. Demographical, biochemical, and echocardiographic data were also obtained during hospitalization.There were positive correlations between sST2 and BNP levels at admission (r = 0.330, P = 0.007) and at discharge (r = 0.320, P = 0.009) in overall patients. However, there was no correlation between them at each timepoint in patients with severe renal insufficiency (eGFR < 30 mL/min/1.73 m(2), n = 17). sST2 level was not changed with the degree of renal function, even though BNP level was much higher in patients with severe renal insufficiency. During 3 month follow-up, 9 (13.6%) died and 16 (24.2%) were readmitted due to HF aggravation.On multivariate analysis, sST2 at discharge was independently associated with death or HF readmission during 3 months after discharge (hazard ratio, 1.038; 95% confidence interval, 1.011-1.066, P = 0.006). In conclusion, sST2 is not affected by renal function compared with BNP in acute HF patients. The measurement of predischarge sST2 can be helpful in predicting short-term outcomes in acute decompensated HF patients with renal insufficiency.

  3. RAD21 cohesin overexpression is a prognostic and predictive marker exacerbating poor prognosis in KRAS mutant colorectal carcinomas

    PubMed Central

    Deb, S; Xu, H; Tuynman, J; George, J; Yan, Y; Li, J; Ward, R L; Mortensen, N; Hawkins, N J; McKay, M J; Ramsay, R G; Fox, S B

    2014-01-01

    Background: RAD21 is a component of the cohesion complex and is integral to chromosome segregation and error-free DNA repair. RAD21 is functionally important in tumour progression but its role in colorectal carcinoma (CRC) is unclear. We therefore assessed its clinicopathological and prognostic significance in CRC, as well as its effect on chemosensitivity. Methods: A retrospective observation study examined RAD21 expression in 652 CRCs using a tissue microarray approach. Correlation with clinicopathological factors including gender, tumour grade, mucinous subtype, TNM stage, disease-specific survival (DSS), BRAF and KRAS mutation status, tumour p53 immunostaining, tumour microsatellite instability and tumour CpG island methylator phenotype was performed. Colorectal cancer cell clones with stable RAD21 knockdown were generated and tested for cellular sensitivity to conventional chemotherapeutic drugs. Results: RAD21 expression was significantly correlated with male gender (56.7% vs 43.3%, P=0.02), well-differentiated histology (14.4% vs 4.0%, P=0.0001), higher T-stage (36.1% vs 27.0%, P=0.01), presence of metastasis (18.8% vs 12.6%, P=0.03), and shorter DSS (hazard ratio (HR) 1.4, 95% CI 1.1 to 1.9, P=0.01) in both univariate and multivariate analysis. RAD21 expression was associated with shorter DSS in patients with KRAS mutant tumours (HR:2.6, 95% CI:1.4–4.3, P=0.001) and in patients receiving adjuvant chemoradiotherapy (HR:1.9, 95% CI:1.2–3.0, P=0.008). Colorectal cancer cells with RAD21 knockdown exhibited enhanced sensitivity to 5-fluorouracil, either alone or in combination with oxaliplatin. Conclusions: RAD21 expression in CRC is associated with aggressive disease especially in KRAS mutant tumours and resistance to chemoradiotherapy. RAD21 may be an important novel therapeutic target. PMID:24548858

  4. Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options.

    PubMed

    Gasparini, Pierluigi; Fassan, Matteo; Cascione, Luciano; Guler, Gulnur; Balci, Serdar; Irkkan, Cigdem; Paisie, Carolyn; Lovat, Francesca; Morrison, Carl; Zhang, Jianying; Scarpa, Aldo; Croce, Carlo M; Shapiro, Charles L; Huebner, Kay

    2014-01-01

    Triple negative breast cancers are a heterogeneous group of tumors characterized by poor patient survival and lack of targeted therapeutics. Androgen receptor has been associated with triple negative breast cancer pathogenesis, but its role in the different subtypes has not been clearly defined. We examined androgen receptor protein expression by immunohistochemical analysis in 678 breast cancers, including 396 triple negative cancers. Fifty matched lymph node metastases were also examined. Association of expression status with clinical (race, survival) and pathological (basal, non-basal subtype, stage, grade) features was also evaluated. In 160 triple negative breast cancers, mRNA microarray expression profiling was performed, and differences according to androgen receptor status were analyzed. In triple negative cancers the percentage of androgen receptor positive cases was lower (24.8% vs 81.6% of non-triple negative cases), especially in African American women (16.7% vs 25.5% of cancers of white women). No significant difference in androgen receptor expression was observed in primary tumors vs matched metastatic lesions. Positive androgen receptor immunoreactivity was inversely correlated with tumor grade (p<0.01) and associated with better overall patient survival (p = 0.032) in the non-basal triple negative cancer group. In the microarray study, expression of three genes (HER4, TNFSF10, CDK6) showed significant deregulation in association with androgen receptor status; eg CDK6, a novel therapeutic target in triple negative cancers, showed significantly higher expression level in androgen receptor negative cases (p<0.01). These findings confirm the prognostic impact of androgen receptor expression in non-basal triple negative breast cancers, and suggest targeting of new androgen receptor-related molecular pathways in patients with these cancers.

  5. ADAMTS6 suppresses tumor progression via the ERK signaling pathway and serves as a prognostic marker in human breast cancer

    PubMed Central

    Xie, Keqi; Wang, Zhu; Wang, Yanping; Zheng, Hong

    2016-01-01

    A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is involved in tumor development. However, how ADAMTS6 influences cancer remains unknown. We investigated the biological function and clinical implications of ADAMTs6 in breast cancer (BC). Its functional significance in BC cell lines was confirmed by ADAMTs6 overexpression or downregulation both in vitro and in vivo studies. Enhanced ADAMTS6 expression suppressed cell migration, invasion, and tumorigenesis, whereas knockdown promoted these characteristics. The extracellular signal-regulated kinase (ERK) pathway was partially involved in ADAMTS6-mediated inhibition of BC development, and miR-221-3p was identified as a predicted target for ADAMTS6. Results from the luciferase assay confirmed that miR-221-3p directly inhibited ADAMTS6 expression by binding its 3′-untranslated region. In addition, immunohistochemistry data from specimens from 182 BC patients showed that high ADAMTS6 expression was significantly correlated with favorable disease-free survival (DFS, p = 0.045). Subgroup analysis of patients with ER positive, PR positive or HER-2 negative tumors revealed that high ADAMTS6 expression more strongly extended DFS compared to low expression (p = 0.004, p = 0.009, p = 0.017). Multivariate analyses confirmed that ADAMTS6 expression was an independent risk factor for DFS (p = 0.011). Together, these data demonstrate that ADAMTS6 inhibits tumor development by regulating the ERK pathway via binding of miR-221-3p. Thus, its expression may be a potential prognostic biomarker for BC. PMID:27542224

  6. HO-1, RET and PML as possible markers for risk stratification of acute myelocytic leukemia and prognostic evaluation.

    PubMed

    Yu, Meisheng; Wang, Jishi; Ma, Dan; Chen, Shuya; Lin, Xiaojing; Fang, Qin; Zhe, Nana

    2015-11-01

    Heme oxygenase-1 (HO-1) is an inducible isoform of HO that is activated in response to oxidative stress and has anti-apoptotic and pro-proliferative effects on leukemia cells. RET, a tyrosine kinase receptor; its expression levels are associated with the differentiation degree of acute myelocytic leukemia (AML) cells. The promyelocytic leukemia (PML) gene inhibits cell proliferation and tumor growth, participates in the differentiation of hematopoietic progenitor cells and induces cell apoptosis. However, the association between the expression levels of HO-1, RET and PML genes and the risk stratification of AML and prognosis have not previously been reported. In the present study, HO-1 was expressed in the human AML Kasumi-1, HL-60 and THP-1 cell lines, and HO-1 expression was regulated by Hemin (20 µmol/l) and ZnPPIX (10 µmol/l). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that expression of RET and PML were positively and negatively correlated with HO-1 expression, respectively. Bone marrow samples (18 favorable, 55 intermediate, 15 adverse and 2 unknown karyotype AML cases and 20 healthy donors) were collected from 90 randomly selected AML patients upon their first visit. The mRNA and protein expression of HO-1, RET and PML in samples was detected by RT-qPCR and western blot analysis. At the mRNA level, the adverse group expressed significantly higher levels of HO-1 and RET compared with the levels in the favorable and normal groups. The PML mRNA expression levels in adverse patient samples was lower compared with those of the intermediate group and favorable group. Western blot analysis demonstrated that the expression levels of HO-1, RET and PML proteins in all risk groups exhibited the same pattern of expression as was observed for the mRNA levels. The overall survival and relapse-free survival rates were shortest in AML patients with high HO-1 expression (Kaplan-Meier; log-rank, P<0.01). The results of the

  7. Prognostic comparison of the proliferation markers (mitotic activity index, phosphohistone H3, Ki67), steroid receptors, HER2, high molecular weight cytokeratins and classical prognostic factors in T₁₋₂N₀M₀ breast cancer.

    PubMed

    Gudlaugsson, Einar; Klos, Jan; Skaland, Ivar; Janssen, Emiel A M; Smaaland, Rune; Feng, Weiwei; Shao, Zhimin; Malpica, Anais; Baak, Jan P A

    2013-04-01

    The proliferation factors: mitotic activity index (MAI), phosphohistone H3 (PPH3) and Ki67 have strong prognostic value in early breast cancer but their independent value to each other and other prognostic factors has not been evaluated. In 237 T₁₋₂N₀M₀ breast cancers without systemic adjuvant treatment, formalized MAI assessment and strictly standardized, fully automated quantitative immunohistochemistry (IHC) for Ki67, PPH3, estrogen (ER) and progesterone receptor (PR), HER2, cytokeratins-5/6 and -14, and automated digital image analysis (DIA) for measuring PPH3 and Ki67 were performed. Section thickness was measured to further control IHC measurements. All features were measured in the periphery of tumors. The different proliferation assessments and other well-established clinicopathological and biomarker prognostic factors were compared. DIA-Ki67 added prognostically to PPH3. None of the other biomarkers or clinicopathological variables added prognostically to this PPH3/Ki67 combination. However, when PPH3 is replaced by MAI the prognostic value is nearly the same. In early operable node negative breast cancer without adjuvant systemic treatment, Ki67 with a threshold of 6.5% assessed by digital image analysis in the periphery of the tumor is prognostically strong. The combination of either PPH3/Ki67 or MAI/Ki67 overshadowed the prognostic value of all other features including Ki67 alone.

  8. C-reactive Protein as a Prognostic Marker after Lacunar Stroke: The Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) Study

    PubMed Central

    Elkind, Mitchell S. V.; Luna, Jorge M.; McClure, Leslie A.; Zhang, Yu; Coffey, Christopher S.; Roldan, Ana; Del Brutto, Oscar H.; Pretell, Edwin Javier; Pettigrew, L. Creed; Meyer, Brett C.; Tapia, Jorge; White, Carole; Benavente, Oscar R.

    2014-01-01

    Background and Purpose Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Methods Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a Phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment, and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (HR, 95%CI) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Results Among 1244 lacunar stroke patients (mean 63.3 ± 10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes), and 115 major vascular events (stroke, myocardial infarction, vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP >4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR 2.54, 95%CI 1.30–4.96), even after adjusting for demographics and risk factors (adjusted HR 2.32, 95%CI 1.15–4.68). HsCRP predicted increased risk of major vascular events (top quartile adjusted HR 2.04, 95%CI 1.14–3.67). There was no interaction with randomized antiplatelet treatment. Conclusions Among recent lacunar stroke patients, hsCRP levels predict risk of recurrent strokes and other vascular events. HsCRP did not predict response to dual antiplatelets. PMID:24523037

  9. Cobalt to Chromium Ratio is Not a Key Marker for Adverse Local Tissue Reaction (ALTR) in Metal on Metal Hips.

    PubMed

    Fehring, Thomas K; Carter, Joshua L; Fehring, Keith A; Odum, Susan M; Griffin, William L

    2015-09-01

    The diagnosis of adverse local tissue reaction (ALTR) after metal-on-metal total hip arthroplasty (MoMTHA) presents a significant challenge. No single biomarker is specific for ALTR. The purpose of this study was to determine if the ratio of cobalt to chromium ions is useful for diagnosing ALTR in MoMTHA. In 89 bearing-related revision THAs, preoperative cobalt and chromium ion levels were compared to an intraoperative soft tissue damage grading scale. The average cobalt to chromium ratio was 2.96 (0-20). There was no correlation between the tissue scale and the cobalt to chromium ratio (R=0.095; P=0.41). Many variables affecting ion production/excretion mitigate the use of the ion ratio. The cobalt to chromium ratio is not a predictive biomarker for ALTR in MoMTHA.

  10. Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy.

    PubMed

    Tam, Frederick W K; Riser, Bruce L; Meeran, Karim; Rambow, JoAnn; Pusey, Charles D; Frankel, Andrew H

    2009-07-01

    Profibrotic growth factors and inflammatory chemokines have been implicated in the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers has not previously been reported, and neither have two such molecules in urine been examined in a single study of DN. In this prospective observational study, 43 adult diabetic patients were studied, 40 were followed up for 6years. Urinary MCP-1/creatinine ratios were found to be significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2 exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine ratios were greatly elevated in both microalbuminuric and macroalbuminuric patients (125- and 74-fold higher than normoalbuminuric patients, respectively, p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1, correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast, MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients (R=0.61, p<0.0001), reflective of its predictive value in patients with macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria. In conclusion, increased urinary CCN2 is associated with the early progression of DN, whereas MCP-1 is associated with later stage disease.

  11. Global histone deacetylase enzymatic activity is an independent prognostic marker associated with a shorter overall survival in chronic lymphocytic leukemia patients.

    PubMed

    Van Damme, Michaël; Crompot, Emerence; Meuleman, Nathalie; Mineur, Philippe; Dessars, Barbara; El Housni, Hakim; Bron, Dominique; Lagneaux, Laurence; Stamatopoulos, Basile

    2014-10-01

    Histone deacetylases (HDAC) play a crucial role in transcriptional regulation and are often deregulated in many cancers. However, global HDAC enzymatic activity has never been investigated in Chronic Lymphocytic Leukemia (CLL). We measured HDAC activity in protein extracts from CD19+ B-cells purified from 114 CLL patients with a median follow-up of 91 months (range: 11-376). HDAC activity was equivalent in CLL and normal B-cells but higher in patients who died during the study than in living patients (152.1 vs. 65.04 pmol; P = 0.0060). Furthermore, HDAC activity correlated with treatment-free survival (TFS; P = 0.0156) and overall survival (OS; P < 0.0001): patients with low HDAC activity (n = 75) had a median TFS and OS of 101 and > 376 months, respectively, whereas patients with high HDAC activity (n = 39) had a median TFS and OS of 47 and 137 months, respectively. Multivariate analyses indicated that HDAC activity is an independent predictor of OS (hazard ratio = 7.68; P = 0.0017). Finally, HDAC activity increased after B-cell receptor stimulation using IgM, suggesting a role for microenvironment stimuli (n = 10; P = 0.0371). In conclusion, high HDAC activity in CLL B-cells is associated with shorter TFS and OS and is an independent marker of OS, refining the use of other prognostic factors. This work provides a biological base for the use of HDAC inhibitors in CLL treatment.

  12. Reg proteins promote acinar-to-ductal metaplasia and act as novel diagnostic and prognostic markers in pancreatic ductal adenocarcinoma

    PubMed Central

    Zogopoulos, George; Shao, Qin; Dong, Kun; Lv, Fudong; Nwilati, Karam; Gui, Xian-yong; Cuggia, Adeline; Liu, Jun-Li; Gao, Zu-hua

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor. Acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) are both precursor lesions that lead to the development of PDAC. Reg family proteins (Reg1A, 1B, 3A/G, 4) are a group of calcium-dependent lectins that promote islet growth in response to inflammation and/or injuries. The aim of this study was to establish a role for Reg proteins in the development of PDAC and their clinical value as biomarkers. We found that Reg1A and Reg3A/G were highly expressed in the ADM tissues by immunohistochemistry. In the 3-dimensional culture of mouse acinar cells, Reg3A promoted ADM formation with concurrent activation of mitogen-acitvated protein kinase. Upregulation of Reg1A and Reg1B levels was observed as benign ductal epithelium progresses from PanIN to invasive PDAC. Patients with PDAC showed significantly higher serum levels of Reg1A and Reg1B than matching healthy subjects. These results were further validated by the quantification of Reg 1A and 1B mRNA levels in the microdissected tissues (22- and 6-fold increases vs. non-tumor tissues). Interestingly, patients with higher levels of Reg1A and 1B exhibited improved survival rate than those with lower levels. Furthermore, tissue expressions of Reg1A, Reg1B, and Reg4 could differentiate metastatic PDAC in the liver from intrahepatic cholangiocarcinoma with 92% sensitivity and 95% specificity. Overall, our results demonstrate the upregulation of Reg proteins during PDAC development. If validated in larger scale, Reg1A and Reg1B could become clinical markers for detecting early stages of PDAC, monitoring therapeutic response, and/or predicting patient's prognosis. PMID:27788482

  13. Hand bone densitometry in rheumatoid arthritis, a five year longitudinal study: an outcome measure and a prognostic marker

    PubMed Central

    Deodhar, A; Brabyn, J; Pande, I; Scott, D; Woolf, A

    2003-01-01

    Methods: Tender and swollen joints in hands and body, HAQ score, Larsen score on hand radiographs, serum CRP, and hand BMC measurement by DXA were studied every six months for five years in 40 patients with early RA. At the final visit, patients completed the SF-36 and Duruoz hand function questionnaires. Results: All patients completed two years and 29 completed five years' follow up. Hand BMC worsened over the first three years (percentage loss from baseline: mean (SD) -5.5 (7.2), -7.5 (8.4), -9.8 (9.4)) and stabilised over last two years (–9.9 (8.8), -10 (7.8)). Baseline disease activity and function correlated with hand BMC loss at five years (swollen joints in hands: r=-0.38, p=0.043; swollen joints in body: r=-0.47, p=0.01; HAQ: r=-0.52, p=0.004). Percentage change in hand BMC over five years correlated with SF-36 physical function (r=0.61, p<0.01), hand function (r=-0.64, p<0.01), HAQ score (r=-0.63, p<0.01) at five years. Relative risk of bad hand functional outcome at five years was significantly higher for patients with hand BMC loss of ⩾1.17 g (smallest detectable difference) than for patients with less bone loss within the first six months (OR=6.9, 95% CI 1.3 to 34.5, p<0.02). Conclusion: Early loss of hand BMC in patients with RA is a composite marker of disease activity and functional status and can predict poor functional outcome. PMID:12860734

  14. Clinically determined type of 18F-fluoro-2-deoxyglucose uptake as an alternative prognostic marker in resectable pancreatic cancer

    PubMed Central

    Chong, Jae Uk; Hwang, Ho Kyoung; Lee, Jin Ho; Yun, Mijin; Kang, Chang Moo; Lee, Woo Jung

    2017-01-01

    Purpose To investigate the association between clinical PET (positron emission tomography) type and oncologic outcome in resectable pancreatic cancer. Methods Between January 2008 and October 2012, patients who underwent potentially curative resection for resectable pancreatic ductal adenocarcinoma without neoadjuvant treatment were retrospectively investigated. Clinical PET type was defined as follows: pancreatic cancer with similar 18FDG uptake to renal calyx was determined as kidney-type (K-type), and relatively lower 18FDG uptake than that of renal calyx was regarded as Non-K type. Results A total of 53 patients were enrolled. After agreement-based reclassification, agreement based K-type (aK-type) was noted in 34 patients (64.2%), and agreement based Non-K type (aNon K-type) was found in 19 patients (35.8%). There was a significant difference between aK-type and aNon K-type pancreatic cancer (tumor size (P = 0.030), adjusted CA 19–9 (P = 0.007), maximum standard uptake value (SUVmax,P<0.001), metabolic tumor volume (MTV2.5, P<0.001), total lesion glycolysis (TLG, P<0.001)). K-type pancreatic cancer (n = 31) showed a significantly shorter disease-free time compared with Non-K type (n = 16) (10.8 vs. 24.1 months, P = 0.013). It was also noted that aK-type showed inferior disease-free survival to that of aNon-K type pancreatic cancer (11.9 vs. 28.6 months, P = 0.012). Conclusions Clinical PET type is a reliable clinical marker to estimate aggressive tumor biology and can be utilized in predicting tumor recurrence and necessity for postoperative chemotherapy. PMID:28235029

  15. The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells.

    PubMed

    Pacurari, Maricica; Addison, Joseph B; Bondalapati, Naveen; Wan, Ying-Wooi; Luo, Dajie; Qian, Yong; Castranova, Vincent; Ivanov, Alexey V; Guo, Nancy Lan

    2013-08-01

    Lung cancer remains the leading cause of cancer-related mortality for both men and women. Tumor recurrence and metastasis is the major cause of lung cancer treatment failure and death. The microRNA‑200 (miR-200) family is a powerful regulator of the epithelial-mesenchymal transition (EMT) process, which is essential in tumor metastasis. Nevertheless, miR-200 family target genes that promote metastasis in non-small cell lung cancer (NSCLC) remain largely unknown. Here, we sought to investigate whether the microRNA-200 family regulates our previously identified NSCLC prognostic marker genes associated with metastasis, as potential molecular targets. Novel miRNA targets were predicted using bioinformatics tools based on correlation analyses of miRNA and mRNA expression in 57 squamous cell lung cancer tumor samples. The predicted target genes were validated with quantitative RT-PCR assays and western blot analysis following re-expression of miR-200a, -200b and -200c in the metastatic NSCLC H1299 cell line. The results show that restoring miR-200a or miR-200c in H1299 cells induces downregulation of DLC1, ATRX and HFE. Reinforced miR-200b expression results in downregulation of DLC1, HNRNPA3 and HFE. Additionally, miR-200 family downregulates HNRNPR3, HFE and ATRX in BEAS-2B immortalized lung epithelial cells in quantitative RT-PCR and western blot assays. The miR-200 family and these potential targets are functionally involved in canonical pathways of immune response, molecular mechanisms of cancer, metastasis signaling, cell-cell communication, proliferation and DNA repair in Ingenuity pathway analysis (IPA). These results indicate that re-expression of miR-200 downregulates our previously identified NSCLC prognostic biomarkers in metastatic NSCLC cells. These results provide new insights into miR-200 regulation in lung cancer metastasis and consequent clinical outcome, and may provide a potential basis for innovative therapeutic approaches for the treatment of this

  16. Markers of insulin resistance and sedentary lifestyle are predictors of preeclampsia in women with adverse obstetric results.

    PubMed

    Hoirisch-Clapauch, S; Benchimol-Barbosa, P R

    2011-12-01

    Some thrombophilias and severe preeclampsia may increase the risk for preterm deliveries and fetal death due to placental insufficiency. Our objective was to evaluate clinical and laboratory data as predictors of preeclampsia in a population of mothers with 3rd trimester fetal losses or preterm deliveries. In a longitudinal retrospective study, 54 consecutive women (age range: 16 to 39 years) with normotensive pregnancies were compared to 79 consecutive women with preeclampsia (age range: 16 to 43 years). Weight accrual rate (WAR) was arbitrarily defined as weight gain from age 18 years to the beginning of pregnancy divided by elapsed years. Independent predictors of preeclampsia were past history of oligomenorrhea, WAR >0.8 kg/years, pre-pregnancy or 1st trimester triglyceridemia >150 mg/dL, and elevated acanthosis nigricans in the neck. In a multivariate logistic regression model, two or more predictors conferred an odds ratio of 15 (95%CI [5.9-37]; P < 0.001) to develop preeclampsia (85% specificity, 73% sensitivity, c-statistic of 81 ± 4%; P < 0.0001). Clinical markers related to insulin resistance and sedentary lifestyles are strong independent predictors of preeclampsia in mothers with 3rd trimester fetal losses or preterm deliveries due to placental insufficiency. Women at risk for preeclampsia in this particular population might benefit from measures focused on overcoming insulin resistance.

  17. Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer

    PubMed Central

    Reddy, Ram Bhupal; Bhat, Anupama Rajan; James, Bonney Lee; Govindan, Sindhu Valiyaveedan; Mathew, Rohit; DR, Ravindra; Hedne, Naveen; Illiayaraja, Jeyaram; Kekatpure, Vikram; Khora, Samanta S.; Hicks, Wesley; Tata, Pramila; Kuriakose, Moni A.; Suresh, Amritha

    2016-01-01

    candidate markers correlated with disease outcome in HNSCC; further validation in a larger cohort of patients will establish their clinical relevance. PMID:26808319

  18. Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts

    PubMed Central

    Usha, Lydia; Tabesh, Bita; Morrison, Larry E; Rao, Ruta D; Jacobson, Kris; Zhu, April; Basu, Sanjib; Coon, John S

    2008-01-01

    Background Amplification of the ERBB2 (Her-2/neu) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for topoisomerase II alpha (TOP2A), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy. Methods and patients Archival tissue samples from 63 breast cancer patients with ERBB2 amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near ERBB2. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available. Results Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted TOP2A had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. TOP2A deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between TOP2A deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06). Conclusion TOP2A deletion is associated with poor prognosis in ERBB2-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study. PMID:18702822

  19. Expression status of CD44 and CD133 as a prognostic marker in esophageal squamous cell carcinoma treated with neoadjuvant chemotherapy followed by radical esophagectomy.

    PubMed

    Okamoto, Koichi; Ninomiya, Itasu; Ohbatake, Yoshinao; Hirose, Atsushi; Tsukada, Tomoya; Nakanuma, Shinichi; Sakai, Seisho; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Hayashi, Hironori; Oyama, Katsunobu; Inokuchi, Masafumi; Nakagawara, Hisatoshi; Miyashita, Tomoharu; Hidehiro, Tajima; Takamura, Hiroyuki; Fushida, Sachio; Ohta, Tetsuo

    2016-12-01

    Cancer stem cells (CSCs) have self-renewal and pluripotency capabilities and contribute to cancer progression and chemoresistance. It has been proposed that the treatment resistance and heterogeneity of CSCs are deeply involved in the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The objective of this study was to identify the influence of the expression status of the CSC markers CD44 and CD133 on chemotherapeutic efficacy and prognosis in ESCC patients who underwent radical esophagectomy after neoadjuvant chemotherapy (NAC). Endoscopically biopsied specimens taken before NAC and surgically resected specimens after NAC were immunohistochemically assessed for CD44 and CD133 expression for 47 ESCC patients who underwent NAC followed by radical esophagectomy. The correlation between CD44 and CD133 expression status and clinicopathological findings and the prognosis of ESCC patients after NAC followed by esophagectomy were analyzed. The percentages of CD44-positive cells and CD133-positive cells in specimens were increased after NAC. CD44 and CD133 expression status before NAC did not correlate with the degree of tumor progression and had no impact on the chemotherapeutic effect. However, strong expression of CD44 or CD133 and a high proportion of CD133-expressing cells before NAC were significantly associated with poorer esophageal cancer-specific survival. Patients with strong expression of CD44 or CD133 and those with a high ratio of CD133-positive tumor cells showed significantly poor prognosis regardless of the effect of chemotherapy. Multivariate analysis showed that simultaneous strong expression of CD44 and CD133 before NAC, a high rate of CD133-positive tumor cells before NAC, and primary tumor remission assessed by preoperative endoscopy were significant independent prognostic factors for ESCC. Our data indicate that CD44 and CD133 expression status prior to treatment dictates the malignant potential of ESCC and may be a novel

  20. Identification of lncRNA FAM83H-AS1 as a novel prognostic marker in luminal subtype breast cancer

    PubMed Central

    Yang, Fan; Lv, Shi-Xu; Lv, Lin; Liu, Ye-Huan; Dong, Si-Yang; Yao, Zhi-Han; Dai, Xuan-xuan; Zhang, Xiao-Hua; Wang, Ou-Chen

    2016-01-01

    Background Luminal subtype breast cancer accounts for a predominant number of breast cancers. Considering the heterogeneity of the disease, it is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choices. Long non-coding RNA (lncRNA) represents an emerging and understudied class of transcripts that play a significant role in cancer biology. Growing knowledge of cancer-associated lncRNAs contributes to the development of molecular markers for prognosis evaluation and gene therapy. Materials and methods Three pairs of primary luminal subtype breast cancer tissues and adjacent non-cancerous tissues were collected and sequenced. EBseq algorithm was used to identify differentially expressed lncRNAs. RNA sequencing data from The Cancer Genome Atlas (TCGA) database were used to validate the robustness of our RNA-seq results. Kaplan–Meier and Cox regression analyses were utilized to assess the association between the lncRNAs and overall survival of patients in TCGA cohort. Results A total of 796 lncRNAs were significantly dysregulated in luminal subtype breast cancer, including 436 upregulated and 360 downregulated lncRNAs. Among them, FAM83H antisense RNA 1 (FAM83H-AS1) was the most upregulated lncRNA, whereas GSN antisense RNA 1 (GSN-AS1) was the most downregulated lncRNA. Moreover, we proved that the high expression level of FAM83H-AS1 indicated unfavorable prognosis not only in luminal subtype breast cancer but also in all subtype breast cancers. To the best of our knowledge, this is the first report indicating that FAM83H-AS1 was involved in luminal subtype breast cancer and was an independent prognostic indicator. Conclusion Our study provides a rich resource to the research community for further identifying lncRNAs with diagnostic and therapeutic potentials and exploring biological function of lncRNAs in luminal subtype breast cancer. PMID:27895496

  1. Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

    PubMed Central

    Min, James K.; Labounty, Troy M.; Gomez, Millie J.; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Cheng, Victor; Chinnaiyan, Kavitha M.; Chow, Benjamin; Cury, Ricardo; Delago, Augustin; Dunning, Allison; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jorg; Kaufmann, Philipp; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y.; Maffei, Erica; Raff, Gilbert; Shaw, Leslee J.; Villines, Todd C.; Berman, Daniel S.

    2015-01-01

    Background Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. Methods From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification. Results Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of

  2. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    PubMed

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  3. Volume-Based F-18 FDG PET/CT Imaging Markers Provide Supplemental Prognostic Information to Histologic Grading in Patients With High-Grade Bone or Soft Tissue Sarcoma.

    PubMed

    Andersen, Kim Francis; Fuglo, Hanna Maria; Rasmussen, Sine Hvid; Petersen, Michael Mork; Loft, Annika

    2015-12-01

    The aim of the study is to assess the prognostic value of different volume-based calculations of tumor metabolic activity in the initial assessment of patients with high-grade bone sarcomas (BS) and soft tissue sarcomas (STS) using F-18 FDG PET/CT.A single-site, retrospective study from 2002 to 2012 including 92 patients with histologically verified high-grade BS (N = 37) or STS (N = 55). All patients underwent a pretreatment F-18 FDG PET/CT scan. Clinical data were registered. Measurements of the accuracy of metabolic tumor volume with a preset threshold of 40% of the maximum standardized uptake value of primary tumor (MTV40%) and total lesion glycolysis (TLG) as prognostic variables and identification of optimal discriminating cut-off values were performed through ROC curve analysis. Patients were grouped according to the cut-off values. All deaths were considered an event in survival analysis. Kaplan-Meier survival estimates and log-rank test were used to compare the degree of equality of survival distributions. Prognostic variables with related hazard ratios (HR) were assessed using Cox proportional hazards regression analysis.Forty-one of 92 patients died during follow-up (45%; 12 BS and 29 STS). Average survival for included patients was 6.5 years (95% CI 5.8-7.3 years) and probability of 5-year survival was 52%. There was a high-significant accuracy of TLG and MTV40% as prognostic variables when looking on all patients and during subgroup analysis. AUCs were higher for TLG than for MTV40%. TLG above optimal cut-off value was the only variable which was independently prognostic for survival throughout multivariate regression analysis of all included patients (P = 0.01, HR 4.78 [95% CI 1.45-15.87]) and subgroup analysis (BS: P = 0.04, HR 11.11 [95% CI 1.09-111.11]; STS: P < 0.05, HR 3.37 [95% CI 1.02-11.11]). No significant results were demonstrated for MTV40%.Volume-based F-18 FDG PET/CT imaging markers in terms of pretreatment estimation

  4. Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

    PubMed

    Chen, Marcus Y; Rochitte, Carlos E; Arbab-Zadeh, Armin; Dewey, Marc; George, Richard T; Miller, Julie M; Niinuma, Hiroyuki; Yoshioka, Kunihiro; Kitagawa, Kakuya; Sakuma, Hajime; Laham, Roger; Vavere, Andrea L; Cerci, Rodrigo J; Mehra, Vishal C; Nomura, Cesar; Kofoed, Klaus F; Jinzaki, Masahiro; Kuribayashi, Sachio; Scholte, Arthur J; Laule, Michael; Tan, Swee Yaw; Hoe, John; Paul, Narinder; Rybicki, Frank J; Brinker, Jeffrey A; Arai, Andrew E; Matheson, Matthew B; Cox, Christopher; Clouse, Melvin E; Di Carli, Marcelo F; Lima, João A C

    2017-03-14

    Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not

  5. Combined expression of metastasis related markers Naa10p, SNCG and PRL-3 and its prognostic value in breast cancer patients.

    PubMed

    Min, Li; Ma, Ruo-Lan; Yuan, Hua; Liu, Cai-Yun; Dong, Bing; Zhang, Cheng; Zeng, Yan; Wang, Li; Guo, Jian-Ping; Qu, Li-Ke; Shou, Cheng-Chao

    2015-01-01

    Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognostic value for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels of N-α-acetyltransferase 10 protein (Naa10p), synuclein-γ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancer were identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3- subgroup showed best prognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+ subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p, SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overall survival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients with lymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, the combined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classification system, may provide a precise estimate of prognosis of breast cancer patients.

  6. [HOMOCYSTEINE AS A PROGNOSTIC MARKER OF ATRIAL REMODELING AND CLINICAL PICTURE IN PATIENTS WITH PAROXYSMAL AND PERSISTENT FORMS OF ATRIAL FIBRILLATION].

    PubMed

    Snezhitsky, V A; Yatskevich, E S; Doroshenko, E M; Smirnov, V Yu; Dolgoshey, T S; Rubinsky, A Yu

    2016-01-01

    The aim of this work was to study prognostic significance of the relationship between the homocysteine level, structural/functional atrial remodeling, and clinical picture of paroxysmal and persistent forms of atrial fibrillation (AF). The study included 75 patients with AF concomitant with coronary heart disease and hypertensive disease without apparent structural changes in myocardium. Group 1 was comprised of 48 patients with paroxysmal AF, group 2 of 27 patients with persistent AF. 19 patients with coronary heart disease and hypertensive disease without AF served as controls. The structural and functional state of the heart was evaluated based on two-dimensional trans-thoracal echocardiography with the use of the formulas for calculating left ventricular characteristics. Blood homocysteine levels were measured The frequency of AF relapses was determined after an 1 year follow-up. The homocysteine level over 11.2 mcmol/l was related to left ventricle enlargement (over 40 mm), high frequency and relapse rate of AF. It is concluded that the relationship between homocysteine levels, left ventricle size, frequency and relapse rate of AF suggests the influence of homocysteine on atrial remodeling. A rise in the homocysteine level above 11 mcmol/l should be regarded as a prognostic factor of increased AF relapse rate.

  7. Comparative analysis of the diagnostic and prognostic value of exercise ECG and thallium-201 scintigraphic markers of myocardial ischemia in asymptomatic and symptomatic patients

    SciTech Connect

    Gibson, R.S. )

    1989-08-01

    A considerable amount of data now exists that indicates that exercise ECG--due to its suboptimal sensitivity and specificity--has limited diagnostic and prognostic value in asymptomatic subjects, patients with chest pain of unclear etiology or those with chronic stable angina pectoris, and in patients recovering from acute myocardial infarction. Because of this and the well-recognized advantages of thallium-201 scintigraphy, there appears to be a strong rationale for recommending exercise perfusion imaging, rather than exercise ECG alone, as the preferred method for detecting CAD and staging its severity. This recommendation seems justified given the fact that (1) thallium-201 scintigraphy is far more sensitive and specific in detecting myocardial ischemia than exercise testing; (2) unlike stress ECG, thallium-201 scintigraphy can localize ischemia to a specific area of areas subtended by a specific coronary artery; and (3) thallium-201 scintigraphy has been shown to be more reliable to risk stratification of individual patients than exercise testing alone. The more optimal prognostic efficiency of thallium-201 scintigraphy is due, in part, to the fact that the error rate in falsely classifying patients as low-risk is substantially and significantly smaller with thallium-201 scintigraphy than with stress ECG. 52 references.

  8. PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy

    PubMed Central

    Yan, Dongwang; Cui, Feifei; Wang, Xiaoliang; Yu, Fudong; Xue, Yingming; Feng, Xiaodong; Wang, Jingtao; Wang, Xiao; Jiang, Tao; Zhang, Meng; Zhao, Senlin; Yu, Yang; Tang, Huamei; Peng, Zhihai

    2015-01-01

    p21-Activated kinase 6 (PAK6) has been implicated in radiotherapy and docetaxel resistance. We have further evaluated PAK6 as a predictor of 5-fluorouracil (5-FU) treatment response in colon cancer. Here we report that in colon cancer PAK6 promotes tumor progression and chemoresistance both in vitro and in vivo. In the clinical analysis, PAK6 was overexpressed in 104 of 147 (70.75%) stage II and III patients who received 5-FU based chemotherapy after surgery. Multivariate Cox regression analysis indicated that PAK6 was an independent prognostic factor for overall survival (P < 0.001) and disease-free survival (P < 0.001). Colon cancer cell lines showed increased PAK6 expression upon 5-FU treatment. In PAK6-knockdown cells treated with 5-FU, cell viability and phosphorylation of BAD decreased, and the number of apoptotic cells, levels of cleaved caspase 3 and PARP increased compared to control cells. The opposite was observed in PAK6 overexpressing cells. Short hairpin RNA knockdown of PAK6 blocked cells in G2-M phase. Furthermore, Animal experiments results in vivo are consistent with outcomes in vitro. This study demonstrates that PAK6 is an independent prognostic factor for adjuvant 5-FU-based chemotherapy in patients with stage II and stage III colon cancer. PMID:25426562

  9. Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

    SciTech Connect

    Moran, Meena S.; Yang Qifeng; Goyal, Sharad; Harris, Lyndsay; Chung, Gina; Haffty, Bruce G.

    2011-12-01

    Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

  10. PTEN expression is a prognostic marker for patients with non-small cell lung cancer: a systematic review and meta-analysis of the literature

    PubMed Central

    Xiao, Jian; Hu, Cheng-Ping; He, Bi-Xiu; Chen, Xi; Lu, Xiao-Xiao; Xie, Ming-Xuan; Li, Wei; He, Shu-Ya; You, Shao-Jin; Chen, Qiong

    2016-01-01

    Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a known tumor suppressor in non-small cell lung cancer (NSCLC). By performing a systematic review and meta-analysis of the literature, we determined the prognostic value of decreased PTEN expression in patients with NSCLC. We comprehensively and systematically searched through multiple online databases up to May 22, 2016 for NSCLC studies reporting on PTEN expression and patient survival outcome. Several criteria, including the Newcastle-Ottawa Quality Assessment Scale (NOS), were used to discriminate between studies. In total, 23 eligible studies with a total of 2,505 NSCLC patients were included in our meta-analysis. Our results demonstrated that decreased expression of PTEN correlated with poor overall survival in NSCLC patients and was indicative of a poor prognosis for disease-free survival and progression-free survival in patients with NSCLC. PMID:27506936

  11. Prognostic value of procalcitonin in hospitalized patients with lower respiratory tract infections

    PubMed Central

    Nobre, Vandack; Borges, Isabela

    2016-01-01

    Lower respiratory tract infections are common and potentially lethal conditions and are a major cause of inadequate antibiotic prescriptions. Characterization of disease severity and prognostic prediction in affected patients can aid disease management and can increase accuracy in determining the need for and place of hospitalization. The inclusion of biomarkers, particularly procalcitonin, in the decision taken process is a promising strategy. This study aims to present a narrative review of the potential applications and limitations of procalcitonin as a prognostic marker in hospitalized patients with lower respiratory tract infections. The studies on this topic are heterogeneous with respect to procalcitonin measurement techniques, cutoff values, clinical settings, and disease severity. The results show that procalcitonin delivers moderate performance for prognostic prediction in patients with lower respiratory tract infections; its predictive performance was not higher than that of classical methods, and knowledge of procalcitonin levels is most useful when interpreted together with other clinical and laboratory results. Overall, repeated measurement of the procalcitonin levels during the first days of treatment provides more prognostic information than a single measurement; however, information on the cost-effectiveness of this procedure in intensive care patients is lacking. The results of studies that evaluated the prognostic value of initial procalcitonin levels in patients with community-acquired pneumonia are more consistent and have greater potential for practical application; in this case, low procalcitonin levels identify those patients with a low risk of adverse outcomes. PMID:27305038

  12. Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients.

    PubMed

    Hiwase, Devendra K; Singhal, Deepak; Strupp, Corinna; Chhetri, Rakchha; Kutyna, Monika M; Wee, L Amilia; Harrison, Peter B; Nath, Shriram V; Wickham, Nicholas; Hui, Chi-Hung; Gray, James X; Bardy, Peter; Ross, David M; Lewis, Ian D; Reynolds, John; To, L Bik; Germing, Ulrich

    2017-03-01

    RBC-transfusion dependency (RBC-TD) is an independent prognostic factor for poor overall survival (OS) in the WHO classification-based prognostic scoring system (WPSS) for MDS patients. However, WPSS did not include cytopenia, whereas revised International Prognostic Scoring System (IPSS-R) did not include RBC-TD. Thus, neither of these prognostic scoring systems incorporates both cytopenia and RBC-TD. We aimed to test whether RBC-TD adds prognostic value to the IPSS-R. We analyzed MDS patients not treated with disease-modifying therapy, and enrolled in SA-MDS Registry (derivation cohort; n = 295) and Dusseldorf registry (Germany; validation cohort; n = 113) using time-dependent Cox proportional regression and serial landmark analyses. In the derivation cohort, RBC-TD patients had inferior OS compared to RBC transfusion-independent (RBC-TI) patients (P < 0.0001) at 6- (18 vs. 64 months), 12- (24 vs. 71 months), and 24-months (40 vs. 87 months). In a Cox proportional regression analysis, RBC-TD was an independent adverse prognostic marker in addition to age, sex, and IPSS-R variables (P < 0.0001). A prognostic index (PI) was derived using these Cox-proportional regression model variables. In the validation cohort, this PI classified patients into four prognostic groups with significantly different OS (P < 0.001) as in the derivation cohort. In conclusion, multivariate analysis by Cox proportional hazards regression and serial landmark analyses clearly demonstrates that development of RBC-TD at any time during the course of MDS is associated with poor OS, independent of IPSS-R. This study demonstrates that dynamic assessment of RBC-TD provides additional prognostic value to IPSS-R and should be included in treatment decision algorithms for MDS patients.

  13. Nasopharyngeal and Oropharyngeal Colonization by Staphylococcus aureus and Streptococcus pneumoniae and Prognostic Markers in Children with Sickle Cell Disease from the Northeast of Brazil

    PubMed Central

    Rocha, Larissa C.; Carvalho, Magda O. S.; Nascimento, Valma M. L.; dos Santos, Milena S.; Barros, Tânia F.; Adorno, Elisângela V.; Reis, Joice N.; da Guarda, Caroline C.; Santiago, Rayra P.; Gonçalves, Marilda de Souza

    2017-01-01

    We investigated the nasopharynx and oropharynx microbiota in sickle cell disease (SCD) to identify the microorganisms, antibiotic sensitivity, prevalent serotypes, and association of with laboratorial markers. Oropharynx/nasopharynx secretions were investigated in 143 SCD children aging 6 months to 17 years. Pathogens were isolated using standard procedures, and laboratorial markers were performed by automated methods. Staphylococcus aureus (S. aureus) was isolated from nasopharynx and oropharynx of 64 and of 17 SCD children respectively. Streptococcus pneumoniae (S. pneumoniae) was isolated from the nasopharynx and oropharynx of eight SCD patients. Serotypes of S. pneumoniae were 19F, 23F, and 14. All isolates were susceptible to penicillin, and patients whose nasopharynx and oropharynx were colonized by S. pneumoniae had high concentrations of aspartate transaminase, alanine transaminase, and ferritin. S. pneumoniae isolated were not penicillin-resistant serotypes suggesting that the use of penicillin for prophylaxis and/or treatment of infections is safe. Our finding of colonization and laboratory evaluation in SCD patients suggests that microorganisms are involved in the modulation of chronic inflammatory. The association of colonized microorganisms and laboratorial markers suggest a new approach to these patients follow-up, and additional studies of microorganism colonization and their association with SCD patients' clinical outcome will improve control and prevention strategies. PMID:28261176

  14. Nasopharyngeal and Oropharyngeal Colonization by Staphylococcus aureus and Streptococcus pneumoniae and Prognostic Markers in Children with Sickle Cell Disease from the Northeast of Brazil.

    PubMed

    Rocha, Larissa C; Carvalho, Magda O S; Nascimento, Valma M L; Dos Santos, Milena S; Barros, Tânia F; Adorno, Elisângela V; Reis, Joice N; da Guarda, Caroline C; Santiago, Rayra P; Gonçalves, Marilda de Souza

    2017-01-01

    We investigated the nasopharynx and oropharynx microbiota in sickle cell disease (SCD) to identify the microorganisms, antibiotic sensitivity, prevalent serotypes, and association of with laboratorial markers. Oropharynx/nasopharynx secretions were investigated in 143 SCD children aging 6 months to 17 years. Pathogens were isolated using standard procedures, and laboratorial markers were performed by automated methods. Staphylococcus aureus (S. aureus) was isolated from nasopharynx and oropharynx of 64 and of 17 SCD children respectively. Streptococcus pneumoniae (S. pneumoniae) was isolated from the nasopharynx and oropharynx of eight SCD patients. Serotypes of S. pneumoniae were 19F, 23F, and 14. All isolates were susceptible to penicillin, and patients whose nasopharynx and oropharynx were colonized by S. pneumoniae had high concentrations of aspartate transaminase, alanine transaminase, and ferritin. S. pneumoniae isolated were not penicillin-resistant serotypes suggesting that the use of penicillin for prophylaxis and/or treatment of infections is safe. Our finding of colonization and laboratory evaluation in SCD patients suggests that microorganisms are involved in the modulation of chronic inflammatory. The association of colonized microorganisms and laboratorial markers suggest a new approach to these patients follow-up, and additional studies of microorganism colonization and their association with SCD patients' clinical outcome will improve control and prevention strategies.

  15. Stratified analysis reveals chemokine-like factor (CKLF) as a potential prognostic marker in the MSI-immune consensus molecular subtype CMS1 of colorectal cancer

    PubMed Central

    Dunne, Philip D.; O'Reilly, Paul G.; Coleman, Helen G.; Gray, Ronan T.; Longley, Daniel B.; Johnston, Patrick G.; Salto-Tellez, Manuel

    2016-01-01

    The Colorectal Cancer (CRC) Subtyping Consortium (CRCSC) recently published four consensus molecular subtypes (CMS's) representing the underlying biology in CRC. The Microsatellite Instable (MSI) immune group, CMS1, has a favorable prognosis in early stage disease, but paradoxically has the worst prognosis following relapse, suggesting the presence of factors enabling neoplastic cells to circumvent this immune response. To identify the genes influencing subsequent poor prognosis in CMS1, we analyzed this subtype, centered on risk of relapse. In a cohort of early stage colon cancer (n=460), we examined, in silico, changes in gene expression within the CMS1 subtype and demonstrated for the first time the favorable prognostic value of chemokine-like factor (CKLF) gene expression in the adjuvant disease setting [HR=0.18, CI=0.04-0.89]. In addition, using transcription profiles originating from cell sorted CRC tumors, we delineated the source of CKLF transcription within the colorectal tumor microenvironment to the leukocyte component of these tumors. Further to this, we confirmed that CKLF gene expression is confined to distinct immune subsets in whole blood samples and primary cell lines, highlighting CKLF as a potential immune cell-derived factor promoting tumor immune-surveillance of nascent neoplastic cells, particularly in CMS1 tumors. Building on the recently reported CRCSC data, we provide compelling evidence that leukocyte-infiltrate derived CKLF expression is a candidate biomarker of favorable prognosis, specifically in MSI-immune stage II/III disease. PMID:27153559

  16. Increased expression of discoidin domain receptor 2 (DDR2): a novel independent prognostic marker of worse outcome in breast cancer patients.

    PubMed

    Ren, Tingting; Zhang, Jian; Zhang, Jing; Liu, Xinping; Yao, Libo

    2013-03-01

    The discoidin domain receptors, DDR1 and DDR2, have been linked with numerous human cancers. We sought to determine expression level and distribution of DDRs in human breast cancer, and investigate prognostic determinates to determine whether levels of DDRs could predict survival. Tumor samples from 122 breast cancer patients were analyzed for relative expression of DDRs. An additional 24 matched tumor and normal tissues were tested for differential expression of DDR1 and DDR2. DDR2 was found to be significantly increased by 6-fold (P = 0.0005) and DDR1 decreased (P = 0.0001) in tumor vs. normal breast tissue. DDR1 expression was not predictive for patient survival; however, DDR2 expression was significantly associated with disease-free (HR = 0.55, 95 % CI = 0.24-0.78, P = 0.026) and overall survival (HR = 0.46, 95 % CI = 0.35-0.84, P = 0.019). Multivariate analysis revealed DDR2 is an independent favorable predictor for prognosis independent of tumor stage, histology, and patient age. The present research provided the first evidence that increased DDR2 mRNA expression in primary human breast cancer might be a powerful, independent predictor of recurrence and outcome.

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

    PubMed

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

    2014-04-01

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

  18. Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer

    PubMed Central

    2011-01-01

    Background The research emphasis in anti-cancer drug discovery has always been to search for a drug with the greatest antitumor potential but fewest side effects. This can only be achieved if the drug used is against a specific target located in the tumor cells. In this study, we evaluated Minichromosome Maintenance Protein 7 (MCM7) as a novel therapeutic target in cancer. Results Immunohistochemical analysis showed that MCM7 was positively stained in 196 of 331 non-small cell lung cancer (NSCLC), 21 of 29 bladder tumor and 25 of 70 liver tumor cases whereas no significant staining was observed in various normal tissues. We also found an elevated expression of MCM7 to be associated with poor prognosis for patients with NSCLC (P = 0.0055). qRT-PCR revealed a higher expression of MCM7 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpressed MCM7 by cDNA microarray analysis. Suppression of MCM7 using specific siRNAs inhibited incorporation of BrdU in lung and bladder cancer cells overexpressing MCM7, and suppressed the growth of those cells more efficiently than that of normal cell strains expressing lower levels of MCM7. Conclusions Since MCM7 expression was generally low in a number of normal tissues we examined, MCM7 has the characteristics of an ideal candidate for molecular targeted cancer therapy in various tumors and also as a good prognostic biomarker for NSCLC patients. PMID:21619671

  19. MicroRNA-543 acts as a prognostic marker and promotes the cell proliferation in cervical cancer by BRCA1-interacting protein 1.

    PubMed

    Dang, Huimin; Zheng, Pengsheng; Liu, Yu; Wu, Xiaoling; Wu, Xili

    2017-02-01

    Human cervical cancer is one of the most common malignancies worldwide. Recent studies have focused on microRNAs that play crucial roles in cancer development and progression of cervical cancer. In this study, we aimed to analyse the biological function of microRNA-543 in cervical cancer. Samples of human cervical cancer and matched adjacent normal cervical tissues were collected, and expression level of microRNA-543 and the clinical characteristics of cervical cancer were investigated. We found that microRNA-543 expression was significantly elevated in cervical cancer and its aberrant expression levels were positively correlated with tumour size ( p = 0.0315), differentiation ( p = 0.0134), clinical stage ( p = 0.0315) and overall ( p = 0.0426) and disease-free survival ( p = 0.0396) of cervical cancer. Overexpression of microRNA-543 in cancer-derived HeLa and SiHa facilitated cell growth and suppressed cell apoptosis, while down-regulation of microRNA-543 exerted a reverse effect on cell growth and apoptosis. In addition, we demonstrated that BRCA1-interacting protein 1 was directly regulated by microRNA-543 and the restoration of BRCA1-interacting protein 1 expression reversed the effects of microRNA-543 on cell proliferation. Taken together, these findings collectively demonstrate that microRNA-543 exerts its oncogene function by directly targeting BRCA1-interacting protein 1 in cervical cancer, indicating a potential novel potential prognostic biomarker and therapeutic target for cervical cancer.

  20. Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers.

    PubMed

    Lucioni, Marco; Berti, Emilio; Arcaini, Luca; Croci, Giorgio A; Maffi, Aldo; Klersy, Catherine; Goteri, Gaia; Tomasini, Carlo; Quaglino, Pietro; Riboni, Roberta; Arra, Mariarosa; Dallera, Elena; Grandi, Vieri; Alaibac, Mauro; Ramponi, Antonio; Rattotti, Sara; Cabras, Maria Giuseppina; Franceschetti, Silvia; Fraternali-Orcioni, Giulio; Zerbinati, Nicola; Onida, Francesco; Ascani, Stefano; Fierro, Maria Teresa; Rupoli, Serena; Gambacorta, Marcello; Zinzani, Pier Luigi; Pimpinelli, Nicola; Santucci, Marco; Paulli, Marco

    2016-10-01

    Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a "double hit score" upon positivity for BCL2 and MYC. PCDLBCL-NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B-cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a "non-germinal B-cell" profile, whereas "germinal center" cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC-LT, which often coexpressed MYC and BCL2. The impact of single factors on 5-year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group-PCDLBCL-NOS-exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.

  1. CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion.

    PubMed

    Zhou, Pengcheng; Erfani, Sonia; Liu, Zeyi; Jia, Changhe; Chen, Yecang; Xu, Bingwei; Deng, Xinyu; Alfáro, Jose E; Chen, Li; Napier, Dana; Lu, Michael; Huang, Jian-An; Liu, Chunming; Thibault, Olivier; Segal, Rosalind; Zhou, Binhua P; Kyprianou, Natasha; Horbinski, Craig; Yang, Xiuwei H

    2015-10-06

    Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based cohort of 96 patient biopsies and TCGA dataset to evaluate the clinical significance of CD151 and α3β1 integrin. Functional and signaling analyses were also conducted to understand how these molecules promote the aggressiveness of glioblastoma at molecular and cellular levels. Results from our analyses showed that CD151 and α3 integrin were significantly elevated in glioblastomas at both protein and mRNA levels, and exhibited strong inverse correlation with patient survival (p < 0.006). These adhesion molecules also formed tight protein complexes and synergized with EGF/EGFR to accelerate tumor cell motility and invasion. Furthermore, disruption of such complexes enhanced the survival of tumor-bearing mice in a xenograft model, and impaired activation of FAK and small GTPases. Also, knockdown- or pharmacological agent-based attenuation of EGFR, FAK or Graf (ARHGAP26)/small GTPase-mediated pathways markedly mitigated the aggressiveness of glioblastoma cells. Collectively, our findings provide clinical, molecular and cellular evidence of CD151-α3β1 integrin complexes as promising prognostic biomarkers and therapeutic targets for glioblastoma.

  2. CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion

    PubMed Central

    Xu, Bingwei; Deng, Xinyu; Alfáro, Jose E.; Chen, Li; Napier, Dana; Lu, Michael; Huang, Jian-An; Liu, Chunming; Thibault, Olivier; Segal, Rosalind; Zhou, Binhua P.; Kyprianou, Natasha; Horbinski, Craig; Yang, Xiuwei H.

    2015-01-01

    Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated α3β1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based cohort of 96 patient biopsies and TCGA dataset to evaluate the clinical significance of CD151 and α3β1 integrin. Functional and signaling analyses were also conducted to understand how these molecules promote the aggressiveness of glioblastoma at molecular and cellular levels. Results from our analyses showed that CD151 and α3 integrin were significantly elevated in glioblastomas at both protein and mRNA levels, and exhibited strong inverse correlation with patient survival (p < 0.006). These adhesion molecules also formed tight protein complexes and synergized with EGF/EGFR to accelerate tumor cell motility and invasion. Furthermore, disruption of such complexes enhanced the survival of tumor-bearing mice in a xenograft model, and impaired activation of FAK and small GTPases. Also, knockdown- or pharmacological agent-based attenuation of EGFR, FAK or Graf (ARHGAP26)/small GTPase-mediated pathways markedly mitigated the aggressiveness of glioblastoma cells. Collectively, our findings provide clinical, molecular and cellular evidence of CD151-α3β1 integrin complexes as promising prognostic biomarkers and therapeutic targets for glioblastoma. PMID:26377974

  3. Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections.

    PubMed

    Huenecke, Sabine; Cappel, Claudia; Esser, Ruth; Pfirrmann, Verena; Salzmann-Manrique, Emilia; Betz, Sibille; Keitl, Eileen; Banisharif-Dehkordi, Julia; Bakhtiar, Shahrzad; Königs, Christoph; Jarisch, Andrea; Soerensen, Jan; Ullrich, Evelyn; Klingebiel, Thomas; Bader, Peter; Bremm, Melanie

    2017-01-01

    Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56(++)CD16(-) (CD56(bright)), CD56(++)CD16(+) (CD56(intermediate=int)), and CD56(+)CD16(++) (CD56(dim)) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56(bright)/CD56(int)/CD56(dim) changed from 15/8/78% in early childhood to 6/4/90% in adults, respectively. Within this study, we first compared the NK cell reconstitution post-HSCT to reference values of NK cell subpopulations of healthy children. Afterward, we investigated the reconstitution of NK cell subpopulations post-HSCT in correlation to acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) as well as to viral infections. Interestingly, after a HSCT follow-up phase of 12 months, the distribution of NK cell subpopulations largely matched the 50th percentile of the reference range for healthy individuals. Patients suffering from aGvHD and cGvHD showed a delayed reconstitution of NK cells. Remarkably, within the first 2 months post-HSCT, patients suffering from aGvHD had significantly lower levels of CD56(bright) NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56(bright) NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56(int) NK cells seemed to be characteristic for the chronification of GvHD. In context of viral infection, a slightly lower CD56 and CD16 receptor expression followed by a considerable reduction in the absolute CD56(dim) NK cell numbers combined with reoccurrence of CD56(int) NK cells was observed. Our

  4. [CD34(+)CD19(+) cells with CD123 overexpression are a novel prognostic marker in Ph chromosome-positive acute lymphoblastic leukemia].

    PubMed

    Kong, Yuan; Huang, Xiao-Jun; Hao, Le; Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Liu, Yan-Rong

    2014-02-01

    This study was aimed to investigate the characteristics of CD123 expression on CD34(+)CD19(+) cells and its prognostic significance as a novel MRD biomarker in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) patients. Consecutive newly diagnosed Ph(+)ALL patients (n = 49) in Peking University Institute of Hematology from January 2010 to April 2012 were prospectively enrolled in this study. At diagnosis and different time points during treatment, CD123 expression on CD34(+)CD19(+) cells was examined by multiparameter flow cytometry(MFC). More than 10 CD34(+)CD19(+) cells with CD123 overexpression in bone marrow samples after complete remission were defined as FCM positive (FCM(+)). The BCR-ABL1[STBZ] transcript was detected by real-time quantitative polymerase chain reaction (RQ-PCR) concurrently. The results showed that mean fluorescence intensity of CD123 on CD34(+)CD19(+) cells in newly diagnosed Ph(+)ALL and relapsed Ph(+)ALL patients was significantly higher than that of normal B-cell progenitors [8.52(3.71-32.35) vs 8.93(4.79-29.74) vs 1.31(0.21-1.75), P < 0.05]. In addition, ratio of the CD34(+)CD19(+) cells with CD123 overexpression in newly diagnosed Ph(+)ALL and relapsed Ph(+)ALL patients were significantly higher than that of normal B-cell progenitors [84.63% (55.07%-99.96%) vs 84.50% (57.68%-99.80%) vs 0.99% (0.45%- 1.83%), P < 0.05]. CD34(+)CD19(+) cells with CD123 overexpression were detected in all newly diagnosed and relapsed Ph(+)ALL patients. A good correlation was found between the MRD results of CD34(+)CD19(+) cells with CD123 overexpression detected by MFC and that detected by RQ-PCR (n = 360 pairs, Spearman r = 0.90, P < 0.0001). Among 13 cases relapsed during follow up, 11 cases of them were detected by FCM(+) at a median time of 60 (30-73) days before the recurrence. It is concluded that as a complementary to RQ-PCR, detection of the CD34(+)CD19(+) cells with CD123 overexpression by MFC promises to be an efficient

  5. Development of Three Different NK Cell Subpopulations during Immune Reconstitution after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Markers in GvHD and Viral Infections

    PubMed Central

    Huenecke, Sabine; Cappel, Claudia; Esser, Ruth; Pfirrmann, Verena; Salzmann-Manrique, Emilia; Betz, Sibille; Keitl, Eileen; Banisharif-Dehkordi, Julia; Bakhtiar, Shahrzad; Königs, Christoph; Jarisch, Andrea; Soerensen, Jan; Ullrich, Evelyn; Klingebiel, Thomas; Bader, Peter; Bremm, Melanie

    2017-01-01

    Natural killer (NK) cells play an important role following allogeneic hematopoietic stem cell transplantation (HSCT) exerting graft-versus-leukemia/tumor effect and mediating pathogen-specific immunity. Although NK cells are the first donor-derived lymphocytes reconstituting post-HSCT, their distribution of CD56++CD16− (CD56bright), CD56++CD16+ (CD56intermediate=int), and CD56+CD16++ (CD56dim) NK cells is explicitly divergent from healthy adults, but to some extent comparable to the NK cell development in early childhood. The proportion of CD56bright/CD56int/CD56dim changed from 15/8/78% in early childhood to 6/4/90% in adults, respectively. Within this study, we first compared the NK cell reconstitution post-HSCT to reference values of NK cell subpopulations of healthy children. Afterward, we investigated the reconstitution of NK cell subpopulations post-HSCT in correlation to acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) as well as to viral infections. Interestingly, after a HSCT follow-up phase of 12 months, the distribution of NK cell subpopulations largely matched the 50th percentile of the reference range for healthy individuals. Patients suffering from aGvHD and cGvHD showed a delayed reconstitution of NK cells. Remarkably, within the first 2 months post-HSCT, patients suffering from aGvHD had significantly lower levels of CD56bright NK cells compared to patients without viral infection or without graft versus host disease (GvHD). Therefore, the amount of CD56bright NK cells might serve as an early prognostic factor for GvHD development. Furthermore, a prolonged and elevated peak in CD56int NK cells seemed to be characteristic for the chronification of GvHD. In context of viral infection, a slightly lower CD56 and CD16 receptor expression followed by a considerable reduction in the absolute CD56dim NK cell numbers combined with reoccurrence of CD56int NK cells was observed. Our results suggest that a precise

  6. Validation of Lysyl Oxidase As a Prognostic Marker for Metastasis and Survival in Head and Neck Squamous Cell Carcinoma: Radiation Therapy Oncology Group Trial 90-03

    PubMed Central

    Le, Quynh-Thu; Harris, Jonathan; Magliocco, Anthony M.; Kong, Christina S.; Diaz, Roman; Shin, Brian; Cao, Hongbin; Trotti, Andy; Erler, Janine T.; Chung, Christine H.; Dicker, Adam; Pajak, Thomas F.; Giaccia, Amato J.; Ang, K. Kian

    2009-01-01

    Purpose To validate lysyl oxidase (LOX), a hypoxia-related protein, as a marker for metastasis in an independent head and neck cancer (HNC) patient group enrolled onto a prospective trial. Patients and Methods We performed traditional immunohistochemical (IHC) staining and automated quantitative analysis (AQUA) for LOX expression in 66 HNC patients from one institution. We also performed AQUA staining for LOX in 306 of 1,113 patients treated on a phase III trial comparing four radiation fractionation schedules in locally advanced HNC (RTOG 90-03). Pretreatment characteristics and outcome were similar between patients with and without LOX assessment. We correlated AQUA LOX expression with time to metastasis (TTM), time to progression (TTP), and overall survival (OS). Results LOX expression from both staining methods predicted for TTM in the first 66 patients. Multivariate analysis, controlling for significant parameters including nodal stage and performance status, revealed tumor LOX expression, as a continuous variable, was an independent predictor for TTM (hazard ratio [HR], 1.21; 95% CI, 1.10 to 1.33; P = .0001), TTP (HR, 1.06; 95% CI, 1.02 to 1.10; P = .0069), and OS (HR, 1.04; 95% CI, 1.00 to 1.07; P = .0311) in RTOG 90-03 patients. This translates into a 259% increase in metastatic risk for a patient at the 75th percentile of LOX compared with one at the 25th percentile. Conclusion AQUA LOX expression was strongly associated with increased metastasis, progression, and death in RTOG 90-03 patients. This study validates that LOX is a marker for metastasis and survival in HNC. PMID:19667273

  7. Serum Cytokinome Profile Evaluation: A Tool to Define New Diagnostic and Prognostic Markers of Cancer Using Multiplexed Bead-Based Immunoassays

    PubMed Central

    Sorice, Angela

    2016-01-01

    In recent years, many researchers are focusing their attention on the link between inflammation and cancer. The inflammation is involved in the tumor development and suppression, by stimulating the immune response. In particular, the transition from chronic inflammation to cancer produces angiogenic and growth factors able to repair the tissue and to promote cancer cell survival, implantation, and growth. In this contest, the cytokines contribute to the development of these processes becoming active before and during the inflammatory process and playing an important function at the various disease levels. Thus, these proteins can represent specific markers of tumor development and progression. Therefore the “cytokinome” term is used to indicate the evaluation of cytokine pattern by using an “omics” approach. Newly, specific protein chips of considerable and improved sensitivity are being developed to determine simultaneously several and different cytokines. This can be achieved by a multiplex technology that, through the use of small amounts of serum or other fluids, is used to determine the presence and the levels of underrepresented cytokines. Since this method is an accurate, sensitive, and reproducible cytokine assay, it is already used in many different studies. Thus, this review focuses on the more latest aspects related to cytokinome profile evaluation in different cancers. PMID:28050120

  8. [Diagnostic and prognostic value of p53 oncogene and the selected neoplastic markers (Ki67, PCNA, DNA ploidy) of the ultrastructure in patients with laryngeal cancer].

    PubMed

    Golusiński, W; Szmeja, Z; Olofsson, J; Biczysko, W; Krygier-Stojałowska, A; Majewski, P

    1996-01-01

    A comparison was performed of staining intensity of immunohistochemical proliferating antigens (p53, PCNA, Ki67), DNA flow cytometry and ultrastructure of the carcinoma cells in 120 cases of laryngeal cancer. Clinically very advanced tumors were in majority (T3 - 43%, T4 - 18%). A 5 graded scale was adapted to evaluate the level of immunohistochemical staining of the carcinoma cell nuclei. A positive staining was obtained in 70% for p53, 57% for Ki67 and in 80(2/3) for PCNA. 62% of the cases were DNA diploid and 38% DNA aneuploid. The DNA diploid carcinomas were accompanied by the enlargement of the cell nuclei, preserving of the nuclei's wide margins of heterochromatine, enlargement of the nuclear area and increase of the number of nuclei. In the aneuploid-polyploid cancer the nuclei had a substantial polymorphism with large cleaved nuclei and with significant variation in size, and with nuclear envelope. A frequent finding was euchromatization of chromatine. Dense chromatine appeared in the form of small clumps spread over the whole area of these irregular nuclei. Enlargement and activation of nucleoli occurred. There was a positive correlation (Chi-square) between T- and N-stage and immunohistochemical staining. There was also a positive correlation in staining intensity between p53, Ki67 and PCNA. There is also strong correlation between these markers of proliferative activity and the degree of aggressiveness of the tumour.

  9. Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas.

    PubMed

    Colman, Howard; Giannini, Caterina; Huang, Li; Gonzalez, Javier; Hess, Kenneth; Bruner, Janet; Fuller, Gregory; Langford, Lauren; Pelloski, Christopher; Aaron, Joann; Burger, Peter; Aldape, Ken

    2006-05-01

    Distinguishing between grade II and grade III diffuse astrocytomas is important both for prognosis and for treatment decision-making. However, current methods for distinguishing between grades based on proliferative potential are suboptimal, making identification of clear cutoffs difficult. In this study, we compared the results from immunohistochemical staining for phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis, with standard mitotic counts (number of mitoses/10 high-power fields) and MIB-1 labeling index values for assessing proliferative activity. We tested the relationship between pHH3 staining and tumor grade and prognosis in a retrospective series of grade II and III infiltrating astrocytomas from a single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade II and III diffuse astrocytomas from patients with clinical follow-up. pHH3 staining was found to be a simple and reliable method for identifying mitotic figures, allowing a true mitotic index to be determined. The pHH3 mitotic index was significantly associated both with the standard mitotic count and with the MIB-1 index. Univariate analyses revealed that all 3 measurements of proliferation were significantly associated with survival. However, the pHH3 mitotic index accounted for a larger proportion of variability in survival than standard mitotic count or MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection, and performance score, the pHH3 mitotic index remained an independent predictor of survival. Thus, pHH3 staining provides a simple and reliable method for quantifying proliferative potential and for the stratification of patients with diffuse astrocytomas into typical grade II and III groups. These results also suggest that pHH3 staining may be a useful method in other neoplasms in which accurate determination of proliferation potential

  10. Peripheral blood lymphocyte-to-monocyte ratio as a prognostic factor in advanced epithelial ovarian cancer: a multicenter retrospective study

    PubMed Central

    Zhu, Jia-yu; Liu, Cheng-cheng; Wang, Liang; Zhong, Mei; Tang, Hai-lin; Wang, Hua

    2017-01-01

    The lymphocyte-to-monocyte ratio (LMR), as a surrogate marker of systemic inflammation, has been found to be a novel prognostic indicator in various malignancies. Data from 672 advanced epithelial ovarian cancer (EOC) patients treated with neoadjuvant chemotherapy (NAC) followed by debulking surgery were analyzed, and the prognostic value of LMR were evaluated. The optimal cutoff point of LMR in prediction of survival was defined as 3.45 through receiver operating characteristics curve analysis. Patients with low LMR (≤3.45) at diagnosis tended to have more adverse clinical features, such as higher histological grade, chemotherapy resistance, and residual tumor >1cm after debulking surgery. No significant correlation was found between LMR level and age and histological type. Moreover, after NAC, the complete remission (CR) rate for the low-LMR group was lower than those for the high-LMR group (P<0.05). Patients with low LMR had poorer progression-free survival (PFS; P<0.001) and overall survival (OS; P<0.001). Multivariate analysis revealed that low LMR was an independent adverse predictor for PFS and OS. Results indicated that low LMR at diagnosis is a novel independent prognostic factor for advanced EOC. However, prospective study is needed to validate this prognostic factor and biological studies should further investigate the mechanisms underlying the correlation between low LMR and poor prognosis in advanced EOC.

  11. Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram

    PubMed Central

    Gu, Liangyou; Ma, Xin; Li, Hongzhao; Chen, Luyao; Xie, Yongpeng; Zhao, Chaofei; Luo, Guoxiong; Zhang, Xu

    2016-01-01

    To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four markers using Kaplan-Meier method and Cox regression models. Additionally, a nomogram was established to predict the prognosis of sRCC patients. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), nevertheless, elevated LMR showed an adverse effect on reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50–11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a prognostic model including T stage, M stage, tumor necrosis and percentage of sarcomatoid generated a nomogram, which accurately predicted OS for sRCC patients. Preoperative NLR may serve as a potential prognostic biomarker in patients with sRCC and may help with clinical decisions about treatment intervention in clinical practice. The proposed nomogram can be used for the prediction of OS in patients with sRCC. PMID:27035802

  12. Bio-pathologic characteristics related to chromosome 11 aneusomy and cyclin D1 gene status in surgically resected stage I and II breast cancer: Identification of an adverse prognostic profile.

    PubMed

    Mottolese, Marcella; Orlandi, Giulia; Sperduti, Isabella; Merola, Roberta; Buglioni, Simonetta; Di Benedetto, Anna; Pinnarò, Paola; Perracchio, Letizia; Venturo, Irene; Cognetti, Francesco; Cianciulli, AnnaMaria

    2007-02-01

    We aimed at developing a more detailed understanding of cyclin D1 in early stage human breast cancer and defining the biologic profiles with different prognostic value correlating cyclin D1 gene amplification and chromosome 11 aneusomy with bio-pathologic variables of known clinical importance. Cyclin D1 gene amplification and chromosome 11 aneusomy were investigated using fluorescence in situ hybridization whereas cyclin D1, PgR, HER-2, Bcl2, p53, and Ki-67 expressions were analyzed by immunohistochemistry in 121 stage I or II breast cancer patients uniformly treated with cyclophosphamide/metotrexate/5-fluorouracil-based chemotherapy. Cyclin D1 was amplified in 6.6% and overexpressed in 32.2% of cases. Amplification was not associated with any selected bio-pathologic variables, whereas the chromosome 11 aneusomy level significantly increased in tumors with higher histologic grade (P < 0.01), higher tumor size (P < 0.003), p53 nuclear accumulation (P < 0.04), and ERalpha negativity (P < 0.049). Multiple correspondence analysis showed 4 different biologic tumor profiles. The first, characterized by high Ki-67 score, p53+, cyclin D1+, HER-2+, aneusomy level > 30%, ratio (cyclin D1 gene/CEP11) > 2, was associated with tumor relapse defining the most unfavorable biologic profile. Kaplan-Meier's method showed significantly shorter disease-free survival in patients with at least 3 variables positive out of the 6 detected by multiple correspondence analysis. In multivariate analysis, the identified biologic profile emerged as the only significant prognostic indicator. Our findings are of particular clinical interest for early stage breast cancer patients, because the assessment of biologic factors predictive of tumor aggressiveness may influence postoperative therapeutic strategies.

  13. Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial

    PubMed Central

    Schmainda, Kathleen M.; Zhang, Zheng; Prah, Melissa; Snyder, Bradley S.; Gilbert, Mark R.; Sorensen, A. Gregory; Barboriak, Daniel P.; Boxerman, Jerrold L.

    2015-01-01

    Background The study goal was to determine whether changes in relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI are predictive of overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) when measured 2, 8, and 16 weeks after treatment initiation. Methods Patients with recurrent GBM (37/123) enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide, consented to DSC-MRI plus conventional MRI, 21 with DSC-MRI at baseline and at least 1 postbaseline scan. Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images. Mean tumor rCBV normalized to white matter (nRCBV) and standardized rCBV (sRCBV) were determined for these regions of interest. The OS rates for patients with positive versus negative changes from baseline in nRCBV and sRCBV were compared using Wilcoxon rank-sum and Kaplan–Meier survival estimates with log-rank tests. Results Patients surviving at least 1 year (OS-1) had significantly larger decreases in nRCBV at week 2 (P = .0451) and sRCBV at week 16 (P = .014). Receiver operating characteristic analysis found the percent changes of nRCBV and sRCBV at week 2 and sRCBV at week 16, but not rCBV data at week 8, to be good prognostic markers for OS-1. Patients with positive change from baseline rCBV had significantly shorter OS than those with negative change at both week 2 and week 16 (P = .0015 and P = .0067 for nRCBV and P = .0251 and P = .0004 for sRCBV, respectively). Conclusions Early decreases in rCBV are predictive of improved survival in patients with recurrent GBM treated with bevacizumab. PMID:25646027

  14. Identification of Prostate Cancer Prognostic Markers

    DTIC Science & Technology

    2015-10-01

    specific AIM 2. Specific probes were generated from BAC clones and hybridized on normal lymphocyte metaphases, with their commercially available...microscopy to assess autophagosome formation, as an alternative to LC3-II/LC3-I ratios in Western blotting [5]. -Generation of stable clones ...Figure 10 A) shows Western blotting of 22Rv1 cell lysates from an independent set of Mock, ECI1-untagged or V5-tagged clones assessing stable ECI1

  15. Potential Prognostic Markers for Human Prostate Cancer

    DTIC Science & Technology

    2001-03-01

    such as proliferation, differentiation and assay [15]. TGF[3 may be produced by metastatic motility. Upregulation of growth factor synthesis or prostate...via mod- ronment include neuroendocrine cells. These cells ulation of tumor cell receptor expression. Control of can secrete bombesin, a gastrin ...controls, indicating that addition ofT015 accelerates tumor expansion. TIl15 synthesis triggered a dramatic increase in cell motility, boosting serum

  16. Regional Longitudinal Myocardial Deformation Provides Incremental Prognostic Information in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Jensen, Jan Skov; Pedersen, Sune H.; Galatius, Søren; Fritz-Hansen, Thomas; Bech, Jan; Olsen, Flemming Javier; Mogelvang, Rasmus

    2016-01-01

    Background Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information. Method In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE). Results During a median-follow-up of 5.3 (IQR 2.5–6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters). Conclusion Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse

  17. Prognostic significance of nestin expression in patients with resected non-small cell lung cancer treated with platinum-based adjuvant chemotherapy; relationship between nestin expression and epithelial to mesenchymal transition related markers

    PubMed Central

    Ryuge, Shinichiro; Sato, Yuichi; Nagashio, Ryo; Hiyoshi, Yasuhiro; Katono, Ken; Igawa, Satoshi; Nakashima, Hiroyasu; Shiomi, Kazu; Ichinoe, Masaaki; Murakumo, Yoshiki; Saegusa, Makoto; Satoh, Yukitoshi; Masuda, Noriyuki

    2017-01-01

    Introduction Although adjuvant platinum-based chemotherapy (AC) has been shown to improve survival of patients with completely resected stage II and stage IIIA non-small cell lung cancer (NSCLC), its effect is limited. Nestin is a class VI intermediate filament protein expressed in neural stem cells and several cancer cells including NSCLC. In the present study, we aimed to determine its prognostic significance concerning survival in NSCLC patients receiving AC. Methods Nestin expression in cancer cells was immunohistochemically studied in 90 patients with completely resected stage II and stage IIIA NSCLC treated with AC and its association with clinicopathologic parameters, including ABCG2, E-cadherin, and vimentin expression, was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of nestin expression on survival. Results Nestin expression was observed in 28 of the 90 (31.1%) NSCLCs. Clinicopathologically, nestin expression was associated with loss of E-cadherin expression (P = 0.006) and vimentin positive expression (P < 0.001). In survival analysis, nestin expression was significantly associated with a poorer prognosis (P = 0.028). Multivariable analysis confirmed that nestin expression is an independent prognostic indicator in NSCLC patients receiving AC (HR = 2.56; 95% CI, 1.23–5.30, P = 0.01). Conclusion The present study reveals that nestin expression is a prognostic indicator of a poorer survival probability in NSCLC patients receiving AC, although its prognostic significance still requires confirmation with larger patient populations. PMID:28358810

  18. Prognostic utility of coronary computed tomographic angiography

    PubMed Central

    Otaki, Yuka; Berman, Daniel S.; Min, James K.

    2013-01-01

    Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a noninvasive method that enables accurate detection and exclusion of anatomically obstructive coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. There are numerous potential advantages of CCTA beyond simply luminal stenosis assessment including quantification of atherosclerotic plaque volume as well as assessment of plaque composition, extent, location and distribution. In recent years, an array of studies has evaluated the prognostic utility of CCTA findings of CAD for the prediction of major adverse cardiac events, all-cause death and plaque instability. This prognostic information enhances risk stratification and, if properly acted upon, may improve medical therapy and/or behavioral changes that may enhance event-free survival. The goal of the present article is to summarize the current status of the prognostic utility of CCTA findings of CAD. PMID:23809386

  19. Prognostics for Microgrid Components

    NASA Technical Reports Server (NTRS)

    Saxena, Abhinav

    2012-01-01

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

  20. Vehicle Integrated Prognostic Reasoner (VIPR) Final Report

    NASA Technical Reports Server (NTRS)

    Bharadwaj, Raj; Mylaraswamy, Dinkar; Cornhill, Dennis; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

    2013-01-01

    A systems view is necessary to detect, diagnose, predict, and mitigate adverse events during the flight of an aircraft. While most aircraft subsystems look for simple threshold exceedances and report them to a central maintenance computer, the vehicle integrated prognostic reasoner (VIPR) proactively generates evidence and takes an active role in aircraft-level health assessment. Establishing the technical feasibility and a design trade-space for this next-generation vehicle-level reasoning system (VLRS) is the focus of our work.

  1. Frequency and prognostic value of cardiac troponin I elevation after coronary stenting.

    PubMed

    Garbarz, E; Iung, B; Lefevre, G; Makita, Y; Farah, B; Michaud, P; Graine, H; Vahanian, A

    1999-09-01

    Mild myocardial injuries after coronary angioplasty are associated with adverse late outcomes. The incidence and prognostic value of this phenomenon when using cardiac troponin I (cTnI) after stent implantation is unknown. We studied cTnI and creatine kinase (CK) release in 109 patients after stenting. Clinical success was achieved in 103 patients (94%). In-hospital major adverse coronary events were: death in 1 patient, Q-wave myocardial infarction in 1 patient, and non-Q-wave myocardial infarction in 2 patients. Twenty-nine patients (27%) had postprocedural cTnI increase, 16 (15%) had CK elevation. No preprocedural variables predicted marker elevation. Marker release was related to the occurrence of in-lab complications (59% vs 29% [p = 0.004 for cTnI] and 69% vs 32% [p = 0.011 for CK]). In 34% no explanation was found for cTnI increase. Success was more frequent in patients without cTnI elevation (100% vs 86%, p <0.001). The negative predictive value of cTnI increase was 100% for in-hospital major adverse coronary events (MACE), whereas its positive predictive value was 14%. cTnI and CK concordant elevation was associated with more intra- and postprocedural adverse events. During a mean follow-up of 8+/-3 months, major adverse coronary events were: death in 2 patients, myocardial infarction in 2 patients, and repeat PTCA in 8 patients. cTnI elevation was not predictive of these late MACE. cTnI elevation is common after stenting, and is related to the occurrence of in-lab complications. Its isolated elevation is not a good predictor of MACE. Patients with concordant cTnI and CK elevation seem to be at higher risk of in-hospital MACE.

  2. New prognostic model for extranodal natural killer/T cell lymphoma, nasal type.

    PubMed

    Cai, Qingqing; Luo, Xiaolin; Zhang, Guanrong; Huang, Huiqiang; Huang, Hui; Lin, Tongyu; Jiang, Wenqi; Xia, Zhongjun; Young, Ken H

    2014-09-01

    Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p < 0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p < 0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.

  3. Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies

    PubMed Central

    Utikal, Jochen; Schadendorf, Dirk

    2007-01-01

    Biomarkers are important tools in clinical diagnosis and prognostic classification of various cutaneous malignancies. Besides clinical and histopathological aspects (e.g. anatomic site and type of the primary tumour, tumour size and invasion depth, ulceration, vascular invasion), an increasing variety of molecular markers have been identified, providing the possibility of a more detailed diagnostic and prognostic subgrouping of tumour entities, up to even changing existing classification systems. Recently published gene expression or proteomic profiling data relate to new marker molecules involved in skin cancer pathogenesis, which may, after validation by suitable studies, represent future prognostic or predictive biomarkers in cutaneous malignancies. We, here, give an overview on currently known serologic and newer immunohistochemical biomarker molecules in the most common cutaneous malignancies, malignant melanoma, squamous cell carcinoma and cutaneous lymphoma, particularly emphasizing their prognostic and predictive significance. PMID:17221215

  4. Toward IVHM Prognostics

    NASA Technical Reports Server (NTRS)

    Walsh, Kevin; Venti, Mike

    2007-01-01

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

  5. Prognostic factors in cancer.

    PubMed

    Gospodarowicz, Mary; O'Sullivan, Brian

    2003-01-01

    Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.

  6. IKZF1 expression is a prognostic marker in newly diagnosed standard-risk multiple myeloma treated with lenalidomide and intensive chemotherapy: a study of the German Myeloma Study Group (DSMM).

    PubMed

    Krönke, J; Kuchenbauer, F; Kull, M; Teleanu, V; Bullinger, L; Bunjes, D; Greiner, A; Kolmus, S; Köpff, S; Schreder, M; Mügge, L-O; Straka, C; Engelhardt, M; Döhner, H; Einsele, H; Bassermann, F; Bargou, R; Knop, S; Langer, C

    2017-01-20

    Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from 60 patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial. We found that IKZF1 mRNA expression levels are significantly associated with progression-free survival (PFS). Patients in the lowest quartile (Q1) of IKZF1 expression had a superior PFS compared with patients in the remaining quartiles (Q2-Q4; 3-year PFS of 86 vs 51%, P=0.01). This translated into a significant better overall survival (100 vs 74%, P=0.03). Subgroup analysis revealed a significant impact of IKZF1, IKZF3 and BSG expression levels on PFS in cytogenetically defined standard-risk but not high-risk patients. Our data suggest a prognostic role of IKZF1, IKZF3 and BSG expression levels in lenalidomide-treated multiple myeloma.Leukemia advance online publication, 20 January 2017; doi:10.1038/leu.2016.384.

  7. The Evolution of Prognostic Factors in Multiple Myeloma

    PubMed Central

    Hassanein, Mona; Rasheed, Walid; Aljurf, Mahmoud; Alsharif, Fahad

    2017-01-01

    Multiple myeloma (MM) is a heterogeneous hematologic malignancy involving the proliferation of plasma cells derived by different genetic events contributing to the development, progression, and prognosis of this disease. Despite improvement in treatment strategies of MM over the last decade, the disease remains incurable. All efforts are currently focused on understanding the prognostic markers of the disease hoping to incorporate the new therapeutic modalities to convert the disease into curable one. We present this comprehensive review to summarize the current standard prognostic markers used in MM along with novel techniques that are still in development and highlight their implications in current clinical practice. PMID:28321258

  8. Snakebite mediated acute kidney injury, prognostic predictors, oxidative and carbonyl stress: A prospective study

    PubMed Central

    Mukhopadhyay, P.; Mishra, R.; Mukherjee, D.; Mishra, R.; Kar, M.

    2016-01-01

    Snake bite is an occupational hazard in India and important preventable cause of acute kidney injury (AKI). This study was done to estimate the magnitude of snakebite-induced AKI (SAKI) who required renal replacement therapy, prognostic predictors, and final outcome, and to measure the oxidative and carbonyl stress (CS) level in SAKI patient who underwent hemodialysis (HD). All SAKI patients dialyzed between April 2010 and July 2011 in NRS Medical College were included. Demographical, clinical, and biochemical data were analyzed, and patients are followed to discharge or death. Oxidative and CS markers (advanced oxidation protein product [AOPP], advanced glycation end product, pentosidine, dityrosine, thioberbituric acid reactive substance, and methylglyoxal [MG]) were measured in 48 SAKI patient requiring HD. About 155 SAKI patients (M: F 2.2:1) received HD. Of them. The age was 36.2 (range 4–74) years. The most common site of the bite was lower limb (88.7%). Oliguria and bleeding manifestation were the common presentation. Hypotension was found in 52 (33.5%) cases, cellulitis and inflammation were found in about 63%. Mean creatinine was 4.56 ± 0.24 mg/dl. About 42 (27.1%) had disseminated intravascular coagulation (DIC). 36 (78.2%) had cellulites, 24 (52.2%) had hypotension or shock at initial presentation (P < 0.05), bleeding manifestation was found in 37 (80.4%), and 22 (47.8%) had DIC (P < 0.05). Forty-six (29.7%) patient died. DIC and hypotension/shock at initial presentation came out as an independent predictor of death. Among all markers measured for oxidative and CS (n = 48) AOPP and MG came out as an independent predictor (P < 0.05) of adverse outcome. Hypotension, DIC, AOPP, and MG were a poor prognostic marker in SAKI patients requiring dialysis. PMID:27942175

  9. No prognostic value added by vitamin D pathway SNPs to current prognostic system for melanoma survival

    PubMed Central

    Orlow, Irene; Kanetsky, Peter A.; Thomas, Nancy E.; Fang, Shenying; Lee, Jeffrey E.; Berwick, Marianne; Lee, Ji-Hyun

    2017-01-01

    The prognostic improvement attributed to genetic markers over current prognostic system has not been well studied for melanoma. The goal of this study is to evaluate the added prognostic value of Vitamin D Pathway (VitD) SNPs to currently known clinical and demographic factors such as age, sex, Breslow thickness, mitosis and ulceration (CDF). We utilized two large independent well-characterized melanoma studies: the Genes, Environment, and Melanoma (GEM) and MD Anderson studies, and performed variable selection of VitD pathway SNPs and CDF using Random Survival Forest (RSF) method in addition to Cox proportional hazards models. The Harrell’s C-index was used to compare the performance of model predictability. The population-based GEM study enrolled 3,578 incident cases of cutaneous melanoma (CM), and the hospital-based MD Anderson study consisted of 1,804 CM patients. Including both VitD SNPs and CDF yielded C-index of 0.85, which provided slight but not significant improvement by CDF alone (C-index = 0.83) in the GEM study. Similar results were observed in the independent MD Anderson study (C-index = 0.84 and 0.83, respectively). The Cox model identified no significant associations after adjusting for multiplicity. Our results do not support clinically significant prognostic improvements attributable to VitD pathway SNPs over current prognostic system for melanoma survival. PMID:28323902

  10. Special considerations in prognostic research in cancer involving genetic polymorphisms

    PubMed Central

    2013-01-01

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

  11. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis.

    PubMed

    Ocio, E M; Schop, R F J; Gonzalez, B; Van Wier, S A; Hernandez-Rivas, J M; Gutierrez, N C; Garcia-Sanz, R; Moro, M J; Aguilera, C; Hernandez, J; Xu, R; Greipp, P R; Dispenzieri, A; Jalal, S M; Lacy, M Q; Gonzalez-Paz, N; Gertz, M A; San Miguel, J F; Fonseca, R

    2007-01-01

    Fluorescence in situ hybridisation (FISH) is an effective technique for the cytogenetic analysis of Waldenström macroglobulinemia (WM), but the potential impact of molecular cytogenetics on disease evolution and as a prognostic marker is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most frequent cytogenetic abnormality in WM. This study analysed the prevalence of this aberration in 102 WM patients, and correlated it with disease characteristics. The incidence of 6q21 deletion was 7% by conventional cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M-FISH was used). Patients with deletion of 6q displayed features of adverse prognosis, such as higher levels of beta2-microglobulin and monoclonal paraprotein and a greater tendency to display anaemia and hypoalbuminemia. Interestingly, there was a correlation between the presence of 6q deletion and the International Staging System prognostic index (incidence of 6q- among patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively). Those patients diagnosed with smouldering WM who displayed the abnormality showed a trend to an earlier requirement of treatment. Finally, the survival analysis did not show differences between the two groups of patients, probably due to the short follow up of our series.

  12. Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

    2016-01-01

    Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

  13. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  14. Prognostics of Power MOSFET

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  15. The preoperative alkaline phosphatase-to-platelet ratio index is an independent prognostic factor for hepatocellular carcinoma after hepatic resection

    PubMed Central

    Yu, Ya-Qun; Li, Jun; Liao, Yan; Chen, Qian; Liao, Wei-Jia; Huang, Jian

    2016-01-01

    Abstract A simple, inexpensive, and readily available prognostic index is highly needed to accurately predict the prognosis of hepatocellular carcinoma (HCC). This study aimed to develop a simple prognostic index using routine laboratory tests, alkaline phosphatase-to-platelet count ratio index (APPRI), to predict the likelihood of postoperative survival in HCC patients. A total of 246 patients with HCC undergoing curative resection were retrospectively analyzed. Cutoff point for APPRI was calculated using receiver operating characteristic curve analysis, and then the patients were divided into the low-APPRI group (APPRI ≤ 4.0) and the high-APPRI group (APPRI > 4.0). The influences of APPRI on disease-free survival (DFS) and overall survival (OS) were tested by the Kaplan–Meier method, and multivariate analysis using Cox regression. Elevated APPRI was associated with age, cirrhosis, and aspartate aminotransferase (AST) in HCC. Univariate analysis showed that APPRI > 4.0, tumor size >6 cm, multiple tumors, Barcelona-clinic liver cancer stages B to C, and AST > 40 U/L were significant predictors of worse DFS and OS. A multivariate analysis suggested that APPRI > 4.0 was an independent factor for DFS (hazard ratio [HR] = 1.689; 95% confidence interval [CI], 1.139–2.505; P = 0.009) and OS (HR = 1.664; 95% CI, 1.123–2.466; P = 0.011). Preoperative APPRI > 4.0 was a powerful prognostic predictor of adverse DFS and OS in HCC after surgery. The APPRI may be a promising prognostic marker for HCC after surgical resection. PMID:28002346

  16. Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1{alpha}-related markers, and hemoglobin levels

    SciTech Connect

    Bache, Matthias; Reddemann, Rolf; Said, Harun M.; Holzhausen, Hans-Juergen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Haensgen, Gabriele; Dunst, Juergen; Vordermark, Dirk . E-mail: vordermark_d@klinik.uni-wuerzburg.de

    2006-12-01

    Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO{sub 2}), the hypoxia-related markers hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1{alpha}, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO{sub 2}), HIF-1{alpha} and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1{alpha} expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO{sub 2} correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1{alpha} or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1{alpha}, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found.

  17. Prognostic Significance of Tumor Hypoxia Inducible Factor-1{alpha} Expression for Outcome After Radiotherapy in Oropharyngeal Cancer

    SciTech Connect

    Silva, Priyamal; Slevin, Nick J.; Sloan, Philip; Valentine, Helen; Cresswell, Jo; Ryder, David; Price, Patricia; Homer, Jarrod J.; West, Catharine

    2008-12-01

    Purpose: Head-and-neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of patients in terms of subsite, treatment, and biology. Currently most management decisions are based on clinical parameters with little appreciation of patient differences in underlying tumor biology. We investigated the prognostic significance of clinicopathologic features and tumor hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) expression in a homogeneous series of patients who underwent radiotherapy. Methods and Materials: An audit identified 133 consecutive patients with histologically proven squamous cell carcinoma of the tonsil or tongue base. All patients received primary radiotherapy between 1996 and 2001. Tumor HIF-1{alpha} expression was examined in 79 patients. Results: Features associated with poor locoregional control were low Hb level (p = 0.05) and advancing T (p = 0.008), N (p = 0.03), and disease (p = 0.008) stage. HIF-1{alpha} expression was a more significant adverse prognostic factor in the tonsil (hazard ratio [HR], 23.1; 95% confidence interval [CI]. 3.04-176.7) than the tongue-base tumor (HR, 2.86; 95% CI, 1.14-7.19) group (p = 0.03, test for interaction). High tumor HIF-1{alpha} expression was associated with low blood Hb levels (p = 0.03). In a multivariate analysis HIF-1{alpha} expression retained prognostic significance for locoregional control (HR, 7.10; 95% CI, 3.07-16.43) and cancer-specific survival (HR, 9.19; 95% CI, 3.90-21.6). Conclusions: There are significant differences in radiation therapy outcome within a homogeneous subsite of the oropharynx related to molecular marker expression. The work highlights the importance of studying homogeneous groups of patients in HNSCC, and the complex interrelationships between tumor biology and clinicopathologic factors. The establishment of tumor-type specific markers would represent a major advance in this area.

  18. Renal tumors: diagnostic and prognostic biomarkers.

    PubMed

    Tan, Puay Hoon; Cheng, Liang; Rioux-Leclercq, Nathalie; Merino, Maria J; Netto, George; Reuter, Victor E; Shen, Steven S; Grignon, David J; Montironi, Rodolfo; Egevad, Lars; Srigley, John R; Delahunt, Brett; Moch, Holger

    2013-10-01

    The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants' responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.

  19. Significance Analysis of Prognostic Signatures

    PubMed Central

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

    2013-01-01

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

  20. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  1. Prognostic Value of Invasion, Markers of Proliferation, and Classification of Giant Pituitary Tumors, in a Georeferred Cohort in Brazil of 50 Patients, with a Long-Term Postoperative Follow-Up

    PubMed Central

    de Magalhães, Albino Verçosa

    2016-01-01

    Although some pituitary adenomas may have an aggressive behavior, the vast majority are benign. There are still controversies about predictive factors regarding the biological behavior of these particular tumors. This study evaluated potential markers of invasion and proliferation compared to current classification patterns and epidemiogeographical parameters. The study included 50 patients, operated on for tumors greater than 30 mm, with a mean postoperative follow-up of 15.2 ± 4.8 years. Pituitary magnetic resonance was used to evaluate regrowth, invasion, and extension to adjacent tissue. Three tissue biomarkers were analyzed: p53, Ki-67, and c-erbB2. Tumors were classified according to a combination of histological and radiological features, ranging from noninvasive and nonproliferative (grade 1A) to invasive-proliferative (grade 2B). Tumors grades 2A and 2B represented 42% and 52%, respectively. Ki-67 (p = 0.23) and c-erbB2 (p = 0.71) had no significant relation to tumor progression status. P53 (p = 0.003), parasellar invasion (p = 0.03), and classification, grade 2B (p = 0.01), were associated with worse clinical outcome. Parasellar invasion prevails as strong predictive factor of tumor recurrence. Severe suprasellar extension should be considered as invasion parameter and could impact prognosis. No environmental factors or geographical cluster were associated with tumor behavior. PMID:27635138

  2. Littoral Refractivity Prognostic Advancement

    DTIC Science & Technology

    2009-09-30

    situational awareness of the 3D radio-frequency (RF) propagation environment and a quantitative diagnostic and prognostic capability for assessing sub- and...Rev. 8-98) Prescribed by ANSI Std Z39-18 2 with the benchmark showing the quantitative improvement with each stage of model development...grid point. Modified the NSWCDD littoral clutter model ( LCM ) to accept COAMPS® derived refractivity fields. Analyzed the impact on ducting of

  3. Prognostic Impact of del(17p) and del(22q) as Assessed by Interphase FISH in Sporadic Colorectal Carcinomas

    PubMed Central

    González-González, María; Muñoz-Bellvis, Luís; Mackintosh, Carlos; Fontanillo, Celia; Gutiérrez, M. Laura; Abad, M. Mar; Bengoechea, Oscar; Teodosio, Cristina; Fonseca, Emilio; Fuentes, Manuel; De Las Rivas, Javier

    2012-01-01

    Background Most sporadic colorectal cancer (sCRC) deaths are caused by metastatic dissemination of the primary tumor. New advances in genetic profiling of sCRC suggest that the primary tumor may contain a cell population with metastatic potential. Here we compare the cytogenetic profile of primary tumors from liver metastatic versus non-metastatic sCRC. Methodology/Principal Findings We prospectively analyzed the frequency of numerical/structural abnormalities of chromosomes 1, 7, 8, 13, 14, 17, 18, 20, and 22 by iFISH in 58 sCRC patients: thirty-one non-metastatic (54%) vs. 27 metastatic (46%) disease. From a total of 18 probes, significant differences emerged only for the 17p11.2 and 22q11.2 chromosomal regions. Patients with liver metastatic sCRC showed an increased frequency of del(17p11.2) (10% vs. 67%;p<.001) and del(22q11.2) (0% vs. 22%;p = .02) versusnon-metastatic cases. Multivariate analysis of prognostic factors for overall survival (OS) showed that the only clinical and cytogenetic parameters that had an independent adverse impact on patient outcome were the presence of del(17p) with a 17p11.2 breakpoint and del(22q11.2). Based on these two cytogenetic variables, patients were classified into three groups: low- (no adverse features), intermediate- (one adverse feature) and high-risk (two adverse features)- with significantly different OS rates at 5-years (p<.001): 92%, 53% and 0%, respectively. Conclusions/Significance Our results unravel the potential implication of del(17p11.2) in sCRC patients with liver metastasis as this cytogenetic alteration appears to be intrinsically related to an increased metastatic potential and a poor outcome, providing additional prognostic information to that associated with other cytogenetic alterations such as del(22q11.2). Additional prospective studies in larger series of patients would be required to confirm the clinical utility of the new prognostic markers identified. PMID:22912721

  4. Marker chromosomes.

    PubMed

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  5. Novel Prognostic and Therapeutic Mutations in Acute Myeloid Leukemia

    PubMed Central

    MEDINGER, MICHAEL; LENGERKE, CLAUDIA; PASSWEG, JAKOB

    2016-01-01

    Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence increases with age. Cytogenetics and mutation testing remain important prognostic tools for treatment after induction therapy. The post-induction treatment is dependent on risk stratification. Despite rapid advances in determination of gene mutations involved in the pathophysiology and biology of AML, and the rapid development of new drugs, treatment improvements changed slowly over the past 30 years, with the majority of patients eventually experiencing relapse and dying of their disease. Allogenic hematopoietic stem cell transplantation remains the best chance of cure for patients with intermediate- or high-risk disease. This review gives an overview about advances in prognostic markers and novel treatment options for AML, focusing on new prognostic and probably therapeutic mutations, and novel drug therapies such as tyrosine kinase inhibitors. PMID:27566651

  6. Prognostic Impact of Thrombospodin-2 (THBS2) Overexpression on Patients with Urothelial Carcinomas of Upper Urinary Tracts and Bladders

    PubMed Central

    Chang, I-Wei; Li, Chien-Feng; Lin, Victor Chia-Hsiang; He, Hong-Lin; Liang, Per-In; Wu, Wen-Jeng; Li, Ching-Chia; Huang, Chun-Nung

    2016-01-01

    Purpose: Urothelial carcinoma (UC) is a type of tumor, especially of the urinary bladder, that affects people worldwide. Clarification of its detailed tumor biology and discovery of potential targets for developing treatment strategies are imperative because of frequent recurrences and poor prognosis of advanced UCs. By data mining a published dataset of UC of bladder (UCB) transcriptome (GSE31684) from Gene Expression Omnibus, National Center of Biotechnology Information (GEO, NCBI), we identified that THBS2 was the most significantly upregulated gene among those related to structural molecule activity (GO:0005198). Therefore, we evaluated the clinical significance and prognostic impact of thrombospondin-2 (THBS2) protein, A.K.A. TSP2, which encoded by THBS2 gene. Materials and Methods: THBS2 immunostaining was performed in 340 UCs of upper urinary tract (UC-UUTs) and 295 UCBs; subsequently, both groups were dichotomized into high- and low-expression subgroups. Moreover, statistical analyses were performed to correlate the association between THBS2 expression and clinicopathological parameters with two survival indexes: disease-specific survival (DSS) and metastasis-free survival (MeFS). Results: High THBS2 immunoexpression was significantly associated with advanced primary tumor status, nodal metastasis, and vascular invasion in both UC-UUT and UCB groups (all P ≤ .001). In addition, THBS2 overexpression was linked to adverse DSS and MeFS in univariate analyses and served as an independent prognosticator indicating poor outcomes in both groups in multivariate analyses. Conclusion: THBS2 may play a crucial role in UC progression and may be a novel prognostic marker. Additional investigations to elucidate the molecular pathway are necessary for developing potential THBS2-targeted therapies for UCs. PMID:27471570

  7. [Diagnostic and prognostic values of troponins in acute coronary syndromes].

    PubMed

    Smiri, Zahreddine; Haggui, Abdeddayem; Barakett, Nadia; M'Henni, Hedi; Haouala, Habib

    2004-05-01

    Coronary disease is a frequent clinical entity which, in some cases, makes a difficult diagnostic problem. However, the very big revolution realised these last decades in both diagnostics and therapeutics, improved management of these patients. Troponins which are specific and sensitive biomarkers of myocardial damage were evaluated in several domains, especially in acute coronary diseases. We purpose to clarify diagnostic and prognostic place of these markers in acute coronary disease in order to optimize their clinical use.

  8. Prognostic Scores for Acute Pulmonary Embolism.

    PubMed

    Morillo, Raquel; Moores, Lisa; Jiménez, David

    2017-02-06

    Rapid and accurate risk stratification is critical in determining the optimal treatment strategy for patients with acute pulmonary embolism (PE). Early identification of patients with normal blood pressure and a favorable prognosis (low-risk PE) might select a subset of patients for outpatient treatment, which is associated with reduced cost and improved patient satisfaction, and has been shown to be effective and safe. Alternatively, identification of normotensive patients deemed as having a high risk for PE-related adverse clinical events (intermediate-high-risk PE) might select a subset of patients for close observation and consideration of escalation of therapy. Clinical prognostic scores have been gaining importance in the classification of patients into these categories. They should be derived and validated following strict methodological standards, and their use in clinical practice should be encouraged.

  9. Genetic Alterations in Medullary Thyroid Cancer: Diagnostic and Prognostic Markers

    PubMed Central

    A, Taccaliti; F, Silvetti; G, Palmonella; M, Boscaro

    2011-01-01

    Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendocrine tumour that originates from the parafollicular C-cells of the thyroid gland. The RET proto-oncogene encodes the RET receptor tyrosine kinase, with consequently essential roles in cell survival, differentiation and proliferation. Somatic or germline mutations of the RET gene play an important role in this neoplasm in development of sporadic and familial forms, respectively. Genetic diagnosis has an important role in differentiating sporadic from familiar MTC. Furthermore, depending on the location of the mutation, patients can be classified into risk classes. Therefore, genetic screening of the RET gene plays a critical role not only in diagnosis but also in assessing the prognosis and course of MTC. PMID:22654561

  10. Arterial ammonia levels: Prognostic marker in traumatic hemorrhage

    PubMed Central

    Singla, Anurag; Kaur, Satinder; Kaur, Navjot; Gill, CS

    2016-01-01

    Background: In blunt trauma, extent of hemorrhage cannot be determined by physical examination, and vital signs may also not give clear picture in all the patients, especially young healthy ones. Hemorrhagic shock has been reported to increase blood ammonia levels. Arterial ammonia was analyzed in blunt trauma abdomen patients and correlated with shock index (SI). Its predictive value was determined for timely decision of intervention. Materials and Methods: Hundred blunt trauma abdomen patients presented in the emergency ward of tertiary care hospital were included in the study. Group I comprised 62 patients requiring either blood transfusion ≥2 units and/or intervention to control bleeding within 24 h following admission. Group II had 38 patients: Not requiring transfusion/intervention during hospital stay. Arterial blood sample was taken immediately after admission; ammonia was analyzed within 20 min of sampling on Cobas 6000 (Roche). SI was calculated. Predictive value of ammonia was determined using receiver operating characteristic curve. Results: Ammonia levels and SI were significantly (P < 0.001) higher in Group I compared to Group II patients (68.55 ± 14.36 umol/L vs. 37.55 ± 7.41 umol/L and 1.28 ± 0.5 vs. 0.74 ± 0.12, respectively). Significantly higher number of patients in Group I (88.7% vs. 13%) had SI > 0.9. Ammonia levels were significantly higher in patients with complications and in those expired. Conclusions: Ammonia levels were significantly higher in patients requiring blood transfusion/intervention in 24 h of admission. The best cutoff value to maximize sensitivity and specificity was ammonia >58.85 μmol/L. Ammonia estimation at admission can be clinically significant indicator of traumatic hemorrhage needing intervention. PMID:27857892

  11. Identification of Novel Prognostic Genetic Markers in Prostate Cancer

    DTIC Science & Technology

    2000-02-01

    early access to new sequence data from the Celera Genomics (http://www.celera.com). We will select UniGene EST contig clusters and predicted genes which...and Macoska, J.A. (1998) Homozygous and Frequent Deletion of Proximal 8p Sequences in Human Prostate Cancers: Identification of a Potential Tumor...correlates with genome instability in human papillomavirus 16 E7 transformed human uroepithelial cells. Oncogene. 14:551-560. 20.) Sutherland, G.R

  12. Identification of Novel Prognostic Genetic Marker in Prostate Cancer

    DTIC Science & Technology

    2001-08-01

    Natl Cancer Inst 1993;85(20):1657-69. 5. Thomas DJ, Robinson M, King P, Hasan T, Charlton R, Martin J, et al. p53 expression and clinical outcome in...microarray to analyse gene expression patterns in human cancer. Nat. Genet. 14, 457-460. 9. Pollack, J. R., Perou, C. M., Alizadeh , A. A., Eisen, M. B

  13. D-Dimer elevation and adverse outcomes.

    PubMed

    Halaby, Rim; Popma, Christopher J; Cohen, Ander; Chi, Gerald; Zacarkim, Marcelo Rodrigues; Romero, Gonzalo; Goldhaber, Samuel Z; Hull, Russell; Hernandez, Adrian; Mentz, Robert; Harrington, Robert; Lip, Gregory; Peacock, Frank; Welker, James; Martin-Loeches, Ignacio; Daaboul, Yazan; Korjian, Serge; Gibson, C Michael

    2015-01-01

    D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

  14. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  15. Prognostic Biomarkers in Ovarian Cancer

    PubMed Central

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

    2014-01-01

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

  16. Platelet to lymphocyte ratio in the prediction of adverse outcomes after acute coronary syndrome: a meta-analysis

    PubMed Central

    Li, Wenzhang; Liu, Qianqian; Tang, Yin

    2017-01-01

    Recent studies have shown platelet to lymphocyte ratio (PLR) to be a potential inflammatory marker in cardiovascular diseases. We performed a meta-analysis to systematically evaluate the prognostic role of PLR in acute coronary syndrome (ACS). A comprehensive literature search up to May 18, 2016 was conducted from PUBMED, EMBASE and Web of science to identify related studies. The risk ratio (RR) with 95% confidence interval (CI) was extracted or calculated for effect estimates. Totally ten studies involving 8932 patients diagnosed with ACS were included in our research. We demonstrated that patients with higher PLR level had significantly higher risk of in-hospital adverse outcomes (RR = 2.24, 95%CI = 1.81–2.77) and long-term adverse outcomes (RR = 2.32, 95%CI = 1.64–3.28). Sensitivity analyses confirmed the stability of our results. We didn’t detect significant publication bias by Begg’s and Egger’s test (p > 0.05). In conclusion, our meta-analysis revealed that PLR is promising biomarker in predicting worse prognosis in ACS patients. The results should be validated by future large-scale, standard investigations. PMID:28071752

  17. Single Nucleotide Polymorphisms as Prognostic and Predictive Factors of Adjuvant Chemotherapy in Colorectal Cancer of Stages I and II

    PubMed Central

    Horvat, Matej; Potočnik, Uroš; Repnik, Katja; Kavalar, Rajko; Štabuc, Borut

    2016-01-01

    Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant. PMID:26884752

  18. In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.

    PubMed

    Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Kohli, Pavneet Singh; Singh, Gurpreet

    2016-12-01

    Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.

  19. Serum markers in early-stage and locally advanced melanoma.

    PubMed

    Lugowska, Iwona; Kowalska, Maria; Fuksiewicz, Małgorzata; Kotowicz, Beata; Mierzejewska, Ewa; Koseła-Paterczyk, Hanna; Szamotulska, Katarzyna; Rutkowski, Piotr

    2015-11-01

    The identification of prognostic factors in cutaneous melanoma allows choosing the most effective treatment, especially in group of patients with locoregional disease. Markers related to carcinogenesis and angiogenesis in particular have effect on the course of the disease. The aim of this study was to evaluate clinical utility of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase 1 (TIMP-1), and YKL-40 in serum of melanoma patients at pathological stages I-III. We included 148 adult patients with melanoma. The median follow-up was 40 months. Disease recurrence was observed in 43 patients; 3-year disease-free survival (DFS) rate was 71.7%; 35 patients died; and the 3-year overall survival (OS) rate was 85%. Concentrations of VEGF, MMP-2, MMP-9, TIMP-1, and YKL-40 were measured by ELISA kits. VEGF, MMP-9, TIMP-1, and YKL-40 were significantly higher in group of patients than in controls. Increased concentrations of TIMP-1 were related to patient survival, which in the group of lower and increased TIMP-1, disease-free survival amounted to 81 vs. 61% (p = 0.014) and overall survival -88 vs. 82% (p = 0.050), respectively. An increased concentration of YKL-40 was observed in 59% of patients with ulceration and in 26% of patients without ulceration (p = 0.012). We have found a clinically significant correlation between YKL-40 and MMP-9 (rho = 0.363; p = 0.004) as well as YKL-40 and VEGF (rho = 0.306; p = 0.018). In melanoma patients at stages I-III, the high concentrations of TIMP-1 in serum predicted adverse prognosis. YKL-40 was associated with ulceration of primary tumor, which is a very important prognostic factor.

  20. Adverse drug reactions.

    PubMed

    O'Reilly-Foley, Georgina

    2017-04-05

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.

  1. Advanced Methods for Determining Prediction Uncertainty in Model-Based Prognostics with Application to Planetary Rovers

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew J.; Sankararaman, Shankar

    2013-01-01

    Prognostics is centered on predicting the time of and time until adverse events in components, subsystems, and systems. It typically involves both a state estimation phase, in which the current health state of a system is identified, and a prediction phase, in which the state is projected forward in time. Since prognostics is mainly a prediction problem, prognostic approaches cannot avoid uncertainty, which arises due to several sources. Prognostics algorithms must both characterize this uncertainty and incorporate it into the predictions so that informed decisions can be made about the system. In this paper, we describe three methods to solve these problems, including Monte Carlo-, unscented transform-, and first-order reliability-based methods. Using a planetary rover as a case study, we demonstrate and compare the different methods in simulation for battery end-of-discharge prediction.

  2. Perspectives on new biomarkers in gastric cancer: diagnostic and prognostic applications.

    PubMed

    Pinheiro, Danilo do Rosário; Ferreira, Wallax Augusto Silva; Barros, Mariceli Baia Leão; Araújo, Mariana Diniz; Rodrigues-Antunes, Symara; Borges, Bárbara do Nascimento

    2014-09-07

    Gastric cancer is considered one of the most deadly tumors worldwide. Even with the decline in its incidence, the mortality rate of this disease has remained high, mainly due to its late diagnosis and to the lack of precise prognostic markers. The main purpose of this review is to present genetic, epigenetic and proteomic molecular markers that may be used in a diagnostic and prognostic manner and to discuss the pros and cons of each type of marker for improving clinical practice. In this sense, we observed that the use of genetic markers, especially mutations and polymorphisms, should be carefully considered, as they are strongly affected by ethnicity. Proteomic-based markers show promise, but the higher costs of the associated techniques continue to make this approach expensive for routine use. Alternatively, epigenetic markers appear to be very promising, as they can be detected in bodily fluids as well as tissues. However, such markers must be used carefully because epigenetic changes may occur due to environmental factors and aging. Despite the advances in technology and its access, to date, there are few defined biomarkers of prognostic and diagnostic use for gastric tumors. Therefore, the use of a panel of several approaches (genetic, epigenetic and proteomic) should be considered the best alternative for clinical practice.

  3. Recommended guidelines for the conduct and evaluation of prognostic studies in veterinary oncology.

    PubMed

    Webster, J D; Dennis, M M; Dervisis, N; Heller, J; Bacon, N J; Bergman, P J; Bienzle, D; Cassali, G; Castagnaro, M; Cullen, J; Esplin, D G; Peña, L; Goldschmidt, M H; Hahn, K A; Henry, C J; Hellmén, E; Kamstock, D; Kirpensteijn, J; Kitchell, B E; Amorim, R L; Lenz, S D; Lipscomb, T P; McEntee, M; McGill, L D; McKnight, C A; McManus, P M; Moore, A S; Moore, P F; Moroff, S D; Nakayama, H; Northrup, N C; Sarli, G; Scase, T; Sorenmo, K; Schulman, F Y; Shoieb, A M; Smedley, R C; Spangler, W L; Teske, E; Thamm, D H; Valli, V E; Vernau, W; von Euler, H; Withrow, S J; Weisbrode, S E; Yager, J; Kiupel, M

    2011-01-01

    There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.

  4. Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates1

    PubMed Central

    Kwok, Man Leung; Yuen, Hon; Lai, Sik To

    2003-01-01

    Severe acute respiratory syndrome (SARS) poses a major threat to the health of people worldwide. We performed a retrospective case series analysis to assess clinical outcome and identify pretreatment prognostic correlates of SARS, managed under a standardized treatment protocol. We studied 127 male and 196 female patients with a mean age of 41±14 (range 18–83). All patients, except two, received ribavirin and steroid combination therapy. In 115 (36%) patients, the course of disease was limited. Pneumonitis progressed rapidly in the remaining patients. Sixty-seven (21%) patients required intensive care, and 42 (13%) required ventilator support. Advanced age, high admission neutrophil count, and high initial lactate dehydrogenase level were independent correlates of an adverse clinical outcome. SARS-associated coronavirus caused severe illnesses in most patients, despite early treatment with ribavirin and steroid. This study has identified three independent pretreatment prognostic correlates. PMID:14519241

  5. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  6. Adverse reactions to vaccines.

    PubMed

    Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M

    2003-06-01

    (The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

  7. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence.

  8. Prognostic relevance of minimal residual disease in colorectal cancer

    PubMed Central

    Bork, Ulrich; Grützmann, Robert; Rahbari, Nuh N; Schölch, Sebastian; Distler, Marius; Reissfelder, Christoph; Koch, Moritz; Weitz, Jürgen

    2014-01-01

    Presence of occult minimal residual disease in patients with colorectal cancer (CRC) has a strong prognostic impact on survival. Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC. Analysis of circulating tumor cells (CTC) in the blood is increasingly used in clinical practice for disease monitoring of CRC patients. In this review article the role of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and isolated tumor cells (ITC) in the lymph nodes will be discussed, including literature published until September 2013. Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes. Minimal residual disease could be used in the future to identify patient groups at risk, who might benefit from individualized treatment options. PMID:25132746

  9. Towards Prognostics of Electrolytic Capacitors

    NASA Technical Reports Server (NTRS)

    Celaya, Jose R.; Kulkarni, Chetan; Biswas, Gautam; Goegel, Kai

    2011-01-01

    A remaining useful life prediction algorithm and degradation model for electrolytic capacitors is presented. Electrolytic capacitors are used in several applications ranging from power supplies on critical avionics equipment to power drivers for electro-mechanical actuators. These devices are known for their low reliability and given their criticality in electronics subsystems they are a good candidate for component level prognostics and health management research. Prognostics provides a way to assess remaining useful life of a capacitor based on its current state of health and its anticipated future usage and operational conditions. In particular, experimental results of an accelerated aging test under electrical stresses are presented. The capacitors used in this test form the basis for a remaining life prediction algorithm where a model of the degradation process is suggested. This preliminary remaining life prediction algorithm serves as a demonstration of how prognostics methodologies could be used for electrolytic capacitors.

  10. Distinguishing hazards and harms, adverse drug effects and adverse drug reactions : implications for drug development, clinical trials, pharmacovigilance, biomarkers, and monitoring.

    PubMed

    Aronson, Jeffrey K

    2013-03-01

    The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and the encounter results in an adverse effect (a physiological or pathological change), which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization), and adverse reactions by their clinical manifestations (symptoms and/or signs). This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction."

  11. The Glasgow Prognostic Score (GPS) as a novel and significant predictor of extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Li, Ya-Jun; Jiang, Wen-Qi; Huang, Jia-Jia; Xia, Zhong-Jun; Huang, Hui-Qiang; Li, Zhi-Ming

    2013-05-01

    The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score including C-reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T-cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T-cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression-free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low-risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL.

  12. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions.

  13. Are Urinary Tubular Injury Markers Useful in Chronic Kidney Disease? A Systematic Review and Meta Analysis

    PubMed Central

    Zhou, Le-Ting; Lv, Lin-Li; Pan, Ming-Ming; Cao, Yu-Han; Liu, Hong; Feng, Ye; Ni, Hai-Feng; Liu, Bi-Cheng

    2016-01-01

    Background Adverse outcome of chronic kidney disease, such as end stage renal disease, is a significant burden on personal health and healthcare costs. Urinary tubular injury markers, such as NGAL, KIM-1 and NAG, could provide useful prognostic value for the early identification of high-risk patients. However, discrepancies between recent large prospective studies have resulted in controversy regarding the potential clinical value of these markers. Therefore, we conducted the first meta-analysis to provide a more persuasive argument to this debate. Methods In the current meta-analysis, based on ten prospective studies involving 29366 participants, we evaluated the role of urinary tubular injury markers (NGAL, KIM-1 and NAG) in predicting clinical outcomes including CKD stage 3, end stage renal disease and mortality. The prognostic values of these biomarkers were estimated using relative risks and 95% confidence interval in adjusted models. All risk estimates were normalized to those of 1 standard deviation increase in log-scale concentrations to minimize heterogeneity. Fixed-effects models were adopted to combine risk estimates. The quality of the research and between-study heterogeneity were evaluated. The level of research evidence was identified according to the GRADE profiler. Results uNGAL was identified as an independent risk predictor of ESRD (pooled adjusted relative risk: 1.40[1.21 to 1.61], p<0.001) and of overall mortality (pooled adjusted relative risk: 1.10[1.03 to 1.18], p = 0.001) in patients with chronic kidney disease. A borderline significance of uKIM-1 in predicting CKD stage 3 independently in the community-based population was observed (pooled adjusted relative risk: 1.13[1.00 to 1.27], p = 0.057). Only the prognostic value of uNGAL for ESRD was supported by a grade B level of evidence. Conclusion The concentration of uNGAL can be used in practice as an independent predictor of end stage renal disease among patients with chronic kidney disease

  14. Genetics and biological markers in urachal cancer

    PubMed Central

    van Rhijn, Bas W. G.

    2016-01-01

    Urachal cancer (UraC) is a rare tumor entity that usually develops at the basis of the remnant embryologic urachus. Consisting of mostly adenocarcinomas, most patients present with secondary symptoms due to an advanced stage with urinary bladder infiltration. One third of patients are already metastasized at presentation rendering them unsuitable for curative surgical treatment. In order to improve staging, treatment and follow-up, adequate knowledge about the genetic origin and potential markers is necessary. This paper reviews the English literature until December 2015. Pathologists argue for and against metaplasia or remnant enteric cells as origin for the adenomatous tissue found in UraC. Mutations in KRAS, BRAF, GNAS and Her2 have been associated with UraC. Immunohistochemical (IHC) markers like CEA, 34βE12, Claudin-18 and RegIV are indicative for mucous producing UraC. So far, IHC markers fail as prognosticators when matched to clinical data. Little is known about serum markers for UraC. CEA, CA19-9, CA125 and CA724 are mentioned as being elevated in UraC by some reports. Regarding the literature for biological markers in UraC, knowledge is mostly derived from case reports or cohort studies mentioning markers or predictors. More genetic research is needed to show whether UraC stems from progenitor cells of the cloaca or is due to metaplasia of transitional cells. Few IHC markers have shown indicative potential for UraC. A useful panel for differential diagnostics and clinicopathologic prognostication needs to be developed. Serum markers show very little potential for neither diagnosis nor follow-up in UraC. Further research on larger cohorts is necessary. PMID:27785422

  15. Cytogenetic Prognostication Within Medulloblastoma Subgroups

    PubMed Central

    Shih, David J.H.; Northcott, Paul A.; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M.; Garzia, Livia; Peacock, John; Mack, Stephen C.; Wu, Xiaochong; Rolider, Adi; Morrissy, A. Sorana; Cavalli, Florence M.G.; Jones, David T.W.; Zitterbart, Karel; Faria, Claudia C.; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A.; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G.; Liau, Linda M.; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K.; Thompson, Reid C.; Bailey, Simon; Lindsey, Janet C.; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M.C.; Scherer, Stephen W.; Phillips, Joanna J.; Gupta, Nalin; Fan, Xing; Muraszko, Karin M.; Vibhakar, Rajeev; Eberhart, Charles G.; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J.; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F.; Weiss, William A.; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R.; Rubin, Joshua B.; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M.; Gajjar, Amar; Packer, Roger J.; Rutkowski, Stefan; Pomeroy, Scott L.; French, Pim J.; Kloosterhof, Nanne K.; Kros, Johan M.; Van Meir, Erwin G.; Clifford, Steven C.; Bourdeaut, Franck; Delattre, Olivier; Doz, François F.; Hawkins, Cynthia E.; Malkin, David; Grajkowska, Wieslawa A.; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T.; Pfister, Stefan M.; Taylor, Michael D.

    2014-01-01

    Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. PMID

  16. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

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

  17. Adverse cutaneous drug reaction.

    PubMed

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.

  18. Diagnostic and prognostic value of mitochondrial DNA minisatellites after stem cell transplantation.

    PubMed

    Won, Eun Jeong; Kim, Hye Ran; Kim, Hwan Young; Kook, Hoon; Kim, Hyeoung Joon; Shin, Jong Hee; Suh, Soon Pal; Ryang, Dong Wook; Shin, Myung Geun

    2013-06-01

    Mitochondrial DNA has been used to investigate phylogenetic relationships and pathophysiologic roles in aging, degenerative diseases, and cancer. We investigated the prognostic usefulness of mitochondrial DNA minisatellite (mtMS) markers compared with nuclear short tandem repeat markers by evaluating the laboratory performance and clinical value of these markers in a large sample of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with various simulated conditions in vitro and in serial follow-up samples. We examined the value of mtMS markers as a prognostic indicator in 100 patients with various hematologic disorders undergoing allo-HSCT, including 35 patients with longitudinal follow-up for 55 months. The mtMS markers showed high sensitivity and accuracy for the quantitative detection of chimerism compared with nuclear short tandem repeat markers, particularly in unrelated transplantation and under inappropriate sampling conditions. Longitudinal follow-up after allo-HSCT disclosed that chimerism precisely reflected the status of engraftment or relapse during the clinicopathological course. Moreover, changes in mtMS markers in recipients before allo-HSCT were associated with clinical outcomes. Our data indicate that mtMS markers have multiple functions in monitoring mixed chimerism and predicting prognosis after allo-HSCT.

  19. Prognostic biomarkers in acute coronary syndrome

    PubMed Central

    Pavan, Chiara

    2016-01-01

    The acute coronary syndrome (ACS) is a leading cause of death around the globe. Beside a still high mortality rate, additional complications of ACS include arrhythmias, left ventricular mural thrombus, cardiac fibrosis, heart failure (HF), cardiogenic shock, mitral valve dysfunction, aneurysms, up to cardiac rupture. Despite many prognostic tools have been developed over the past decades, efforts are still ongoing to identify reliable and predictive biomarkers, which may help predict the prognosis of these patients and especially the risk of HF. Recent evidence suggests that the value of a discrete number of biomarkers of myocardial fibrosis, namely the soluble form of suppression of tumorigenicity 2 (sST2) and galectin-3 (GAL-3), may be predictive of HF and death in patients with ACS. Interestingly, the already promising predictive value of these biomarkers when measured alone was shown to be consistently magnified when combined with other and well-established cardiac biomarkers such natriuretic peptides and cardiac troponins. This article is hence aimed to review the current knowledge about cardiac biomarkers of fibrosis and adverse remodeling. PMID:27500159

  20. Relationship between Inflammatory Markers and New Cardiovascular Events in Patients with Acute Myocardial Infarction Who Underwent Primary Angioplasty

    PubMed Central

    Franca, Eluisa La; Caruso, Marco; Sansone, Angela; Iacona, Rosanna; Ajello, Laura; Mancuso, Dario; Castellano, Fabiana; Novo, Salvatore; Assennato, Pasquale

    2013-01-01

    Introduction: The determination of inflammation markers in circulation has enabled an important improvement in the study of cardiovascular diseases. It was tested the hypothesis that non-specific markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen may provide prognostic information in patients with acute myocardial infarction with persistent ST-segment elevation (STEMI) undergoing primary angioplasty (PCI). Methods: Patients: A cohort of 197 consecutive patients with STEMI undergoing primary PCI was enrolled, evaluating during hospitalization, the peak values of the following markers of inflammation: ESR, CRP and fibrinogen. A telephone follow-up has been made in order to investigate any possible new cardiovascular events after hospital discharge and the procedure performed. Results: Higher values of CRP were statistically associated with adverse future events as composite endpoint and with the single endpoint of death. Furthermore, higher age, presence of hypertension, history of previous cardiovascular events, were statistically significantly associated with cardiac events at follow up. In this group were also overrepresented subjects with anterior myocardial infarction in the anterior localization and with an EF ≤ 35% at discharge. Conclusions: CRP appears to be a predictor of future cardiovascular events, confirming that a pro-inflammatory state promotes the progression of atherosclerotic disease and its complications. PMID:23777720

  1. Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor

    PubMed Central

    Komatsu, Yoshito; Ohki, Emiko; Ueno, Naomi; Yoshida, Ai; Toyoshima, Yasuharu; Ueda, Eiji; Houzawa, Hiroyuki; Togo, Kanae; Nishida, Toshirou

    2015-01-01

    Objective This study was conducted to expand the sunitinib safety database in Japanese imatinib-resistant/-intolerant gastrointestinal stromal tumor patients. Retrospective analyses investigated common adverse events as potential prognostic markers. Methods Four hundred and seventy patients who received sunitinib between June 2008 and November 2009 were analyzed for safety, progression-free survival and overall survival; 386 for objective response rate; 88% received sunitinib on Schedule 4/2 starting at 50 mg/day. Results No unexpected safety issues occurred. Grade ≥ 3 adverse events occurred in 70%, most commonly thrombocytopenia (33%), neutropenia (22%) and leukopenia (15%). Objective response rate was 20% (95% confidence interval 16–24). Median progression-free survival was 22.4 weeks (95% confidence interval, 21.7–24.0). The overall survival rate at 24 weeks was 91% (95% confidence interval, 88–94). Higher relative dose intensity (≥70 vs. <70%) during the first 6 weeks and better Eastern Cooperative Oncology Group performance status (0 vs. ≥1) were associated with longer progression-free survival (24.0 vs. 20.1 weeks; P = 0.011; and 24.1 vs. 16.9 weeks; P < 0.001) and higher 24-week overall survival rate (94 vs. 83%; P < 0.001; and 96 vs. 83%; P < 0.001). Increased progression-free survival and overall survival rates were associated with specific adverse events. Cox proportional hazard modeling adjusted for relative dose intensity and performance status established hand–foot syndrome (hazard ratio = 0.636; 95% confidence interval, 0.456–0.888) and leukopenia (hazard ratio = 0.683; 95% confidence interval, 0.492–0.948) occurring within 12 weeks were significantly correlated with increased progression-free survival. Conclusion Sunitinib showed good efficacy and tolerable safety. Factors associated with greater efficacy were relative dose intensity, performance status and specific early adverse events. PMID:26373318

  2. Telithromycin: review of adverse effects.

    PubMed

    2014-11-01

    Telithromycin is a macrolide antibiotic that has been marketed since the early 2000s. It has not been shown to be more effective against any bacteria than other macrolide antibiotics. Its antibacterial activity is in no way remarkable. In early 2014, we reviewed its adverse effect profile using data from periodic safety update reports, drug regulatory agencies, and detailed published case reports. In addition to the adverse effect profile telithromycin shares with the other macrolides, it provokes several specific adverse effects: visual disturbances due to impaired accommodation; taste and smell disorders; severe liver damage; worsening of myasthenia gravis; rhabdomyolysis; and loss of consciousness. Prolongation of the QT interval with standard oral doses is a worrisome adverse effect. In practice, it is better not to use telithromycin as it exposes patients to disproportionate, serious adverse effects. When treatment with a macrolide antibiotic appears necessary, it is prudent to choose a different macrolide, such as spiramycin or azithromycin, which have fewer adverse effects.

  3. Vehicle Integrated Prognostic Reasoner (VIPR) 2010 Annual Final Report

    NASA Technical Reports Server (NTRS)

    Hadden, George D.; Mylaraswamy, Dinkar; Schimmel, Craig; Biswas, Gautam; Koutsoukos, Xenofon; Mack, Daniel

    2011-01-01

    Honeywell's Central Maintenance Computer Function (CMCF) and Aircraft Condition Monitoring Function (ACMF) represent the state-of-the art in integrated vehicle health management (IVHM). Underlying these technologies is a fault propagation modeling system that provides nose-to-tail coverage and root cause diagnostics. The Vehicle Integrated Prognostic Reasoner (VIPR) extends this technology to interpret evidence generated by advanced diagnostic and prognostic monitors provided by component suppliers to detect, isolate, and predict adverse events that affect flight safety. This report describes year one work that included defining the architecture and communication protocols and establishing the user requirements for such a system. Based on these and a set of ConOps scenarios, we designed and implemented a demonstration of communication pathways and associated three-tiered health management architecture. A series of scripted scenarios showed how VIPR would detect adverse events before they escalate as safety incidents through a combination of advanced reasoning and additional aircraft data collected from an aircraft condition monitoring system. Demonstrating VIPR capability for cases recorded in the ASIAS database and cross linking them with historical aircraft data is planned for year two.

  4. Long-term outcome of patients with triphasic mitral flow with a mid-diastolic L wave: prognostic role of left atrial volume and N-terminal pro-brain natriuretic peptide.

    PubMed

    Kim, Sung-Ai; Son, Jungwoo; Shim, Chi-Young; Choi, Eui-Young; Ha, Jong-Won

    2017-03-27

    A mid-diastolic L wave has been recognized as a marker of advanced left ventricular (LV) diastolic dysfunction. However, its prognostic implication is unclear. This study assessed long-term prognosis and independent predictors of adverse outcomes in patients with a mid-diastolic L wave. A total of 144 consecutive patients (mean age 63 ± 12 years, 88 female) with a mid-diastolic L wave of ≥0.2 m/s and in sinus rhythm were identified. Patients with significant valvular heart disease, low LV ejection fraction and arrhythmias were excluded. Subjects were followed up for cardiovascular (CV) mortality and hospitalization for heart failure (HF). During follow-up for a median of 44 months (1-76), CV deaths and hospitalization for HF occurred in 41 (28%) patients. In multivariate Cox analysis, age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.11; p = 0.001), log N-terminal pro-brain natriuretic peptide (NT-proBNP)(HR 3.81; 95% CI 1.78-8.15; p = 0.001), and left atrial volume index (HR 1.02; 95% CI 1.01-1.04; p = 0.019) were independent predictors of adverse outcomes in patients with a mid-diastolic L wave. In a stepwise model, NT-proBNP showed an incremental prognostic value for prediction of adverse outcomes when added to the clinical and echocardiographic parameters (Chi square from 30.1 to 41.1, p < 0.001). Patients with a mid-diastolic L wave and clinical, biochemical, and echocardiographic evidence of advanced diastolic dysfunction showed poor long-term clinical outcome.

  5. The biological and prognostic significance of angiotropism in uveal melanoma.

    PubMed

    Barnhill, Raymond L; Ye, Mengliang; Batistella, Aude; Stern, Marc-Henri; Roman-Roman, Sergio; Dendale, Rémi; Lantz, Olivier; Piperno-Neumann, Sophie; Desjardins, Laurence; Cassoux, Nathalie; Lugassy, Claire

    2017-02-27

    Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of

  6. Towards Prognostics for Electronics Components

    NASA Technical Reports Server (NTRS)

    Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

    2013-01-01

    Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  7. Analyzing risks of adverse pregnancy outcomes.

    PubMed

    Kramer, Michael S; Zhang, Xun; Platt, Robert W

    2014-02-01

    Approaches for analyzing the risks of adverse pregnancy outcomes have been the source of much debate and many publications. Much of the problem, in our view, is the conflation of time at risk with gestational age at birth (or birth weight, a proxy for gestational age). We consider the causal questions underlying such analyses with the help of a generic directed acyclic graph. We discuss competing risks and populations at risk in the context of appropriate numerators and denominators, respectively. We summarize 3 different approaches to quantifying risks with respect to gestational age, each of which addresses a distinct etiological or prognostic question (i.e., cumulative risk, prospective risk, or instantaneous risk (hazard)) and suggest the appropriate denominators for each. We show how the gestational age-specific risk of perinatal death (PND) can be decomposed as the product of the gestational age-specific risk of birth and the risk of PND conditional on birth at a given gestational age. Finally, we demonstrate how failure to consider the first of these 2 risks leads to selection bias. This selection bias creates the well-known crossover paradox, thus obviating the need to posit common causes of early birth and PND other than the study exposure.

  8. Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.

    PubMed

    Sumazin, Pavel; Chen, Yidong; Treviño, Lisa R; Sarabia, Stephen F; Hampton, Oliver A; Patel, Kayuri; Mistretta, Toni-Ann; Zorman, Barry; Thompson, Patrick; Heczey, Andras; Comerford, Sarah; Wheeler, David A; Chintagumpala, Murali; Meyers, Rebecka; Rakheja, Dinesh; Finegold, Milton J; Tomlinson, Gail; Parsons, D Williams; López-Terrada, Dolores

    2017-01-01

    Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2-like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity.

  9. Prognostic relevance of sunitinib toxicities and comparison of continuous vs. intermittent sunitinib dosing schedule in metastatic renal cell cancer patients

    PubMed Central

    Pilanci, Kezban N.; Avcı, Nilüfer; Yıldız, İbrahim; Alço, Gül; Demirhan, Özkan; Köksal, Ülkühan I.; Elbüken, Filiz; Tecimer, Coskun; Demir, Gökhan

    2016-01-01

    Aim of the study Sunitinib-related side effects may develop as a result of the pharmacokinetic pathway affects the of the drug. Material and methods Data on mRCC patients were obtained from the hospital archives. Outcomes of patients were evaluated in terms of related prognostic factors, sunitinib adverse events during the treatment, and two different sunitinib dosing schedules. Results Seventy patients diagnosed with mRCC and treated with sunitinib were analyzed for prognostic factors and survival rates. During the mean follow-up of 33.5 months, 38 (54%) patients were alive and 32 (46%) patients died. The median time of overall survival (OS) and progression-free survival (PFS) was 27 months (12–61) and 19 months (5–45), respectively. In univariate analysis, good prognostic risk group according to the Memorial Sloan-Kettering Cancer Center (MSKCC), hypothyroidism as sunitinib toxicity and patients on sunitinib treatment more than 1 year were favorable prognostic factors for OS. Leukopenia and fatigue as sunitinib toxicity were poor prognostic factors for OS. PFS and OS of the patients were not significantly different when we compared intermittent (4/2) vs. continuous treatment dosing schedules. Conclusions As a result of this trial, having hypothyroidism as an adverse effect of sunitinib was a favorable prognostic factor for OS and PFS in mRCC patients. It was also found that 4/2 and continuous dosing schedules of sunitinib did not give rise to different outcomes in mRCC patients. PMID:27358594

  10. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukaemia definition.

    PubMed

    Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara M; Teixidó, Montserrat; Gimenez, Maria Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Blade, Joan; Fernández de Larrea, Carlos

    2017-03-02

    The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the present study, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analysed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukaemia were reviewed and patients were classified in four categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20% and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%) respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95%CI 2.6-9.3) independently of age, creatinine, Durie-Salmon and international stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86x109/L vs. 214x109/L, p<0.0001) and higher bone marrow plasma cells (median 53% vs. 36%, p=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has similar adverse prognostic impact as plasma cell leukemia.

  11. Cell Surface Markers in Colorectal Cancer Prognosis

    PubMed Central

    Belov, Larissa; Zhou, Jerry; Christopherson, Richard I.

    2011-01-01

    The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC. PMID:21339979

  12. The immunophenotypic spectrum of primary mediastinal large B-cell lymphoma reveals prognostic biomarkers associated with outcome.

    PubMed

    Bledsoe, Jacob R; Redd, Robert A; Hasserjian, Robert P; Soumerai, Jacob D; Nishino, Ha T; Boyer, Daniel F; Ferry, Judith A; Zukerberg, Lawrence R; Harris, Nancy Lee; Abramson, Jeremy S; Sohani, Aliyah R

    2016-10-01

    Primary mediastinal large B-cell lymphoma (PMBL) is a distinct subtype of diffuse large B-cell lymphoma (DLBCL) that shows overlap with classical Hodgkin lymphoma (CHL) and a favorable prognosis compared to mediastinal gray-zone lymphoma (MGZL). We performed immunohistochemistry on initial diagnostic specimens of 49 cases of uniformly treated PMBL to determine the frequency and clinical significance of expression of antigens commonly seen in CHL and MGZL, along with markers previously shown to be prognostic in DLBCL, not otherwise specified. The median age was 37 years with a female:male ratio of 2.3. After a median follow-up of 78 months, 24% of patients had relapsed or refractory disease and 22% had died; the 5-year PFS was 70%. Variable CD15 expression was seen in 31% of cases, but was not associated with adverse outcome. Hans cell-of-origin, proliferation index, and MYC/BCL2 coexpression were not associated with outcome, while low PDL1 (P = 0.011) and high MUM1 (P = 0.065) staining were each associated with shorter PFS. A biologic risk score (one point each for low PDL1 and high MUM1) stratified patients into three prognostic risk groups for PFS (P = 0.001) and OS (P = 0.032). On separate multivariate models, low PDL1 was independent of R-IPI risk group for PFS (HR 6.0, P = 0.023), as was a biologic risk score of 2 (HR 5.6, P = 0.011). Incorporation of the biologic risk score sub-stratified patients within R-IPI groups for both PFS (P < 0.001) and OS (P < 0.001). In summary, we characterize the immunophenotypic spectrum of PMBL and identify PDL1 and MUM1 as prognostic biomarkers for high-risk disease. Am. J. Hematol. 91:E436-E441, 2016. © 2016 Wiley Periodicals, Inc.

  13. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  14. Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

    PubMed Central

    Yang, Fang; Cao, Lulu; Sun, Zijia; Jin, Juan; Fang, Hehui; Zhang, Wenwen; Guan, Xiaoxiang

    2016-01-01

    Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44+/CD24-, aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases. We found that a few patients displayed spatial heterogeneity of the BCSC markers in expression, which was defined as intratumor stemness heterogeneity (ITSH) below. There was no significant correlation between any BCSC marker alone or ITSH and progression-free survival (PFS). Interestingly, the combined BCSC phenotype by CD44+/CD24- and ALDH1A1 was significantly associated with worse PFS (P = 0.009). Further stratification analysis revealed that this combined BCSC phenotype was an independent prognostic factor for PFS in some subgroups. In conclusion, we demonstrated the existence of ITSH in TNBC and found that the ITSH as well as a single BCSC marker was not significantly associated with survival, whereas combing the analysis of BCSC markers could improve prognostic value. Our findings may lead to an improvement of prognostic indicators in TNBC. PMID:27994520

  15. Generic Software Architecture for Prognostics (GSAP) User Guide

    NASA Technical Reports Server (NTRS)

    Teubert, Christopher Allen; Daigle, Matthew John; Watkins, Jason; Sankararaman, Shankar; Goebel, Kai

    2016-01-01

    The Generic Software Architecture for Prognostics (GSAP) is a framework for applying prognostics. It makes applying prognostics easier by implementing many of the common elements across prognostic applications. The standard interface enables reuse of prognostic algorithms and models across systems using the GSAP framework.

  16. Specimen banks for cancer prognostic factor research.

    PubMed

    Burke, H B; Henson, D E

    1998-10-01

    Prognostic factors are necessary for determining whether a patient will require therapy, for selecting the optimal therapy, and for evaluating the effectiveness of the therapy chosen. Research in prognostic factors has been hampered by long waiting times and a paucity of outcomes. Specimen banks can solve these problems, but their implementation and use give rise to many important and complex issues. This paper presents an overview of some of the issues related to the use of specimen banks in prognostic factor research.

  17. Invasion front-specific expression and prognostic significance of microRNA in colorectal liver metastases.

    PubMed

    Kahlert, Christoph; Klupp, Fee; Brand, Karsten; Lasitschka, Felix; Diederichs, Sven; Kirchberg, Johanna; Rahbari, Nuh; Dutta, Shamik; Bork, Ulrich; Fritzmann, Johannes; Reissfelder, Christoph; Koch, Moritz; Weitz, Juergen

    2011-10-01

    The tumor edge of colorectal cancer and its adjacent peritumoral tissue is characterized by an invasion front-specific expression of genes that contribute to angiogenesis or epithelial-to-mesenchymal transition. Dysregulation of these genes has a strong impact on the invasion behavior of tumor cells. However, the invasion front-specific expression of microRNA (miRNA) still remains unclear. Therefore, the aim of the present study was to investigate miRNA expression patterns at the invasion front of colorectal liver metastases. Laser microdissection of colorectal liver metastases was performed to obtain separate tissue compartments from the tumor center, tumor invasion front, liver invasion front and pure liver parenchyma. Microarray expression analysis revealed 23 miRNA downregulated in samples from the tumor invasion front with respect to the same miRNA in the liver, the liver invasion front or the tumor center. By comparing samples from the liver invasion front with samples from pure liver parenchyma, the tumor invasion front and the tumor center, 13 miRNA were downregulated. By quantitative RT-PCR, we validated the liver invasion front-specific downregulation of miR-19b, miR-194, let-7b and miR-1275 and the tumor invasion front-specific downregulation of miR-143, miR- 145, let-7b and miR-638. Univariate analysis demonstrated that enhanced expression of miR-19b and miR-194 at the liver invasion front, and decreased expression of let-7 at the tumor invasion front, is an adverse prognostic marker of tumor recurrence and overall survival. In conclusion, the present study suggests that invasion front-specific downregulation of miRNA in colorectal liver metastases plays a pivotal role in tumor progression.

  18. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    PubMed

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse <12 months, including refractory patients), FLT3-ITD-positive status and high-risk cytogenetics were the three strongest independent adverse prognostic factors for OS and EFS in this series. We then defined three subgroups with striking different outcomes at 2 years: no adverse factor (favourable, N=36): OS 58%, EFS 45%; one adverse factor (intermediate, N=54): OS 37%, EFS 31%; two or three adverse factors (poor, N=43): OS 12%, EFS 12% (P<10(-4), P=0.001). This new simplified Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

  19. Distilling the Verification Process for Prognostics Algorithms

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  20. Time-dependent Predictive Values of Prognostic Biomarkers with Failure Time Outcome.

    PubMed

    Zheng, Yingye; Cai, Tianxi; Pepe, Margaret S; Levy, Wayne C

    2008-01-01

    In a prospective cohort study, information on clinical parameters, tests and molecular markers is often collected. Such information is useful to predict patient prognosis and to select patients for targeted therapy. We propose a new graphical approach, the positive predictive value (PPV) curve, to quantify the predictive accuracy of prognostic markers measured on a continuous scale with censored failure time outcome. The proposed method highlights the need to consider both predictive values and the marker distribution in the population when evaluating a marker, and it provides a common scale for comparing different markers. We consider both semiparametric and nonparametric based estimating procedures. In addition, we provide asymptotic distribution theory and resampling based procedures for making statistical inference. We illustrate our approach with numerical studies and datasets from the Seattle Heart Failure Study.

  1. Prognostic significance of the expression of nuclear eukaryotic translation initiation factor 5A2 in human melanoma.

    PubMed

    Khosravi, Shahram; Martinka, Magdalena; Zhou, Youwen; Ong, Christopher J

    2016-11-01

    Eukaryotic translation initiation factor 5A2 (EIF5A2) expression is upregulated in various cancers. The present authors previously demonstrated that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with patient survival. Other studies have suggested that nuclear EIF5A2 may also play a role in oncogenesis. The present study used immunohistochemistry and tissue microarray with a large number of melanocytic lesions (n=459) and demonstrated that nuclear EIF5A2 expression was significantly upregulated between common acquired nevi, dysplastic nevi and primary melanomas, and between primary melanomas and metastatic melanomas. Nuclear EIF5A2 expression was inversely associated with overall and disease-specific 5-year survival rate for all (P<0.001) and primary (P=0.014 and P=0.015, respectively) melanoma patients. Nuclear EIF5A2 expression was directly associated with melanoma thickness (P=0.036) and American Joint Committee on Cancer staging (P<0.001), which suggests the possible role of nuclear EIF5A2 in melanoma cell invasion. Subsequently, the present study investigated the association between the expression of nuclear EIF5A2 and matrix metalloproteinase-2 (MMP-2), which is an important factor for promoting cancer cell invasion. Nuclear EIF5A2 and a strong MMP-2 expression were directly associated, and their concurrent expression was significantly associated with a poorer overall and disease-specific 5-year survival rate for all and primary melanoma patients. Nuclear and cytoplasmic EIF5A2 expression were also demonstrated to be significantly associated, and simultaneous expression of the two forms of EIF5A2 was significantly associated with poor overall and disease-specific 5-year survival rates for all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear EIF5A2 expression alone and in combination with cytoplasmic EIF5A2 expression was an adverse independent prognostic factor for all and

  2. Prognostic significance of the expression of nuclear eukaryotic translation initiation factor 5A2 in human melanoma

    PubMed Central

    Khosravi, Shahram; Martinka, Magdalena; Zhou, Youwen; Ong, Christopher J.

    2016-01-01

    Eukaryotic translation initiation factor 5A2 (EIF5A2) expression is upregulated in various cancers. The present authors previously demonstrated that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with patient survival. Other studies have suggested that nuclear EIF5A2 may also play a role in oncogenesis. The present study used immunohistochemistry and tissue microarray with a large number of melanocytic lesions (n=459) and demonstrated that nuclear EIF5A2 expression was significantly upregulated between common acquired nevi, dysplastic nevi and primary melanomas, and between primary melanomas and metastatic melanomas. Nuclear EIF5A2 expression was inversely associated with overall and disease-specific 5-year survival rate for all (P<0.001) and primary (P=0.014 and P=0.015, respectively) melanoma patients. Nuclear EIF5A2 expression was directly associated with melanoma thickness (P=0.036) and American Joint Committee on Cancer staging (P<0.001), which suggests the possible role of nuclear EIF5A2 in melanoma cell invasion. Subsequently, the present study investigated the association between the expression of nuclear EIF5A2 and matrix metalloproteinase-2 (MMP-2), which is an important factor for promoting cancer cell invasion. Nuclear EIF5A2 and a strong MMP-2 expression were directly associated, and their concurrent expression was significantly associated with a poorer overall and disease-specific 5-year survival rate for all and primary melanoma patients. Nuclear and cytoplasmic EIF5A2 expression were also demonstrated to be significantly associated, and simultaneous expression of the two forms of EIF5A2 was significantly associated with poor overall and disease-specific 5-year survival rates for all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear EIF5A2 expression alone and in combination with cytoplasmic EIF5A2 expression was an adverse independent prognostic factor for all and

  3. Meeting report: Vienna 2008 Workshop of the German-Austrian Working Group for Studying Prognostic Factors in Myelodysplastic Syndromes.

    PubMed

    Valent, Peter; Hofmann, Wolf-Karsten; Büsche, Guntram; Sotlar, Karl; Horny, Hans-Peter; Haase, Detlef; Haferlach, Torsten; Kern, Wolfgang; Bettelheim, Peter; Baumgartner, Christian; Sperr, Wolfgang R; Nösslinger, Thomas; Wimazal, Friedrich; Giagounidis, Aristoteles A; Lübbert, Michael; Krieger, Otto; Kolb, Hans-Jochem; Stauder, Reinhard; Pfeilstöcker, Michael; Gattermann, Norbert; Fonatsch, Christa; Aul, Carlo; Germing, Ulrich

    2009-07-01

    Criteria, scoring systems, and treatment algorithms for myelodysplastic syndromes (MDS) have been updated repeatedly in recent years. This apparently results from increased awareness and early recognition of the disease, an increasing number of new diagnostic and prognostic markers and tools, and new therapeutic options that may change the course and thus prognosis in MDS. To address these challenges and to create useful new diagnostic and prognostic parameters and scores, the German-Austrian Working Group for Studying Prognostic Factors in MDS was established in 2003 and later was extended to centers in Switzerland (D-A-CH group). In addition, the group cooperates with the European LeukemiaNet, the MDS Foundation, and other national and international working groups in order to improve diagnosis and prognostication. The current article represents a meeting report from the latest workshop organized by the group in Vienna in October 2008.

  4. Hybrid Bearing Prognostic Test Rig

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Certo, Joseph M.; Handschuh, Robert F.; Dimofte, Florin

    2005-01-01

    The NASA Glenn Research Center has developed a new Hybrid Bearing Prognostic Test Rig to evaluate the performance of sensors and algorithms in predicting failures of rolling element bearings for aeronautics and space applications. The failure progression of both conventional and hybrid (ceramic rolling elements, metal races) bearings can be tested from fault initiation to total failure. The effects of different lubricants on bearing life can also be evaluated. Test conditions monitored and recorded during the test include load, oil temperature, vibration, and oil debris. New diagnostic research instrumentation will also be evaluated for hybrid bearing damage detection. This paper summarizes the capabilities of this new test rig.

  5. Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients

    PubMed Central

    Wang, Lin-Fang; Fokas, Emmanouil; Juricko, Janko; You, An; Rose, Frank; Pagenstecher, Axel; Engenhart-Cabillic, Rita; An, Han-Xiang

    2008-01-01

    Background Malignant gliomas are lethal cancers, highly dependent on angiogenesis and treatment options and prognosis still remain poor for patients with recurrent glioblastoma multiforme (GBM). Ephs and ephrins have many well-defined functions during embryonic development of central nervous system such as axon mapping, neural crest cell migration, hindbrain segmentation and synapse formation as well as physiological and abnormal angiogenesis. Accumulating evidence indicates that Eph and ephrins are frequently overexpressed in different tumor types including GBM. However, their role in tumorigenesis remains controversial, as both tumor growth promoter and suppressor potential have been ascribed to Eph and ephrins while the function of EphA7 in GBM pathogenesis remains largely unknown. Methods In this study, we investigated the immunohistochemical expression of EphA7 in a series of 32 primary and recurrent GBM and correlated it with clinical pathological parameters and patient outcome. In addition, intratumor microvascular density (MVD) was quantified by immunostaining for endothelial cell marker von Willebrand factor (vWF). Results Overexpression of EphA7 protein was predictive of the adverse outcome in GBM patients, independent of MVD expression (p = 0.02). Moreover, high density of MVD as well as higher EphA7 expression predicted the disease outcome more accurately than EphA7 variable alone (p = 0.01). There was no correlation between MVD and overall survival or recurrence-free survival (p > 0.05). However, a statistically significant correlation between lower MVD and tumor recurrence was observed (p = 0.003). Conclusion The immunohistochemical assessment of tissue EphA7 provides important prognostic information in GBM and would justify its use as surrogate marker to screen patients for tyrosine kinase inhibitor therapy. PMID:18366728

  6. Cutaneous adverse reactions to lenalidomide.

    PubMed

    Imbesi, S; Allegra, A; Calapai, G; Musolino, C; Gangemi, S

    2015-01-01

    Lenalidomide is an immunomodulatory drug (IMiD) used principally in the treatment of multiple myeloma (MM), myelodysplastic syndromes (MS) and amyloidosis. Adverse reactions related to lenalidomide include myelosuppression (mainly neutropenia but also thrombocytopenia), gastrointestinal problems, skin eruption, atrial fibrillation and asthenia, decreased peripheral blood stem cell yield during stem cell collection, venous thromboembolism, and secondary malignances. In this review we focused our attention on the cutaneous adverse reactions to lenalidomide.

  7. Cytokines as biochemical markers for knee osteoarthritis

    PubMed Central

    Mabey, Thomas; Honsawek, Sittisak

    2015-01-01

    Osteoarthritis (OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly being considered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and anti-inflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin (IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates. PMID:25621214

  8. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  9. Prognostic factors of palatal mucoepidermoid carcinoma: a retrospective analysis based on a double-center study.

    PubMed

    Xu, Wenguang; Wang, Yufeng; Qi, Xiaofeng; Xie, Junqi; Wei, Zheng; Yin, Xiteng; Wang, Zhiyong; Meng, Jian; Han, Wei

    2017-03-06

    Mucoepidermoid carcinoma (MEC) of the palate is a common malignancy of minor salivary glands. This study was designed to identify the prognostic factors for MEC of the palate. The medical records of patients diagnosed with MEC of the palate who visited the Department of Oral and Maxillofacial Surgery at Nanjing Stomatological Hospital and the Department of Stomatology at Central Hospital of Xuzhou were retrospectively studied. The prognostic factors were determined using a Cox proportional hazards model. Furthermore, the expression of cancer stem cell (CSC) markers CD44, CD133, Nanog and Sox2 were detected in neoplastic samples of these patients by immunohistochemistry. As a result, both univariate analysis and multivariate analysis proved a high histological grade and an advanced tumor stage as negative prognostic factors for overall survival. By immunohistochemistry staining and survival analysis, a combination of CD44/CD133/SOX2 was found to have the strongest prognostic value for palatal MEC patients. In conclusion, the proposed nomogram which include histological grade and tumor stage along with cancer stem cell markers provides a more accurate long-term prediction for palatal MEC patients.

  10. Prognostic factors of palatal mucoepidermoid carcinoma: a retrospective analysis based on a double-center study

    PubMed Central

    Xu, Wenguang; Wang, Yufeng; Qi, Xiaofeng; Xie, Junqi; Wei, Zheng; Yin, Xiteng; Wang, Zhiyong; Meng, Jian; Han, Wei

    2017-01-01

    Mucoepidermoid carcinoma (MEC) of the palate is a common malignancy of minor salivary glands. This study was designed to identify the prognostic factors for MEC of the palate. The medical records of patients diagnosed with MEC of the palate who visited the Department of Oral and Maxillofacial Surgery at Nanjing Stomatological Hospital and the Department of Stomatology at Central Hospital of Xuzhou were retrospectively studied. The prognostic factors were determined using a Cox proportional hazards model. Furthermore, the expression of cancer stem cell (CSC) markers CD44, CD133, Nanog and Sox2 were detected in neoplastic samples of these patients by immunohistochemistry. As a result, both univariate analysis and multivariate analysis proved a high histological grade and an advanced tumor stage as negative prognostic factors for overall survival. By immunohistochemistry staining and survival analysis, a combination of CD44/CD133/SOX2 was found to have the strongest prognostic value for palatal MEC patients. In conclusion, the proposed nomogram which include histological grade and tumor stage along with cancer stem cell markers provides a more accurate long-term prediction for palatal MEC patients. PMID:28262804

  11. Fuzzy logic-based prognostic score for outcome prediction in esophageal cancer.

    PubMed

    Wang, Chang-Yu; Lee, Tsair-Fwu; Fang, Chun-Hsiung; Chou, Jyh-Horng

    2012-11-01

    Given the poor prognosis of esophageal cancer and the invasiveness of combined modality treatment, improved prognostic scoring systems are needed. We developed a fuzzy logic-based system to improve the predictive performance of a risk score based on the serum concentrations of C-reactive protein (CRP) and albumin in a cohort of 271 patients with esophageal cancer before radiotherapy. Univariate and multivariate survival analyses were employed to validate the independent prognostic value of the fuzzy risk score. To further compare the predictive performance of the fuzzy risk score with other prognostic scoring systems, time-dependent receiver operating characteristic curve (ROC) analysis was used. Application of fuzzy logic to the serum values of CRP and albumin increased predictive performance for 1-year overall survival (AUC=0.773) compared with that of a single marker (AUC=0.743 and 0.700 for CRP and albumin, respectively), where the AUC denotes the area under curve. This fuzzy logic-based approach also performed consistently better than the Glasgow Prognostic Score (GPS) (AUC=0.745). Thus, application of fuzzy logic to the analysis of serum markers can more accurately predict the outcome for patients with esophageal cancer.

  12. Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients.

    PubMed

    Simpson, K; Jones, R E; Grimstead, J W; Hills, R; Pepper, C; Baird, D M

    2015-06-01

    Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer.

  13. Prognostic evaluation of feline mammary carcinomas: a review of the literature.

    PubMed

    Zappulli, V; Rasotto, R; Caliari, D; Mainenti, M; Peña, L; Goldschmidt, M H; Kiupel, M

    2015-01-01

    A large number of studies have investigated feline mammary tumors in an attempt to identify prognostic markers and generate comparative analyses with human breast cancer. Nevertheless, a retrospective base of assessments and the lack of standardization in methodology and study design have caused weakness in study results, making comparison difficult. We examined feline mammary tumor publications and evaluated postulated prognostic parameters according to the recently published "Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology." Using these criteria, we determined with statistically significant reliability that prognostic parameters for feline mammary tumors are tumor grading and lymph node/lymphovascular invasion. Furthermore, tumor subtype, size, and staging are worthy of further standardized investigation. We present statistical significance for each studied parameter as well as its relevance to disease progression and survival. Our evaluation suggests that marker expression (ie, Ki67, HER2, ER) may provide relevant information applicable for therapeutic predictions; however, consensus efforts and protocol standardization are needed. We identify and discuss major points of concern--such as sample preservation and selection, standardization of immunohistochemical protocols, and evaluation of results--to provide support for subsequent reliable analyses.

  14. [Prognostic study of liver abscess].

    PubMed

    Nouira, Ramzi; Bedoui, Riadh; Miaadi, Naoufel; Guesmi, Fethi; Ben Achour, Jamel; Hani, Mohamed; Daghfous, Mounir; Ben Osman, Samia; Zoghlami, Ayoub; Najah, Nabil

    2003-04-01

    The objective of this work is to study factors of prognostic of mortality of abscesses of the liver. We have treated between 1990 and 2000 in our service, 38 patient for abscess of the liver. The symptoms are dominated by the pain of the right hypochondria (37 cases) and the fever (34 cases). An unique abscess has been recovered in 25 cases. Some multiple localizations have been observed in 12 cases. 21 patients have been operated. The bacteriological study at all patients revealed the presence of germ in 27 cases. In 6 cases, there were two germs. It was a bacillus negative gram in 26 cases and a cocci positive gram in 7 cases. Six complications have been observed at the operated patients. In 5 cases, it was a septic shock having leads to the death. After survey univariate and multivariate the only factor of bad prognostic recovered is the septic shock. The aetiology was identified in only 9 cases; it was abscess cholangiotis.

  15. Prognostic Analysis System and Methods of Operation

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  16. Distributed Prognostics based on Structural Model Decomposition

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  17. Model-Based Prognostics of Hybrid Systems

    NASA Technical Reports Server (NTRS)

    Daigle, Matthew; Roychoudhury, Indranil; Bregon, Anibal

    2015-01-01

    Model-based prognostics has become a popular approach to solving the prognostics problem. However, almost all work has focused on prognostics of systems with continuous dynamics. In this paper, we extend the model-based prognostics framework to hybrid systems models that combine both continuous and discrete dynamics. In general, most systems are hybrid in nature, including those that combine physical processes with software. We generalize the model-based prognostics formulation to hybrid systems, and describe the challenges involved. We present a general approach for modeling hybrid systems, and overview methods for solving estimation and prediction in hybrid systems. As a case study, we consider the problem of conflict (i.e., loss of separation) prediction in the National Airspace System, in which the aircraft models are hybrid dynamical systems.

  18. TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis.

    PubMed

    Loghavi, Sanam; Al-Ibraheemi, Alyaa; Zuo, Zhuang; Garcia-Manero, Guillermo; Yabe, Mariko; Wang, Sa A; Kantarjian, Hagop M; Yin, Cameron C; Miranda, Roberto N; Luthra, Raja; Medeiros, L Jeffrey; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2015-10-01

    Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis (MDS-F). Expression of TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 expression (3 +  in ≥10% cells) were associated with higher BM blast counts (P = 0·0149); alterations of chromosomes 5 (P = 0·0009) or 7 (P = 0·0141); complex karyotype (P = 0·0002); high- and very-high risk IPSS-R groups (P = 0·009); and TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = <0·001). Expression of TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F.

  19. A Comparison of Prognostic Value of the Levels of ProBNP and Troponin T in Patients with Acute Coronary Syndrome (ACS)

    PubMed Central

    Vogiatzis, Ioannis; Dapcevic, Irena; Datsios, Antonis; Koutsambasopoulos, Kostas; Gontopoulos, Argirios; Grigoriadis, Savas

    2016-01-01

    Introduction: The propeptide of brain natriuretic peptide (ProBNP) is used for the diagnosis of left ventricle dysfunction and heart failure. In patients with an Acute Coronary Syndrome (ACS) it can contribute to both short and long term prognosis of cardiovascular events that could be very important for management and therapy of these patients. Aim: The aim of this study was to evaluate the prognostic value of ProBNP for the clinical course after an acute coronary syndrome, compared with that of cardiac troponine T (cTnT) and the risk stratification of patients with acute coronary syndrome, both during hospitalization and six months later. Methods: We studied 390 patients (256 men, 134 women, mean age 66.04+12.38) with an acute coronary syndrome who were hospitalized in the Coronary Unit of our cardiology clinic. We studied epidemiological and clinical data and biochemical markers were examined as prognostic factors for clinical course intrahospital and during six months follow-up. Results: In the majority of patients, a myocardial infarction without ST elevation was diagnosed (NSTEMI) (193 patients 49.49%) while 167 patients (42.82%) had a myocardial infarction with ST elevation (STEMI) and the remaining 30 patients (7.69%) had unstable angina. Patients had multiple risk factors for coronary heart disease. The levels of ProBNP were significantly elevated in patients with STEMI (p=0.003) and NSTEMI (p=0.002) who died or experienced an adverse event (angina, myocardial infarction, cardiogenic shock, congestive heart failure, arrhythmias) during hospitalization. After six months of follow-up, patients who had an adverse event had higher levels of ProBNP. There was no difference in troponine T levels in patients with STEMI and NSTEMI who had adverse events compared with the others, either during hospitalization or after six months. Conclusion: The level of ProBNP is an important predictor of cardiovascular events in patients with acute coronary syndrome. This study

  20. Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy

    PubMed Central

    Liu, Yongping; Ling, Yang; Qi, Qiufeng; Lan, Feng; Zhu, Ming; Zhang, Yaping; Bao, Yanqing; Zhang, Changsong

    2017-01-01

    The identification of circulating tumor cells (CTCs) may provide important prognostic information in several types of solid tumors, including gastric cancer. The aim of this study was to investigate whether CTC count may be used to predict survival in patients with advanced gastric cancer treated with chemotherapy. The CELLection™ Epithelial Enrich kit was used to isolate and purify CTCs from samples of peripheral blood. Immunofluorescent staining was used for CTC counting. High CTC counts were associated with poor tumor differentiation and high serum CEA levels (P=0.021 and 0.005, respectively). After 3 months, 16 patients with decreasing CTC counts after the first cycle of chemotherapy obtained complete response, partial response or stable disease, while 13 patients with increasing CTC counts developed progressive disease. The patients with decreasing CTC counts also exhibited longer progression-free survival (PFS) (P≤0.001) and overall survival (OS) (P=0.002) compared with those with increasing CTC counts. Among all 59 patients, those with a CTC count of ≤2 cells/5 ml blood exhibited longer PFS (P≤0.001) and OS (P≤0.001) compared with those with a CTC count of >2 cells/5 ml blood. The multivariate analysis suggested that an increase of the CTC count after the first cycle of chemotherapy was only an independent prognostic marker of poor PFS (P=0.019). However, a baseline CTC count of >2 cells/5 ml blood was an independent poor prognostic marker for PFS (P=0.008) and OS (P=0.001) in all 59 patients. Our study suggested that patients with a low baseline CTC count or decrease of the CTC count after the first cycle of chemotherapy may benefit significantly from palliative chemotherapy. In conclusion, CTC count may be a good chemotherapy monitoring marker and an ideal prognostic marker for patients receiving palliative chemotherapy. PMID:28357102

  1. Expression and Prognostic Value of Oct-4 in Astrocytic Brain Tumors

    PubMed Central

    Dahl Sørensen, Mia; Winther Kristensen, Bjarne

    2016-01-01

    Background Glioblastomas are the most frequent type of malignant primary brain tumor with a median overall survival less than 15 months. Therapy resistance of glioblastomas has been attributed to the presence of tumor initiating stem-like cells (TSCs). TSC-related markers have therefore been suggested to have promising potentials as prognostic markers in gliomas. Methodology/Principal Findings The aim of the present study was to investigate the expression and prognostic impact of the TSC-related marker Oct-4 in astrocytic brain tumors of increasing grade. In total 114 grade II, III and IV astrocytic brain tumors were immunohistochemically stained for Oct-4, and the fraction and intensity of Oct-4 positive cells were determined by morphometric analysis of full tumor sections. Oct-4 was expressed in all tumors, and the Oct-4 positive cell fraction increased with tumor grade (p = 0.045). There was no association between survival and Oct-4 positive cell fraction, neither when combining all tumor grades nor in analysis of individual grades. Oct-4 intensity was not associated with grade, but taking IDH1 status into account we found a tendency for high Oct-4 intensity to be associated with poor prognosis in anaplastic astrocytomas. Double immunofluorescence stainings showed co-localization in the perivascular niches of Oct-4 and two other TSC markers CD133 and nestin in glioblastomas. In some areas Oct-4 was expressed independently of CD133 and nestin. Conclusions In conclusion, high Oct-4 fraction was associated with tumor malignancy, but seemed to be without independent prognostic influence in glioblastomas. Identification of a potential prognostic value in anaplastic astrocytomas requires additional studies using larger patient cohorts. PMID:28030635

  2. Gastroschisis: Antenatal Sonographic Predictors of Adverse Neonatal Outcome

    PubMed Central

    Ferraro, Zachary Michael; Moretti, Felipe; Fung Kee Fung, Karen

    2014-01-01

    Objectives. The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis. Methods. A quasi-systematic review was conducted in PubMed and Ovid using the key terms “gastroschisis,” “predictors,” “outcome,” and “ultrasound.” Results. A total of 18 papers were included. The most common sonographic predictors were intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR), and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were consistently found to be statistically insignificant with respect to predicting adverse outcome including abdominal circumference, stomach herniation and dilatation, and extra-abdominal bowel dilatation (EABD). Conclusions. Gastroschisis is associated with several comorbidities, yet there is much discrepancy in the literature regarding which specific ultrasound markers best predict adverse neonatal outcomes. Future research should include prospective trials with larger sample sizes and use well-defined and consistent definitions of the adverse outcomes investigated with consideration given to IABD. PMID:25587450

  3. Prenatal programming: adverse cardiac programming by gestational testosterone excess

    PubMed Central

    Vyas, Arpita K.; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A.

    2016-01-01

    Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30–90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells –c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820

  4. Prognostic Value of Serum Free Light Chains Measurements in Multiple Myeloma Patients

    PubMed Central

    Bermudo Guitarte, Carmen; Menéndez Valladares, Paloma; Rojas Noboa, Johanna Carolina; Kestler, Krysta; Duro Millán, Rafael

    2016-01-01

    Background The outcome for patients with Multiple Myeloma (MM) is highly variable, therefore, the existence of robust and easy to determine prognostic markers is extremely important for an efficient management of these patients. Presently, there is a debate about the role of the serum free light chains (sFLC) in the prognosis of MM patients both at diagnosis and after treatment. The aim of this study is to evaluate in a cohort of newly diagnosed MM patients from the Southern area of Spain, the prognostic value of sFLC both at baseline and after treatment. Materials and Methods 180 patients with a median age of 69 years were followed-up for a median time of 35 (18–61) months. The sFLC ratio (sFLCR) was calculated using the monoclonal sFLC as numerator. Patients were divided in two groups according to a sFLCR cut-off based on ROC analysis. The primary endpoints were the Overall Survival (OS) and the Progression-free Survival (PFS). Additionally, thirty-six MM patients treated with novel agents (Bortezomib/Dexamethasone) that achieved Complete Response (CR) or stringent CR (sCR) before autologous stem cell transplantation were studied to assess the impact of sCR in Disease Free Survival (DFS) and OS. Results During follow-up there were 72 disease-related deaths. The 5-years OS for the whole group was 51%. However, separate analysis of patients with sFLCR above (group “high”) or below (groups “low”) the cut-off value of 47 shows an OS of 23% and 73%, respectively (HR = 5.03, 95%CI 2.99–8.50, p<0.001). In addition, analysis by ISS stage, showed that the presence of high sFLCR was always significantly associated with a worse OS. Multivariate analysis identified sFLCR (HR = 4.42, 95%CI 2.57–7.60, p<0.001) and beta-2-microglobulin (B2M) (HR = 3.04, 95%IC 1.75–5.31, p<0.001) as independent risk factors for adverse outcome. A new risk stratification model based on sFLCR≥47 and B2M>3.5 mg/L provided a statistically more significant result for this cohort

  5. The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction

    PubMed Central

    Cho, Jung Sun; Youn, Ho-Joong; Her, Sung-Ho; Park, Maen Won; Kim, Chan Joon; Park, Gyung-Min; Cho, Jae Yeong; Ahn, Youngkeun; Kim, Kye Hun; Park, Jong Chun; Seung, Ki Bae; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo; Han, Kyoo Rok; Kim, Hyo Soo

    2015-01-01

    The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR. PMID:26130953

  6. The Prognostic Value of the Left Ventricular Ejection Fraction Is Dependent upon the Severity of Mitral Regurgitation in Patients with Acute Myocardial Infarction.

    PubMed

    Cho, Jung Sun; Youn, Ho-Joong; Her, Sung-Ho; Park, Maen Won; Kim, Chan Joon; Park, Gyung-Min; Jeong, Myung Ho; Cho, Jae Yeong; Ahn, Youngkeun; Kim, Kye Hun; Park, Jong Chun; Seung, Ki Bae; Cho, Myeong Chan; Kim, Chong Jin; Kim, Young Jo; Han, Kyoo Rok; Kim, Hyo Soo

    2015-07-01

    The prognostic value of the left ventricle ejection fraction (LVEF) after acute myocardial infarction (AMI) has been questioned even though it is an accurate marker of left ventricle (LV) systolic dysfunction. This study aimed to examine the prognostic impact of LVEF in patients with AMI with or without high-grade mitral regurgitation (MR). A total of 15,097 patients with AMI who received echocardiography were registered in the Korean Acute Myocardial Infarction Registry (KAMIR) between January 2005 and July 2011. Patients with low-grade MR (grades 0-2) and high-grade MR (grades 3-4) were divided into the following two sub-groups according to LVEF: LVEF ≤ 40% (n = 2,422 and 197, respectively) and LVEF > 40% (n = 12,252 and 226, respectively). The primary endpoints were major adverse cardiac events (MACE), cardiac death, and all-cause death during the first year after registration. Independent predictors of mortality in the multivariate analysis in AMI patients with low-grade MR were age ≥ 75 yr, Killip class ≥ III, N-terminal pro-B-type natriuretic peptide > 4,000 pg/mL, high-sensitivity C-reactive protein ≥ 2.59 mg/L, LVEF ≤ 40%, estimated glomerular filtration rate (eGFR), and percutaneous coronary intervention (PCI). However, PCI was an independent predictor in AMI patients with high-grade MR. No differences in primary endpoints between AMI patients with high-grade MR (grades 3-4) and EF ≤ 40% or EF > 40% were noted. MR is a predictor of a poor outcome regardless of ejection fraction. LVEF is an inadequate method to evaluate contractile function of the ischemic heart in the face of significant MR.

  7. A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma.

    PubMed

    Mai, Elias K; Hielscher, Thomas; Kloth, Jost K; Merz, Maximilian; Shah, Sofia; Raab, Marc S; Hillengass, Michaela; Wagner, Barbara; Jauch, Anna; Hose, Dirk; Weber, Marc-André; Delorme, Stefan; Goldschmidt, Hartmut; Hillengass, Jens

    2015-06-01

    Diffuse and focal bone marrow infiltration patterns detected by magnetic resonance imaging have been shown to be of prognostic significance in all stages of monoclonal plasma cell disorders and have, therefore, been incorporated into the definition of the disease. The aim of this retrospective analysis was to develop a rapidly evaluable prognostic scoring system, incorporating the most significant information acquired from magnetic resonance imaging. Therefore, the impact of bone marrow infiltration patterns on progression-free and overall survival in 161 transplant-eligible myeloma patients was evaluated. Compared to salt and pepper/minimal diffuse infiltration, moderate/severe diffuse infiltration had a negative prognostic impact on both progression-free survival (P<0.001) and overall survival (P=0.003). More than 25 focal lesions on whole-body magnetic resonance imaging or more than seven on axial magnetic resonance imaging were associated with an adverse prognosis (progression-free survival: P=0.001/0.003 and overall survival: P=0.04/0.02). A magnetic resonance imaging-based prognostic scoring system, combining grouped diffuse and focal infiltration patterns, was formulated and is applicable to whole-body as well as axial magnetic resonance imaging. The score identified high-risk patients with median progression-free and overall survival of 23.4 and 55.9 months, respectively (whole-body-based). Multivariate analyses demonstrated that the magnetic resonance imaging-based prognostic score stage III (high-risk) and adverse cytogenetics are independent prognostic factors for both progression-free and overall survival (whole-body-based, progression-free survival: hazard ratio=3.65, P<0.001; overall survival: hazard ratio=5.19, P=0.005). In conclusion, we suggest a magnetic resonance imaging-based prognostic scoring system which is a robust, easy to assess and interpret parameter summarizing significant magnetic resonance imaging findings in transplant

  8. Prognostic value of glycated hemoglobin in colorectal cancer

    PubMed Central

    Ferroni, Patrizia; Formica, Vincenzo; Della-Morte, David; Lucchetti, Jessica; Spila, Antonella; D'Alessandro, Roberta; Riondino, Silvia; Guadagni, Fiorella; Roselli, Mario

    2016-01-01

    AIM To investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer (CRC) patients. METHODS Pre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment (HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid profile. Furthermore, the prognostic value of routinely used glycemic parameters towards progression-free (PFS) and overall survival (OS) was prospectively evaluated. RESULTS Fasting blood glucose, insulin, HOMA-IR and HbA1c (all P < 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage (P = 0.018) was an independent predictor of increased HbA1c levels, which were also higher in patients who had disease progression compared with those who did not (P = 0.05). Elevated HbA1c levels showed a negative prognostic value both in terms of PFS (HR = 1.24) and OS (HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic patients. CONCLUSION HbA1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes. PMID:28018105

  9. An Integrated Approach for Gear Health Prognostics

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  10. Infarct volume after glioblastoma surgery as an independent prognostic factor

    PubMed Central

    Bette, Stefanie; Wiestler, Benedikt; Kaesmacher, Johannes; Huber, Thomas; Gerhardt, Julia; Barz, Melanie; Delbridge, Claire; Ryang, Yu-Mi; Ringel, Florian; Zimmer, Claus; Meyer, Bernhard; Boeckh-Behrens, Tobias; Kirschke, Jan S.; Gempt, Jens

    2016-01-01

    Postoperative ischemia is associated with reduced functional independence measured by karnofsky performance score (KPS), which correlates well with overall survival. Other studies suggest that postoperative hypoxia might initiate infiltrative tumor growth. Therefore, aim of this study was to analyze the impact of infarct volume on overall survival and progression free survival (PFS) of glioblastoma patients. 251 patients with surgery for a newly diagnosed glioblastoma (WHO IV) were retrospectively assessed. Pre- and postoperative KPS, date of death/last follow-up and histopathological markers were recorded. Pre- and postoperative tumor volume and the volume of postoperative infarction were manually segmented. A significant correlation of infarct volume with postoperative KPS decrease (P = 0.001) was observed. Infarct volume showed a significant impact on overall survival (P = 0.014), but not on PFS (P = 0.112) in univariate analysis. This effect increased in the subgroup of patients with near-total tumor resection (> 90%) (overall survival: P = 0.006, PFS: P = 0.066). Infarct volume remained as an independent prognostic factor for overall survival in multivariate analysis (HR 1.013 [1.000–1.026], P = 0.042) including other prognostic factors (age, extent of resection, postoperative KPS). Postoperative infarct volume significantly correlates as an independent factor with overall survival after glioblastoma surgery. Besides the influence of perioperative infarction on postoperative KPS, postoperative hypoxia might also have an effect on tumor biology initiating infiltrative growth and therefore impaired survival. PMID:27566556

  11. Prognostic value of circulating tumor cells in esophageal cancer

    PubMed Central

    Xu, Hai-Tao; Miao, Jing; Liu, Jian-Wei; Zhang, Lian-Guo; Zhang, Qing-Guang

    2017-01-01

    AIM To perform a meta-analysis of the related studies to assess whether circulating tumor cells (CTCs) can be used as a prognostic marker of esophageal cancer. METHODS PubMed, Embase, Cochrane Library and references in relevant studies were searched to assess the prognostic relevance of CTCs in patients with esophageal cancer. The primary outcome assessed was overall survival (OS). The meta-analysis was performed using the random effects model, with hazard ratio (HR), risk ratio (RR) and 95% confidence intervals (95%CIs) as effect measures. RESULTS Nine eligible studies were included involving a total of 911 esophageal cancer patients. Overall analyses revealed that CTCs-positivity predicted disease progression (HR = 2.77, 95%CI: 1.75-4.40, P < 0.0001) and reduced OS (HR = 2.67, 95%CI: 1.99-3.58, P < 0.00001). Further subgroup analyses demonstrated that CTCs-positive patients also had poor OS in different subsets. Moreover, CTCs-positivity was also significantly associated with TNM stage (RR = 1.48, 95%CI: 1.07-2.06, P = 0.02) and T stage (RR = 1.44, 95%CI: 1.13-1.84, P = 0.003) in esophageal cancer. CONCLUSION Detection of CTCs at baseline indicates poor prognosis in patients with esophageal cancer. However, this finding relies on data from observational studies and is potentially subject to selection bias. Prospective trials are warranted. PMID:28275311

  12. Prognostic significance of KLF4 expression in gastric cancer

    PubMed Central

    Hashimoto, Isaya; Nagata, Takuya; Sekine, Shinichi; Moriyama, Makoto; Shibuya, Kazuto; Hojo, Shozo; Matsui, Koshi; Yoshioka, Isaku; Okumura, Tomoyuki; Hori, Takashi; Shimada, Yutaka; Tsukada, Kazuhiro

    2017-01-01

    To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. PMID:28356964

  13. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  14. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  15. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  16. Reverse engineering adverse outcome pathways.

    PubMed

    Perkins, Edward J; Chipman, J Kevin; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-01

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.

  17. Expression and prognostic significance of unique ULBPs in pancreatic cancer

    PubMed Central

    Chen, Jiong; Zhu, Xing-Xing; Xu, Hong; Fang, Heng-Zhong; Zhao, Jin-Qian

    2016-01-01

    Background Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers. Materials and methods Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs. Results Statistics showed that high expression of membrane ULBP1 was a good biomarker of overall survival (18 months vs 13 months), and a high level of soluble ULBP2 was deemed an independent poor indicator for both overall survival (P<0.001) and disease-free survival (P<0.001). Conclusion ULBP1 provides additional information for early diagnosis, and soluble ULBP2 can be used as a novel tumor marker to evaluate the risk of pancreatic cancer patients. PMID:27621649

  18. DNA Methylation Biomarkers for Nasopharyngeal Carcinoma: Diagnostic and Prognostic Tools.

    PubMed

    Jiang, Wei; Cai, Rui; Chen, Qiu-Qiu

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a common tumor in southern China and south-eastern Asia. Effective strategies for the prevention or screening of NPC are limited. Exploring effective biomarkers for the early diagnosis and prognosis of NPC continues to be a rigorous challenge. Evidence is accumulating that DNA methylation alterations are involved in the initiation and progression of NPC. Over the past few decades, aberrant DNA methylation in single or multiple tumor suppressor genes (TSGs) in various biologic samples have been described in NPC, which potentially represents useful biomarkers. Recently, large-scale DNA methylation analysis by genome-wide methylation platform provides a new way to identify candidate DNA methylated markers of NPC. This review summarizes the published research on the diagnostic and prognostic potential biomarkers of DNA methylation for NPC and discusses the current knowledge on DNA methylation as a biomarker for the early detection and monitoring of progression of NPC.

  19. BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence

    PubMed Central

    Oczko-Wojciechowska, Małgorzata; Barczyński, Marcin

    2016-01-01

    Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk or persistent disease is related to ~30%. Currently, attention is paid to the possibility of patient group selection of different risk of unfavorable outcome to match a particular therapeutic approach. Therefore, interest in new prognostic and predictive markers known preoperatively is observed. BRAF V600E mutation is such a marker. Many studies analyzing the prevalence of the mutation and its relationship with other clinico-pathological risk factors were reported but with controversial conclusions. The prognostic significance of BRAF mutation was confirmed by some single centre studies, a few meta-analyses and a large multicenter retrospective international study. They confirmed a correlation between the mutation and the risk of recurrence. The strongest argument against using BRAF mutation as an independent prognostic and predictive factor in PTC is its high prevalence (30–80%). At present it seems that BRAF mutation is one of the factors influencing the prognosis and it should be analyzed in correlation with other prognostic factors. The most recent ATA recommendations do not indicate a routine application of BRAF status for initial risk stratification in differentiated thyroid cancer due to a lack of evident confirmation of a direct influence of mutation on the increase in relapse risk. However, ATA demonstrates the continuous risk scale for the relapse risk assessment, considering BRAF and/or TERT status. At present, researchers are working on determining the role of BRAF mutation in patients from a low-risk group and its correlations with others molecular events. Currently, BRAF mutation cannot be used as a single, independent predictive factor. However, its usefulness in the context of other molecular and clinico-pathological risk factors cannot be excluded. They may be used to make modern prognostic scales of relapse risk and be applied to individualized diagnostic and

  20. WIPP marker development

    SciTech Connect

    1994-04-01

    This article discusses the development of permanent, passive markers for the Waste Isolation Pilot Plant (WIPP) and presents some preliminary concepts in drawings and a table of components for the markers. The panel, convened by Sandia National Laboratories, was charged with developing design characteristics for permanent markers and judging the efficacy of markers in deterring inadvertent human intrusion. 6 figs., 2 tabs.

  1. Diagnostic and Prognostic Biomarkers in Melanoma

    PubMed Central

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan

    2014-01-01

    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  2. Do Holocaust survivors show increased vulnerability or resilience to post-Holocaust cumulative adversity?

    PubMed

    Shrira, Amit; Palgi, Yuval; Ben-Ezra, Menachem; Shmotkin, Dov

    2010-06-01

    Prior trauma can hinder coping with additional adversity or inoculate against the effect of recurrent adversity. The present study further addressed this issue by examining whether a subsample of Holocaust survivors and comparison groups, drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe, were differentially affected by post-Holocaust cumulative adversity. Post-Holocaust cumulative adversity had a stronger effect on the lifetime depression of Holocaust survivors than on that of comparisons. However, comparisons were more negatively affected by post-Holocaust cumulative adversity when examining markers of physical and cognitive functioning. Our findings suggest that previous trauma can both sensitize and immunize, as Holocaust survivors show general resilience intertwined with specific vulnerability when confronted with additional cumulative adversity.

  3. Metrics for Offline Evaluation of Prognostic Performance

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  4. Vehicle Integrated Prognostic Reasoner (VIPR) Metric Report

    NASA Technical Reports Server (NTRS)

    Cornhill, Dennis; Bharadwaj, Raj; Mylaraswamy, Dinkar

    2013-01-01

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

  5. On Applying the Prognostic Performance Metrics

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    Prognostics performance evaluation has gained significant attention in the past few years. As prognostics technology matures and more sophisticated methods for prognostic uncertainty management are developed, a standardized methodology for performance evaluation becomes extremely important to guide improvement efforts in a constructive manner. This paper is in continuation of previous efforts where several new evaluation metrics tailored for prognostics were introduced and were shown to effectively evaluate various algorithms as compared to other conventional metrics. Specifically, this paper presents a detailed discussion on how these metrics should be interpreted and used. Several shortcomings identified, while applying these metrics to a variety of real applications, are also summarized along with discussions that attempt to alleviate these problems. Further, these metrics have been enhanced to include the capability of incorporating probability distribution information from prognostic algorithms as opposed to evaluation based on point estimates only. Several methods have been suggested and guidelines have been provided to help choose one method over another based on probability distribution characteristics. These approaches also offer a convenient and intuitive visualization of algorithm performance with respect to some of these new metrics like prognostic horizon and alpha-lambda performance, and also quantify the corresponding performance while incorporating the uncertainty information.

  6. Adverse drug reactions: part II.

    PubMed

    Wooten, James M

    2010-11-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.

  7. Adverse drug reactions: Part I.

    PubMed

    Wooten, James M

    2010-10-01

    Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.

  8. [Finasteride adverse effects: An update].

    PubMed

    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  9. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.

  10. Utility of Noninvasive Markers of Fibrosis in Cholestatic Liver Diseases.

    PubMed

    Corpechot, Christophe

    2016-02-01

    Methods of liver fibrosis assessment have changed considerably in the last 20 years, and noninvasive markers now have been recognized as major first-line tools in the management of patients with chronic viral hepatitis infection. But what about the efficiency and utility of these surrogate indices for the more uncommon chronic cholestatic liver diseases, namely primary biliary cirrhosis and primary sclerosing cholangitis? This article provides clinicians with a global overview of what is currently known in the field. Both diagnostic and prognostic aspects of noninvasive markers of fibrosis in cholestatic liver diseases are presented and discussed.

  11. Cryocooler Prognostic Health Management System

    NASA Astrophysics Data System (ADS)

    Shah, A.; Penswick, L.; Dodson, C.; Roberts, T.

    2008-03-01

    High performance sensors are playing an increasingly important role in all aspects of all critical DoD missions. There is a family of sensors that operate with improved sensitivities if cooled to very low (cryogenic) temperatures. For these sensors, a healthy and reliable mechanical refrigeration system (cryocooler) is required. The ability to accurately predict the "health" or remaining useful life of the cryocooler has significant benefits from the viewpoint of ensuring that mission critical functions can be carried out with a high probability of success. The paper provides an overview and approaches used for the development of a Cryocooler Prognostic Health Management System (CPHMS) capable of assessing the cryocooler "health" from the viewpoint of the level of performance degradation and/or the potential for near term failure. Additionally, it quantifies the reliable remaining useful life of the cryocooler. While the proposed system is focused on the specific application to linear drive cryocoolers, especially for DoD, many of the attributes of the system can be applied to other specialized system hardware in both commercial and U.S. Government agency for situations where it is critical that all aspects of the hardware "health" and "remaining useful life" be fully understood. Several benefits of the health monitoring system are also described in the paper.

  12. Thiocolchicoside: review of adverse effects.

    PubMed

    2016-02-01

    Thiocolchicoside has long been used as a muscle relaxant, despite a lack of proven efficacy beyond the placebo effect. Its chemical structure consists of colchicine, a sugar (ose) and a sulphur-containing radical (thio), and its adverse effects are therefore likely to be similar to those of colchicine. Using the standard Prescrire methodology, we reviewed the available data on the adverse effects of thiocolchicoside. Liver injury, pancreatitis, seizures, blood cell disorders, severe cutaneous disorders, rhabdomyolysis and reproductive disorders have all been recorded in the French and European pharmacovigilance databases and in the periodic updates that the companies concerned submit to regulatory agencies. These data do not specify the frequency of the disorders nor do they identify the most susceptible patient populations. Thiocolchicoside is teratogenic in experimental animals and also damages chromosomes. Human data are limited to a follow-up of about 30 pregnant women (no major malformations) and reports of altered spermatogenesis, including cases of azoospermia. In practice, there is no justification for exposing patients to the adverse effects of thiocolchicoside. It is better to use an effective, well-known analgesic for patients complaining of muscle pain, starting with paracetamol.

  13. Adverse food-drug interactions.

    PubMed

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.

  14. The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy

    PubMed Central

    Shimizu, Dai; Kanda, Mitsuro; Sugimoto, Hiroyuki; Shibata, Masahiro; Tanaka, Haruyoshi; Takami, Hideki; Iwata, Naoki; Hayashi, Masamichi; Tanaka, Chie; Kobayashi, Daisuke; Yamada, Suguru; Nakayama, Goro; Koike, Masahiko; Fujiwara, Michitaka; Fujii, Tsutomu; Kodera, Yasuhiro

    2017-01-01

    The prognosis of advanced hepatocellular carcinoma (HCC) is dismal. Novel molecular targets for diagnosis and therapy is urgently required. This study evaluated expression and functions of the protein arginine methyltransferase 5 (PRMT5) in HCC. Using HCC cell lines, the expression levels of PRMT5 mRNA were determined using the quantitative real-time reverse-transcription polymerase chain reaction, and the effect of a small interfering PRMT5-siRNA on cell phenotype was evaluated. Further, PRMT5 expression was determined in 144 pairs of resected liver tissues to evaluate its clinical significance. Regardless of their differentiated phenotypes, nine HCC cell lines expressed different levels of PRMT5 mRNA. Inhibition of PRMT5 expression significantly decreased the proliferation, invasion, and migration of HCC cell lines. Although the level of PRMT5 mRNA was not influenced by patient's background liver status, it was significantly higher in HCC tissues than in the corresponding noncancerous tissues. High levels of PRMT5 mRNA in HCC tissues were significantly associated with advanced disease stage and adverse prognosis. In conclusion, our results indicate that PRMT5 may act as a putative oncogene in HCC and that the levels of PRMT5 mRNA represent a promising prognostic marker and a potential target of molecular therapy for HCC. PMID:28101581

  15. Prognostic significance of X-ray cross-complementing gene 1 expression in gastric cancer

    PubMed Central

    Wang, Jian; Wang, Tongshan; Xu, Jun; Chen, WenJiao; Shi, Wei; Cheng, Jianfeng

    2016-01-01

    Objective The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCC1) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods Immunohistochemistry (IHC) was used to evaluate XRCC1 protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Among 612 patients staged Ⅱ/Ⅲ in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P = 0.347) or DFS (P = 0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P = 0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P = 0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P < 0.05). Though XRCC1 plays an important role in DNA repair pathways, no significant relationship is found in XRCC1 expression and OS among gastric cancer in our study. Conclusions XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy. PMID:27478321

  16. Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer

    PubMed Central

    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Iseki, Yasuhito; Ikeya, Tetsuro; Hirakawa, Kosei

    2017-01-01

    A correlation between the lymphocyte-to-monocyte ratio (LMR) and the survival of patients with hematological malignancies has been reported previously. However, there have been few studies investigating the prognostic significance of LMR in patients with solid tumors. The aim of the present study was to evaluate the prognostic significance of preoperative LMR in patients with colorectal cancer (CRC). A total of 189 patients undergoing potentially curative surgery for CRC were enrolled. The LMR was calculated from preoperative blood samples by dividing absolute lymphocyte count by absolute monocyte count. A cut-off value of 4.8 was set based on the receiver operating characteristic curve; 116 patients were classified as high-LMR, and 73 patients classified as low-LMR. The high-LMR group exhibited significantly better relapse-free survival (P=0.0018) and overall survival (P=0.0127) rates than the low-LMR group. According to the multivariate analysis of survival, preoperative LMR was identified as an independent prognostic factor for relapse-free survival (P=0.041) and overall survival (P=0.031). Therefore, preoperative LMR is a useful prognostic marker in patients with CRC.

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

    PubMed Central

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

    2013-01-01

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

  18. Clinical determinants and prognostic significance of the electrocardiographic strain pattern in chronic kidney disease patients.

    PubMed

    Cordeiro, Antonio C; Moraes, Aline A I; Cerutti, Virginia; França, Faustino; Quiroga, Borja; Amodeo, Celso; Picotti, Juliano C; Dutra, Lucas V; Rodrigues, Gabriel D; Amparo, Fernanda C; Lindholm, Bengt; Carrero, Juan Jesús

    2014-05-01

    The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that provides additional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluate its clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men). Patients were followed for 23 months (range, 13-32 months) for cardiovascular (CV) events and/or death. Strain patients (n = 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking, and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors of Strain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI. Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in 12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that of ECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients.

  19. The recurrence frequency of breast cancer and its prognostic factors in Iranian patients

    PubMed Central

    Shahriari-Ahmadi, Ali; Arabi, Mohsen; Payandeh, Mehrdad; Sadeghi, Masoud

    2017-01-01

    Background: Recurrent breast cancer (BC) after initial treatments is usually associated with poor outcome. The objective of this study is to evaluate baseline characteristics of BC patients to determine their prognostic influence of recurrences. Materials and Methods: In this retrospective study of 481 BC patients, 182 patients who had recurrence within the first, second, or third 5 years after diagnosis were included in the study. The significant prognostic factors associated with late or very late recurrence were selected according to the Akaike Information Criterion. Early recurrence was defined as initial recurrence within 5 years following curative surgery irrespective of site. Likewise, late recurrence was defined as initial recurrence after 5 years. Also, very late recurrence was defined as initial recurrence after 10 years. Results: During the follow-up period, 182 recurrences occurred (local recurrence or distant metastasis). All patients were treated with chemotherapy and radiotherapy and the patients with estrogen receptor (ER)- or progesterone receptor (PR)-positive had hormone therapy. There was a significant correlation between histological grade and receptors status with recurrence. In binary logistic regression analysis, ER and PR were significant prognostic factors for early recurrence. Conclusion: High histological grade and immunohistochemical markers (ER- and PR-negative or human epidermal growth factor receptor 2-positive) are risk factors for recurrence, especially in early recurrence and also between of them, ER is the more significant prognostic factor in early recurrence.

  20. Abnormal pancreatic enzymes and their prognostic role after acute paraquat poisoning.

    PubMed

    Li, Yi; Wang, Meng; Gao, Yanxia; Yang, Wen; Xu, Qun; Eddleston, Michael; Li, Li; Yu, Xuezhong

    2015-11-25

    Ingestion of paraquat causes multi-organ failure. Prognosis is best estimated through measurement of blood paraquat concentrations but this facility is not available in most hospitals. We studied the prognostic significance of abnormal pancreatic enzymes for survival. Patients with acute paraquat poisoning were recruited. An extensive series of blood tests including serum amylase were serially checked. Patients were sorted according to their serum amylase activity (normal [<220 U/L], mildly elevated [220 to 660 U/L], elevated [>660 U/L]), and survival compared between groups. 177 patients were enrolled to the study, of whom 67 died and 110 survived. 122 (70.62%), 27 (15.25%) and 25 (14.13%) patients were in the normal, mildly elevated and elevated amylase activity groups, respectively. The case fatality in the elevated group was 100% compared to 17% in the normal group (P < 0.001). We found four independent factors for paraquat death prediction: amylase, PaCO2, leukocyte number, and neutrophil percentage. Models using pancreatic enzyme activity showed good prediction power. We have found that abnormal pancreatic enzymes are useful prognostic marker of death after acute paraquat poisoning. Including serum amylase activity into a prognostic model provides a good prognostication.

  1. A comparison of the prognostic value of preoperative inflammation-based scores and TNM stage in patients with gastric cancer

    PubMed Central

    Pan, Qun-Xiong; Su, Zi-Jian; Zhang, Jian-Hua; Wang, Chong-Ren; Ke, Shao-Ying

    2015-01-01

    Background People’s Republic of China is one of the countries with the highest incidence of gastric cancer, accounting for 45% of all new gastric cancer cases in the world. Therefore, strong prognostic markers are critical for the diagnosis and survival of Chinese patients suffering from gastric cancer. Recent studies have begun to unravel the mechanisms linking the host inflammatory response to tumor growth, invasion and metastasis in gastric cancers. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have prognostic value in many types of malignant solid tumors. Objective To compare the prognostic value of inflammation-based prognostic scores and tumor node metastasis (TNM) stage in patients undergoing gastric cancer resection. Methods The inflammation-based prognostic scores were calculated for 207 patients with gastric cancer who underwent surgery. Glasgow prognostic score (GPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic nutritional index (PNI), and prognostic index (PI) were analyzed. Linear trend chi-square test, likelihood ratio chi-square test, and receiver operating characteristic were performed to compare the prognostic value of the selected scores and TNM stage. Results In univariate analysis, preoperative serum C-reactive protein (P<0.001), serum albumin (P<0.001), GPS (P<0.001), PLR (P=0.002), NLR (P<0.001), PI (P<0.001), PNI (P<0.001), and TNM stage (P<0.001) were significantly associated with both overall survival and disease-free survival of patients with gastric cancer. In multivariate analysis, GPS (P=0.024), NLR (P=0.012), PI (P=0.001), TNM stage (P<0.001), and degree of differentiation (P=0.002) were independent predictors of gastric cancer survival. GPS and TNM stage had a comparable prognostic value and higher linear trend chi-square value, likelihood ratio chi-square value, and larger area under the receiver operating

  2. Prognostic Disclosures to Children: A Historical Perspective

    PubMed Central

    Sisk, Bryan A.; Bluebond-Langner, Myra; Wiener, Lori; Mack, Jennifer; Wolfe, Joanne

    2016-01-01

    Prognostic disclosure to children has perpetually challenged clinicians and parents. In this article, we review the historical literature on prognostic disclosure to children in the United States using cancer as an illness model. Prior to 1948, there was virtually no literature focused on prognostic disclosure to children. As articles began to be published in the 1950s and 1960s, many clinicians and researchers initially recommended a “protective” approach to disclosure, where children were shielded from the harms of bad news. We identified four main arguments in the literature at this time supporting this “protective” approach. By the late 1960s, however, a growing number of clinicians and researchers were recommending a more “open” approach, where children were included in discussions of diagnosis, which at the time was often synonymous with a terminal prognosis. Four different arguments in the literature were used at this time supporting this “open” approach. Then by the late 1980s, the recommended approach to prognostic disclosure in pediatrics shifted largely from “never tell” to “always tell”. In recent years, however, there has been a growing appreciation for the complexity of prognostic disclosure in pediatrics. Current understanding of pediatric disclosure does not lead to simple “black and white” recommendations for disclosure practices. As with most difficult questions, we are left to balance competing factors on a case-by-case basis. We highlight four categories of current considerations related to prognostic disclosure in pediatrics, and we offer several approaches to prognostic disclosure for clinicians who care for these young patients and their families. PMID:27561728

  3. Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

    PubMed Central

    Gemmill, Alison; Weir, David; Adler, Nancy E.; Prather, Aric A.

    2016-01-01

    Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. PMID:27698131

  4. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

    PubMed

    Wilczynski, Milosz; Danielska, Justyna; Dzieniecka, Monika; Szymanska, Bozena; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

  5. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer

    PubMed Central

    Wilczynski, Milosz; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients’ clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker. PMID:27737015

  6. Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma

    PubMed Central

    Jeong, Dae Cheon; Han, Myoung-Eun; Kim, Ji-Young; Liu, Liangwen; Jung, Jin-Sup; Oh, Sae-Ock

    2017-01-01

    Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage. Furthermore, Kaplan-Meier and multivariate regression analysis showed that reduction in the mRNA expression of ZHX1 was associated with poorer survival. Taken together, the present study shows loss of ZHX1 is correlated with ccRCC progression and suggests it is an independent prognostic marker in ccRCC. PMID:28152006

  7. The prognostic factors for patients with hematological malignancies admitted to the intensive care unit.

    PubMed

    Cheng, Qian; Tang, Yishu; Yang, Qing; Wang, Erhua; Liu, Jing; Li, Xin

    2016-01-01

    Owing to the nature of acute illness and adverse effects derived from intensive chemotherapy, patients with hematological malignancies (HM) who are admitted to the Intensive Care Unit (ICU) often present with poor prognosis. However, with advances in life-sustaining therapies and close collaborations between hematologists and intensive care specialists, the prognosis for these patients has improved substantially. Many studies from different countries have examined the prognostic factors of these critically ill HM patients. However, there has not been an up-to-date review on this subject, and very few studies have focused on the prognosis of patients with HM admitted to the ICU in Asian countries. Herein, we aim to explore the current situation and prognostic factors in patients with HM admitted to ICU, mainly focusing on studies published in the last 10 years.

  8. Age-Related Prognostic Impact of Different Types of DNMT3A Mutations in Adults With Primary Cytogenetically Normal Acute Myeloid Leukemia

    PubMed Central

    Marcucci, Guido; Metzeler, Klaus H.; Schwind, Sebastian; Becker, Heiko; Maharry, Kati; Mrózek, Krzysztof; Radmacher, Michael D.; Kohlschmidt, Jessica; Nicolet, Deedra; Whitman, Susan P.; Wu, Yue-Zhong; Powell, Bayard L.; Carter, Thomas H.; Kolitz, Jonathan E.; Wetzler, Meir; Carroll, Andrew J.; Baer, Maria R.; Moore, Joseph O.; Caligiuri, Michael A.; Larson, Richard A.; Bloomfield, Clara D.

    2012-01-01

    Purpose To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods Four hundred fifteen previously untreated adults were analyzed for DNMT3A mutations and established prognostic gene mutations and expression markers. Gene- and microRNA-expression profiles were derived using microarrays. Results Younger (< 60 years; n = 181) and older (≥ 60 years; n = 234) patients had similar frequencies of DNMT3A mutations (35.3% v 33.3%). Missense mutations affecting arginine codon 882 (R882-DNMT3A) were more common (n = 92; 62%) than those affecting other codons (non–R882-DNMT3A). DNMT3A-mutated patients did not differ regarding complete remission rate, but had shorter disease-free survival (DFS; P = .03) and, by trend, overall survival (OS; P = .07) than DNMT3A–wild-type patients. In multivariable analyses, DNMT3A mutations remained associated with shorter DFS (P = .01), but not with shorter OS. When analyzed separately, the two DNMT3A mutation types had different significance by age group. Younger patients with non–R882-DNMT3A mutations had shorter DFS (P = .002) and OS (P = .02), whereas older patients with R882-DNMT3A mutations had shorter DFS (P = .005) and OS (P = .002) after adjustment for other clinical and molecular prognosticators. Gene- and microRNA-expression signatures did not accurately predict DNMT3A mutational status. Conclusion DNMT3A mutations are frequent in CN-AML, and their clinical significance seems to be age dependent. DNMT3A-R882 mutations are associated with adverse prognosis in older patients, and non–R882-DNMT3A mutations are associated with adverse prognosis in younger patients. Low accuracy of gene- and microRNA-expression signatures in predicting DNMT3A mutation status suggested that the role of these mutations in AML remains to

  9. Tumor markers in breast cancer- European Group on Tumor Markers recommendations.

    PubMed

    Molina, Rafael; Barak, Vivian; van Dalen, Arie; Duffy, Michael J; Einarsson, Roland; Gion, Massimo; Goike, Helenka; Lamerz, Rolf; Nap, Marius; Sölétormos, György; Stieber, Petra

    2005-01-01

    Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins (CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin (trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy.

  10. Prognostic implications of imaging in atrophic macular degeneration and its use in clinical practice and clinical trial design.

    PubMed

    Lim, Paul Cc; Layton, Christopher J

    2016-07-01

    Clinical prognostic markers in atrophic age-related macular degeneration include the extent of existing atrophy, fundus autofluorescence (FAF) patterns and optical coherence tomography changes in the outer retina/retinal pigment epithelium interface. The prognostic implications of these findings may be used to determine not just the rate of disease progression but also influence the likelihood, magnitude and clinical relevance of therapy responses. FAF phenotypes have been extensively investigated; however, the pathophysiological mechanisms behind their appearance have not been fully elucidated. Optical coherence tomography imaging is additive to FAF imaging in atrophic age-related macular degeneration, allowing the visualization of detail not available through FAF imaging whilst also displaying subtle changes correlating with the FAF phenotypes themselves, thereby giving clues to their histological determinates. The developing understanding of these imaging modalities and consequent development of prognostically useful classification systems have widespread implication in clinical care and clinical trial design.

  11. Adverse responses to local anaesthetics.

    PubMed

    Fisher, M M; Graham, R

    1984-11-01

    Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.

  12. Adverse Outcomes in Group Psychotherapy

    PubMed Central

    Roback, Howard B.

    2000-01-01

    Group forms of therapy have been growing at a rapid rate, in part because of their documented effectiveness and economic considerations such as managed care. It is therefore becoming increasingly important to assess the psychological risks of these interventions. The author provides an overview of the published literature and conference presentations on negative effects in adult outpatient groups. Although much of the literature on adverse outcomes in group therapy focuses on single risk factors (e.g., negative leader, group process, or patient characteristics), the author argues that an interactional model should be encouraged. Means of reducing casualties are also discussed, as well as methodological issues and research directions. PMID:10896735

  13. Ceramic subsurface marker prototypes

    SciTech Connect

    Lukens, C.E.

    1985-05-02

    The client submitted 5 sets of porcelain and stoneware subsurface (radioactive site) marker prototypes (31 markers each set). The following were determined: compressive strength, thermal shock resistance, thermal crazing resistance, alkali resistance, color retention, and chemical resistance.

  14. p27KIP1 is abnormally expressed in Diffuse Large B-Cell Lymphomas and is associated with an adverse clinical outcome

    PubMed Central

    Sáez, Al; Sánchez, E; Sánchez-Beato, M; Cruz, M A; Chacón, I; Muñoz, E; Camacho, F I; Martínez-Montero, J C; Mollejo, M; Garcia, J F; Piris, M A

    1999-01-01

    Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27KIP1 is a CDKi key in cell cycle regulation, whose degradation is required for G1/S transition. In spite of the absence of p27KIP1 expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27KIP1 staining. We analysed p27KIP1 expression in a series of Diffuse Large B-cell Lymphoma (DLBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesis in greater depth. For the above mentioned purposes, an immunohistochemical technique in paraffin-embedded tissues was employed, using commercially available antibodies, in a series of 133 patients with known clinical outcomes. Statistical analysis was performed in order to ascertain which clinical and molecular variables may influence outcome, in terms of disease-free survival (DFS) and overall survival (OS). The relationships between p27KIP1 and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27KIP1 was found in lymphomas of this type. The overall correlation between p27KIP1 and MIB-1 showed there to be no significant relationship between these two parameters, this differing from observations in reactive lymphoid and other tissues. Analysis of the clinical relevance of these findings showed that a high level of p27KIP1 expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. These results show that there is abnormal p27KIP1 expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27KIP1 protein may be rendered non-functional through interaction with other cell cycle regulator proteins. © 1999 Cancer Research Campaign PMID:10424746

  15. A Distributed Prognostic Health Management Architecture

    NASA Technical Reports Server (NTRS)

    Bhaskar, Saha; Saha, Sankalita; Goebel, Kai

    2009-01-01

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

  16. Evaluating Algorithm Performance Metrics Tailored for Prognostics

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used i