Os possíveis papéis da S100B na esquizofrenia Potential roles of S100B in schizophrenia

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Johann Steiner

2013-01-01

Full Text Available CONTEXTO: Evidências científicas do aumento da concentração da proteína S100B no sangue de pacientes esquizofrênicos são muito consistentes. No passado essa informação era principalmente considerada como reflexo da disfunção astroglial ou da barreira hematoencefálica. MÉTODOS: Pesquisa de publicações no PubMed até o dia 15 de junho de 2011 visando estabelecer potenciais ligações entre a proteína S100B e as hipóteses correntes da esquizofrenia. RESULTADOS: A S100B está potencialmente associada com as hipóteses dopaminérgica e glutamatérgica. O aumento da expressão de S100B tem sido detectado em astrócitos corticais em casos de esquizofrenia paranoide, enquanto se observa uma redução da expressão em oligodendrócitos na esquizofrenia residual, dando suporte à hipótese glial. Recentemente, a hipótese da neuroinflamação da esquizofrenia tem recebido atenção crescente. Nesse sentido, a S100B pode funcionar como uma citocina secretada por células gliais, linfócitos CD8+ e células NK, levando à ativação de monócitos e microglia. Além disso, a S100B apresenta propriedades do tipo adipocina e pode estar desregulada na esquizofrenia, devido a distúrbios da sinalização de insulina, levando ao aumento da liberação de S100B e ácidos graxos do tecido adiposo. CONCLUSÃO: A expressão de S100B em diferentes tipos celulares está envolvida em muitos processos regulatórios. Atualmente, não pode ser respondido qual mecanismo relacionado à esquizofrenia é o mais importante.BACKGROUND: Scientific evidence for increased S100B concentrations in the peripheral blood of acutely ill schizophrenia patients is consistent. In the past, this finding was mainly considered to reflect astroglial or blood-brain barrier dysfunction. METHODS: Using Entrez, PubMed was searched for articles published on or before June 15, 2011, including electronic early release publications, in order to determine other potential links between S

Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns.

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Zaigham, Mehreen; Lundberg, Fredrik; Olofsson, Per

2017-09-01

Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating condition resulting from a sustained lack of oxygen during birth. The interest in identifying a relevant biomarker of HIE has thrown into limelight the role of protein S100B as a clinical diagnostic marker of hypoxic brain damage in neonates. To evaluate the diagnostic value of protein S100B, measured in umbilical cord blood immediately after birth, as a useful biomarker in the diagnosis of HIE Sarnat stages II-III as well as a marker for long-term mortality and morbidity. Protein S100B was analyzed in cord blood sampled at birth from 13 newborns later diagnosed with stage II-III HIE and compared with 21 healthy controls. S100B concentrations were related to cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death/sequelae up to an age of 6years. Both parametric and non-parametric statistics were used with a two-sided P<0.05 considered significant. The difference in S100B concentration was marginally statistically significant between HIE cases and controls (P=0.056). Cord blood acidosis (P=0.046), aEEG pattern severity (P=0.030), HIE severity (P=0.027), and condition at 6-year follow-up (healthy/permanent sequelae/death; P=0.027) were all related to an increase in S100B concentration. Protein S100B in neonates suffering from HIE stages II-III appeared elevated in umbilical cord blood at birth. The S100B concentrations were positively associated to the severity of disease and the risk of suffering from neurodevelopmental sequelae and even death. Copyright © 2017. Published by Elsevier B.V.

Oxidative stress and S-100B protein in children with bacterial meningitis

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Hamed Enas A

2009-10-01

Full Text Available Abstract Background Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO and reactive oxygen species in the complex pathophysiology of bacterial meningitis. Methods In the present study, serum and CSF levels of NO, lipid peroxide (LPO (mediators for oxidative stress and lipid peroxidation; total thiol, superoxide dismutase (SOD (antioxidant mediators and S-100B protein (mediator of astrocytes activation and injury, were investigated in children with bacterial meningitis (n = 40. Albumin ratio (CSF/serum is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio is indicative of intrathecal synthesis. Results Compared to normal children (n = 20, patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p Conclusion This study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.

Subject-specific increases in serum S-100B distinguish sports-related concussion from sports-related exertion.

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Kiechle, Karin; Bazarian, Jeffrey J; Merchant-Borna, Kian; Stoecklein, Veit; Rozen, Eric; Blyth, Brian; Huang, Jason H; Dayawansa, Samantha; Kanz, Karl; Biberthaler, Peter

2014-01-01

The on-field diagnosis of sports-related concussion (SRC) is complicated by the lack of an accurate and objective marker of brain injury. To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion. Longitudinal cohort study. From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels. Forty-six athletes (30 Munich, 16 Rochester) underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich) sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002). Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively). A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC. Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.

Subject-specific increases in serum S-100B distinguish sports-related concussion from sports-related exertion.

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Karin Kiechle

Full Text Available The on-field diagnosis of sports-related concussion (SRC is complicated by the lack of an accurate and objective marker of brain injury.To compare subject-specific changes in the astroglial protein, S100B, before and after SRC among collegiate and semi-professional contact sport athletes, and compare these changes to differences in S100B before and after non-contact exertion.Longitudinal cohort study.From 2009-2011, we performed a prospective study of athletes from Munich, Germany, and Rochester, New York, USA. Serum S100B was measured in all SRC athletes at pre-season baseline, within 3 hours of injury, and at days 2, 3 and 7 post-SRC. Among a subset of athletes, S100B was measured after non-contact exertion but before injury. All samples were collected identically and analyzed using an automated electrochemiluminescent assay to quantify serum S100B levels.Forty-six athletes (30 Munich, 16 Rochester underwent baseline testing. Thirty underwent additional post-exertion S100B testing. Twenty-two athletes (16 Rochester, 6 Munich sustained a SRC, and 17 had S100B testing within 3 hours post-injury. The mean 3-hour post-SRC S100B was significantly higher than pre-season baseline (0.099±0.008 µg/L vs. 0.058±0.006 µg/L, p = 0.0002. Mean post-exertion S100B was not significantly different than the preseason baseline. S100B levels at post-injury days 2, 3 and 7 were significantly lower than the 3-hour level, and not different than baseline. Both the absolute change and proportional increase in S100B 3-hour post-injury were accurate discriminators of SRC from non-contact exertion without SRC (AUC 0.772 and 0.904, respectively. A 3-hour post-concussion S100B >0.122 µg/L and a proportional S100B increase of >45.9% over baseline were both 96.7% specific for SRC.Relative and absolute increases in serum S100B can accurately distinguish SRC from sports-related exertion, and may be a useful adjunct to the diagnosis of SRC.

Tumour markers in gynaecological practice

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Adewole, I.F.

1999-02-01

Gynaecological cancers are fairly common in developing countries and represent about 26 % f all cancers. Application of cervical cytology screening nationally has made cervical cancer one of the most preventable malignant diseases thus eliminating the challenges of advanced cancer management. Tumour markers has played a most crucial role in this respect

CLINICAL APPLICATION OF TUMOUR MARKERS: A REvIEw

African Journals Online (AJOL)

2009-12-02

Dec 2, 2009 ... for use in treatment monitoring of colorectal, hepatocellular, prostatic, ovarian and pancreatic carcinomas ... for cancer in the clinical setting (1,3-6). Primary ... presentation is one of the determinants of prognosis in cancer. If a tumour marker concentration is related to the tumour size then it may be useful for.

Clinical utility of a combination of tumour markers in the diagnosis of malignant pleural effusions.

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Gaspar, M J; De Miguel, J; García Díaz, J D; Díez, M

2008-01-01

The aim of the present study was to evaluate the diagnostic value of the tumour markers carcinoembryonic antigen (CEA), carbohydrate antigens CA 125, CA 15.3, CA 19.9 and tumor-associated glycoprotein 72 (TAG 72) in the pleural fluid (PF) of patients with pleural effusions of different etiologies. One hundred and fifty-five patients with pleural effusions (40 malignant, 84 benign and 31 paraneoplastic) were studied prospectively. The concentration of the tumour markers in serum and PF were measured by magnetic particle enzyme immunoassay. The PF to serum (PF/S) concentration ratios were calculated. The concentrations of CEA, CA 15.3, CA 19.9 and TAG 72 in PF and the PF/serum ratios were significantly higher in effusions of malignant and paraneoplastic origin than in those of benign origin. The receiver operating characteristic (ROC) curves were calculated for each marker and the diagnostic cut-off point was selected as the value that offered a specificity of 100% (CEA: 6.5 ng/ml; CA 15.3:62.4 IU/l; TAG 72:10.9 IU/l). CEA presented the greatest sensitivity [45% in the malignant group, 38.7% in the paraneoplastic group, and 41.4% in the pooled group (combined malignant and paraneoplastic)]. TAG 72 presented the largest area under the curve (0.89 in the malignant group and 0.80 in the pooled group). The diagnostic efficacy of the PF/S ratios was not better than measurement of the tumour markers in pleural fluid. The highest diagnostic accuracy for the diagnosis of malignant pleural effusions was achieved by grouping the markers in a panel comprising CEA, CA 15.3 and TAG 72; this showed a sensitivity of 75% and a negative predictive value of 79.1% . In the subgroup of patients with negative cytology, the sensitivity was 41.2% for CEA, 35.5% for CA 15.3 and 33.3% for TAG 72. The combination of these three markers achieved a sensitivity of 84.6%. The combined measurement of CEA, CA 15.3 and TAG 72 in pleural fluid is a useful complementary test in the differential

Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression

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Farina, Antonietta Rosella; Mackay, Andrew Reay, E-mail: andrewreay.mackay@univaq.it [Department of Applied Clinical and Biotechnological Sciences, University of L’Aquila, Via Vetoio, Coppito 2, L’Aquila 67100 (Italy)

2014-01-27

Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many ways in which gelatinase B/MMP-9 influences tumour biology. Following a brief outline of the gelatinase B/MMP-9 gene and protein, we analyse the role(s) of gelatinase B/MMP-9 in different phases of the tumorigenic process, and compare the importance of gelatinase B/MMP-9 source in the carcinogenic process. What becomes apparent is the importance of inflammatory cell-derived gelatinase B/MMP-9 in tumour promotion, early progression and triggering of the “angiogenic switch”, the integral relationship between inflammatory, stromal and tumour components with respect to gelatinase B/MMP-9 production and activation, and the fundamental role for gelatinase B/MMP-9 in the formation and maintenance of tumour stem cell and metastatic niches. It is also apparent that gelatinase B/MMP-9 plays important tumour suppressing functions, producing endogenous angiogenesis inhibitors, promoting inflammatory anti-tumour activity, and inducing apoptosis. The fundamental roles of gelatinase B/MMP-9 in cancer biology underpins the need for specific therapeutic inhibitors of gelatinase B/MMP-9 function, the use of which must take into account and substitute for tumour-suppressing gelatinase B/MMP-9 activity and also limit inhibition of physiological gelatinase B/MMP-9 function.

S100 chemokines mediate bookmarking of premetastatic niches

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Rafii, Shahin; Lyden, David

2010-01-01

Primary tumours release soluble factors, including VEGF-A, TGFβ and TNFα, which induce expression of the chemokines S100A8 and S100A9 in the myeloid and endothelial cells within the lung before tumour metastasis. These chemokine-activated premetastatic niches support adhesion and invasion of disseminating malignant cells, thereby establishing a fertile habitat for metastatic tumours. PMID:17139281

Role of serum S100B and PET-CT in follow-up of patients with cutaneous melanoma

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Novakovic Srdjan

2011-08-01

Full Text Available Abstract Background Increased level of serum S100B can serve as a marker of metastatic spread in patients with cutaneous melanoma (CM. In patients with elevated S100 B and/or clinical signs of disease progression PET-CT scan is a valuable tool for discovering metastases and planning treatment. The aims of this study were to determine whether regular measurements of serum S100B are a useful tool for discovering patients with CM metastases and to evaluate the diagnostic value of PET-CT during the follow-up. Methods From September 2007 to February 2010, 115 CM patients included in regular follow up at the Institute of Oncology Ljubljana were appointed to PET-CT. There were 82 (71.3% patients with clinical signs of disease progression and 33 (28.7% asymptomatic patients with two subsequent elevated values of S100B. Sensitivity, specificity, positive and negative predictive value (PPV, NPV of S100B and PET-CT were calculated using standard procedures. Results Disease progression was confirmed in 81.7% of patients (in 86.5% of patients with clinical signs of disease progression and in 69.7% of asymptomatic patients with elevated S100B. Sensitivity, specificity, PPV and NPV of S100B was 33.8%, 90.9%, 96.0% and 17.5% in patients with clinical signs of disease progression. In 20.0% of patients increased serum S100B was the only sign of disease progression. Sensitivity and PPV of S100 in this group of patients were 100.0% and 69.7%. With PET-CT disease progression was diagnosed in 84.2% of symptomatic patients and in 72.7% of asymptomatic patients with elevated S100B. The sensitivity, specificity, PPV and NPV of PET-CT for symptomatic patients was 98.5%, 90.9%, 98.5% and 90.9% and 100%, 90.0%, 95.8% and 100% for asymptomatic patients with elevated S100. Conclusions Measurements of serum S100B during regular follow-up of patients with CM are a useful tool for discovering disease progression in asymptomatic patients. The value of its use increases if

S100B increases in cyanotic versus noncyanotic infants undergoing heart surgery and cardiopulmonary bypass (CPB).

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Varrica, Alessandro; Satriano, Angela; Gavilanes, Antonio D W; Zimmermann, Luc J; Vles, Hans J S; Pluchinotta, Francesca; Anastasia, Luigi; Giamberti, Alessandro; Baryshnikova, Ekaterina; Gazzolo, Diego

2017-11-28

S100B has been proposed as a consolidated marker of brain damage in infants with congenital heart disease (CHD) undergoing cardiac surgery and cardiopulmonary bypass (CPB). The present study aimed to investigate whether S100B blood levels in the perioperative period differed in infants complicated or not by cyanotic CHD (CHDc) and correlated with oxygenation status (PaO 2 ). We conducted a case-control study of 48 CHD infants without pre-existing neurological disorders undergoing surgical repair and CPB. 24 infants were CHDc and 24 were CHD controls. Blood samples for S100B assessment were collected at six monitoring time-points: before the surgical procedure (T0), after sternotomy but before CPB (T1), at the end of the cross-clamp CPB phase (T2), at the end of CPB (T3), at the end of the surgical procedure (T4), at 24 h postsurgery (T5). In the CHDc group, S100B multiples of median (MoM) were significantly higher (p  .05, for all) were found at T2, T3, T5. Linear regression analysis showed a positive correlation between S100B MoM at T3 and PaO 2 (R = 0.84; p < .001). The present data showing higher hypoxia/hyperoxia-mediated S100B concentrations in CHDc infants suggest that CHDc are more prone to perioperative brain stress/damage and suggest the usefulness of further investigations to detect the "optimal" PaO 2 target in order to avoid the side effects associated with reoxygenation during CPB.

Tumour markers in urology

International Nuclear Information System (INIS)

Schmid, L.; Fornara, P.; Fabricius, P.G.

1988-01-01

The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.) [de

Cortisol, Interleukins and S100B in Delirium in the Elderly

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van Munster, Barbara C.; Bisschop, Peter H.; Zwinderman, Aeilko H.; Korevaar, Johanna C.; Endert, Erik; Wiersinga, W. Joost; van Oosten, Hannah E.; Goslings, J. Carel; de Rooij, Sophia E. J. A.

2010-01-01

In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65 years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in…

Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts

International Nuclear Information System (INIS)

Tuomela, Johanna; Solin, Olof; Minn, Heikki; Härkönen, Pirkko L; Grönroos, Tove J; Valta, Maija P; Sandholm, Jouko; Schrey, Aleksi; Seppänen, Jani; Marjamäki, Päivi; Forsback, Sarita; Kinnunen, Ilpo

2010-01-01

Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([ 18 F]FDG) and hypoxia ([ 18 F]EF5), and intratumoral polarographic measurements of pO 2 . Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO 2 measurements, [ 18 F]EF5 and [ 18 F]FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts

Cancer and tumour markers

International Nuclear Information System (INIS)

Osifo, B.

1999-02-01

Cancer has been a major cause of death world wide and in Nigeria there are six commonest forms of manifestation of cancer known. Of these prostrate cancer is the highest with 16% occurrence of all known cancers according to a study by the Histopathology Department of the UCH. Many factors, amongst them dietary, environmental, lifestyle, age and sedentary work are possible causes. With the global rise in incidents, the IAEA initiated the Tumour Marker Project as a means of screening cancers in 15 African countries including Nigeria. In Nigeria, 4 groups of the commonest cancers have been chosen for screening. These are prostrate cancer, primary liver cancer, cancer of the GI tract and trophoblastic cancer

The calcium-modulated proteins, S100A1 and S100B, as potential regulators of the dynamics of type III intermediate filaments

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M. Garbuglia

1999-10-01

Full Text Available The Ca2+-modulated, dimeric proteins of the EF-hand (helix-loop-helix type, S100A1 and S100B, that have been shown to inhibit microtubule (MT protein assembly and to promote MT disassembly, interact with the type III intermediate filament (IF subunits, desmin and glial fibrillary acidic protein (GFAP, with a stoichiometry of 2 mol of IF subunit/mol of S100A1 or S100B dimer and an affinity of 0.5-1.0 µM in the presence of a few micromolar concentrations of Ca2+. Binding of S100A1 and S100B results in inhibition of desmin and GFAP assemblies into IFs and stimulation of the disassembly of preformed desmin and GFAP IFs. S100A1 and S100B interact with a stretch of residues in the N-terminal (head domain of desmin and GFAP, thereby blocking the head-to-tail process of IF elongation. The C-terminal extension of S100A1 (and, likely, S100B represents a critical part of the site that recognizes desmin and GFAP. S100B is localized to IFs within cells, suggesting that it might have a role in remodeling IFs upon elevation of cytosolic Ca2+ concentration by avoiding excess IF assembly and/or promoting IF disassembly in vivo. S100A1, that is not localized to IFs, might also play a role in the regulation of IF dynamics by binding to and sequestering unassembled IF subunits. Together, these observations suggest that S100A1 and S100B may be regarded as Ca2+-dependent regulators of the state of assembly of two important elements of the cytoskeleton, IFs and MTs, and, potentially, of MT- and IF-based activities.

S100B protein in serum is elevated after global cerebral ischemic injury

Institute of Scientific and Technical Information of China (English)

Bao-di Sun; Hong-mei Liu; Shi-nan Nie

2013-01-01

BACKGROUND:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of global cerebral ischemic injury will be dramatically increased.Ischemic brain injury may elevate the level of serum S100 B protein and the severity of brain damage.METHODS:This article is a critical and descriptive review on S100 B protein in serum after ischemic brain injury.We searched Pubmed database with key words or terms such as 'S100B protein', 'cardiac arrest', 'hemorrhagic shock' and 'ischemia reperfusion injury' appeared in the last five years.RESULTS:S100B protein in patients with cardiac arrest,hemorrhagic shock and other causes of ischemic brain injury will be dramatically increased.Ischemic brain injury elevated the level of serum S100 B protein,and the severity of brain damage.CONCLUSION:The level of S100 B protein in serum is elevated after ischemic brain injury,but its mechanism is unclear.

Can S100B predict cerebral vasospasms in patients suffering from subarachnoid hemorrhage?

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Moshgan eAmiri

2013-06-01

Full Text Available Background: Protein S100B has proven to be a useful biomarker for cerebral damages. Increased levels of serum and CSF S100B have been shown in patients suffering subarachnoid hemorrhage, severe head injury and stroke. In patients with subarachnoid hemorrhage, the course of S100B levels has been correlated with neurological deficits and outcome. Cerebral vasospasm is a major contributor to morbidity and mortality. The primary aim of this study was to investigate the potential of S100B protein as a predictor of cerebral vasospasm in patients with severe subarachnoid hemorrhage.Methods: Patients with SAH, Fisher grade 3 and 4, were included in the study. Five samples of CSF and serum S100B were collected from each patient. The first sample (baseline sample was drawn within the first three days following ictus and the following four samples, once a day on days 5 to 8, with day of ictus defined as day 1. Clinical suspicion of cerebral vasospasm confirmed by computed tomography angiography was used to diagnose cerebral vasospasm.Results: A total of 18 patients were included. Five patients (28 % developed cerebral vasospasm, two (11 % developed ventriculitis. There were no significant differences between S100B for those with and without vasospasm. Serum S100B levels in patients with vasospasm were slightly lower within the first 5 days following ictus, compared to patients without vasospasm. Two out of 5 patients had elevated and increasing serum S100B prior to vasospasm. Only one showed a peak level of S100B one day before vasospasm could be diagnosed. Due to the low number of patients in the study, statistical significance could not be reached. Conclusion: Neither serum nor CSF S100B can be used as predictor of cerebral vasospasm in patients suffering from subarachnoid hemorrhage.

Serum S100B in elderly patients with and without delirium

NARCIS (Netherlands)

van Munster, Barbara C.; Korevaar, Johanna C.; Korse, Catharina M.; Bonfrer, Johannes M.; Zwinderman, Aeilko H.; de Rooij, Sophia E.

2010-01-01

Objective: Elevation of S100B has been shown after various neurologic diseases with cognitive dysfunction. The aim of this study was to compare the serum level of S100B of patients with and without delirium and investigate the possible associations with different subtypes of delirium. Methods:

Serum S100B in elderly patients with and without delirium.

NARCIS (Netherlands)

Munster, B.C. van; Korevaar, J.C.; Korse, C.M.; Bonfrer, J.M.; Zwinderman, A.H.; Rooij, S.E. de

2010-01-01

Objective: Elevation of S100B has been shown after various neurologic diseases with cognitive dysfunction. The aim of this study was to compare the serum level of S100B of patients with and without delirium and investigate the possible associations with different subtypes of delirium. Methods:

How does extracerebral trauma affect the clinical value of S100B measurements?

DEFF Research Database (Denmark)

Ohrt-Nissen, Søren; Friis-Hansen, Lennart; Dahl, Benny

2011-01-01

Background Protein S100B has proven to be a useful biomarker for cerebral damage. The predictive ability of S100B may, however, be affected by extracerebral injuries. The aim of this study was to investigate serum levels of S100B in patients with either isolated head injury (IHI), multi trauma...

S100B proteins in febrile seizures

DEFF Research Database (Denmark)

Mikkonen, Kirsi; Pekkala, Niina; Pokka, Tytti

2011-01-01

at the hospital after FS and S100B concentration in serum (r=-0.130, P=0.28) or in cerebrospinal fluid samples (r=-0.091, P=0.52). Our findings indicate that FS does not cause significant blood-brain barrier openings, and increase the evidence that these seizures are relatively harmless for the developing brain....

Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

Science.gov (United States)

Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

2016-06-01

Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

International scientific communications in the field of colorectal tumour markers.

Science.gov (United States)

Ivanov, Krasimir; Donev, Ivan

2017-05-27

To analyze scientometrically the dynamic science internationalization on colorectal tumour markers as reflected in five information portals and to outline the significant journals, scientists and institutions. A retrospective problem-oriented search was performed in Web of Science Core Collection (WoS), MEDLINE, BIOSIS Citation Index (BIOSIS) and Scopus for 1986-2015 as well as in Dervent Innovations Index (Derwent) for 1995-2015. Several specific scientometric parameters of the publication output and citation activity were comparatively analyzed. The following scientometric parameters were analyzed: (1) annual dynamics of publications; (2) scientific institutions; (3) journals; (4) authors; (5) scientific forums; (6) patents - number of patents, names and countries of inventors, and (7) citations (number of citations to publications by single authors received in WoS, BIOSIS Citation Index and Scopus). There is a trend towards increasing publication output on colorectal tumour markers worldwide along with high citation rates. Authors from 70 countries have published their research results in journals and conference proceedings in 21 languages. There is considerable country stratification similar to that in most systematic investigations. The information provided to end users and scientometricians varies between these data-bases in terms of most parameters due to different journal coverage, indexing systems and editorial policy. The lists of the so-called "core" journals and most productive authors in WoS, BIOSIS, MEDLINE and Scopus along with the list of the most productive authors - inventors in Derwent present a particular interest to the beginners in the field, the institutional and national science managers and the journal editorial board members. The role of the purposeful assessment of scientific forums and patents is emphasized. Our results along with this problem-oriented collection containing the researchers' names, addresses and publications could

Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma

Science.gov (United States)

Xu, Rui-Hua; Wei, Wei; Krawczyk, Michal; Wang, Wenqiu; Luo, Huiyan; Flagg, Ken; Yi, Shaohua; Shi, William; Quan, Qingli; Li, Kang; Zheng, Lianghong; Zhang, Heng; Caughey, Bennett A.; Zhao, Qi; Hou, Jiayi; Zhang, Runze; Xu, Yanxin; Cai, Huimin; Li, Gen; Hou, Rui; Zhong, Zheng; Lin, Danni; Fu, Xin; Zhu, Jie; Duan, Yaou; Yu, Meixing; Ying, Binwu; Zhang, Wengeng; Wang, Juan; Zhang, Edward; Zhang, Charlotte; Li, Oulan; Guo, Rongping; Carter, Hannah; Zhu, Jian-Kang; Hao, Xiaoke; Zhang, Kang

2017-11-01

An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive `liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (P < 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (P < 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.

Os possíveis papéis da S100B na esquizofrenia

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Johann Steiner

2013-01-01

Full Text Available CONTEXTO: Evidências científicas do aumento da concentração da proteína S100B no sangue de pacientes esquizofrênicos são muito consistentes. No passado essa informação era principalmente considerada como reflexo da disfunção astroglial ou da barreira hematoencefálica. MÉTODOS: Pesquisa de publicações no PubMed até o dia 15 de junho de 2011 visando estabelecer potenciais ligações entre a proteína S100B e as hipóteses correntes da esquizofrenia. RESULTADOS: A S100B está potencialmente associada com as hipóteses dopaminérgica e glutamatérgica. O aumento da expressão de S100B tem sido detectado em astrócitos corticais em casos de esquizofrenia paranoide, enquanto se observa uma redução da expressão em oligodendrócitos na esquizofrenia residual, dando suporte à hipótese glial. Recentemente, a hipótese da neuroinflamação da esquizofrenia tem recebido atenção crescente. Nesse sentido, a S100B pode funcionar como uma citocina secretada por células gliais, linfócitos CD8+ e células NK, levando à ativação de monócitos e microglia. Além disso, a S100B apresenta propriedades do tipo adipocina e pode estar desregulada na esquizofrenia, devido a distúrbios da sinalização de insulina, levando ao aumento da liberação de S100B e ácidos graxos do tecido adiposo. CONCLUSÃO: A expressão de S100B em diferentes tipos celulares está envolvida em muitos processos regulatórios. Atualmente, não pode ser respondido qual mecanismo relacionado à esquizofrenia é o mais importante.

Holder pasteurization affects S100B concentrations in human milk.

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Peila, Chiara; Coscia, Alessandra; Bertino, Enrico; Li Volti, Giovanni; Galvano, Fabio; Visser, Gerard H A; Gazzolo, Diego

2018-02-01

Donor milk (DM) represents an important nutrition source for high-risk newborns. Holder pasteurization (HoP) is the most recommended procedure for DM treatment, providing a good compromise between microbiological safety and biological quality. HoP was previously shown to affect DM cytokines, growth factors and hormones levels, whilst no data concerning the possible effects of HoP on neurobiomarkers (NB) are available. Therefore, our study investigated whether the concentration in DM of a well-known NB involved in brain development/damage, namely S100B, changes due to HoP. We conducted a pretest-test study in 11 mothers, whose DM samples were sub-divided into two parts: the first was immediately frozen (-80 °C); the second was pasteurized with Holder method before freezing. S100B DM levels were measured using a commercially available immunoluminometric assay. S100B protein was detected in all milk samples. Results showed significant differences between groups (p pasteurization stresses and the need to develop new storage techniques to preserve the biological quality of human milk.

Expression of Selected Markers in Immunohistochemical Diagnosis of Canine and Human Testicular Tumours

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Ciaputa Rafał

2015-04-01

Full Text Available Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII, chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++ than in men (62.5% had +++ in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.

Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033

International Nuclear Information System (INIS)

Dorow, Donna S.; Cullinane, Carleen; Conus, Nelly; Roselt, Peter; Binns, David; McCarthy, Timothy J.; McArthur, Grant A.; Hicks, Rodney J.

2006-01-01

This study was designed as ''proof of concept'' for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses to molecularly targeted therapy. Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6-8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6 or 7) with [ 18 F]fluorodeoxyglucose, [ 18 F]fluoro-L-thymidine, [ 18 F]fluoro-azoazomycinarabinoside or [ 18 F]fluoromisonidazole. Separate cohorts (n=3) were treated identically and tumours were assessed ex vivo for markers of glucose metabolism, proliferation and hypoxia. During the study period, mean uptake of all PET tracers generally increased for control tumours compared to baseline. In contrast, tracer uptake into CI-1033-treated tumours decreased by 20-60% during treatment. Expression of the glucose transporter Glut-1 and cell cycle markers was unchanged or increased in control tumours and generally decreased with CI-1033 treatment, compared to baseline. Thymidine kinase activity was reduced in all tumours compared to baseline at day 3 but was sevenfold higher in control versus CI-1033-treated tumours by day 6 of treatment. Uptake of the hypoxia marker pimonidazole was stable in control tumours but was severely reduced following 7 days of CI-1033 treatment. CI-1033 treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET. The PET findings correlated well with ex vivo biomarkers for each of the cellular processes studied. These results confirm the utility of small animal PET for evaluation of the effectiveness of molecularly targeted therapies and simultaneously definition of specific cellular processes involved in the therapeutic response. (orig.)

Reference values for venous and capillary S100B in children

DEFF Research Database (Denmark)

Astrand, Ramona; Romner, Bertil; Lanke, Jan

2011-01-01

The current management guidelines for pediatric mild head injury (MHI) liberally recommend computed tomography (CT) and frequent admission. Serum protein S100B, currently used in management of adult head injury, has recently shown potential for reducing unnecessary CT scans after pediatric mild h...... head injury. Capillary sampling in children is commonly used when venous sampling fails or is inappropriate. We present reference values for both venous and capillary samples of protein S100B in children....

Circadian rhythms of cysteine proteinases and cystatins, potential tumour markers, in normal sera

International Nuclear Information System (INIS)

Cimerman, N.; Krasovec, M.; Mesko-Brguljan, P.; Suskovic, S.; Kos, J.

2002-01-01

Circadian day/night variations have been evidenced in all major groups of organisms and at all levels of organisation of the organism. Circadian intra-individual variations are known for a number of analyses in serum including tumour-associated markers. It was suggested that the serum levels of cysteine proteinases and their inhibitors may be of clinical importance for prognosis and diagnosis in cancer. Since known circadian rhythms are important for choosing the best sampling time, interpretation of the results of a diagnostic test, patient monitoring, and timing of a therapy, our objective was to establish 24-h variations of cysteine proteinases, cathepsins B, H, L, and their low molecular weight inhibitors, stefin A, stefin B, and cystatin C, in sera from healthy subjects. (author)

Lectin I of Ulex europaeus as a marker for a subset of histiocytic tumours of the lymph node.

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Ruco, L P; Pescarmona, E; Pezzella, F; Uccini, S; Testi, A M; Cartoni, C; Baroni, C D

1985-01-01

We describe four lymph node based tumours in which numerous neoplastic cells and some mitotic figures were characterized by staining affinity for Lectin I of Ulex europaeus (UEA-I). The patients had no vascular or epithelial tumours and presented symptoms suggestive of a systemic lymphoproliferative disease. Histologically, the tumours were composed of large, cohesive, cells which were mainly located in the paracortex. UEA-I reactivity was more evident in the Golgi area and was present in large mononucleated cells often arranged to delimit vascular-like spaces. The neoplastic cells were weakly muramidase-positive in one case, and were ANAE+/AP+ in two other cases. Large dots of UEA-I reactivity were detected in S-100+/muramidase-negative Langerhans-like cells present in one case of Letterer-Siwe disease. UEA-I staining was consistently negative in 20 cases of B cell- or T cell lymphoma and in 9 other cases of histiocytic lymphoma. It is suggested that UEA-I+ tumours of the lymph nodes are part of a distinct subset of histiocytic malignancies whose neoplastic cells present some morphological and phenotypic properties normally associated with endothelial cells.

Systematic review and meta-analysis of circulating S100B blood levels in schizophrenia.

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Katina Aleksovska

Full Text Available S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and psychiatric disorders. S100B levels have been reported to be higher in schizophrenics than healthy controls. To quantify the relationship between S100B blood levels and schizophrenia a systematic literature review of case-control studies published on this topic within July 3rd 2014 was carried out using three bibliographic databases: Medline, Scopus and Web of Science. Studies reporting mean and standard deviation of S100B blood levels both in cases and controls were included in the meta-analysis. The meta-Mean Ratio (mMR of S100B blood levels in cases compared to controls was used as a measure of effect along with its 95% Confidence Intervals (CI. 20 studies were included totaling for 994 cases and 785 controls. Schizophrenia patients showed 76% higher S100B blood levels than controls with mMR = 1.76 95% CI: 1.44-2.15. No difference could be found between drug-free patients with mMR = 1.84 95%CI: 1.24-2.74 and patients on antipsychotic medication with mMR = 1.75 95% CI: 1.41-2.16. Similarly, ethnicity and stage of disease didn't affect results. Although S100B could be regarded as a possible biomarker of schizophrenia, limitations should be accounted when interpreting results, especially because of the high heterogeneity that remained >70%, even after carrying out subgroups analyses. These results point out that approaches based on traditional categorical diagnoses may be too restrictive and new approaches based on the characterization of new complex phenotypes should be considered.

Serum S100B levels after meningioma surgery: A comparison of two laboratory assays

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Weiniger Carolyn F

2008-09-01

Full Text Available Abstract Background S100B protein is a potential biomarker of central nervous system insult. This study quantitatively compared two methods for assessing serum concentration of S100B. Methods A prospective, observational study performed in a single tertiary medical center. Included were fifty two consecutive adult patients undergoing surgery for meningioma that provided blood samples for determination of S100B concentrations. Eighty samples (40 pre-operative and 40 postoperative were randomly selected for batch testing. Each sample was divided into two aliquots. These were analyzed by ELISA (Sangtec and a commercial kit (Roche Elecsys® for S100B concentrations. Statistical analysis included regression modelling and Bland-Altman analysis. Results A parsimonious linear model best described the prediction of commercial kit values by those determined by ELISA (y = 0.045 + 0.277*x, x = ELISA value, R2 = 0.732. ELISA measurements tended to be higher than commercial kit measurements. This discrepancy increased linearly with increasing S100B concentrations. At concentrations above 0.7 μg/L the paired measurements were consistently outside the limits of agreement in the Bland-Altman display. Similar to other studies that used alternative measurement methods, sex and age related differences in serum S100B levels were not detected using the Elecsys® (p = 0.643 and 0.728 respectively. Conclusion Although a generally linear relationship exists between serum S100B concentrations measured by ELISA and a commercially available kit, ELISA values tended to be higher than commercial kit measurements particularly at concentrations over 0.7 μg/L, which are suggestive of brain injury. International standardization of commercial kits is required before the predictive validity of S100B for brain damage can be effectively assessed in clinical practice.

Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis.

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Awad, S M; Attallah, D A; Salama, R H; Mahran, A M; Abu El-Hamed, E

2018-04-01

Psoriasin (S100A7) and koebnerisin (S100A15) are proinflammatory proteins upregulated in psoriasis, but their relation to atherosclerosis remains unclear. To evaluate the role of serum psoriasin and koebnerisin as possible markers for subclinical atherosclerosis in patients with psoriasis. Serum levels of psoriasin and koebnerisin were measured by ELISA in 45 patients with psoriasis and in 45 healthy controls (HCs). Intima-media thickness (IMT) of the right and left common carotid arteries was measured to detect the presence of subclinical atherosclerosis. Clinical severity of psoriasis was estimated using the Psoriasis Area and Severity Index (PASI). Compared with HCs, patients with psoriasis had significantly higher levels of psoriasin (26.61 ± 22.45 ng/mL vs. 6.31 ± 1.68 ng/mL, P  0.01) and serum koebnerisin (r = 0.48, P psoriasis with subclinical atherosclerosis had higher serum levels of koebnerisin compared with patients without subclinical atherosclerosis (P = 0.04), which was not observed for psoriasin (P = 0.94). Serum psoriasin and koebnerisin correlate with IMT, underlining their value as a potential link between psoriasis and atherosclerosis. In particular, koebnerisin seems to be a useful marker of subclinical atherosclerosis in patients with psoriasis. © 2018 British Association of Dermatologists.

A systematic review of the biomarker S100B: implications for sport-related concussion management.

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Schulte, Stefanie; Podlog, Leslie W; Hamson-Utley, J Jordan; Strathmann, Frederick G; Strüder, Heiko K

2014-01-01

Elevated levels of the astroglial protein S100B have been shown to predict sport-related concussion. However, S100B levels within an athlete can vary depending on the type of physical activity (PA) engaged in and the methodologic approach used to measure them. Thus, appropriate reference values in the diagnosis of concussed athletes remain undefined. The purpose of our systematic literature review was to provide an overview of the current literature examining S100B measurement in the context of PA. The overall goal is to improve the use of the biomarker S100B in the context of sport-related concussion management. PubMed, SciVerse Scopus, SPORTDiscus, CINAHL, and Cochrane. We selected articles that contained (1) research studies focusing exclusively on humans in which (2) either PA was used as an intervention or the test participants or athletes were involved in PA and (3) S100B was measured as a dependent variable. We identified 24 articles. Study variations included the mode of PA used as an intervention, sample types, sample-processing procedures, and analytic techniques. Given the nonuniformity of the analytical methods used and the data samples collected, as well as differences in the types of PA investigated, we were not able to determine a single consistent reference value of S100B in the context of PA. Thus, a clear distinction between a concussed athlete and a healthy athlete based solely on the existing S100B cutoff value of 0.1 μg/L remains unclear. However, because of its high sensitivity and excellent negative predictive value, S100B measurement seems to have the potential to be a diagnostic adjunct for concussion in sports settings. We recommend that the interpretation of S100B values be based on congruent study designs to ensure measurement reliability and validity.

Expression of S100B during the innate immune of corneal epithelium against fungi invasion

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Jie Zhang

2016-02-01

Full Text Available AIM: To explore the expression of S100B in corneal epithelial cells under Aspergillus stimulation both in vivo and in vitro. METHODS: Immortalized human corneal epithelial cells (HCECs were exposed to inactive Aspergillus fumigatus (A. fumigatus conidia at 0, 4, 8, 12, 16, and 24h respectively. The corneas of Wistar rats were exposed to active A. fumigatus at 0, 12, 24, 48h and the normal rat corneas were used for normal control. The mRNA level of S100B was evaluated by real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR. S100B protein expression in cornea epithelium was detected by immunohistochemical/immunocytochemical staining (IHC/ICC. RESULTS: Histopathology revealed a significant inflammatory cell infiltration in fungal keratitis human and rat cornea. Corneal epithelial cells didn’t express or rarely express S100B at baseline. A. fumigatus significantly induced S100B mRNA expression in cultured corneal epithelial cells in a time depended manner in vitro, the mRNA began to rise significantly at 8h in vitro (P<0.05 and continue to rise as time prolonged (P<0.01. In vivo, S100B mRNA level was low in the normal corneas. However, it was increased in keratitis corneas from 12h after infection (P<0.05 and reached to a peak at 24h (P<0.001. Immunochemistry revealed an obvious staining in fungal keratitis corneas as well as immortalized HCECs compared to the normal ones respectively, indicating an increased expression of S100B protein. CONCLUSION: S100B exists in corneal epithelial cells and is over-expressed under A. fumigatus stimulation. S100B may play an important role in the innate immune response of the corneal epithelium during A. fumigatus infection.

Expression of S100B during the innate immune of corneal epithelium against fungi invasion

Science.gov (United States)

Zhang, Jie; Zhao, Gui-Qiu; Qu, Jing; Che, Cheng-Ye; Lin, Jing; Jiang, Nan; Zhao, Han; Wang, Xue-Jun

2016-01-01

AIM To explore the expression of S100B in corneal epithelial cells under Aspergillus stimulation both in vivo and in vitro. METHODS Immortalized human corneal epithelial cells (HCECs) were exposed to inactive Aspergillus fumigatus (A. fumigatus) conidia at 0, 4, 8, 12, 16, and 24h respectively. The corneas of Wistar rats were exposed to active A. fumigatus at 0, 12, 24, 48h and the normal rat corneas were used for normal control. The mRNA level of S100B was evaluated by real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). S100B protein expression in cornea epithelium was detected by immunohistochemical/immunocytochemical staining (IHC/ICC). RESULTS Histopathology revealed a significant inflammatory cell infiltration in fungal keratitis human and rat cornea. Corneal epithelial cells didn't express or rarely express S100B at baseline. A. fumigatus significantly induced S100B mRNA expression in cultured corneal epithelial cells in a time depended manner in vitro, the mRNA began to rise significantly at 8h in vitro (P<0.05) and continue to rise as time prolonged (P<0.01). In vivo, S100B mRNA level was low in the normal corneas. However, it was increased in keratitis corneas from 12h after infection (P<0.05) and reached to a peak at 24h (P<0.001). Immunochemistry revealed an obvious staining in fungal keratitis corneas as well as immortalized HCECs compared to the normal ones respectively, indicating an increased expression of S100B protein. CONCLUSION S100B exists in corneal epithelial cells and is over-expressed under A. fumigatus stimulation. S100B may play an important role in the innate immune response of the corneal epithelium during A. fumigatus infection. PMID:26949634

BIOMARKERS S100B AND NSE PREDICT OUTCOME IN HYPOTHERMIA-TREATED ENCEPHALOPATHIC NEWBORNS

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Massaro, An N.; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B.; Glass, Penny

2014-01-01

Objective To evaluate if serum S100B protein and neuron specific enolase (NSE) measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy (NE). Design Prospective longitudinal cohort study Setting A level IV neonatal intensive care unit in a free-standing children’s hospital. Patients Term newborns with moderate to severe NE referred for therapeutic hypothermia during the study period. Interventions Serum NSE and S100B were measured at 0, 12, 24 and 72 hrs of hypothermia. Measurements and Main Reseults Of the 83 infants were enrolled, fifteen (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development (BSID-II) at 15 months of age. Outcomes were assessed in 49/68 (72%) survivors at a mean age of 15.2±2.7 months. Neurodevelopmental outcome was classified by BSID-II Mental (MDI) and Psychomotor (PDI) Developmental Index scores, reflecting cognitive and motor outcomes respectively. Four-level outcome classifications were defined a priori: normal= MDI/PDI within 1SD (>85), mild= MDI/PDI <1SD (70–85), moderate/severe= MDI/PDI <2SD (<70), or died. Elevated serum S100B and NSE levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and soceioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were: S100B 2.5 (95% CI 1.3–4.8) and NSE 2.1 (1.2–3.6); for motor outcome: S100B 2.6 (1.2–5.6) and NSE 2.1 (1.2–3.6). Conclusions Serum S100B and NSE levels in babies with NE are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia. PMID:24777302

Prognostic value of tumour endothelial markers in patients with endometrial cancer

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BERSINGER, NICK A.; SCHNEIDER, BRIGITTE; VORBURGER, STEPHAN A.; JOHANN, SILKE; CANDINAS, DANIEL; MUELLER, MICHAEL D.

2010-01-01

Endometrial cancer is one of the more frequent and most lethal gynaecological cancer types. Since it occurs more frequently in elderly and overweight patients, a pre-operative staging method would be beneficial. The growth of solid neoplasms is always accompanied by neovascularisation. Tumour endothelial markers (TEMs) are a group of recently described endothelial cell surface markers that appear to be specific to neoplastic tissue. This study aimed to investigate the potential usefulness of TEM assessment in the endometrium by comparing the transcriptional expression of TEMs in the normal endometrium with endometroid adenocarcinoma tissue. Tissues were lysed and the RNA was extracted, assessed and reverse transcribed in one batch. Real-time quantitative PCR was performed for TEM-1, -2, -6, -7, -7r and -8. GAPDH, β-actin and ribosomal protein L13A (RPL13A) were used as control genes. TEM-8 showed the highest expression level in all of the groups. TEM-1 showed higher expression levels in the normal endometrium than in the tumour tissues. For the remaining TEMs, we found a higher expression in the cancer samples than in the normal endometria. Statistical significance of this difference was achieved for TEM-1, -2 and-7. No clear correlation was noted between the tumour stage and the level of TEM-1, -6 and -8 expression. Apart from TEM-6, the highest expression in FIGO I cancer stages was noted in the remaining TEMs. Our results showed that for most of these tumour endothelial markers, gene expression was slightly higher in the endometrial carcinoma tissue samples than in the endometrium of normal cycling women. However, with the possible exception of TEM-8 and -6, absolute expression levels were generally low, indicating that most TEMs may only be specifically expressed in a restricted number of cancer types (e.g., colorectal). Therefore, TEMs may not be useful in the context of endometrial cancer. PMID:22966283

Prognostic value of tumour endothelial markers in patients with endometrial cancer.

Science.gov (United States)

Bersinger, Nick A; Schneider, Brigitte; Vorburger, Stephan A; Johann, Silke; Candinas, Daniel; Mueller, Michael D

2010-01-01

Endometrial cancer is one of the more frequent and most lethal gynaecological cancer types. Since it occurs more frequently in elderly and overweight patients, a pre-operative staging method would be beneficial. The growth of solid neoplasms is always accompanied by neovascularisation. Tumour endothelial markers (TEMs) are a group of recently described endothelial cell surface markers that appear to be specific to neoplastic tissue. This study aimed to investigate the potential usefulness of TEM assessment in the endometrium by comparing the transcriptional expression of TEMs in the normal endometrium with endometroid adenocarcinoma tissue. Tissues were lysed and the RNA was extracted, assessed and reverse transcribed in one batch. Real-time quantitative PCR was performed for TEM-1, -2, -6, -7, -7r and -8. GAPDH, β-actin and ribosomal protein L13A (RPL13A) were used as control genes. TEM-8 showed the highest expression level in all of the groups. TEM-1 showed higher expression levels in the normal endometrium than in the tumour tissues. For the remaining TEMs, we found a higher expression in the cancer samples than in the normal endometria. Statistical significance of this difference was achieved for TEM-1, -2 and-7. No clear correlation was noted between the tumour stage and the level of TEM-1, -6 and -8 expression. Apart from TEM-6, the highest expression in FIGO I cancer stages was noted in the remaining TEMs. Our results showed that for most of these tumour endothelial markers, gene expression was slightly higher in the endometrial carcinoma tissue samples than in the endometrium of normal cycling women. However, with the possible exception of TEM-8 and -6, absolute expression levels were generally low, indicating that most TEMs may only be specifically expressed in a restricted number of cancer types (e.g., colorectal). Therefore, TEMs may not be useful in the context of endometrial cancer.

Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

Science.gov (United States)

Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

2017-12-01

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV 50% ). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV 50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

XIAP and Ki-67: A Correlation Between Antiapoptotic and Proliferative Marker Expression in Benign and Malignant Tumours of Salivary Gland: An Immunohistochemical Study.

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Bagulkar, Bhupesh Bhayyaji; Gawande, Madhuri; Chaudhary, Minal; Gadbail, Amol Ramchandra; Patil, Swati; Bagulkar, Smita

2015-02-01

Impaired balance between cell proliferation and apoptosis is crucial to the development of malignant neoplasm. The purpose of this study was to evaluate and compare the expression of X-Linked inhibitor of apoptotic protein (XIAP) (antiapoptotic marker) and Ki-67 (proliferative marker) expression in benign and malignant salivary gland (SG) tumours. The study consisted of 40 cases of benign SG tumours and 50 cases of malignant SG tumours. The immunohistochemistry was carried out by using Ki-67 antibody (clone MIB-1) and XIAP antibody in all the groups. XIAP expression was significantly higher in malignant SG tumours than benign SG tumours (p = 0.016). Ki-67 LI was significantly higher in malignant SG tumours than benign SG tumours (p = 0.0002). Statistically significant positive correlation between Ki-67 count and XIAP expression was noted in benign and malignant SG tumours (p = 0.000). As the expression of an antiapoptotic marker (XIAP) increases, the expression of a proliferative marker (Ki-67) also increases from benign to malignant SG tumours. Thus, targeted therapy of XIAP may play a future role in the management of SG malignancy.

Case report: Extreme levels of serum S-100B in a patient with chronic subdural hematoma

Directory of Open Access Journals (Sweden)

Malin Elisabet Persson

2012-12-01

Full Text Available The protein S-100B is a biomarker increasingly used within neurosurgery and neurointensive care. As a relatively sensitive, yet unspecific, indicator of CNS pathology, potential sources of error must be clearly understood when interpreting serum S-100B levels. This case report studied the course of a 46-year-old gentleman with a chronic subdural haemorrhage, serum S-100B levels of 22 μg/L and a history of malignant melanoma. Both intra- and extra-cranial sources of S-100B are evaluated and imply an unclear contribution of several sources to the total serum concentration. Potential sources of error when interpreting serum concentrations of S-100B are discussed

Serum S100B: A possible biomarker for severity of obstructive sleep apnea

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Eman Riad

2017-10-01

Conclusion: Serum S100B protein was significantly elevated in OSA patients and its serum levels correlated with the severity of the disease. Increased serum S100B could indicat brain injury and could be a potential serum biomarker for detection of early neurological complications in OSA patients that could improve the management and care of these patients.

Comparison between capillary, venous and arterial levels of protein S100B in patients with severe brain pathology

DEFF Research Database (Denmark)

Astrand, Ramona; Romner, Bertil; Reinstrup, Peter

2012-01-01

of the study was to investigate the relation between capillary, venous and arterial measurements of protein S100B, primarily by determining whether capillary S100B differ from venous and if capillary S100B can predict venous S100B levels, and secondarily, if arterial S100B samples can substitute venous samples...... in severely brain-injured patients....

Attention-deficit hyperactivity disorder (ADHD and glial integrity: S100B, cytokines and kynurenine metabolism - effects of medication

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Schwarz Markus J

2010-05-01

Full Text Available Abstract Background Children with attention-deficit/hyperactivity disorder (ADHD show a marked temporal variability in their display of symptoms and neuropsychological performance. This could be explained in terms of an impaired glial supply of energy to support neuronal activity. Method We pursued one test of the idea with measures of a neurotrophin reflecting glial integrity (S100B and the influences of 8 cytokines on the metabolism of amino-acids, and of tryptophan/kynurenine to neuroprotective or potentially toxic products that could modulate glial function. Serum samples from 21 medication-naïve children with ADHD, 21 typically-developing controls, 14 medicated children with ADHD and 7 healthy siblings were analysed in this preliminary exploration of group differences and associations. Results There were no marked group differences in levels of S100B, no major imbalance in the ratios of pro- to anti-inflammatory interleukins nor in the metabolism of kynurenine to toxic metabolites in ADHD. However, four trends are described that may be worthy of closer examination in a more extensive study. First, S100B levels tended to be lower in ADHD children that did not show oppositional/conduct problems. Second, in medicated children raised interleukin levels showed a trend to normalisation. Third, while across all children the sensitivity to allergy reflected increased levels of IL-16 and IL-10, the latter showed a significant inverse relationship to measures of S100B in the ADHD group. Fourthly, against expectations healthy controls tended to show higher levels of toxic 3-hydroxykynurenine (3 HK than those with ADHD. Conclusions Thus, there were no clear signs (S100B that the glial functions were compromised in ADHD. However, other markers of glial function require examination. Nonetheless there is preliminary evidence that a minor imbalance of the immunological system was improved on medication. Finally, if lower levels of the potentially toxic 3

Mechanism of S100b release from rat cortical slices determined under basal and stimulated conditions.

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Gürsoy, Murat; Büyükuysal, R Levent

2010-03-01

Incubation of rat cortical slices in a medium that was not containing oxygen and glucose (oxygen-glucose deprivation, OGD) caused a 200% increase in the release of S100B. However, when slices were transferred to a medium containing oxygen and glucose (reoxygenation conditions, or REO), S100B release reached 500% of its control value. Neither inhibition of nitric oxide (NO) synthase by L-NAME nor addition of the NO donors sodium nitroprussid (SNP) or hydroxylamine (HA) to the medium altered basal S100B release. Similarly, the presence of SNP, HA or NO precursor L: -arginine in the medium, or inhibition of NO synthase by L-NAME also failed to alter OGD- and REO-induced S100B outputs. Moreover, individual inhibition of PKC, PLA(2) or PLC all failed to attenuate the S100B release determined under control condition or enhanced by either OGD or REO. Blockade of calcium channels with verapamil, chelating the Ca(+2) ions with BAPTA or blockade of sodium channels with tetrodotoxin (TTX) did not alter OGD- and REO-induced S100B release. In contrast to the pharmacologic manipulations mentioned above, glutamate and alpha-ketoglutarate added at high concentrations to the medium prevented both OGD- and REO-induced S100B outputs. These results indicate that neither NO nor the activation of PKC, PLA(2) or PLC seem to be involved in basal or OGD- and REO-induced S100B outputs. Additionally, calcium and sodium currents that are sensitive to verapamil and TTX, respectively, are unlikely to contribute to the enhanced S100B release observed under these conditions.

Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression

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Juan Du

2018-04-01

Full Text Available Andrographolide (ANDRO has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains were subjected to 3 and 21% of O2 for various times (0–12 h to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.

GFAP and S100B in the acute phase of mild traumatic brain injury

NARCIS (Netherlands)

Metting, Z.; Wilczak, N.; Rodiger, L. A.; Schaaf, J. M.; van der Naalt, J.

Objective: The biomarkers glial fibrillary acid protein (GFAP) and S100B are increasingly used as prognostic tools in severe traumatic brain injury (TBI). Data for mild TBI are scarce. This study aims to analyze the predictive value of GFAP and S100B for outcome in mild TBI and the relation with

Development of kits for radioimmunometric assays for tumour markers. Final report of a co-ordinated research project 1997-2001

International Nuclear Information System (INIS)

2002-08-01

Many tumour marker assays have been reported over the years and their role is well recognized and acknowledged in the follow-up of known cancer cases. However, their true potential for use in primary diagnosis or screening of high risk groups is still to be fully realized due to the need to achieve better specificity. Among the various tumour markers, the one for prostate cancer - prostate specific antigen (PSA) - appears to have better specificity, coming close to a tumour specific antigen. Prostate cancer is a commonly encountered cancer in men, and can be effectively treated if detected early. PSA levels in serum appear to provide good correlation with tumour burden. Estimation of free PSA in serum is reported to further improve the diagnosis. In several developed countries routine screening of men above 50 years of age for prostate cancer using serum PSA as marker is recommended. Radioimmunometric assay techniques offer themselves as attractive candidates for measurement of tumour markers. They are robust, economical and didactic, thus eminently suitable for technology transfer, training and teaching. Preparation of primary reagents is relatively easy. The methodology is flexible. As a result of co-operation projects of the IAEA, many developing Member States have built up indigenous capabilities to perform radioimmunometric assays, which can be extended to development of kits for tumour marker assays. Considering the need for indigenous development of capabilities to produce reliable kits for radioimmunometric assays for PSA, in 1997 the IAEA initiated a Co-ordinated Research Project (CRP) on Development of Kits for Radioimmunometric Assays for Tumour Markers. Even though the focus of the project was PSA, it was expected that the expertise to be gained by the participants would also help them undertake development of kits for other tumour markers, essentially using the same methodology. Ten laboratories from Europe, Asia, Africa and the Americas participated

Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

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Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

2011-10-15

Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect.

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Wang, Xingmin; Yang, Yonghong; Huycke, Mark M

2015-03-01

Commensal bacteria and innate immunity play a major role in the development of colorectal cancer (CRC). We propose that selected commensals polarise colon macrophages to produce endogenous mutagens that initiate chromosomal instability (CIN), lead to expression of progenitor and tumour stem cell markers, and drive CRC through a bystander effect. Primary murine colon epithelial cells were repetitively exposed to Enterococcus faecalis-infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)-an endogenous mutagen and spindle poison produced by macrophages. CIN, gene expression, growth as allografts in immunodeficient mice were examined for clones and expression of markers confirmed using interleukin (IL) 10 knockout mice colonised by E. faecalis. Primary colon epithelial cells exposed to polarised macrophages or 4-hydroxy-2-nonenal developed CIN and were transformed after 10 weekly treatments. In immunodeficient mice, 8 of 25 transformed clones grew as poorly differentiated carcinomas with 3 tumours invading skin and/or muscle. All tumours stained for cytokeratins confirming their epithelial cell origin. Gene expression profiling of clones showed alterations in 3 to 7 cancer driver genes per clone. Clones also strongly expressed stem/progenitor cell markers Ly6A and Ly6E. Although not differentially expressed in clones, murine allografts positively stained for the tumour stem cell marker doublecortin-like kinase 1. Doublecortin-like kinase 1 and Ly6A/E were expressed by epithelial cells in colon biopsies for areas of inflamed and dysplastic tissue from E. faecalis-colonised IL-10 knockout mice. These results validate a novel mechanism for CRC that involves endogenous CIN and cellular transformation arising through a microbiome-driven bystander effect. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

S100B-immunopositive glia is elevated in paranoid as compared to residual schizophrenia: a morphometric study.

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Steiner, Johann; Bernstein, Hans-Gert; Bielau, Hendrik; Farkas, Nadine; Winter, Jana; Dobrowolny, Henrik; Brisch, Ralf; Gos, Tomasz; Mawrin, Christian; Myint, Aye Mu; Bogerts, Bernhard

2008-08-01

Several studies have revealed increased S100B levels in peripheral blood and cerebrospinal fluid (CSF) of patients with schizophrenia. In this context, it was postulated that elevated levels of S100B may indicate changes of pathophysiological significance to brain tissue in general and astrocytes in particular. However, no histological study has been published on the cellular distribution of S100B in the brain of individuals with schizophrenia to clarify this hypothesis. The cell-density of S100B-immunopositive glia was analyzed in the anterior cingulate, dorsolateral prefrontal (DLPF), orbitofrontal, and superior temporal cortices/adjacent white matter, pyramidal layer/alveus of the hippocampus, and the mediodorsal thalamic nucleus of 18 patients with schizophrenia and 16 matched control subjects. Cortical brain regions contained more S100B-immunopositive glia in the schizophrenia group relative to controls (P=0.046). This effect was caused by the paranoid schizophrenia subgroup (P=0.018). Separate analysis of white matter revealed no diagnostic main group effect (P=0.846). However, the white matter of patients with paranoid schizophrenia contained more (mainly oligodendrocytic) S100B-positive glia as compared to residual schizophrenia (P=0.021). These effects were particularly pronounced in the DLPF brain area. Our study reveals distinct histological patterns of S100B immunoeactive glia in two schizophrenia subtypes. This may be indicative of a heterogenic pathophysiology or distinct compensatory abilities: Astro-/oligodendroglial activation may result in increased cellular S100B in paranoid schizophrenia. On the contrary, residual schizophrenia may be caused by white matter oligodendroglial damage or dysfunction, associated with a release of S100B into body fluids.

Biochemical Markers in Neurocritical Care

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Omidvar Rezae

2016-07-01

Full Text Available During the past two decades, a variety of serum or cerebrospinal fluid (CSF biochemical markers in daily clinical practice have been recommended to diagnose and monitor diverse diseases or pathologic situations. It will be essential to develop a panel of biomarkers, to be suitable for evaluation of treatment efficacy, representing distinct phases of injury and recovery and consider the temporal profile of those. Among the possible and different biochemical markers, S100b appeared to fulfill many of optimized criteria of an ideal marker. S100b, a cytosolic low molecular weight dimeric calciumbinding protein from chromosome 21, synthesized in glial cells throughout the CNS, an homodimeric diffusible, belongs to a family of closely related protein, predominantly expressed by astrocytes and Schwann cells and a classic immunohistochemical marker for these cells, is implicated in brain development and neurophysiology. Of the 3 isoforms of S-100, the BB subunit (S100B is present in high concentrations in central and peripheral glial and Schwann cells, Langerhans and anterior pituitary cells, fat, muscle, and bone marrow tissues. The biomarker has shown to be a sensitive marker of clinical and subclinical cerebral damage, such as stroke, traumatic brain injury, and spinal cord injury. Increasing evidence suggests that the biomarker plays a double function as an intracellular regulator and an extracellular signal of the CNS. S100b is found in the cytoplasm in a soluble form and also is associated with intracellular membranes, centrosomes, microtubules, and type III intermediate filaments. Their genomic organization now is known, and many of their target proteins have been identified, although the mechanisms of regulating S100b secretion are not completely understood and appear to be related to many factors, such as the proinflammatory cytokines, tumor necrosis factor alpha (TNF-a, interleukin (IL-1b, and metabolic stress. 

Molecular dynamics simulation of S100B protein to explore ligand blockage of the interaction with p53 protein

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Zhou, Zhigang; Li, Yumin

2009-10-01

As a tumor suppressor, p53 plays an important role in cancer suppression. The biological function of p53 as a tumor suppressor is disabled when it binds to S100B. Developing the ligands to block the S100B-p53 interaction has been proposed as one of the most important approaches to the development of anti-cancer agents. We screened a small compound library against the binding interface of S100B and p53 to identify potential compounds to interfere with the interaction. The ligand-binding effect on the S100B-p53 interaction was explored by molecular dynamics at the atomic level. The results show that the ligand bound between S100B and p53 propels the two proteins apart by about 2 Å compared to the unligated S100B-p53 complex. The binding affinity of S100B and p53 decreases by 8.5-14.6 kcal/mol after a ligand binds to the interface from the original unligated state of the S100B-p53 complex. Ligand-binding interferes with the interaction of S100B and p53. Such interference could impact the association of S100B and p53, which would free more p53 protein from the pairing with S100B and restore the biological function of p53 as a tumor suppressor. The analysis of the binding mode and ligand structural features would facilitate our effort to identify and design ligands to block S100B-p53 interaction effectively. The results from the work suggest that developing ligands targeting the interface of S100B and p53 could be a promising approach to recover the normal function of p53 as a tumor suppressor.

The prognostic value of serum S100B in patients with cutaneous melanoma: a meta-analysis.

Science.gov (United States)

Mocellin, Simone; Zavagno, Giorgio; Nitti, Donato

2008-11-15

S100B protein detected in the serum of patients with cutaneous melanoma has been long reported as a prognostic biomarker. However, no consensus exists on its implementation in the routine clinical setting. This study aimed to comprehensively and quantitatively summarize the evidence on the suitability of serum S100B to predict patients' survival. Twenty-two series enrolling 3393 patients with TNM stage I to IV cutaneous melanoma were reviewed. Standard meta-analysis methods were applied to evaluate the overall relationship between S100B serum levels and patients' survival (meta-risk). Serum S100B positivity was associated with significantly poorer survival (hazard ratio [HR] = 2.23, 95% CI: 1.92-2.58, p < 0.0001). Between-study heterogeneity was significant, which appeared to be related mainly to dissemination bias and the inclusion of patients with stage IV disease. Considering stage I to III melanoma (n = 1594), the meta-risk remained highly significant (HR = 2.28, 95% CI: 1.8-2.89; p < 0.0001) and studies' estimates were homogeneous. Subgroup analysis of series reporting multivariate survival analysis supported S100B as a prognostic factor independent of the TNM staging system. Our findings suggest that serum S100B detection has a clinically valuable independent prognostic value in patients with melanoma, with particular regard to stage I-III disease. Further investigation focusing on this subset of patients is justified and warranted before S100B can be implemented in the routine clinical management of melanoma. (c) 2008 Wiley-Liss, Inc.

Identification and characterization of small molecule inhibitors of the calcium-dependent S100B-p53 tumor suppressor interaction.

Science.gov (United States)

Markowitz, Joseph; Chen, Ijen; Gitti, Rossi; Baldisseri, Donna M; Pan, Yongping; Udan, Ryan; Carrier, France; MacKerell, Alexander D; Weber, David J

2004-10-07

The binding of S100B to p53 down-regulates wild-type p53 tumor suppressor activity in cancer cells such as malignant melanoma, so a search for small molecules that bind S100B and prevent S100B-p53 complex formation was undertaken. Chemical databases were computationally searched for potential inhibitors of S100B, and 60 compounds were selected for testing on the basis of energy scoring, commercial availability, and chemical similarity clustering. Seven of these compounds bound to S100B as determined by steady state fluorescence spectroscopy (1.0 microM model of one such inhibitor, pentamidine, bound to Ca(2+)-loaded S100B was calculated using intermolecular NOE data between S100B and the drug, and indicates that pentamidine binds into the p53 binding site on S100B defined by helices 3 and 4 and loop 2 (termed the hinge region).

Perfusion imaging of parotid gland tumours: usefulness of arterial spin labeling for differentiating Warthin's tumours

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Kato, Hiroki; Watanabe, Haruo [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Kanematsu, Masayuki [Gifu University School of Medicine, Department of Radiology, Gifu (Japan); Gifu University Hospital, High-level Imaging Diagnosis Center, Gifu (Japan); Kajita, Kimihiro [Gifu University Hospital, High-level Imaging Diagnosis Center, Gifu (Japan); Mizuta, Keisuke; Aoki, Mitsuhiro [Gifu University School of Medicine, Department of Otolaryngology, Gifu (Japan); Okuaki, Tomoyuki [Philips Healthcare, Tokyo (Japan)

2015-11-15

To assess prospectively the efficacy of arterial spin labelling (ASL) against conventional and diffusion-weighted (DW) MR imaging for differentiating parotid gland tumours. We included 10 pleomorphic adenomas, 12 Warthin's tumours, and nine malignant tumours of the parotid glands. Only tumours larger than 10 mm were included in this study. All parotid gland tumours underwent T1-weighted, T2-weighted, DW, and ASL imaging. Tumour-to-parotid gland signal intensity ratios (SIRs) and apparent diffusion coefficients (ADCs) of solid components were correlated with these pathologies. SIRs on T2-weighted images and ADCs were higher in pleomorphic adenomas than in Warthin's tumours (p <.01) and malignant tumours (p <.01). SIRs on ASL were higher in Warthin's tumours than in pleomorphic adenomas (p <.01) and malignant tumours (p <.05). Az value of SIRs on ASL for differentiating Warthin's tumours from the other pathologies was 0.982. The sensitivity, specificity, and accuracy of SIRs on ASL for the diagnosis of Warthin's tumours at an optimal SIR threshold of over 8.70 were 91.7 %, 94.7 %, and 93.5 %, respectively. ASL with SIR measurements could non-invasively evaluate tumour blood flow of parotid gland tumours and differentiate Warthin's tumours from pleomorphic adenomas and malignant tumours. (orig.)

FAM107B is regulated by S100A4 and mediates the effect of S100A4 on the proliferation and migration of MGC803 gastric cancer cells.

Science.gov (United States)

Guo, Junfu; Bian, Yue; Wang, Yu; Chen, Lisha; Yu, Aiwen; Sun, Xiuju

2017-10-01

FAM107B expression was decreased in stomach cancer and many other kinds of cancer. The forced expression of FAM107B in HeLa cells diminished proliferation in response to growth factors, suggesting that FAM107B might play important roles in many types of cancers. But the mechanisms underlying the decreased expression of FAM107B in cancers are not clear, the functional significance needs to be further clarified. Our previous findings from cDNA microarray showed that there are 179 differentially expressed genes after S100A4 inhibition in gastric cancer cells MGC803. FAM107B was an upregulated one among them. In the present study, we confirmed that FAM107B expression was upregulated in MGC803 cells after S100A4 inhibition by qRT-PCR. We demonstrated for the first time that FAM107B was downregulated by S100A4. The results from CCK-8 and transwell assay showed that FAM107B inhibition by siRNA led to significantly increased proliferation and migrating abilities of MGC803 cells, respectively, indicating that FAM107B plays important roles in inhibiting the proliferation and migration of MGC803 cells. The rescue experiment showed that FAM107B-siRNA transfection reversed the reduced proliferation and migration abilities induced by S100A4 inhibition in the cells. These findings suggest that, as a downstream effector, FAM107B at least partly mediates the effect of S100A4 on the proliferation and migration of MGC803 cells. In conclusion, we first provide experimental evidence suggesting that FAM107B was downregulated by S100A4 in gastric cancer MGC803 cells. And FAM107B at least partially mediates the biological effect of S100A4 in the cells. © 2017 International Federation for Cell Biology.

CD117 immunoexpression in canine mast cell tumours: correlations with pathological variables and proliferation markers

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Pires Maria A

2007-08-01

Full Text Available Abstract Background Cutaneous mast cell tumours are one of the most common neoplasms in dogs and show a highly variable biologic behaviour. Several prognosis tools have been proposed for canine mast cell tumours, including histological grading and cell proliferation markers. CD117 is a receptor tyrosine kinase thought to play a key role in human and canine mast cell neoplasms. Normal (membrane-associated and aberrant (cytoplasmic, focal or diffuse CD117 immunoexpression patterns have been identified in canine mast cell tumours. Cytoplasmic CD117 expression has been found to correlate with higher histological grade and with a worsened post-surgical prognosis. This study addresses the role of CD117 in canine mast cell tumours by studying the correlations between CD117 immunoexpression patterns, two proliferation markers (Ki67 and AgNORs histological grade, and several other pathological variables. Results Highly significant (p Conclusion These findings highlight the key role of CD117 in the biopathology of canine MCTs and confirm the relationship between aberrant CD117 expression and increased cell proliferation and higher histological grade. Further studies are needed to unravel the cellular mechanisms underlying focal and diffuse cytoplasmic CD117 staining patterns, and their respective biopathologic relevance.

New insight into benign tumours of major salivary glands by proteomic approach.

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Elena Donadio

Full Text Available Major salivary gland tumours are uncommon neoplasms of the head and neck. The increase of precise pre-operative diagnosis is crucial for their correct management and the identification of molecular markers would surely improve the required accuracy. In this study we performed a comparative proteomic analysis of fine needle aspiration fluids of the most frequent benign neoplasms of major salivary glands, namely pleomorphic adenoma and Warthin's tumour, in order to draw their proteomic profiles and to point out their significant features. Thirty-five patients submitted to parotidectomy were included in the study, 22 were identified to have pleomorphic adenoma and 14 Warthin's tumour. Fine needle aspiration samples were processed using a two-dimensional electrophoresis/mass spectrometry-based approach. A total of 26 differentially expressed proteins were identified. Ingenuity software was used to search the biological processes to which these proteins belong and to construct potential networks. Intriguingly, all Warthin's tumour up-regulated proteins such as Ig gamma-1 chain C region, Ig kappa chain C region and Ig alpha-1 chain C region and S100A9 were correlated to immunological and inflammatory diseases, while pleomorphic adenomas such as annexin A1, annexin A4, macrophage-capping protein, apolipoprotein E and alpha crystalline B chain were associated with cell death, apoptosis and tumorigenesis, showing different features of two benign tumours. Overall, our results shed new light on the potential usefulness of a proteomic approach to study parotid tumours and in particular up regulated proteins are able to discriminate two types of benign parotid lesions.

Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin

International Nuclear Information System (INIS)

Demartis, S.; Tarli, L.; Neri, D.; Borsi, L.; Zardi, L.

2001-01-01

Angiogenesis is a characteristic feature of many aggressive tumours and other disorders. Antibodies capable of binding to new blood vessels, but not to mature vessels, could be used as selective targeting agents for immunoscintigraphic and radioimmunotherapeutic applications. Here we show that scFv(L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably labelled with iodine-125 and astatine-211 with full retention of immunoreactivity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistribution studies in mice bearing two different types of tumour grafted subcutaneously, followed by ex vivo micro-autoradiographic analysis, revealed that scFv(L19) rapidly localises around tumour blood vessels, but not around normal vessels. Four hours after intravenous injection of the stably radioiodinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 murine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expected, all other organs (including kidney) contained significantly less radioactivity than the tumour. Since the ED-B domain of fibronectin has an identical sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it should now be possible to investigate scFv(L19) for the selective delivery of 211 At to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse. (orig.)

Inflammation and pancreatic cancer: molecular and functional interactions between S100A8, S100A9, NT-S100A8 and TGFβ1.

Science.gov (United States)

Basso, Daniela; Bozzato, Dania; Padoan, Andrea; Moz, Stefania; Zambon, Carlo-Federico; Fogar, Paola; Greco, Eliana; Scorzeto, Michele; Simonato, Francesca; Navaglia, Filippo; Fassan, Matteo; Pelloso, Michela; Dupont, Sirio; Pedrazzoli, Sergio; Fassina, Ambrogio; Plebani, Mario

2014-03-26

In order to gain further insight on the crosstalk between pancreatic cancer (PDAC) and stromal cells, we investigated interactions occurring between TGFβ1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC-associated S100A8 derived peptide, in cell signaling, intracellular calcium (Cai2+) and epithelial to mesenchymal transition (EMT). NF-κB, Akt and mTOR pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly differentiated (Panc1 and MiaPaCa2) cell lines. NT-S100A8, one of the low molecular weight N-terminal peptides from S100A8 to be released by PDAC-derived proteases, shared many effects on NF-κB, Akt and mTOR signaling with S100A8, but mainly with TGFβ1. The chief effects of S100A8, S100A9 and NT-S100A8 were to inhibit NF-κB and stimulate mTOR; the molecules inhibited Akt in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were shown to inhibit NF-κB and Akt in the presence of an intact TGFβ1 canonical signaling pathway. TGFβ1 counteracted S100A8, S100A9 and NT-S100A8 effects in Smad4 expressing, not in Smad4 negative cells, while it synergized with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of TGFβ1 on both EMT (increased Twist and decreased N-Cadherin expression) and Cai2+ were antagonized by S100A9, which formed heterodimers with TGFβ1 (MALDI-TOF/MS and co-immuno-precipitation). The effects of S100A8 and S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT-S100A8 mimics the effects of TGFβ1 on cell signaling, and the formation of complexes between TGFβ1 with S100A9 appears to be the molecular mechanism underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+ and EMT.

The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice.

Science.gov (United States)

Jansen, Natalie; Walach, Harald

2016-01-01

Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, Pketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials.

S100B Protein concentration in milk-formulas for preterm and term infants. Correlation with industrial preparation procedures.

Science.gov (United States)

Nigro, Francesco; Gagliardi, Luigi; Ciotti, Sabina; Galvano, Fabio; Pietri, Amedeo; Tina, Gabriella Lucia; Cavallaro, Daniela; La Fauci, Luca; Iacopino, Leonardo; Bognanno, Matteo; Li Volti, Giovanni; Scacco, Antonio; Michetti, Fabrizio; Gazzolo, Diego

2008-05-01

Human milk S100B protein possesses important neurotrophic properties. However, in some conditions human milk is substituted by milk formulas. The aims of the present study were: to assess S100B concentrations in milk formulas, to verify any differences in S100B levels between preterm and term infant formulas and to evaluate the impact of industrial preparation at predetermined phases on S100B content. Two different set of samples were tested: (i) commercial preterm (n = 36) and term (n = 36) infant milk formulas; ii) milk preterm (n = 10) and term infant (n = 10) formulas sampled at the following predetermined industrial preparation time points: skimmed cow milk (Time 0); after protein sources supplementation (Time 1); after pasteurization (Time 2); after spray-drying (Time 3). Our results showed that S100B concentration in preterm formulas were higher than in term ones (p 0.05) at Time 2, whereas a significant (p pasteurization but not spry-drying. New feeding strategies in preterm and term infants are therefore warranted in order to preserve S100B protein during industrial preparation.

Correlation between Amitriptyline-Induced Cardiotoxic Effects and Cardiac S100b Protein in Isolated Rat Hearts

Directory of Open Access Journals (Sweden)

Nil Hocaoğlu

2016-12-01

Full Text Available Background: Amitriptyline is an important cause of mortality due to its cardiovascular toxicity. Aims: To investigate the changes in levels of cardiac S100b protein on amitriptyline-induced cardiotoxicity and also to examine the correlation between amitriptyline-induced cardiotoxic effects and cardiac S100b protein in an isolated rat heart model. Study Design: Animal experimentation, isolated heart model. Methods: After a stabilization period, isolated hearts were randomized to two groups (n=5 and n=7. In the control group, isolated hearts were subjected to an infusion of 5% dextrose for 60 minutes. In the amitriptyline group, 5.5×10-5 M amitriptyline was infused for 60 minutes to achieve amitriptyline toxicity. After the infusion period, heart tissues were removed for histological examination. Results: In comparison to control treatment, amitriptyline infusion decreased left ventricular developed pressure (LVDP, dp/dtmax and heart rate (HR and significantly prolonged QRS duration (p<0.05. The semiquantitative scores for S100b protein levels in amitriptyline-infused hearts were higher than in the control group (p<0.01. At the end of the experiment, in the amitriptyline-infused group, significant correlations were found between LVDP and S100b protein scores (r=-0.807, p=0.003 and between QRS duration and S100b protein scores (r=0.859, p=0.001. Conclusion: Our results indicate that the S100b protein may be a helpful indicator or biomarker in studying the cardiotoxic effects of amitriptyline.

Evaluation of oxidant, antioxidant, and S100B levels in patients with conversion disorder.

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Büyükaslan, Hasan; Kandemir, Sultan Basmacı; Asoğlu, Mehmet; Kaya, Halil; Gökdemir, Mehmet Tahir; Karababa, İbrahim Fatih; Güngörmez, Fatih; Kılıçaslan, Fethiye; Şavik, Emin

2016-01-01

Various psychodynamic, neurobiological, genetic, and sociocultural factors are believed to be involved in the etiology of conversion disorder (CD). Oxidative metabolism has been shown to deteriorate in association with many health problems and psychiatric disorders. We evaluated oxidative metabolism and S100B levels in the context of this multifactorial disease. Thirty-seven patients with CD (25 females and 12 males) and 42 healthy volunteers (21 females and 21 males), all matched for age and sex, were included in this study. The total oxidant status, total antioxidant status, oxidative stress index, and S100B levels were compared between the two groups. The total oxidant status, oxidative stress index, and S100B levels were significantly higher in patients with CD than in the control group, whereas the total antioxidant status was significantly lower. CD is associated with deterioration of oxidative metabolism and increased neuronal damage.

Dynamic change of serum protein S100b and its clinical significance in patients with traumatic brain injury

Institute of Scientific and Technical Information of China (English)

CHEN Da-qing; ZHU Lie-lie

2005-01-01

Objective: To analyze the dynamic change of serum protein S100b in patients with traumatic brain injury and its clinical value in assessing brain damage. Methods: According to Glasgow coma scale (GCS), 102 cases of traumatic brain injury were divided into mild brain injury group (GCS≥13, n=31, Group A), moderate brain injury group (8B) and severe brain injury group (GCS≤8, n=34, Group C). Serial S100b concentrations were analyzed by enzyme-linked immunosorbent assay (ELISA) in blood samples taken on admission, 12 h, 24 h, 48 h, 72 h and 7 days after traumatic brain injury. Results: The severe brain injury group showed significantly higher concentration of serum S100b, with earlier increase and longer duration, than the mild and moderate brain injury groups. The patients with higher S100b exhibited lower GCS scores and poor clinical prognosis. The increase in S100b could emerge before clinical image evidence indicated so. Conclusions: Serum S100b can be used as a sensitive index for assessment and prediction of traumatic brain injury severity and prognosis.

ADM3, TFF3 and LGALS3 are discriminative molecular markers in fine-needle aspiration biopsies of benign and malignant thyroid tumours

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Karger, S; Krause, K; Gutknecht, M; Schierle, K; Graf, D; Steinert, F; Dralle, H; Führer, D

2012-01-01

Background: Previously, we reported a six-marker gene set, which allowed a molecular discrimination of benign and malignant thyroid tumours. Now, we evaluated these markers in fine-needle aspiration biopsies (FNAB) in a prospective, independent series of thyroid tumours with proven histological outcome. Methods: Quantitative RT–PCR was performed (ADM3, HGD1, LGALS3, PLAB, TFF3, TG) in the needle wash-out of 156 FNAB of follicular adenoma (FA), adenomatous nodules, follicular and papillary thyroid cancers (TC) and normal thyroid tissues (NT). Results: Significant expression differences were found for TFF3, HGD1, ADM3 and LGALS3 in FNAB of TC compared with benign thyroid nodules and NT. Using two-marker gene sets, a specific FNAB distinction of benign and malignant tumours was achieved with negative predictive values (NPV) up to 0.78 and positive predictive values (PPV) up to 0.84. Two FNAB marker gene combinations (ADM3/TFF3; ADM3/ACTB) allowed the distinction of FA and malignant follicular neoplasia with NPV up to 0.94 and PPV up to 0.86. Conclusion: We demonstrate that molecular FNAB diagnosis of benign and malignant thyroid tumours including follicular neoplasia is possible with recently identified marker gene combinations. We propose multi-centre FNAB studies on these markers to bring this promising diagnostic tool closer to clinical practice. PMID:22223087

Large-scale proteomic identification of S100 proteins in breast cancer tissues

International Nuclear Information System (INIS)

Cancemi, Patrizia; Di Cara, Gianluca; Albanese, Nadia Ninfa; Costantini, Francesca; Marabeti, Maria Rita; Musso, Rosa; Lupo, Carmelo; Roz, Elena; Pucci-Minafra, Ida

2010-01-01

Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression. Samples of breast cancer tissues were obtained during surgical intervention, according to the bioethical recommendations, and cryo-preserved until used. Tissue extracts were submitted to proteomic preparations for 2D-IPG. Protein identification was performed by N-terminal sequencing and/or peptide mass finger printing. The majority of the detected S100 proteins were absent, or present at very low levels, in the non-tumoral tissues adjacent to the primary tumor. This finding strengthens the role of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo-preserved breast cancer tissues showed that some proteins were ubiquitously expressed in almost all patients while others appeared more sporadic. Most, if not all, of the detected S100 members appeared reciprocally correlated. Finally, from the perspective of biomarkers establishment, a promising finding was the observation that patients which developed distant metastases after a three year follow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group. This article reports for the first time the comparative proteomic screening of several S100 protein members among a large group of breast cancer patients. The results obtained strongly support the hypothesis that a significant deregulation of multiple S100 protein members is

How does extracerebral trauma affect the clinical value of S100B measurements?

DEFF Research Database (Denmark)

Ohrt-Nissen, Søren; Friis-Hansen, Lennart; Dahl, Benny

2011-01-01

with head injury (MTHI), or no head injury (NHI). The primary aim was to assess if a significant difference in serum levels of S100B could be found between IHI and MTHI patients. Methods Patients (233) were primarily admitted to the trauma centre. Serum samples were drawn on admission and 6 h after...... trauma and then stored at -80°C until analysed. Variables included Abbreviated Injury Scale (AIS) for head trauma, Injury Severity Score (ISS) and 30-day survival. Results Two patients could not be classified. IHI occurred in 28, MTHI in 102 and NHI was found in 101. The median S100B concentrations...

Lobatin B inhibits NPM/ALK and NF-κB attenuating anaplastic-large-cell-lymphomagenesis and lymphendothelial tumour intravasation.

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Kiss, Izabella; Unger, Christine; Huu, Chi Nguyen; Atanasov, Atanas Georgiev; Kramer, Nina; Chatruphonprasert, Waranya; Brenner, Stefan; McKinnon, Ruxandra; Peschel, Andrea; Vasas, Andrea; Lajter, Ildiko; Kain, Renate; Saiko, Philipp; Szekeres, Thomas; Kenner, Lukas; Hassler, Melanie R; Diaz, Rene; Frisch, Richard; Dirsch, Verena M; Jäger, Walter; de Martin, Rainer; Bochkov, Valery N; Passreiter, Claus M; Peter-Vörösmarty, Barbara; Mader, Robert M; Grusch, Michael; Dolznig, Helmut; Kopp, Brigitte; Zupko, Istvan; Hohmann, Judit; Krupitza, Georg

2015-01-28

An apolar extract of the traditional medicinal plant Neurolaena lobata inhibited the expression of the NPM/ALK chimera, which is causal for the majority of anaplastic large cell lymphomas (ALCLs). Therefore, an active principle of the extract, the furanoheliangolide sesquiterpene lactone lobatin B, was isolated and tested regarding the inhibition of ALCL expansion and tumour cell intravasation through the lymphendothelium. ALCL cell lines, HL-60 cells and PBMCs were treated with plant compounds and the ALK inhibitor TAE-684 to measure mitochondrial activity, proliferation and cell cycle progression and to correlate the results with protein- and mRNA-expression of selected gene products. Several endpoints indicative for cell death were analysed after lobatin B treatment. Tumour cell intravasation through lymphendothelial monolayers was measured and potential causal mechanisms were investigated analysing NF-κB- and cytochrome P450 activity, and 12(S)-HETE production. Lobatin B inhibited the expression of NPM/ALK, JunB and PDGF-Rβ, and attenuated proliferation of ALCL cells by arresting them in late M phase. Mitochondrial activity remained largely unaffected upon lobatin B treatment. Nevertheless, caspase 3 became activated in ALCL cells. Also HL-60 cell proliferation was attenuated whereas PBMCs of healthy donors were not affected by lobatin B. Additionally, tumour cell intravasation, which partly depends on NF-κB, was significantly suppressed by lobatin B most likely due to its NF-κB-inhibitory property. Lobatin B, which was isolated from a plant used in ethnomedicine, targets malignant cells by at least two properties: I) inhibition of NPM/ALK, thereby providing high specificity in combating this most prevalent fusion protein occurring in ALCL; II) inhibition of NF-κB, thereby not affecting normal cells with low constitutive NF-κB activity. This property also inhibits tumour cell intravasation into the lymphatic system and may provide an option to manage this

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

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Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production.

Science.gov (United States)

Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

2015-09-29

S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis.

Influence of the 100% w/v perfluorooctyl bromide (PFOB) emulsion dose on tumour radiosensitivity

International Nuclear Information System (INIS)

Thomas, C.; Guichard, M.; Riess, J.

1991-01-01

The radiosensitizing effect of a 100% w/v emulsion of a fluuorocarbon PFOB, which carries 4 times more oxygen than Fluosol-DA 20% emulsion, was studied on two human tumour xenografts (HRT18 and HT29) and murine tumour EMT6. This effect was compared to that of carbogen alone. The fluorocrit (amount of fluorocarbon in the blood) and haematocrit remained unchanged from 7 to 65 min post-injection of the emulsion (8ml/kg). Significant tumour radiosensitization was obtained with relatively low amounts of 100% w/v concentrated emulsion of PFOB plus carbogen. Maximum radiosensitization occurs at low fluorocarbon dose of about 3g/kg. These results are comparable to those obtained with Fluosol-DA 20% or Therox emulsion. Since this radiosensitization occurs only at relatively low fluorocrit without haematocrit modification, the oxygen-carrying capacity of the fluorocarbon is not the only factor involved in radiosensitization of tumor cells, regardless of the effect of carbogen on radiosensitivity. (author)

S100A4, a link between metastasis and inflammation

DEFF Research Database (Denmark)

Ambartsumian, N.; Grigorian, M.

2016-01-01

Chronic inflammation is acknowledged to be a hallmark of neoplasia—both in cancer initiation and metastasis progression. Here we summarise data suggesting that S100A4 is а trigger of the cascade events that establish an inflammatory milieu and provide a potent flame for primary tumour growth......-communicable diseases (NCD), such as autoimmune diseases, fibrosis, and other disorders. Therefore, we suggest that S100A4 is a common pro-inflammatory factor involved in the pathogenesis of diverse NCD including cancer....

Demonstration of S-100 protein in sustentacular cells of phaeochromocytomas and paragangliomas

DEFF Research Database (Denmark)

Schroder, H D; Johannsen, L

1986-01-01

to the sustentacular cells of normal paraganglia and adrenal medulla were found in all paragangliomas and in the benign and aggressively growing phaeochromocytomas. In the two malignant tumours no positive reaction was demonstrated. In one tumour the sustentacular cells were shown to contain glial fibrillary acidic......Eighteen phaeochromocytomas, including both sporadic and familial cases, four cervical paragangliomas, two jugular paragangliomas, and one abdominal paraganglioma were examined immunohistochemically for the presence of S-100 protein. Positive staining in cells morphologically similar...... protein further supporting their Schwann cell relationship. The number of S-100 positive cells varied considerably. They demonstrated a spindle celled or elongated configuration with long slender processes. The nature of the sustentacular cell proliferation, neoplastic versus reactive, is discussed....

Gamma-enolase: a well-known tumour marker, with a less-known role in cancer

International Nuclear Information System (INIS)

Vizin, Tjasa; Kos, Janko

2015-01-01

Gamma-enolase, known also as neuron-specific enolase (NSE), is an enzyme of the glycolytic pathway, which is expressed predominantly in neurons and cells of the neuroendocrine system. As a tumour marker it is used in diagnosis and prognosis of cancer; however, the mechanisms enrolling it in malignant progression remain elusive. As a cytoplasmic enzyme gamma-enolase is involved in increased aerobic glycolysis, the main source of energy in cancer cells, supporting cell proliferation. However, different cellular localisation at pathophysiological conditions, proposes other cellular engagements. The C-terminal part of the molecule, which is not related to glycolytic pathway, was shown to promote survival of neuronal cells by regulating neuronal growth factor receptor dependent signalling pathways, resulting also in extensive actin cytoskeleton remodelling. This additional function could be important also in cancer cells either to protect cells from stressful conditions and therapeutic agents or to promote tumour cell migration and invasion. Gamma-enolase might therefore have a multifunctional role in cancer progression: it supports increased tumour cell metabolic demands, protects tumour cells from stressful conditions and promotes their invasion and migration

Comparison of the Serum Tumor Markers S100 and Melanoma-inhibitory Activity (MIA) in the Monitoring of Patients with Metastatic Melanoma Receiving Vaccination Immunotherapy with Dendritic Cells.

Science.gov (United States)

Uslu, Ugur; Schliep, Stefan; Schliep, Klaus; Erdmann, Michael; Koch, Hans-Uwe; Parsch, Hans; Rosenheinrich, Stina; Anzengruber, Doris; Bosserhoff, Anja Katrin; Schuler, Gerold; Schuler-Thurner, Beatrice

2017-09-01

In patients with melanoma, early dissemination via lymphatic and hematogenous routes is frequently seen. Thus, besides clinical follow-up examination and imaging, reliable melanoma-specific serological tumor markers are needed. We retrospectively compared two serum markers for melanoma, S100 and melanoma-inhibitory activity (MIA), for monitoring of patients with metastatic melanoma under either adjuvant or therapeutic vaccination immunotherapy with dendritic cells (DC). Serum was obtained from a total of 100 patients (28 patients in stage III and 72 patients in stage IV, according to the American Joint Committee on Cancer 2002) at regular intervals during therapy, accompanied by follow-up imaging. When relapse was detected, both markers often remained within normal range. In contrast, in patients with metastatic measurable disease receiving therapeutic and not adjuvant DC vaccination, an increase of both markers was a strong indicator for disease progression. When comparing both markers in the whole study population, MIA showed a superior sensitivity to detect disease progression. S100 and MIA are highly sensitive tumor markers for monitoring of patients with melanoma with current metastases, but less sensitive for monitoring of tumor-free patients. In the current study, MIA had a slightly superior sensitivity to detect progressive disease compared to S100 and seems to be more useful in monitoring of patients with metastatic melanoma receiving immunotherapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Tumour T1 changes in vivo are highly predictive of response to chemotherapy and reflect the number of viable tumour cells – a preclinical MR study in mice

International Nuclear Information System (INIS)

Weidensteiner, Claudia; Allegrini, Peter R; Sticker-Jantscheff, Melanie; Romanet, Vincent; Ferretti, Stephane; McSheehy, Paul MJ

2014-01-01

Effective chemotherapy rapidly reduces the spin–lattice relaxation of water protons (T 1 ) in solid tumours and this change (ΔT 1 ) often precedes and strongly correlates with the eventual change in tumour volume (TVol). To understand the biological nature of ΔT 1 , we have performed studies in vivo and ex vivo with the allosteric mTOR inhibitor, everolimus. Mice bearing RIF-1 tumours were studied by magnetic resonance imaging (MRI) to determine TVol and T 1 , and MR spectroscopy (MRS) to determine levels of the proliferation marker choline and levels of lipid apoptosis markers, prior to and 5 days (endpoint) after daily treatment with vehicle or everolimus (10 mg/kg). At the endpoint, tumours were ablated and an entire section analysed for cellular and necrotic quantification and staining for the proliferation antigen Ki67 and cleaved-caspase-3 as a measure of apoptosis. The number of blood-vessels (BV) was evaluated by CD31 staining. Mice bearing B16/BL6 melanoma tumours were studied by MRI to determine T 1 under similar everolimus treatment. At the endpoint, cell bioluminescence of the tumours was measured ex vivo. Everolimus blocked RIF-1 tumour growth and significantly reduced tumour T 1 and total choline (Cho) levels, and increased polyunsaturated fatty-acids which are markers of apoptosis. Immunohistochemistry showed that everolimus reduced the %Ki67 + cells but did not affect caspase-3 apoptosis, necrosis, BV-number or cell density. The change in T 1 (ΔT 1 ) correlated strongly with the changes in TVol and Cho and %Ki67 + . In B16/BL6 tumours, everolimus also decreased T 1 and this correlated with cell bioluminescence; another marker of cell viability. Receiver-operating-characteristic curves (ROC) for everolimus on RIF-1 tumours showed that ΔT 1 had very high levels of sensitivity and specificity (ROC AUC = 0.84) and this was confirmed for the cytotoxic patupilone in the same tumour model (ROC AUC = 0.97). These studies suggest that ΔT 1 is not a

Evaluation of tumour markers as differential diagnostic tool in patients with suspicion of liver metastases from breast cancer.

Science.gov (United States)

Liska, Vaclav; Holubec, Lubos; Treska, Vladislav; Vrzalova, Jindra; Skalicky, Tomas; Sutnar, Alan; Kormunda, Stanislav; Bruha, Jan; Vycital, Ondrej; Finek, Jindrich; Pesta, Martin; Pecen, Ladislav; Topolcan, Ondrej

2011-04-01

The liver is the site of breast cancer metastasis in 50% of patients with advanced disease. Tumour markers have been demonstrated as being useful in follow-up of patients with breast cancer, in early detection of recurrence of breast cancer after radical surgical treatments, and in assessing oncologic therapy effect, but no study has been carried out on their usefullness in distinguishing benign liver lesions from breast cancer metastases. The aim of this study was therefore to evaluate the importance of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen CA19-9 (CA19-9), thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin 19 fragment (CYFRA 21-1) in differential diagnosis between benign liver lesions and liver metastases of breast cancer. The study includes 3 groups: 22 patients with liver metastases of breast cancer; 39 patients with benign liver lesions (hemangioma, focal nodular hyperplasia, liver cyst, hepatocellular adenoma); and 21 patients without any liver disease or lesion that were operated on for benign extrahepatic diseases (groin hernia, varices of lower limbs) as a control group. The serum levels of tumour markers were assessed by means of immunoanalytical methods. Preoperative serum levels of CYFRA 21-1, TPA, TPS and CEA were significantly higher in patients with liver metastases of breast cancer in contrast to healthy controls and patients with benign liver lesions (p-value<0.05). Serum levels of CA19-9 and TK were higher in patients with malignancy in comparison with benign liver disease and healthy controls but these differences were not statistically significant. Tumour markers CEA, CYFRA 21-1, TPA and TPS can be recommended as a good tool for differential diagnosis between liver metastases of breast cancer and benign liver lesions.

Evaluation of oxidant, antioxidant, and S100B levels in patients with conversion disorder

Directory of Open Access Journals (Sweden)

Büyükaslan H

2016-07-01

Full Text Available Hasan Büyükaslan,1 Sultan Basmacı Kandemir,2 Mehmet Asoğlu,3 Halil Kaya,4 Mehmet Tahir Gökdemir,1 İbrahim Fatih Karababa,3 Fatih Güngörmez,5 Fethiye Kılıçaslan,6 Emin Şavik7 1Department of Emergency Medicine, Faculty of Medicine, Harran University, 2Department of Psychiatry, Balıklıgöl State Hospital, 3Department of Psychiatry, Faculty of Medicine, Harran University, Sanliurfa, 4Bursa Yüksek Ihtisas Training and Research Hospital, Bursa, 5Department of Emergency Medicine, Mehmet Akif İnan Research Hospital, 6Department of Child and Adolescent Psychiatry, 7Department of Biochemistry, Faculty of Medicine, Harran University, Sanliurfa, Turkey Introduction: Various psychodynamic, neurobiological, genetic, and sociocultural factors are believed to be involved in the etiology of conversion disorder (CD. Oxidative metabolism has been shown to deteriorate in association with many health problems and psychiatric disorders. We evaluated oxidative metabolism and S100B levels in the context of this multifactorial disease.Methods: Thirty-seven patients with CD (25 females and 12 males and 42 healthy volunteers (21 females and 21 males, all matched for age and sex, were included in this study. The total oxidant status, total antioxidant status, oxidative stress index, and S100B levels were compared between the two groups.Results: The total oxidant status, oxidative stress index, and S100B levels were significantly higher in patients with CD than in the control group, whereas the total antioxidant status was significantly lower.Conclusion: CD is associated with deterioration of oxidative metabolism and increased neuronal damage. Keywords: conversion disorder, oxidative stress, S100B

Establishing tumour tracking accuracy in free-breathing respiratory gated SBRT of lung cancer

International Nuclear Information System (INIS)

Wen, Chuan-Dong; Wong, C; Ackerly, T; Ruben, J; Millar, J

2014-01-01

Free-breathing respiratory gated SBRT of surgically inoperable lung cancer has been clinically commissioned. This study was to establish the tumour tracking accuracy under clinical conditions based on an implanted fiducial marker. A Visicoil TM marker embedded in tissue-equivalent material mounted in a phantom (ET Gating Phantom TM Brainlab) driven by a patient's breathing data was treated with the ExacTrac TM system. This one-dimensional moving marker represented a tumour motion in superior-inferior (S-I) direction measured through 4DCT study of the same patient. Both Gafchromic TM films and the stereoscopic kV images were used for tracking the position of the marker. For tumour motion at magnitudes of 10, 20 and 29 mm and treated with corresponding gate widths of 50%, 33% and 20% of free breathing amplitude, the implanted marker was able to be tracked with a deviation ≤1.53 mm to its planned position.

Gamma-enolase: a well-known tumour marker, with a less-known role in cancer

Science.gov (United States)

Vizin, Tjasa; Kos, Janko

2015-01-01

Background Gamma-enolase, known also as neuron-specific enolase (NSE), is an enzyme of the glycolytic pathway, which is expressed predominantly in neurons and cells of the neuroendocrine system. As a tumour marker it is used in diagnosis and prognosis of cancer; however, the mechanisms enrolling it in malignant progression remain elusive. As a cytoplasmic enzyme gamma-enolase is involved in increased aerobic glycolysis, the main source of energy in cancer cells, supporting cell proliferation. However, different cellular localisation at pathophysiological conditions, proposes other cellular engagements. Conclusions The C-terminal part of the molecule, which is not related to glycolytic pathway, was shown to promote survival of neuronal cells by regulating neuronal growth factor receptor dependent signalling pathways, resulting also in extensive actin cytoskeleton remodelling. This additional function could be important also in cancer cells either to protect cells from stressful conditions and therapeutic agents or to promote tumour cell migration and invasion. Gamma-enolase might therefore have a multifunctional role in cancer progression: it supports increased tumour cell metabolic demands, protects tumour cells from stressful conditions and promotes their invasion and migration. PMID:26401126

S100B protein, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in human milk.

Directory of Open Access Journals (Sweden)

Ruisong Li

Full Text Available Human milk contains a wide variety of nutrients that contribute to the fulfillment of its functions, which include the regulation of newborn development. However, few studies have investigated the concentrations of S100B protein, brain-derived neurotrophic factor (BDNF, and glial cell line-derived neurotrophic factor (GDNF in human milk. The associations of the concentrations of S100B protein, BDNF, and GDNF with maternal factors are not well explored.To investigate the concentrations of S100B protein, BDNF, and GDNF in human milk and characterize the maternal factors associated with their levels in human milk, human milk samples were collected at days 3, 10, 30, and 90 after parturition. Levels of S100B protein, BDNF, and GDNF, and their mRNAs in the samples were detected. Then, these concentrations were compared with lactation and other maternal factors. S100B protein levels in human milk samples collected at 3, 10, 30, and 90 d after parturition were 1249.79±398.10, 1345.05±539.16, 1481.83±573.30, and 1414.39±621.31 ng/L, respectively. On the other hand, the BDNF concentrations in human milk samples were 10.99±4.55, 13.01±5.88, 13.35±6.43, and 2.83±5.47 µg/L, while those of GDNF were 10.90±1.65, 11.38±1., 11.29±3.10, and 11.40±2.21 g/L for the same time periods. Maternal post-pregnancy body mass index was positively associated with S100B levels in human milk (r = 0.335, P = 0.030<0.05. In addition, there was a significant correlation between the levels of S100B protein and BDNF (z = 2.09, P = 0.037<0.05. Delivery modes were negatively associated with the concentration of GDNF in human milk.S100B protein, BDNF, and GDNF are present in all samples of human milk, and they may be responsible for the long term effects of breast feeding.

Tumour markers in Chernobyl accident recovery workers in the late post-accident period

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Dryguina, L.; Strukov, E.; Nikiforov, A.

1997-01-01

Tumour markers (TM) are base plasma proteins with a carbohydrate component, produced by various types of tumor cells. 84 male liquidators aged from 30 to 50 y.o. were examined in the clinic of All-Russian Center of Emergency and Radiation Medicine in September 1994-April 1995. External irradiation exposure amongst liquidators varied from 2 to 30 sGr. TM concentration in serum and plasma were determined by conventional ELISA methods (CEA. AFP, CA19-9. PSA, NSE). The first (control) group was composed of liquidators with no GI tract pathology. The second group consisted of 28 liquidators with irradiation - induced cytogenetical disturbances in peripheral blood lymphocytes. The third group consisted included 28 liquidators with chronic GI tract diseases. In control group, levels of CA 19-9, CEA and AFP amounted to 4.7± 0.4 U/ml, 2.4± 0.8mg/ml, 2.1± 0.2 IU/ml, correspondingly. The CA 19-9 level has been shown to increase statistically significantly in the second (14.5±1.5 U/ml) and in the third group (17.8± 1.2 U/ml). A simultaneous elevation of CA 19-9 and CEA was found in 7.1% of the liquidators of the third group, the CA 19-9 level changes ranging from 63 to 708 U/ml. The mean value of PSA in all three groups remained within the discrimination concentration limits and amounted to 2.5± 0.4 U/ml. Concentration of NSE was equal to 29.9± 7.2 mg/ml in all three groups. Based on the data on frequencies of the tumour marker elevation, a group of 6 was selected.This group required a detailed dynamic examination because of the problem of remote consequences of the effect of complex factors of the Chernobyl Atomic Station accident upon its victims. (author)

Isolation of dendritic-cell-like S100β-positive cells in rat anterior pituitary gland.

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Horiguchi, Kotaro; Fujiwara, Ken; Yoshida, Saishu; Higuchi, Masashi; Tsukada, Takehiro; Kanno, Naoko; Yashiro, Takashi; Tateno, Kozue; Osako, Shunji; Kato, Takako; Kato, Yukio

2014-07-01

S100β-protein-positive cells in the anterior pituitary gland appear to possess multifunctional properties. Because of their pleiotropic features, S100β-positive cells are assumed to be of a heterogeneous or even a non-pituitary origin. The observation of various markers has allowed these cells to be classified into populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. The isolation and characterization of each heterogeneous population is a prerequisite for clarifying the functional character and origin of the cells. We attempt to isolate two of the subpopulations of S100β-positive cells from the anterior lobe. First, from transgenic rats that express green fluorescent protein (GFP) driven by the S100β protein promoter, we fractionate GFP-positive cells with a cell sorter and culture them so that they can interact with laminin, a component of the extracellular matrix. We observe that one morphological type of GFP-positive cells possesses extended cytoplasmic processes and shows high adhesiveness to laminin (process type), whereas the other is round in shape and exhibits low adherence to laminin (round type). We successfully isolate cells of the round type from the cultured GFP-positive cells by taking advantage of their low affinity to laminin and then measure mRNA levels of the two cell types by real-time polymerase chain reaction. The resultant data show that the process type expresses vimentin (mesenchymal cell marker) and glial fibrillary acidic protein (astrocyte marker). The round type expresses dendritic cell markers, CD11b and interleukin-6. Thus, we found a method for isolating dendritic-cell-like S100β-positive cells by means of their property of adhering to laminin.

[Association between S100B gene polymorphisms and hand, foot and mouth disease caused by enterovirus 71 infection].

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Li, Jing; Shan, Ruo-Bing; Liu, Rui-Hai; Xu, Ying-Jun; Qu, Ni-Yan; Pan, Gui-Mei; Zhang, Na; Yang, Na; Chen, Zhen-Zhen; Zhang, Wen-Xiang; Li, Zi-Pu

2017-08-01

To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71. A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children. The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (Penterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (Penterovirus 71 infection.

HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma.

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Zubovits, Judit; Buzney, Elizabeth; Yu, Lawrence; Duncan, Lyn M

2004-02-01

The diagnosis of melanoma metastatic to lymph node remains a difficult problem given its histological diversity. We examined the staining patterns of S-100, NK1/C3, HMB-45, and MART-1 (DC10) in melanoma metastases to lymph nodes. Immunohistochemical stains were performed on tissue sections of 126 formalin-fixed lymph nodes from 126 patients with an established diagnosis of metastatic melanoma. A total of 98% of cases (123 of 126) stained positive for S-100, 93% (117 of 125) stained positive for NK1/C3, 82% (103 of 126) stained positive for MART-1, and 76% (95 of 125) stained positive for HMB-45. The distribution and intensity of staining varied among these markers. A diffuse staining pattern, defined as >50% of tumor cells stained, was observed in 83% of MART-1-positive cases but in only 56% of S-100-positive cases, 48% of NK1/C3-positive cases, and 34% of HMB-45-positive cases. A maximally intense signal was almost always observed for MART-1 (83% of positive cases) but was rarely observed for NK1/C3 (20%). S-100 and HMB-45 showed maximally intense staining in 50% and 54% of cases, respectively. S-100 and NK1/C3 stained both histiocytes and melanocytes, whereas MART-1 and HMB-45 stained only melanocytes. Seventy-eight cases (63%) stained positive for all 4 markers, 17 cases (14%) stained for all markers except HMB-45, 13 cases (10%) stained for all markers except MART-1, 6 cases (5%) stained only with S-100 and NK1/C3, 4 cases (3%) stained only with S-100 and HMB-45, and 2 cases stained for all markers except S-100. One case each stained for the following: only S-100, only S-100 and HMB-45, and all markers except NK1/C3. One case exhibited absence of staining for any of these markers. We demonstrate that lymph node metastases of melanoma are heterogeneous with regard to tumor marker expression. S-100 and NK1/C3 were the most sensitive stains for detecting metastatic melanoma; however, they both also stain other nontumor cells in lymph nodes. MART-1 did not stain

Use of biomarker S100B for traumatic brain damage in the emergency department may change observation strategy

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Hansen-Schwartz, Jacob; Bouchelouche, Pierre Nourdine

2014-01-01

patients had their blood sampled for analysis. In all, 12 patients were excluded in pursuance of SNC guidelines, which left 27 patients for analysis. A total of 15 patients had abnormally high S100B levels. Using the SNC criteria, only eight of these qualified a priori for blood sampling. Furthermore...... evaluation. Using S100B as a screening tool may lead to an increase in the use of CTs of the brain. In relation to admission, measurement of S100B may contribute to the adoption of an appropriate observation strategy. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....

Diffusion-weighted imaging in the evaluation of odontogenic cysts and tumours.

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Srinivasan, K; Seith Bhalla, A; Sharma, R; Kumar, A; Roychoudhury, A; Bhutia, O

2012-10-01

The differentiation between keratocystic odontogenic tumour (KCOT) and other cystic/predominantly cystic odontogenic tumours is difficult on conventional CT and MR sequences as there is overlap in the imaging characteristics of these lesions. The purpose of this study was to evaluate the role of diffusion-weighted imaging (DWI) and to assess the performance of apparent diffusion coefficients (ADCs) in the differential diagnosis of odontogenic cysts and tumours. 20 patients with odontogenic cysts and tumours of the maxillomandibular region were examined with DWI. Diffusion-weighted images were obtained with a single-shot echoplanar technique with b-values of 0, 500 and 1000 s mm(-2). An ADC map was obtained at each slice position. The cystic areas of ameloblastoma (n=10) showed free diffusion with a mean ADC value of 2.192±0.33×10(-3) mm(2) s(-1), whereas the solid areas showed restricted diffusion with a mean ADC value of 1.041±0.41×10(-3) mm(2) s(-1). KCOT (n=5) showed restricted diffusion with a mean ADC value of 1.019±0.07×10(-3) mm(2) s(-1). There was a significant difference between the ADC values of KCOT and cystic ameloblastoma (p<0.01, Mann-Whitney U-test). The cut-off with which KCOT and predominantly cystic ameloblastomas were optimally differentiated was 2.013×10(-3) mm(2) s(-1), which yielded 100% sensitivity and 100% specificity. DWI can be used to differentiate KCOT from cystic (or predominantly cystic) odontogenic tumours.

Computed tomography, conventional X-ray examination, scintigraphy and tumour markers in thyroid carcinomas and suspected metastisation into the thoracic region

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Heintz, P.

1986-01-01

In 43 patients suffering from differentiated carcinomas of thyroid, who had previously been subjected to thyroidectomy and curative radioiodine treatment, CT scans of the thorax were used in addition to the usual X-ray examinations in order to exclude the formation of pulmonary metastases. Separate analyses of 45 records on the basis of the stage of the tumour when it was diagnosed and the behaviour of tumour marker hTg under suppression with L-thyroxin and endogenous stimulation during the follow-up permitted patient groups to be defined that are most at risk of metastisation. The results of the three methods of medical imaging were compared to those obtained using tumour marker hTg. The rate of findings revealed by CT, scintigraphy and X-ray examination was calculated with reference to the total number of results suggesting pulmonary metastisation and amounted to 89%, 48% and 44%, respectively. (orig./MG) [de

Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment

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Locker Gottfried J

2006-03-01

Full Text Available Abstract Background At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] ≥ 6 months, de novo disease progression (PD and secondary PD in patients receiving fulvestrant ('Faslodex' 250 mg/month for the treatment of metastatic breast cancer (MBC. Methods Changes in cancer antigen 15–3 (CA 15-3 and carcinoembryonic antigen (CEA were prospectively monitored (monthly and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. Results In patients with a PR (n = 7 [10.4%], a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165. In patients with SD ≥ 6 months (n = 28 [41.8%], both CA 15-3 (P P = 0.0399 levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%], CA 15-3 increased significantly (P P = 0.0002 during the same time period. Both CA 15-3 (P P Conclusion CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant.

Diagnostic accuracy of S100B urinary testing at birth in full-term asphyxiated newborns to predict neonatal death.

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Diego Gazzolo

Full Text Available BACKGROUND: Neonatal death in full-term infants who suffer from perinatal asphyxia (PA is a major subject of investigation, since few tools exist to predict patients at risk of ominous outcome. We studied the possibility that urine S100B measurement may identify which PA-affected infants are at risk of early postnatal death. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study between January 1, 2001 and December 1, 2006 we measured S100B protein in urine collected from term infants (n = 132, 60 of whom suffered PA. According to their outcome at 7 days, infants with PA were subsequently classified either as asphyxiated infants complicated by hypoxic ischemic encephalopathy with no ominous outcome (HIE Group; n = 48, or as newborns who died within the first post-natal week (Ominous Outcome Group; n = 12. Routine laboratory variables, cerebral ultrasound, neurological patterns and urine concentrations of S100B protein were determined at first urination and after 24, 48 and 96 hours. The severity of illness in the first 24 hours after birth was measured using the Score for Neonatal Acute Physiology-Perinatal Extension (SNAP-PE. Urine S100B levels were higher from the first urination in the ominous outcome group than in healthy or HIE Groups (p1.0 microg/L S100B had a sensitivity/specificity of 100% for predicting neonatal death. CONCLUSIONS/SIGNIFICANCE: Increased S100B protein urine levels in term newborns suffering PA seem to suggest a higher risk of neonatal death for these infants.

Neurohypophysis granular cell tumours. Upon neurohypophysis rare tumours

International Nuclear Information System (INIS)

Barrande, G.; Kujas, M.; Gancel, A.; Turpin, G.; Bruckert, E.; Kuhn, J.M.; Luton, J.P.

1995-01-01

Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17 % of unselected adult autopsy cases. There are few reports of para-sellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotrophic micro-adenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyper-prolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intra-sellar and supra-sellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted-images. Trans-sphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GEAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of post operative radiation therapy on postoperative recurrences. (authors). 23 refs., 4 figs., 1 tab

Diagnostic significance of combined detention of multiple tumour markers in lung cancer

International Nuclear Information System (INIS)

Chen Yanming; Qiu Jianming

2003-01-01

Objective: To explore the diagnostic value of combined detection of multiple markers in the determination of lung cancer. Methods: Using enzyme-linked immunosorbent assay (ELISA), the serum CEA, CA19-9, CA125, CA15-3 was determined in eighty-six lung cancer patients, thirty benign lung disease patients and thirty healthy persons. Results; Serum concentrations of CEA, CA19-9, CA125 and CA15-3 were significantly higher in patents with lung cancer than that in the patients with benign lung disease patients and healthy persons. The single test sensitivity of CEA, CA19-9, CA125 and CA15-3 for diagnosis of lung cancer is 41.9%, 37.2%, 48.9%, 36% respectively; the combined test sensitivity is 94.2%. Conclusions: Assessing several tumour markers can help differentiating various histological type of lung cancer and increase the sensitivity

The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer.

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Hong, Sung Pil; Min, Byung So; Kim, Tae Il; Cheon, Jae Hee; Kim, Nam Kyu; Kim, Hoguen; Kim, Won Ho

2012-05-01

Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response. PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer. Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104). These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours. Copyright © 2011 Elsevier Ltd. All rights reserved.

S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland.

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Kotaro Horiguchi

Full Text Available The anterior and intermediate lobes of the pituitary gland develop through invagination of the oral ectoderm and as they are endocrine tissues, they participate in the maintenance of vital functions via the synthesis and secretion of numerous hormones. We recently observed that several extrapituitary cells invade the anterior lobe of the developing pituitary gland. This raised the question of the origin(s of these S100β-positive cells, which are not classic endocrine cells but instead comprise a heterogeneous cell population with plural roles, especially as stem/progenitor cells. To better understand the roles of these S100β-positive cells, we performed immunohistochemical analysis using several markers in S100β/GFP-TG rats, which express GFP in S100β-expressing cells under control of the S100β promoter. GFP-positive cells were present as mesenchymal cells surrounding the developing pituitary gland and at Atwell's recess but were not present in the anterior lobe on embryonic day 15.5. These cells were negative for SOX2, a pituitary stem/progenitor marker, and PRRX1, a mesenchyme and pituitary stem/progenitor marker. However, three days later, GFP-positive and PRRX1-positive (but SOX2-negative cells were observed in the parenchyma of the anterior lobe. Furthermore, some GFP-positive cells were positive for vimentin, p75, isolectin B4, DESMIN, and Ki67. These data suggest that S100β-positive cells of extrapituitary origin invade the anterior lobe, undergoing proliferation and diverse transformation during pituitary organogenesis.

S100β-Positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland.

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Horiguchi, Kotaro; Yako, Hideji; Yoshida, Saishu; Fujiwara, Ken; Tsukada, Takehiro; Kanno, Naoko; Ueharu, Hiroki; Nishihara, Hiroto; Kato, Takako; Yashiro, Takashi; Kato, Yukio

2016-01-01

The anterior and intermediate lobes of the pituitary gland develop through invagination of the oral ectoderm and as they are endocrine tissues, they participate in the maintenance of vital functions via the synthesis and secretion of numerous hormones. We recently observed that several extrapituitary cells invade the anterior lobe of the developing pituitary gland. This raised the question of the origin(s) of these S100β-positive cells, which are not classic endocrine cells but instead comprise a heterogeneous cell population with plural roles, especially as stem/progenitor cells. To better understand the roles of these S100β-positive cells, we performed immunohistochemical analysis using several markers in S100β/GFP-TG rats, which express GFP in S100β-expressing cells under control of the S100β promoter. GFP-positive cells were present as mesenchymal cells surrounding the developing pituitary gland and at Atwell's recess but were not present in the anterior lobe on embryonic day 15.5. These cells were negative for SOX2, a pituitary stem/progenitor marker, and PRRX1, a mesenchyme and pituitary stem/progenitor marker. However, three days later, GFP-positive and PRRX1-positive (but SOX2-negative) cells were observed in the parenchyma of the anterior lobe. Furthermore, some GFP-positive cells were positive for vimentin, p75, isolectin B4, DESMIN, and Ki67. These data suggest that S100β-positive cells of extrapituitary origin invade the anterior lobe, undergoing proliferation and diverse transformation during pituitary organogenesis.

Clinical significance of determination of plasma Leptin and serum Hcy, S100B and NSE levels in patients with alzheimer disease

International Nuclear Information System (INIS)

Dou Huanzhi; Lu Meng

2011-01-01

To explore the clinical significance of changes of plasma leptin and serun Hcy, S100B and NSE levels in patients with Alzheimer Disease (AD). The plasma leptin and serum NSE levels in 32 AD patients and 30 controls were determined by using RIA, and the serum Hcy and S100B levels were measured by using CLIA. The results showed that the plasma leptin and serun Hcy, S100B and NSE levels in AD patients were significantly higher than these in controls (P<0.01). The plasma leptin levels in AD patients was mutually positively correlated with serum Hcy, S100B and NSE levels (r=0.5982, 0.4762, 0.6014, P<0.01). The detection of plasma leptin and serum Hcy, S100B and NSE levels may be helpful for the prediction of treatment efficiency in patients with Alzheimer disease. (authors)

S-100b and neuron-specific enolase in patients with fulminant hepatic failure

DEFF Research Database (Denmark)

Strauss, Gitte Irene; Christiansen, Michael; Møller, Kirsten

2001-01-01

, the cerebral flux of S-100b and NSE was measured. We included 35 patients with FHF, 6 patients with acute on chronic liver disease (AOCLD), 13 patients with cirrhosis of the liver without hepatic encephalopathy, and 8 healthy subjects. Blood samples were obtained from catheters placed in the radial artery...

Shared features of S100B immunohistochemistry and cytochrome oxidase histochemistry in the ventroposterior thalamus and lateral habenula in neonatal rats.

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Muneoka, Katsumasa; Funahashi, Hisayuki; Ogawa, Tetsuo; Whitaker-Azmitia, Patricia M; Shioda, Seiji

2012-10-01

The ventroposterior thalamus and the habenular nuclei of the epithalamus are relevant to the monoaminergic system functionally and anatomically. The glia-derived S100B protein plays a critical role in the development of the nervous system including the monoaminergic systems. In this study, we performed an immunohistochemical study of glia-related proteins including S100B, serotonin transporter, and microtubule-associated protein 2, as well as cytochrome oxidase histochemistry in neonatal rats. Results showed the same findings for S100B immunohistochemistry between the ventroposterior thalamus and the lateral habenula at postnatal day 7: intense staining in cell bodies of astrocytes, diffusely spread immunoproduct in the intercellular space, and S100B-free areas as well as a strong reaction to cytochrome oxidase histochemistry. Further common features were the scarcity of glial fibrillary acidic protein-positive astrocytes and the few apoptotic cells observed. The results of the cytochrome oxidase reaction suggested that S100B is released actively into intercellular areas in restricted brain regions showing high neuronal activity at postnatal day 7. Pathology of the ventroposterior thalamus and the habenula is suggested in mental disorders, and S100B might be a key factor for investigations in these areas. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Correlation of Apo B-48 and Apo B-100 with Oxidized LDL in Men with Central Obesity

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Maria Diah Fibriani

2010-08-01

Full Text Available BACKGROUND: Obesity has a central role in the metabolic syndrome, which raises the risk for atherosclerotic cardiovascular disease (ASVCD. Apo B-48 and Apo B-100 are the necessary structural proteins required for the assembly and secretion of chylomicron and VLDL which have role in atherogenesis. The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B-containing lipoproteins. Oxidation of LDL is a hallmark of atherosclerosis development. The aim of this study was to asses the association between Apo B-48 and Apo B-100 with Oxidized-LDL as marker of atherosclerosis risk in central obesity. We hope that the result of this study can help to make a new strategy for the prevention and treatment of vascular disease. RESULTS: There were 68 patients aged 39.6±7.3 years, Apo B-48 concentration was 7.47±5.36 μg/mL, Apo B-100 was 117.26±25.74 mg/dL, and ox-LDL was 137.05±18.88 U/L. This study showed a significant correlation between Apo B-100 and ox-LDL (r=0.608, p<0.05 and correlation between Apo B-48 and ox-LDL (r= 0.171, p<0.05. The levels of Apo B-100 were significantly different between obese with Mets and obese without Mets individuals (p<0.05. CONCLUSIONS: This study suggested that Apo B-100 concentration increase in obese in Mets as compared with obese without Mets. Apo B-48 and Apo B-100 were correlated with Oxidized LDL, but correlation between Apo B-100 and ox-LDL more significant that Apo B-48and ox-LDL. KEYWORDS: obesity, atherogenesis, Apo B-48, Apo B-100, ox-LDL.

The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers

International Nuclear Information System (INIS)

Apostolova, Ivayla; Ego, Kilian; Steffen, Ingo G.; Buchert, Ralph; Wertzel, Heinz; Achenbach, H.J.; Riedel, Sandra; Schreiber, Jens; Schultz, Meinald; Furth, Christian; Amthauer, Holger; Derlin, Thorsten; Hofheinz, Frank; Kalinski, Thomas

2016-01-01

Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC). The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with 18 F-FDG had been performed prior to therapy. Primary tumour resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures. SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with

The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers

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Apostolova, Ivayla; Ego, Kilian; Steffen, Ingo G. [University Hospital, Otto-von-Guericke University Magdeburg, Clinic of Radiology and Nuclear Medicine, Magdeburg (Germany); Buchert, Ralph [University Medicine Charite, Clinic of Nuclear Medicine, Berlin (Germany); Wertzel, Heinz; Achenbach, H.J. [Lung Clinic Lostau GmbH, Lostau (Germany); Riedel, Sandra; Schreiber, Jens [University Hospital, Otto-von-Guericke University Magdeburg, Clinic of Pneumology, Magdeburg (Germany); Schultz, Meinald [Institute of Pathology Stendal, Stendal (Germany); Furth, Christian; Amthauer, Holger [University Hospital, Otto-von-Guericke University Magdeburg, Clinic of Radiology and Nuclear Medicine, Magdeburg (Germany); University Medicine Charite, Clinic of Nuclear Medicine, Berlin (Germany); Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Hofheinz, Frank [Helmholtz-Center Dresden-Rossendorf, Dresden (Germany); Kalinski, Thomas [University Hospital Magdeburg, Otto-von-Guericke University Magdeburg, Institute for Pathology, Magdeburg (Germany); Institute for Pathology Lademannbogen, Hamburg (Germany)

2016-12-15

Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC). The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with {sup 18}F-FDG had been performed prior to therapy. Primary tumour resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures. SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with

Ovarian tumours in children : A review of 18 cases

Directory of Open Access Journals (Sweden)

Abdelouhab Ammor

2012-01-01

Full Text Available Background : To review the experience of Children′s Hospital of Rabat in managing ovarian tumours in children. Materials and Methods: There were 18 patients between 2 and 15 years of age who presented with an ovarian tumour at Children′s Hospital of Rabat between January 2000 and December 2008. Data collected from the hospital medical records included age at diagnosis, patient′s history, presenting complaints, radiological examination, tumour markers, management, operative procedure, histopathological examination and outcome of the patients. Results : The most common presenting complaint was abdominal pain in 10 (55% patient. 77% of ovarian tumours were germ cell tumours; 71% of these were teratomas which were benign in 66% of cases. Unilateral salpingo-oophorectomy was the most common surgical procedure performed in 15 patients (83% through laparotomy. Laparoscopic ovarian cystectomy was carried out in 2 (11% patients with benign cystic teratoma. Of the 7 (39% patients with malignant tumours, three received postoperative chemotherapy. Outcome was good in most cases. There were no cases of resistance to treatment, or death. Conclusion : Early diagnosis of ovarian tumours in children and adolescents is important. Since most of these tumours are benign, surgical treatment should be conservative to minimise the risk of subsequent infertility, while the treatment of malignant tumours should include complete staging, resection of the tumour, postoperative chemotherapy when indicated, to give the patient a chance for future childbearing.

Can tumour marker assays be a guide in the prescription of bone scan for breast and lung cancers?

Energy Technology Data Exchange (ETDEWEB)

Buffaz, P.-D.; Gauchez, A.S.; Caravel, J.P.; Vuillez, J.P.; Cura, C.; Agnius-Delord, C.; Fagret, D. [Service de Medecine Nucleaire, Centre Hospitalier Universitaire de Grenoble (France)

1999-01-01

Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy. (orig.) With 3 figs., 21 refs.

Inverse relationship between tumour proliferation markers and connexin expression in a malignant cardiac tumour originating from mesenchymal stem cell engineered tissue in a rat in-vivo model.

Directory of Open Access Journals (Sweden)

Cathleen eSpath

2013-04-01

Full Text Available Background: Recently, we demonstrated the beneficial effects of engineered heart tissues for the treatment of dilated cardiomyopathy in rats. For further development of this technique we started to produce engineered tissue (ET from mesenchymal stem cells. Interestingly, we observed a malignant tumour invading the heart with an inverse relationship between proliferation markers and connexin-expression.Methods: Commercial CD54+/CD90+/CD34-/CD45- bone marrow derived mesenchymal rat stem cells (cBM-MSC, characterized were used for production of mesenchymal stem-cell-ET (MSC-ET by suspending them in a collagen-I, matrigel-mixture and cultivating for 14 days with electrical stimulation. 3 MSC-ET were implanted around the beating heart of adult rats for days. Another 3 MSC-ET were produced from freshly isolated rat bone marrow derived stem cells (sBM-MSC.Results: 3 weeks after implantation of the MSC-ETs the hearts were surgically excised. While in 5/6 cases the ET was clearly distinguishable and was found as a ring containing mostly connective tissue around the heart, in 1/6 the heart was completely surrounded by a huge, undifferentiated, pleomorphic tumour originating from the cMSC-ET (cBM-MSC, classified as a high grade malignant sarcoma. Quantitatively we found a clear inverse relationship between cardiac connexin-expression (Cx43, Cx40 or Cx45 and increased Ki-67 expression (Cx43: p<0.0001, Cx45: p<0.03, Cx40: p<0.014. At the tumour-heart border there were significantly more Ki-67 positive cells (p=0.001, and only 2% Cx45 and Ki-67-expressing cells, while the other connexins were nearly completely absent (p<0.0001.Conclusions and hypothesis: These observations strongly suggest the hypothesis, that invasive tumour growth is accompanied by reduction in connexins. This implicates that gap junction communication between tumour and normal tissue is reduced or absent, which could mean that growth and differentiation signals can not be exchanged.

Unilateral testicular tumour associated to congenital adrenal hyperplasia: Failure of specific tumoral molecular markers to discriminate between adrenal rest and leydigioma.

Science.gov (United States)

Fenichel, P; Bstandig, B; Roger, C; Chevallier, D; Michels, J-F; Sadoul, J-L; Hieronimus, S; Brucker-Davis, F

2008-11-01

Testicular adrenal rest tumours are frequently associated with congenital adrenal hyperplasia (CAH). These ACTH-dependent tumours cannot be easily distinguished histologically from Leydig-cell tumours. We report the case of a 30-year-old man who was explored for infertility, azoospermia and unilateral testicular tumour. High levels of 17-OH progesterone and ACTH, low cortisol and undetectable gonadotropins levels, associated to bilateral adrenal hyperplasia, led to the diagnosis of CAH by 21-OH deficiency with a composite heterozygoty. The testicular tumour was first considered as adrenal rest. However, histological analysis of this unilateral painful tumour showed a steroid-hormone-secreting cell proliferation with atypical and frequent mitosis. To discriminate between a benign adrenal rest tumour and a possible malignant leydigioma, tumoral expression of specific gene products was analyzed by RT-PCR. No 11-beta-hydroxylase nor ACTH receptor mRNAs could be found in the tumour, which did not behave like usual adrenal rest cells. For this unilateral testicular tumour, the lack of adrenal-specific markers associated with a high rate of mitosis and pleiomorphism supported a leydigian origin with malignant potential. However, lack of tumoral LH-R mRNA expression and a tumour-free 3-year follow-up led us to retain the diagnosis of adrenal rest tumour with loss of adrenal gene expression and progressive autonomous behaviour.

Detection of viral hepatitis B markers by radioimmunoassay in medical personnel

International Nuclear Information System (INIS)

Marievskij, V.F.; Lejbenzon, A.S.

1990-01-01

Results of revealing B markers of viral hepatitis (VHB) in medical personnel in the city of Zaporozhe by radioimmunoassay method are presented. By the frequency of revealing two markers (HB s Ag and anti-HB s ) risk groups are indicated depending on the profession, age (length of service) of medical personnel

High frequency of albinism and tumours in free-living birds around Chernobyl.

Science.gov (United States)

Møller, A P; Bonisoli-Alquati, A; Mousseau, T A

2013-09-18

The effects of radioactive contamination on the phenotype of free-living organisms are poorly understood, mainly because of the difficulty of capturing the large numbers of individual specimens that are required to quantify rare events such as albinism and tumour formation. We hypothesized that the frequency of abnormalities like albinism and the frequency of radiation-induced diseases like cancer would increase with the level of background radiation, that the two markers of radiation would be positively correlated, and that the reduction in abundance of animals would be greater in species with a higher frequency of albinism and tumour formation, if these markers reliably reflected poor viability. Here we analyzed the frequency of albinistic feathers and tumours in a sample of 1669 birds captured during 2010-2012 at eight sites around Chernobyl that varied in level of background radiation from 0.02 to more than 200μSv/h. We recorded 111 cases of partial albinism and 25 cases of tumour formation. Nominal logistic models were used to partition the variance into components due to species and background radiation. Radiation was a strong predictor of the two markers in birds, with a small, but significant effect of species for albinism. The slope of the relationship between abundance and radiation in different bird species was significantly inversely correlated with the frequency of albinism and tumours, as was to be expected if a common underlying cause (i.e. radiation) affects both variables. These findings are consistent with the hypothesis that background radiation is a cause of albinism and tumours, that albinism and tumours are biomarkers of radiation exposure, and that high frequencies of albinism and tumours were present despite the low viability of birds with these conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of an MRI/x-ray/ultrasound compatible marker for pre-operative breast tumour localization

International Nuclear Information System (INIS)

Li Yangmei; Wang, Jianxiong; Holloway, Claire; Plewes, Donald B

2005-01-01

This paper describes an in vitro investigation into the composition, structure and development of an magnetic resonance imaging (MRI), ultrasound (US) and x-ray imaging compatible marker for breast tumour localization. The marker is composed of 0.4-0.6 mm glass and iron-containing aluminium microspheres suspended in a gelatin matrix. The final form of the marker is a cylindrical shape 7 mm long with 2.05 mm diameter to facilitate delivery through a 12 gauge biopsy needle. To get optimal reflectivity for the US contrast, the glass microsphere concentration was found to be 40% by weight. US contrast is independent of marker orientation and the cylindrical shape made its US signal appearance distinctive thus ensuring confident identification. To control the MRI contrast, iron content was varied to generate a clear and local susceptibility signal void to reflect the marker position. Optimal iron content was found to be 52 μg iron which produced a clear signal void in spoiled gradient recalled MR images. The appearance of the susceptibility artefact is determined by the marker's shape, orientation and echo time. The final marker produces a dark artefact in MRI while appears as a clear hyperintense structure with acoustic shadowing in US images. The x-ray image showed the marker as a radio-opaque structure. This in vitro study demonstrates that the marker forms an alternative to traditional wire localization currently used for breast surgical procedures and creates new opportunities for US guided surgical procedures

Dermatofibroma-like granular cell tumour: a potential diagnostic pitfall

Directory of Open Access Journals (Sweden)

Jiri Soukup

2016-11-01

Full Text Available Dermatofibroma-like granular cell tumour (GCT is a rare entity, with only two cases having been described so far. We report another case in a 62-year-old woman, discuss histopathological features, and review other tumours in which granular changes have been observed. Our tumour was composed predominantly of oval-to-spindle granular cells with prominent nucleoli, arranged in short fascicles and storiform pattern, infiltrating around collagen bundles. Immunohistochemical analysis with antibodies against CD31, CD56, CD68, CD117, S-100 protein, inhibin, calretinin, EMA, p53 and MIB-1 was performed, showing expression of CD56, CD68, S-100 protein, inhibin and calretinin. The diagnosis of atypical dermatofibroma-like GCT was made.

Testicular tumours in prepubertal children: About eight cases ...

African Journals Online (AJOL)

Conclusion: In prepubertal children, most testicular tumours are benign. If tumour markers were negative testis-preserving surgery can be proposed, complete excision of the tumour should be ascertained. In the case of testicular teratoma, the possibility of contralateral tumour should be considered in the follow-up.

Peroxidase activity as a marker for estrogenicity

International Nuclear Information System (INIS)

Levy, J.; Liel, Y.; Glick, S.M.

1981-01-01

We examined the possibility that peroxidase activity might be a marker for estrogen activity in established estrogen-dependent tissues: dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumours and human breast cancer. In DMBA-induced tumours undergoing regression after ovariectomy or tamoxifen treatment, tumour size decreased by 50%, estradiol receptors (ER) and progesterone receptors (PgR) decreased by 25 and 20%, respectively, but peroxidase activity paradoxically increased six- to sevenfold. In DMBA tumours stimulated by estradiol treatment or by the cessation of tamoxifen administration in intact rats, tumour size increased threefold. ER and PgR increased two- and threefold, respectively, while peroxidase activity decreased 50%. These data indicate an inverse relation between tumour growth, ER and PgR on the one hand, and peroxidase activity on the other. In the human breast cancers there was a singificant negative relation between the presence of ER and peroxidase activity. By using a calibrated Sephadex G-100 column it was shown that uterine peroxidase differs in molecular weight from the peroxidase of rat mammary tumours and that of human breast cancer. (author)

Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival

International Nuclear Information System (INIS)

Ganeshan, Balaji; Miles, Ken; Panayiotou, Elleny; Burnand, Kate; Dizdarevic, Sabina

2012-01-01

To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing 18 F-fluorodeoxyglucose (FDG) PET-CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. (orig.)

High glutamate attenuates S100B and LDH outputs from rat cortical slices enhanced by either oxygen-glucose deprivation or menadione.

Science.gov (United States)

Demircan, Celaleddin; Gül, Zülfiye; Büyükuysal, R Levent

2014-07-01

One hour incubation of rat cortical slices in a medium without oxygen and glucose (oxygen-glucose deprivation, OGD) increased S100B release to 6.53 ± 0.3 ng/ml/mg protein from its control value of 3.61 ± 0.2 ng/ml/mg protein. When these slices were then transferred to a medium containing oxygen and glucose (reoxygenation, REO), S100B release rose to 344 % of its control value. REO also caused 192 % increase in lactate dehydrogenase (LDH) leakage. Glutamate added at millimolar concentration into the medium decreased OGD or REO-induced S100B release and REO-induced LDH leakage. Alpha-ketoglutarate, a metabolic product of glutamate, was found to be as effective as glutamate in decreasing the S100B and LDH outputs. Similarly lactate, 2-ketobutyrate and ethyl pyruvate, a lipophilic derivative of pyruvate, also exerted a glutamate-like effect on S100B and LDH outputs. Preincubation with menadione, which produces H2O2 intracellularly, significantly increased S100B and LDH levels in normoxic medium. All drugs tested in the present study, with the exception of pyruvate, showed a complete protection against menadione preincubation. Additionally, each OGD-REO, menadione or H2O2-induced mitochondrial energy impairments determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and OGD-REO or menadione-induced increases in reactive oxygen substances (ROS) determined by 2,7-dichlorofluorescin diacetate (DCFH-DA) were also recovered by glutamate. Interestingly, H2O2-induced increase in fluorescence intensity derived from DCFH-DA in a slice-free physiological medium was attenuated significantly by glutamate and alpha-keto acids. All these drug actions support the conclusion that high glutamate, such as alpha-ketoglutarate and other keto acids, protects the slices against OGD- and REO-induced S100B and LDH outputs probably by scavenging ROS in addition to its energy substrate metabolite property.

Technetium-99m-labelled monoclonal antibody fragment (99mTc-DD-3B6/22Fab') for ovarian cancer

International Nuclear Information System (INIS)

Fernandes, V.; Donaghy, T.; Prabakaran, K.; Smith, S.; Clingan, P.; Bartolo, N.; Bundesen, P.; Hillyard, C.

1998-01-01

Full text: This study is the first to assess 99m Tc-DD-3B6/22Fab'' as an agent for detecting OC recurrence. Five informed consenting volunteers with stages 3 or 4 OC (mean age 54.2 y) and with negative skin prick test to Fab'' were recruited. All had suspicion of OC recurrence, with elevated serum tumour marker CA125, and in some, OC confirmation on CT scans. Aggressive treatment was continued so that tumour regression was possible prior to 99m Tc-DD-3B6/22Fab''scan. CA125, FBC, biochemical and clot markers were measured pre-and post-study. All received IV 600-800 MBq of 99 mTc-DD-3B6/22Fab''. Temperature, pulse and BP were monitored for one hour. Data were acquired with a single head LFOV gamma camera and HIRES collimator at 1,4,6 and 24 hours. Studies were read for OC lesions which were scored as probably normal (PN) or abnormal (PAb), definitely abnormal (DAb). The gold standard was CA125 immediately post-scan and, when possible, confirmation with CT. Of 5 patients, 1 was disease negative with 99 mTc-DD-3B6/22Fab'', CA125 suggesting remission, and 4 were positive on all modalities (Sensitivity, specificity, 100% respectively). 99 mTc-DD-3B6/22Fab'' identified 15 lesions (100% DAb). CT detected 7 lesions (71% Dab) pre- 99 mTc-DD-3B6/22Fab''. Repeat CT detected 8 (100% DAb). Correlation with CA125 levels was best with 99 mTc-DD3B6/22Fab''. No side effects or adverse change in serum markers were noted. 99 mTc-DD-3B6/22Fab'' is sensitive and specific for detecting OC recurrence

miR-125b induces cellular senescence in malignant melanoma

DEFF Research Database (Denmark)

Nyholm, Anne Marie; Lerche, Catharina M; Manfé, Valentina

2014-01-01

transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further...... examined with in-situ-hybridization. RESULTS: In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block...... and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki...

Contrast enhancement pattern on multidetector CT predicts malignancy in pancreatic endocrine tumours

Energy Technology Data Exchange (ETDEWEB)

Cappelli, Carla [University of Pisa, Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Azienda Ospedaliero-Universitaria Pisana-Radiodiagnostica I, Pisa (Italy); Boggi, Ugo [University of Pisa, General and Transplant Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Mazzeo, Salvatore; Cervelli, Rosa; Contillo, Benedetta Pontillo; Bartolozzi, Carlo [University of Pisa, Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Campani, Daniela; Funel, Niccola [University of Pisa, Pathology, Department of Surgical, Medical, Molecular and Critical Area Pathology, Pisa (Italy)

2014-12-02

Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness. Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations. Nineteen pNETs showed type A CEP (5-20 mm), 29 type B1 CEP (5-80 mm) and 12 type B2 (15-100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions ≤2cm were WDC. CEP showed correlation with all histological prognostic indicators. Correlating with the lesion grading and other histological prognostic predictors, CEP may preoperatively suggest the behaviour of pNETs, assisting decisions about treatment. Moreover CEP allows recognition of malignant small tumours, incorrectly classified on the basis of their dimension. (orig.)

Contrast enhancement pattern on multidetector CT predicts malignancy in pancreatic endocrine tumours

International Nuclear Information System (INIS)

Cappelli, Carla; Boggi, Ugo; Mazzeo, Salvatore; Cervelli, Rosa; Contillo, Benedetta Pontillo; Bartolozzi, Carlo; Campani, Daniela; Funel, Niccola

2015-01-01

Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness. Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations. Nineteen pNETs showed type A CEP (5-20 mm), 29 type B1 CEP (5-80 mm) and 12 type B2 (15-100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions ≤2cm were WDC. CEP showed correlation with all histological prognostic indicators. Correlating with the lesion grading and other histological prognostic predictors, CEP may preoperatively suggest the behaviour of pNETs, assisting decisions about treatment. Moreover CEP allows recognition of malignant small tumours, incorrectly classified on the basis of their dimension. (orig.)

First evidence for glial pathology in late life minor depression:S100B is increased in males with minor depression

Directory of Open Access Journals (Sweden)

Maryna ePolyakova

2015-10-01

Full Text Available Minor depression is diagnosed when a patient suffers from two to four depressive symptoms for at least two weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF, S100B and neuron specific enolase (NSE. 27 subjects with minor depressive episode and 82 healthy subjects over 60 years of age were selected from the database of the Leipzig population-based study of civilization diseases (LIFE. Serum levels of BDNF, S100B and NSE were compared between groups, and correlated with age, body-mass index, and degree of white matter hyperintensities (score on Fazekas scale. S100B was significantly increased in males with minor depression in comparison to healthy males, whereas other biomarkers did not differ between groups (p=0.10-0.66. NSE correlated with Fazekas score in patients with minor depression (r=0.436, p=0.048 and in the whole sample (r=0.252, p=0.019. S100B correlated with body mass index (r=0.246, p=0.031 and with age in healthy subjects (r=0.345, p=0.002. Increased S100B in males with minor depression, without alterations in BDNF and NSE, supports the glial hypothesis of depression. Correlation between white matter hyperintensities and NSE underscores the vascular hypothesis of late life depression.

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.

Science.gov (United States)

Ciezka, Magdalena; Acosta, Milena; Herranz, Cristina; Canals, Josep M; Pumarola, Martí; Candiota, Ana Paula; Arús, Carles

2016-08-01

The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

Science.gov (United States)

Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-01-01

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

Science.gov (United States)

Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-02-07

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

FDG-PET/CT and FLT-PET/CT for differentiating between lipid-poor benign and malignant adrenal tumours

Energy Technology Data Exchange (ETDEWEB)

Nakajo, Masatoyo; Jinguji, Megumi; Fukukura, Yoshihiko; Nakabeppu, Yoshiaki; Nakamura, Fumihiko; Yoshiura, Takashi [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kajiya, Yoriko; Tani, Atushi; Nakajo, Masayuki [Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Arimura, Hiroshi; Nishio, Yoshihiko [Kagoshima University, Department of Diabetes and Endocrine Medicine, Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

2015-12-15

To compare F-18-fluorodeoxyglucose (FDG) and F-18-fluorothymidine (FLT) PET/CT examinations for differentiating between benign and malignant adrenal tumours. Thirty lipid-poor benign and 11 malignant tumours of 40 patients were included. FDG- and FLT-based indices including visual score, maximum standardized uptake value (SUVmax) and FDG adrenal lesion/liver SUVmax (A/L SUVmax) or FLT adrenal lesion/back muscle SUVmax (A/B SUVmax) ratio were compared between benign and malignant tumours using the Mann-Whitney's U or Wilcoxon signed-rank test, and their diagnostic performances were evaluated by means of the area under the curve (AUC) values derived from the receiver operating characteristic analysis. All indices were significantly higher in malignant than benign tumours on both images (p < 0.05 each). On FDG-PET/CT, the sensitivity, specificity, and accuracy were 91 %, 63 % and 71 % for visual score, 91 %, 67 % and 73 % for SUVmax, and 100 %, 70 % and 78 % for A/L SUVmax ratio, respectively. On FLT-PET/CT, they were 100 %, 97 % and 98 % for visual score, SUVmax and A/B SUVmax ratio, respectively. All FLT indices were significantly higher than those of FDG in AUC (p < 0.05 each). FLT-PET/CT may be superior to FDG-PET/CT in differentiating lipid-poor benign from malignant adrenal tumours because of higher specificity and accuracy. (orig.)

Questioning the role of actinfree Gc-Globulin as actin scavenger in neurodegenerative central nervous system disease: relationship to S-100B levels and blood-brain barrier function.

Science.gov (United States)

Gressner, Olav A; Schifflers, Marie-Claire; Kim, Philipp; Heuts, Leo; Lahme, Birgit; Gressner, Axel M

2009-02-01

Preliminary studies report on significantly higher levels of the major cytoskeleton protein actin in CSF of patients with neurodegenerative conditions and that the dynamics of these levels obviously correlates with disease progression and clinical disability. One of the primary functions of actinfree Gc-Globulin is to bind and neutralize extracellular monomeric actin, released into the circulation by necrotic or ruptured cells, and thus ameliorating the clinical outcome in situations of severe organ damage. This is the first study to investigate actinfree Gc-Globulin and S100-B levels (as reliable marker of neurodegeneration) in paired CSF and serum samples of patients with multietiological CNS diseases. 42% of all patients with CNS disease displayed serum concentrations of actinfree Gc-Globulin above the established reference range. CSF concentrations of actinfree Gc-Globulin and S100-B were positively correlated with the severity of blood-brain barrier (BBB) dysfunction. Furthermore, patients with severe BBB dysfunction presented a higher percentage of intrathecal synthesis of actinfree Gc-Globulin compared to patients with mild to moderate dysfunction and to patients with normal BBB function. Representative longitudinal data from selected patients demonstrated an inverse behaviour of actinfree Gc-Globulin and S100-B CSF concentrations, suggesting a consumption of the actin scavenger capacity of Gc-Globulin in times of increased neuronal damage. This presumption was supported by the fact that those conditions associated with a severe neuronal damage, in particular CNS trauma, and highest S100-B concentrations simultaneously displayed lowest actinfree Gc-Globulin levels, and thus residual actin binding capacity of Gc-Globulin. In summary, our data propose a function of actinfree Gc-Globulin also in the clearance of actin filaments from CSF of patients with neuronal damage. However, active recruitment of hepatic derived actinfree Gc-Globulin to the site of CNS

Radiofrequency ablation of renal tumours: diagnostic accuracy of contrast-enhanced ultrasound for early detection of residual tumour

International Nuclear Information System (INIS)

Hoeffel, Christine; Pousset, Maud; Elie, Caroline; Timsit, Marc-Olivier; Mejean, Arnaud; Merran, Samuel; Tranquart, Francois; Khairoune, Ahmed; Helenon, Olivier; Correas, Jean-Michel; Joly, Dominique; Richard, Stephane

2010-01-01

To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in the early detection of residual tumour after radiofrequency ablation (RFA) of renal tumours. Patients referred to our institution for RFA of renal tumours prospectively underwent CEUS and computed tomography (CT) or magnetic resonance imaging (MRI) before, within 1 day and 6 weeks after treatment. Identification of residual tumour was assessed by three blinded radiologists. Reference standard was CT/MRI performed at least 1 year after RFA. A total of 66 renal tumours in 43 patients (median age 62 years; range 44-71.5) were studied. Inter-reader agreement (κ value) was 0.84 for CEUS. Prevalence of residual disease was 19%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), respectively, were as follows: 64% [confidence interval (CI) 39-84], 98% [CI 91-100], 82% [CI 52-95] and 92% [CI 83-97] on 24-h CEUS; 79% [CI 52-92], 100% [CI 94-100], 100% [CI 74-100] and 95% [CI 87-100] on 6-week CEUS; 79% [CI 52-92], 95% [CI 86-98], 79% [CI 52-92] and 95% [CI 86-98] on 24-h CT/MRI; and 100% [CI 72-100], 98% [CI 90-100], 91% [CI 62-98] and 100% [CI 93-100] on 6-week CT/MRI. CEUS has high specificity for the early diagnosis of residual tumour after renal RFA. (orig.)

Investigation of pancreas tumour movements and of their potential markers by four-dimensional scanography: implication for image-guided radiotherapy

International Nuclear Information System (INIS)

Huguet, F.; Yorke, E.; Davidson, M.; Zhang, Z.; Jackson, A.; Mageras, G.; Wu, A.; Goodman, K.

2011-01-01

The authors report the study which aimed at quantifying pancreas tumour movements induced by breathing by using four-dimensional scanography, and at assessing the reliability of biliary prosthesis, of intra-tumor fiducials, and of an external maker as position markers of the gross tumour volume (GTV). The authors analyzed scanography images acquired during the simulation of 22 patients treated for locally advanced pancreas cancer by intensity-modulated conformational irradiation with respiratory gating. Average movements in different directions have measured. Respiratory gating limits the GTV movement amplitude by 40 to 60 per cent. GTV movements are in good correlation with that of biliary prostheses and intra-tumor fiducials. Short communication

Assessment and association of two useful tumour markers: alpha feto protein and human chornionic gonodotropin (beta hCG) hormone

International Nuclear Information System (INIS)

Subhan, F.; Tahir, F.; Sultan, S.; Subhan, K.

2008-01-01

This study was designed to determine serum Alpha-fetoprotein (AFP) and beta-h Chornionic Gonodotropin hormone (beta-hCG) levels among adult Pakistani population, and to observe their correlation. Serum AFP and beta-hCG levels were evaluated, using Micro-particle Enzyme Immuno Assay (MEIA) technology of M/s Abbott Laboratories. Data were compared using students t-test and correlation was computed. In the patients advised serum AFP assessment, 52% had normal AFP levels. comprising 37% male and 63% female subjects. For patients having a non-pathological picture, AFP levels varied non-significantly (p>0.05) between the Genders however, age varied highly significantly (p 0.05) and highly significant (p 0.05). Comparison of the population in the same age groups of both genders revealed significant (p 0.05), due to a large standard error. Although the differences in beta-hCG levels were highly significant (p 0.05). Among the studied cases, 67% patients had normal and 33% patients had raised beta-hCG levels. Beta-hCG levels show a decreasing trend with increasing age and beta-hCG levels were statistically significant (p<0.05) when patients under 50 years of age were compared with patients above 50 years. The coefficient of correlation between serum AFP and beta- hCG levels was 0.996454, which indicated a very strong. Significant positive correlation between the two tumour markers. The study showed that both serum AFP and beta-hCG are useful tumour markers and had a very strong positive correlation. (author)

100-B area technical baseline report

International Nuclear Information System (INIS)

Carpenter, R.W.

1994-01-01

This document supports the environmental remediation effort of the 100-B Area by providing remediation planners with key data that characterize the 100-B and 100-C Reactor sites. It provides operational histories of the 100-B and 100-C Reactors and each of their associated liquid and solid waste sites

100-B area technical baseline report

Energy Technology Data Exchange (ETDEWEB)

Carpenter, R.W.

1994-09-01

This document supports the environmental remediation effort of the 100-B Area by providing remediation planners with key data that characterize the 100-B and 100-C Reactor sites. It provides operational histories of the 100-B and 100-C Reactors and each of their associated liquid and solid waste sites.

Some aspects of the endocrine tumours of the digestive tract

International Nuclear Information System (INIS)

Sassolas, G.

1996-01-01

Endocrine tumours of digestive tract (GEP) synthesize many hormonal products which are responsible for clinical expression in relation with their nature, amount and biological activity, some of these tumours being non-functioning or silent. Moreover these tumours have some characteristics related to neuroendocrine differentiation, which provide tumour markers in addition to hormonal markers, such as chromogranin. A which is of special interest in non-functioning tumours. Pancreatic tumours are the most frequently recognized tumours in systematic screening procedures performed in MEN 1 patients. They are multi-secreting and multifocal, and they exhibit a loss of heterozygosity in the 11q13 locus. Growth factors such as IGF-1 and PDGF and their specific receptors are expressed in GEP tumours but their role in tumour growth remains to be determined. Somatostatin receptors are present on most endocrine digestive tumours, conditioning the therapeutic effects of somatostatin analogues that reduce hormonal tumoral production and alleviate the related symptoms. In addition, in vivo visualization of somatostatin receptor positive tumours by scintigraphy using radiolabelled somatostatin analogues is of clinical interest. (author)

Comparison of mRNA, Protein, and Urinary Nucleic Acid Levels of S100A8 and S100A9 between Prostate Cancer and BPH.

Science.gov (United States)

Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kang, Ho Won; Kim, Ye-Hwan; Kim, Eun-Ah; Lee, Ok-Jun; Kim, Won Tae; Moon, Sung-Kwon; Kim, Isaac Yi; Choi, Yung-Hyun; Kim, Wun-Jae

2015-07-01

Infections and inflammation in the prostate play a critical role in carcinogenesis, and S100A8 and S100A9 are key mediators in acute and chronic inflammation. Therefore, we investigated the differences of S100A8/A9 expression between prostate cancer (CaP) and benign prostatic hyperplasia (BPH) tissues, and we evaluated the possibilities of urinary nucleic acids of S100A8/A9 as diagnostic and prognostic markers. Tissues from 132 CaP patients who underwent prostatectomy or transurethral resection and 90 BPH patients who underwent transurethral prostatectomy were assessed.sd In addition, S100A8 and S100A9 nucleic acid levels were measured in the urine of 283 CaP patients and 363 BPH controls. S100A8 and S100A9 mRNA levels were lower in CaP than BPH tissues (P BPH tissues stained more strongly for both S100A8 and S100A9 than CaP tissues (P BPH (P = 0.001 and BPH. Both were more highly expressed in patients with aggressive disease and shorter biochemical recurrence-free time. S100A8/A9 urinary cell-free nucleic acid levels correlated positively with expression levels obtained from tissue staining. Therefore, S100A8/A9 measurement in tissues and urine may have diagnostic and prognostic value in CaP.

The biomarkers neuron-specific enolase and S100b measured the day following admission for severe accidental hypothermia have high predictive values for poor outcome

DEFF Research Database (Denmark)

Wiberg, Sebastian; Kjaergaard, Jesper; Kjærgaard, Benedict

2017-01-01

was analyzed for NSE and S100b. Follow-up was conducted after 30days and poor neurologic outcome was defined as a Cerebral Performance Category (CPC) score of 3-5. The predictive value of NSE and S100b was assessed as the area under the receiver-operating characteristics curve (AUC). RESULTS: A total of 34......AIM: The aim of the present study was to assess the ability of the biomarkers neuron-specific enolase (NSE) and S100 calcium-binding protein b (S100b) to predict mortality and poor neurologic outcome after 30days in patients admitted with severe accidental hypothermia. METHODS: Consecutive patients...... in 30 unconscious and/or sedated patients. NSE and S100b achieved AUCs of 0.93 and 0.88, respectively, for prediction of 30day mortality and AUCs of 0.88 and 0.87, respectively, for prediction of poor neurologic outcome. CONCLUSIONS: In patients remaining unconscious the day following admission...

VEGF(121)b, a new member of the VEGF(xxx)b family of VEGF-A splice isoforms, inhibits neovascularisation and tumour growth in vivo.

Science.gov (United States)

Rennel, E S; Varey, A H R; Churchill, A J; Wheatley, E R; Stewart, L; Mather, S; Bates, D O; Harper, S J

2009-10-06

The key mediator of new vessel formation in cancer and other diseases is VEGF-A. VEGF-A exists as alternatively spliced isoforms - the pro-angiogenic VEGF(xxx) family generated by exon 8 proximal splicing, and a sister family, termed VEGF(xxx)b, exemplified by VEGF(165)b, generated by distal splicing of exon 8. However, it is unknown whether this anti-angiogenic property of VEGF(165)b is a general property of the VEGF(xxx)b family of isoforms. The mRNA and protein expression of VEGF(121)b was studied in human tissue. The effect of VEGF(121)b was analysed by saturation binding to VEGF receptors, endothelial migration, apoptosis, xenograft tumour growth, pre-retinal neovascularisation and imaging of biodistribution in tumour-bearing mice with radioactive VEGF(121)b. The existence of VEGF(121)b was confirmed in normal human tissues. VEGF(121)b binds both VEGF receptors with similar affinity as other VEGF isoforms, but inhibits endothelial cell migration and is cytoprotective to endothelial cells through VEGFR-2 activation. Administration of VEGF(121)b normalised retinal vasculature by reducing both angiogenesis and ischaemia. VEGF(121)b reduced the growth of xenografted human colon tumours in association with reduced microvascular density, and an intravenous bolus of VEGF(121)b is taken up into colon tumour xenografts. Here we identify a second member of the family, VEGF(121)b, with similar properties to those of VEGF(165)b, and underline the importance of the six amino acids of exon 8b in the anti-angiogenic activity of the VEGF(xxx)b isoforms.

Detection of S-gene 'a' determinant variants in hepatitis B patients with both positive HBsAg and HBsAb markers

International Nuclear Information System (INIS)

Wu Yueping; Ling Yongwu; Huang Songping; Wang Shipeng; Chen Yufeng; Mao Liping; Lu Jianrong

2005-01-01

Objective: To explore the S-gene 'a' determinant variants in hepatitis B patients with both positive HBsAg and HBsAb markers and the effect on the antigenicity of HBsAg. Methods: Quantitative determination of HBV - DNA with competent PCR microfluidic chit method was performed in eight sera specimens from seven hepatitis B patients with both positive HBsAg and HBsAb markers. HBV S-gene was amplified with nested PCR, the PCR product was directly examined for any sequence variant of the amino acids. HBV markers were tested with the very sensitive ELISA/MEIA method in these seven patients. The above rests were also performed in 15 children after failed immunization with hepatitis B vaccine and 9 recipients of liver transplantation for terminal hepatitis B treated with HBIG and lamivudine, serving as controls. Results: The HBsAb contents in the seven patients were all below 80 mIu/ml. Two of the patients with positive HBV-DNA showed no 'a' determinant variant. Two of the four HBV-DNA negative patients demonstrated amino-acid variants (126, 131). One patients who was originally HBV-DNA positive but later turned negative after treatment with interferon and lamivudine demonstrated variant (126). In the 9 patients after successful liver transplantation, the HBsAb contents were all about 150mIu/ml with negative HBV-DNA and no variant. In the 15 immunization failures, HBV-DNA was positive in 14 of them, with 2 cases of variant at 145, 1 case at 126 and 1 case at 134. Conclusion: In some patients with chronic B hepatitis with both positive HBsAg and HBsAb markers, as well as in some vaccine immunization failures, there were 'a' determinant variants, which might alter the antigenicity of HBsAg with escape from the neutralization of low HBsAb. The 'a' determinant variant might also affect the replication of the virus. In this study, no variant was shown in patients after successful liver transplantation. However, the number of patients was too small and the result was of no

Mathematical modeling of liver metastases tumour growth and control with radiotherapy

International Nuclear Information System (INIS)

Campbell, Adrienne; Sivakumaran, Thiru; Wong, Eugene; Davidson, Melanie; Lock, Michael

2008-01-01

Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumour sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian-Exponential growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof of concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.52% per day; the fractional radiation cell kill for the prescribed dose (60 Gy in 15 fractions) was 42% per day, and the tumour repopulation rate was 2.9% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

Science.gov (United States)

Smina, T P; Mathew, J; Janardhanan, K K

2016-04-30

G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities.

Role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes via TLR4/ROS/NF-κB pathway.

Science.gov (United States)

Yu, Jiangkun; Lu, Yanyu; Li, Yapeng; Xiao, Lili; Xing, Yu; Li, Yanshen; Wu, Leiming

2015-09-01

S100A1 plays a crucial role in hypoxia-induced inflammatory response in cardiomyocytes. However, the role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes is still unknown. enzyme-linked immunosorbent assay (ELISA) was performed for the determination of inflammatory cytokines. Immunocytochemistry and immunofluorescence, Western blot analysis and Real-time polymerase chain reaction (RT-PCR) were conducted to assess protein or mRNA expressions. Fluorogenic probe dihydroethidium (DHE) was used to evaluate the generation of reactive oxygen species (ROS) while Hoechst 33342 staining for apoptosis. Small interfering RNA (siRNA) for S100A1 was used to evaluate the role of S100A1. The levels of ROS and inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-8 in H9c2 cells were increased remarkably by hypoxia. However, IL-37 protein or mRNA levels were decreased significantly. Both Toll-like receptor 4 (TLR4) inhibitor Ethyl (6R)-6-[N-(2-Chloro-4fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242) treatment or siRNA S100A1 downregulated TLR4 expression and inflammatory cytokine level and mRNA in H9c2 cells, as well as weakening ROS and phospho-p65 Nuclear factor (NF)-κB levels. Further, S100A1 treatment significantly reduced TNF-α protein or mRNA level whereas enhanced IL-37 protein or mRNA level, and could attenuate ROS and phospho-p65 NF-κB levels. Our results demonstrate that S100A1 can regulate the inflammatory response and oxidative stress in H9C2 cells via TLR4/ROS/NF-κB pathway. These findings provide an interesting strategy for protecting cardiomyocytes from hypoxia-induced inflammatory response. © 2015 Royal Pharmaceutical Society.

Alpha particles induce expression of immunogenic markers on tumour cells

International Nuclear Information System (INIS)

Gorin, J.B.; Gouard, S.; Cherel, M.; Davodeau, F.; Gaschet, J.; Morgenstern, A.; Bruchertseifer, F.

2013-01-01

The full text of the publication follows. Radioimmunotherapy (RIT) is an approach aiming at targeting the radioelements to tumours, usually through the use of antibodies specific for tumour antigens. The radiations emitted by the radioelements then induce direct killing of the targeted cells as well as indirect killing through bystander effect. Interestingly, it has been shown that ionizing radiations, in some settings of external radiotherapy, can foster an immune response directed against tumour cells. Our research team is dedicated to the development of alpha RIT, i.e RIT using alpha particle emitters, we therefore decided to study the effects of such particles on tumour cells in regards to their immunogenicity. First, we studied the effects of bismuth 213, an alpha emitter, on cellular death and autophagy in six different tumour cell lines. Then, we measured the expression of 'danger' signals and MHC molecules at the cell surface to determine whether irradiation with 213 Bi could cause the tumour cells to be recognized by the immune system. Finally a co-culture of dendritic cells with irradiated tumour cells was performed to test whether it would induce dendritic cells to mature. No apoptosis was detected within 48 hours after irradiation in any cell line, however half of them exhibited signs of autophagy. No increase in membrane expression of 'danger' signals was observed after treatment with 213 Bi, but we showed an increase in expression of MHC class I and II for some cell lines. Moreover, the co-culture experiment indicated that the immunogenicity of a human adenocarcinoma cell line (LS 174T) was enhanced in vitro after irradiation with alpha rays. These preliminary data suggest that alpha particles could be of interest in raising an immune response associated to RIT. (authors)

Dose estimation in B16 tumour bearing mice for future irradiation in the thermal column of the TRIGA reactor after B/Gd/LDL adduct infusion

Energy Technology Data Exchange (ETDEWEB)

Protti, N., E-mail: nicoletta.protti@pv.infn.it [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Ballarini, F.; Bortolussi, S. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bruschi, P. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy); Stella, S. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Geninatti, S.; Alberti, D.; Aime, S. [University of Torino, Chemistry Department, via Nizza 52, 10126 Torino (Italy); Altieri, S. [University of Pavia, Department of Nuclear and Theoretical Physics, via Bassi 6, 27100 Pavia (Italy)] [National Institute of Nuclear Physics (INFN) Section of Pavia, via Bassi 6, 27100 Pavia (Italy)

2011-12-15

To test the efficacy of a new {sup 10}B-vector compound, the B/Gd/LDL adduct synthesised at Torino University, in vivo irradiations of murine tumours are in progress at the TRIGA Mark II reactor of the Pavia University. A localised B16 melanoma tumour is generated in C57BL/6 mice and subsequently infused with the adduct. During the irradiation, the mouse will be put in a shield to protect the whole body except the tumour in the back-neck area. To optimise the treatment set-up, MCNP simulations were performed. A very simplified mouse model was built using MCNP geometry capabilities, as well as the geometry of the shield made of 99% {sup 10}B enriched boric acid. A hole in the shield is foreseen in correspondence of the back-neck region. Many configurations of the shield were tested in terms of neutron flux, dose distribution and mean induced activity in the tumour region and in the radiosensitive organs of the mouse. In the final set-up, up to five mice can be treated simultaneously in the reactor thermal column and the neutron fluence in the tumour region for 10 min of irradiation is of about 5 Multiplication-Sign 10{sup 12} cm{sup -2}.

S100 calcium binding protein B as a biomarker of delirium duration in the intensive care unit – an exploratory analysis

Directory of Open Access Journals (Sweden)

Khan BA

2013-12-01

Full Text Available Babar A Khan,1–3 Mark O Farber,1 Noll Campbell,2–5 Anthony Perkins,2,3 Nagendra K Prasad,6 Siu L Hui,1–3 Douglas K Miller,1–3 Enrique Calvo-Ayala,1 John D Buckley,1 Ruxandra Ionescu,1 Anantha Shekhar,1 E Wesley Ely,7,8 Malaz A Boustani1–3 1Indiana University School of Medicine, 2Indiana University Center for Aging Research, 3Regenstrief Institute, Inc., 4Wishard Health Services, Indianapolis, 5Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, 6Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, 7Vanderbilt University School of Medicine, 8VA Tennessee Valley Geriatric Research Education Clinical Center (GRECC, Nashville, TN, USA Background: Currently, there are no valid and reliable biomarkers to identify delirious patients predisposed to longer delirium duration. We investigated the hypothesis that elevated S100 calcium binding protein B (S100β levels will be associated with longer delirium duration in critically ill patients. Methods: A prospective observational cohort study was performed in the medical, surgical, and progressive intensive care units (ICUs of a tertiary care, university affiliated, and urban hospital. Sixty-three delirious patients were selected for the analysis, with two samples of S100β collected on days 1 and 8 of enrollment. The main outcome measure was delirium duration. Using the cutoff of <0.1 ng/mL and $0.1 ng/mL as normal and abnormal levels of S100β, respectively, on day 1 and day 8, four exposure groups were created: Group A, normal S100β levels on day 1 and day 8; Group B, normal S100β level on day 1 and abnormal S100β level on day 8; Group C, abnormal S100β level on day 1 and normal on day 8; and Group D, abnormal S100β levels on both day 1 and day 8. Results: Patients with abnormal levels of S100β showed a trend towards higher delirium duration (P=0.076; Group B (standard deviation (7.0 [3.2] days, Group C (5.5 [6.3] days, and Group D

MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

Science.gov (United States)

Klingenstein, Annemarie; Schaumberger, Markus M; Freeman, William R; Folberg, Robert; Mueller, Arthur J; Schaller, Ulrich C

2016-03-01

To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Newly-derived neuroblastoma cell lines propagated in serum-free media recapitulate the genotype and phenotype of primary neuroblastoma tumours.

Science.gov (United States)

Bate-Eya, Laurel T; Ebus, Marli E; Koster, Jan; den Hartog, Ilona J M; Zwijnenburg, Danny A; Schild, Linda; van der Ploeg, Ida; Dolman, M Emmy M; Caron, Huib N; Versteeg, Rogier; Molenaar, Jan J

2014-02-01

Recently protocols have been devised for the culturing of cell lines from fresh tumours under serum-free conditions in defined neural stem cell medium. These cells, frequently called tumour initiating cells (TICs) closely retained characteristics of the tumours of origin. We report the isolation of eight newly-derived neuroblastoma TICs from six primary neuroblastoma tumours and two bone marrow metastases. The primary tumours from which these TICs were generated have previously been fully typed by whole genome sequencing (WGS). Array comparative genomic hybridisation (aCGH) analysis showed that TIC lines retained essential characteristics of the primary tumours and exhibited typical neuroblastoma chromosomal aberrations such as MYCN amplification, gain of chromosome 17q and deletion of 1p36. Protein analysis showed expression for neuroblastoma markers MYCN, NCAM, CHGA, DBH and TH while haematopoietic markers CD19 and CD11b were absent. We analysed the growth characteristics and confirmed tumour-forming potential using sphere-forming assays, subcutaneous and orthotopic injection of these cells into immune-compromised mice. Affymetrix mRNA expression profiling of TIC line xenografts showed an expression pattern more closely mimicking primary tumours compared to xenografts from classical cell lines. This establishes that these neuroblastoma TICs cultured under serum-free conditions are relevant and useful neuroblastoma tumour models. Copyright © 2013 Elsevier Ltd. All rights reserved.

Correlation of serum S100B protein with depressive episode of bipolar disorder and its prognosis%血清S100B蛋白与双相障碍抑郁发作及其预后的相关性研究

Institute of Scientific and Technical Information of China (English)

张载福; 杨帆; 王卫平; 施波; 赵俊雄; 吕望强; 喻跃国; 贾玉萍; 张晨

2017-01-01

目的·探讨血清S100B蛋白水平与双相障碍抑郁发作及其预后的相关性.方法·根据美国精神病协会《精神障碍诊断与统计手册》第4版(DSM-Ⅳ)诊断标准,入组双相障碍抑郁发作患者80例(病例组)以及健康对照者42名(对照组).病例组患者采用随机数字表法进入碳酸锂联合喹硫平治疗组(喹硫平组)及碳酸锂合并改良无抽搐电休克治疗组(MECT组);治疗前及治疗4周末分别测定2组血清S100B水平并评定汉密尔顿抑郁量表(HAMD).结果·经过4周随访,喹硫平组共完成36例,MECT组完成31例.病例组治疗前血清S100B水平显著高于对照组(P=0.000);治疗后,喹硫平组与MECT组患者血清S100B水平均较治疗前显著下降,HAMD评分均较治疗前显著降低(P=0.000);PearSon相关分析显示病例组治疗前后血清S100B变化水平与HAMD评分变化值呈正相关(r=0.33,P=0.013).结论·S100B可能与双相障碍抑郁发作以及预后有关.%Objective · To explore the correlation of serum S100B protein with depressive episode of bipolar disorder (BD) and its prognosis.Methods· Based on BD criteria of Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-Ⅳ),80 patients with depressive episode of BD (case group) and 42 healthy controls (control group) were enrolled.Patients were randomly assigned into quetiapine group who were treated with lithium and quetiapine and modified electroconvulsive therapy (MECT) group who received lithium and MECT.The serum S100B level and Hamilton Rating Scale for Depression (HAMD) were assayed before and after 4-week treatment.Results· The serum S100B levels before treatment in patients with depressive episode of BD were significantly higher than those in healthy controls (P=0.000).The levels of S100B in both drug and MECT groups decreased after 4-week treatment.The HAMD score after treatment significantly decreased than that before treatment (P=0.000).Pearson correlation analysis

Adaptation to statins restricts human tumour growth in Nude mice

International Nuclear Information System (INIS)

Follet, Julie; Rémy, Lionel; Hesry, Vincent; Simon, Brigitte; Gillet, Danièle; Auvray, Pierrick; Corcos, Laurent; Le Jossic-Corcos, Catherine

2011-01-01

Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice. HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry. L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis. Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years

Correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury

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Bing-Feng Tian

2018-07-01

Full Text Available Objective: To study the correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury. Methods: A total of 110 patients with traumatic brain injury who were treated in our hospital between January 2015 and December 2016 were collected as the observation group, and 60 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. Serum GFAP, S100B and NSE levels as well as oxidative stress index and insulin resistance index levels of two groups of subjects were detected, and Pearson test was used to further evaluate the correlation of serum GFAP, S100B and NSE contents with oxidative stress response and insulin resistance in patients with traumatic brain injury. Results: Serum GFAP, S100B and NSE contents of observation group were significantly higher than those of normal control group; serum oxidative stress indexes MDA, MPO and LPO contents were higher than those of normal control group while SOD and TAC contents were lower than those of normal control group; serum insulin resistance indexes GLU, INS and HOMA-IR levels were higher than those of control group. Pearson test showed that serum GFAP, S100B and NSE contents in patients with traumatic brain injury were directly correlated with post-traumatic oxidative stress and insulin resistance. Conclusion: The serum GFAP, S100B and NSE contents increase in patients with traumatic brain injury, and the increase is directly correlated with the oxidative stress and insulin resistance.

Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood.

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Mesman, Esther; Hillegers, Manon Hj; Ambree, Oliver; Arolt, Volker; Nolen, Willem A; Drexhage, Hemmo A

2015-02-01

There is increasing evidence that both immune and neurochemical alterations are involved in the pathogenesis of bipolar disorder; however, their precise role remains unclear. In this study, we aimed to evaluate neuro-immune changes in a prospective study on children of patients with bipolar disorder. Bipolar offspring, from the prospective Dutch bipolar offspring study (n = 140), were evaluated cross-sectionally within a longitudinal context at adolescence, young adulthood, and adulthood. We examined the expression of 44 inflammation-related genes in monocytes, the cytokines pentraxin 3 (PTX3), chemokine ligand 2 (CCL2), and interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) and S100 calcium binding protein B (S100B) in the serum of bipolar offspring and healthy controls. During adolescence, bipolar offspring showed increased inflammatory gene expression in monocytes, high serum PTX3 levels, but normal CCL2 levels. BDNF levels were decreased, while S100B levels were normal. During young adulthood, monocyte activation remained, although to a lesser degree. Serum PTX3 levels remained high, and signs of monocyte migration became apparent through increased CCL2 levels. BDNF and S100B levels were not measured. At adulthood, circulating monocytes had lost their activation state, but CCL2 levels remained increased. Both BDNF and S100B were now increased. Abnormalities were independent of psychopathology state at all stages. This study suggests an aberrant neuro-immune state in bipolar offspring, which followed a dynamic course from adolescence into adulthood and was present irrespective of lifetime or future mood disorders. We therefore assumed that the aberrant neuro-immune state reflects a general state of vulnerability for mood disorders rather than being of direct predictive value. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1

International Nuclear Information System (INIS)

Williams, Kaye J.; Telfer, Brian A.; Xenaki, Dia; Sheridan, Mary R.; Desbaillets, Isabelle; Peters, Hans J.W.; Honess, Davina; Harris, Adrian L.; Dachs, Gabi U.; Kogel, Albert van der; Stratford, Ian J.

2005-01-01

Background and purpose: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. Patients and methods: Tumours comprising mouse hepatoma cells lacking HIF-1β (and thereby HIF-1 function) were grown in nude mice and radiation-induced growth delay compared with that seen for wild-type tumours and tumours derived from HIF-1β negative cells where HIF-1 function had been restored. Results: The xenografts that lack HIF-1 activity take longer to establish their growth and are more radioresponsive than both parental xenografts and those with restored HIF-1 function. Pre-treatment of the HIF-1 deficient xenografts with the hypoxic radiosensitizer misonidazole, had little effect on radioresponse. In contrast this treatment radiosensitized the parental xenografts. In spite of this, no difference in oxygenation status was found between the tumour types as measured by Eppendorf O 2 -electrodes and by binding of the hypoxic cell marker NITP. Admixing wild type and HIF-1 deficient cells in the same tumour at ratios of 1 in 10 and 1 in 100 restores the growth of the mixed tumours to that of a 100% HIF-1 proficient cell population. However, when comparing the effects of radiation on the mixed tumours, radioresponsiveness is maintained in those tumours containing the high proportion of HIF-1 deficient cells. Conclusions: The differences in radioresponse do not correlate with tumour oxygenation, suggesting that the hypoxic cells within the HIF-1 deficient tumours do not contribute to the outcome of radiotherapy. Thus, hypoxia impacts on tumour radioresponsiveness not simply because of the physio-chemical mechanism of oxygen with radiation-induced radicals causing damage 'fixation', but also because hypoxia/HIF-1 promotes expression of genes that allow tumour cells to survive under these adverse conditions. Further, the results from the cell mixing experiments uncouple the growth

Prognosticating and pharmacological prophylaxis of radiogenic malignant tumours

International Nuclear Information System (INIS)

Muksinova, K.N.; Kirillova, E.N.; Rabinovich, E.I.; Mushkacheva, G.S.; Revina, E.S.; Lemberg, V.K.

1996-01-01

Cancerogenic effect risks due to ionizing radiation, that impacted on large population groups because of Chernobyl and other accidents, cause the actuality of early diagnosis problems and of radiogenic tumour prevention. Since canceroembryonic antigen and α-fetoprotein had been found, the tumour markers began to be frequently used by oncologists. However, attempt to use onco-markers, as test for earlier pre-clinic determination, have been unsuccessful. The secondary messengers of hormonal signal, cyclic nucleotides, that take the leading place in system of organism self-regulation, had attracted our attention. As known, the increase of cell division number and suppression of morphological and biochemical developments of differentiation are the fundamental characteristics of tumour growth and are proceeding together with participating of cyclic nucleotide system. The including of both nucleotides in neoplastic transformation and at the same time their constant presence in extracellular fluid (blood serum, urine) makes the perspective use of these compounds as indicators of tumour growth before the appearance of clinic signs of diseases. This coincides with the modern viewpoints on the developments of optimum programs for pre-clinic diagnosing of tumours, that needs to base on the change in homeostasis preceded the malignant tumour development. (author)

History of 100-B Area

International Nuclear Information System (INIS)

Wahlen, R.K.

1989-10-01

The initial three production reactors and their support facilities were designated as the 100-B, 100-D, and 100-F areas. In subsequent years, six additional plutonium-producing reactors were constructed and operated at the Hanford Site. Among them was one dual-purpose reactor (100-N) designed to supply steam for the production of electricity as a by-product. Figure 1 pinpoints the location of each of the nine Hanford Site reactors along the Columbia River. This report documents a brief description of the 105-B reactor, support facilities, and significant events that are considered to be of historical interest. 21 figs

Detection of viral hepatitis B markers by radioimmunoassay in medical personnel. Vyyavlenie markerov virusnogo gepatita B u meditsinskogo personala radioimmunologicheskim metodom

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Marievskij, V F; Lejbenzon, A S

1990-10-01

Results of revealing B markers of viral hepatitis (VHB) in medical personnel in the city of Zaporozhe by radioimmunoassay method are presented. By the frequency of revealing two markers (HB {sub s}Ag and anti-HB{sub s}) risk groups are indicated depending on the profession, age (length of service) of medical personnel.

Histopathological features of breast tumours in BRCA1, BRCA2 and mutation-negative breast cancer families

International Nuclear Information System (INIS)

Eerola, Hannaleena; Heikkilä, Päivi; Tamminen, Anitta; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli

2005-01-01

Histopathological features of BRCA1 and BRCA2 tumours have previously been characterised and compared with unselected breast tumours; however, familial non-BRCA1/2 tumours are less well known. The aim of this study was to characterise familial non-BRCA1/2 tumours and to evaluate routine immunohistochemical and pathological markers that could help us to further distinguish families carrying BRCA1/2 mutations from other breast cancer families. Breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2 and 74 non-BRCA1/2 families were studied on a tumour tissue microarray. Immunohistochemical staining of oestrogen receptor (ER), progesterone receptor (PgR) and p53 as well as the histology and grade of these three groups were compared with each other and with the respective information on 862 unselected control patients from the archives of the Pathology Department of Helsinki University Central Hospital. Immunohistochemical staining of erbB2 was also performed among familial cases. BRCA1-associated cancers were diagnosed younger and were more ER-negative and PgR-negative, p53-positive and of higher grade than the other tumours. However, in multivariate analysis the independent factors compared with non-BRCA1/2 tumours were age, grade and PgR negativity. BRCA2 cases did not have such distinctive features compared with non-BRCA1/2 tumours or with unselected control tumours. Familial cases without BRCA1/2 mutations had tumours of lower grade than the other groups. BRCA1 families differed from mutation-negative families by age, grade and PgR status, whereas ER status was not an independent marker

Biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*.

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Massaro, An N; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B; Glass, Penny

2014-09-01

To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy. Prospective longitudinal cohort study. A level IV neonatal ICU in a freestanding children's hospital. Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period. Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia. Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia.

Electroacupuncture Attenuates CFA-induced Inflammatory Pain by suppressing Nav1.8 through S100B, TRPV1, Opioid, and Adenosine Pathways in Mice.

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Liao, Hsien-Yin; Hsieh, Ching-Liang; Huang, Chun-Ping; Lin, Yi-Wen

2017-02-13

Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund's adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion. The expression of the astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, receptor for advanced glycation end-products (RAGE), TRPV1, and other related molecules was dramatically increased in the dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) of CFA-treated mice. This effect was reversed by EA and TRPV1 gene deletion. In addition, endomorphin (EM) and N 6 -cyclopentyladenosine (CPA) administration reliably reduced mechanical and thermal hyperalgesia, thereby suggesting the involvement of opioid and adenosine receptors. Furthermore, blocking of opioid and adenosine A1 receptors reversed the analgesic effects of EA. Our study illustrates the substantial therapeutic effects of EA against inflammatory pain and provides a novel and detailed mechanism underlying EA-mediated analgesia via neuronal and non-neuronal pathways.

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study

Science.gov (United States)

2011-01-01

Background To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD. Methods The study included 127 patients with autopsy-confirmed sCJD (prevalence = 12.7%) and 873 with probable non-CJD diagnoses. Standard statistical measures of diagnostic accuracy were employed, including sensitivity (Se), specificity (Sp), predictive values (PVs), likelihood ratios (LRs), and Receiver Operating Characteristic (ROC) analysis. Results At optimal cutoff thresholds (empirically selected for 14-3-3, assayed by immunoblot; 976 pg/mL for tau and 2.5 ng/mL for S100B, both assayed by ELISA), Se and Sp respectively were 0.88 (95% CI, 0.81-0.93) and 0.72 (0.69-0.75) for 14-3-3; 0.91 (0.84-0.95) and 0.88 (0.85-0.90) for tau; and 0.87 (0.80-0.92) and 0.87 (0.84-0.89) for S100B. The observed differences in Sp between 14-3-3 and either of the other 2 markers were statistically significant. Positive LRs were 3.1 (2.8-3.6) for 14-3-3; 7.4 (6.9-7.8) for tau; and 6.6 (6.1-7.1) for S100B. Negative LRs were 0.16 (0.10-0.26) for 14-3-3; 0.10 (0.06-0.20) for tau; and 0.15 (0.09-0.20) for S100B. Estimates of areas under ROC curves were 0.947 (0.931-0.961) for tau and 0.908 (0.888-0.926) for S100B. Use of interval LRs (iLRs) significantly enhanced accuracy for patient subsets [e.g., 41/120 (34.2%) of tested sCJD patients displayed tau levels > 10,000 pg/mL, with an iLR of 56.4 (22.8-140.0)], as did combining tau and S100B [e.g., for tau > 976 pg/mL and S100B > 2.5 ng/mL, positive LR = 18.0 (12.9-25.0) and negative LR = 0.02 (0.01-0.09)]. Conclusions CSF 14-3-3, tau and S100B proteins are useful diagnostic markers of sCJD even in a low

Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

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Rodríguez, F; Castro, P; Ramírez, G A

2016-05-01

A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum S-100β protein as a biomarker for brain damage in patients with encephalopathy

International Nuclear Information System (INIS)

Takeda, Munekazu; Yaguchi, Arino; Yamada, Sou; Nagai, Atsushi; Yuzawa, Junji

2008-01-01

Cerebrospinal fluid concentrations of S-100β protein, an acidic calcium-binding protein found in astrocytes and Schwann cells, increase after central nervous system damage. Serum S-100β protein, thus, has been expected to be a biochemical marker of brain cell damage. Several reports show a relation between severity of head injury and serum S-100β protein levels, although, there are still not significant advances in the study of S-100β regarding the prediction of the clinical outcome in brain diseases. The objective of the present study was to verify S-100β as a marker for the clinical outcome in patients with encephalopathy. Serum S-100β protein concentrations (pg/ml) were measured daily using enzyme-linked immunosorbent assay (ELISA) until discharge from the intensive care unit (ICU) in 82 patients (54 men, 28 women; age 20-93 years [mean 61.0±19.2]) with moderate or severe encephalopathy. There were 50 survivors and 32 non-survivors. S-100β levels were significantly lower in survivors (240.2 pg/ml) than in non-survivors (1,594.8 pg/ml) from day 1 until ICU discharge. The electroencephalogram (EEG) and computed tomography (CT) abnormalities were correlated with S-100β levels. The optimal cut-off value at 451.2 pg/ml calculated from receiver operating characteristic (ROC) curve analysis showed the sensitivity of 80.2% and specificity of 78.1% for ICU mortality. Our results indicate that serum S-100β protein could be a useful biomarker to assess brain damage and predict prognosis in patients with encephalopathy. (author)

Investigating the effect of longitudinal micro-CT imaging on tumour growth in mice

International Nuclear Information System (INIS)

Foster, W Kyle; Ford, Nancy L

2011-01-01

The aim of this study is to determine the impact of longitudinal micro-CT imaging on the growth of B16F1 tumours in C57BL/6 mice. Sixty mice received 2 x 10 5 B16F1 cells subcutaneously in the hind flank and were divided into control (no scan), 'low-dose' (80 kVp, 70 mA, 8 s, 0.07 Gy), 'medium-dose' (80 kVp, 50 mA, 30 s, 0.18 Gy) and 'high-dose' (80 kVp, 50 mA, 50 s, 0.30 Gy) groups. All imaging was performed on a fast volumetric micro-CT scanner (GE Locus Ultra, London, Canada). Each mouse was imaged on days 4, 8, 12 and 16. After the final imaging session, each tumour was excised, weighed on an electronic balance, imaged to obtain the final tumour volume and processed for histology. Final tumour volume was used to evaluate the impact of longitudinal micro-CT imaging on the tumour growth. An ANOVA indicated no statistically significant difference in tumour volume (p = 0.331, α = β = 0.1) when discriminating against a treatment-sized effect. Histological samples revealed no observable differences in apoptosis or cell proliferation. We conclude that four imaging sessions, using standard protocols, over the course of 16 days did not cause significant changes in final tumour volume for B16F1 tumours in female C57BL/6 mice (ANOVA, α = β = 0.1, p = 0.331).

Role of S100A12 in the pathogenesis of osteoarthritis

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Nakashima, Motoshige [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Sakai, Tadahiro, E-mail: tadsakai@med.nagoya-u.ac.jp [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Hiraiwa, Hideki; Hamada, Takashi; Omachi, Takaaki [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Ono, Yohei [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd., Greenville, NC 27834 (United States); Inukai, Norio [Department of Orthopaedic Surgery, Nishio Municipal Hospital, 6 Kumami-cho, Nishio 445-8510 (Japan); Ishizuka, Shinya; Matsukawa, Tetsuya; Oda, Tomoyuki; Takamatsu, Akira; Yamashita, Satoshi; Ishiguro, Naoki [Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan)

2012-06-08

Highlights: Black-Right-Pointing-Pointer This is the first report of S100A12 expression in human OA articular cartilages. Black-Right-Pointing-Pointer Exogenous S100A12 increased the production of MMP13 and VEGF in OA chondrocytes. Black-Right-Pointing-Pointer Soluble RAGE suppressed the increased production of MMP13 and VEGF. Black-Right-Pointing-Pointer p38MAPK and NF-{kappa}B inhibitors abrogated S100A12-induced MMP13 and VEGF production. Black-Right-Pointing-Pointer S100A12 may contribute to OA progression by increasing MMP13 and VEGF production. -- Abstract: S100A12 is a member of the S100 protein family, which are intracellular calcium-binding proteins. Although there are many reports on the involvement of S100A12 in inflammatory diseases, its presence in osteoarthritic cartilage has not been reported. The purpose of this study was to investigate the expression of S100A12 in human articular cartilage in osteoarthritis (OA) and to evaluate the role of S100A12 in human OA chondrocytes. We analyzed S100A12 expression by immunohistochemical staining of cartilage samples obtained from OA and non-OA patients. In addition, chondrocytes were isolated from knee cartilage of OA patients and treated with recombinant human S100A12. Real-time RT-PCR was performed to analyze mRNA expression. Protein production of matrix metalloproteinase 13 (MMP-13) and vascular endothelial growth factor (VEGF) in the culture medium were measured by ELISA. Immunohistochemical analyses revealed that S100A12 expression was markedly increased in OA cartilages. Protein production and mRNA expression of MMP-13 and VEGF in cultured OA chondrocytes were significantly increased by treatment with exogenous S100A12. These increases in mRNA expression and protein production were suppressed by administration of soluble receptor for advanced glycation end products (RAGE). Both p38 mitogen-activated protein kinase (MAPK) and nuclear factor-{kappa}B (NF-{kappa}B) inhibitors also suppressed the increases

PREVALENCE OF HEPATITIS B VIRUS MARKERS IN SURGEONS ...

African Journals Online (AJOL)

hi-tech

Objective: To determine the prevalence of hepatitis B virus (HBV) markers in surgeons in a major city in Nigeria. ... Interventions: Blood samples were taken from subjects and analysed for hepatitis B virus markers ( HBsAg, antiHBs and .... Lagos was comparable to those of Romieu et al (10) who found HBsAg seropositivity ...

A FIVE-YEAR HISTOPATHOLOGICAL REVIEW OF CNS TUMOURS IN A TERTIARY CENTRE WITH EMPHASIS ON DIAGNOSTIC ASPECTS OF UNCOMMON TUMOURS

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Premalatha Pidakala

2016-06-01

Full Text Available BACKGROUND Tumours of central nervous system (CNS are of varied histogenesis and show divergent lines of differentiation and morphological features. These tumours show specific predilection for age and sex groups, more commonly than of tumours of other systems. Though tumours of glial tissue are more common, other tumours of neural, ependymal and meningeal origin are not uncommon. Metastatic disease is the common encounter in elderly. Tumour diagnosis is not always straight forward as many non-neoplastic lesions and reactive proliferations mimic tumours. Immunohistochemistry may help in problematic cases and thus can be used as an adjuvant tool in the diagnosis of such cases in addition to the routine histopathological staining methods. An accurate histological diagnosis is of extreme importance in these sites as exact diagnosis helps in proper management and favourable clinical outcome. MATERIAL & METHODS This study is on a retrospective and prospective basis in our institution from January 2011 to January, 2016. Our institute is a tertiary care center attached to a medical college catering to the needs of a rural based population. During this period, a total of 717 central nervous system tumour specimens were received and diagnosed based on examination of Haematoxylin and Eosin stained sections of formalin fixed and paraffin embedded specimens. Immunohistochemical markers (IHC were applied in selective cases for an accurate diagnosis and a number of rare cases were diagnosed based on morphology and IHC marker studies. RESULTS Age and sex incidence and anatomic distribution of various tumours were studied. In adults, meningiomas occurred most frequently in the present study followed by nerve sheath tumours, astrocytomas, metastatic deposits, glioblastomas and pituitary adenomas. Embryonal tumours occurred frequently in children. Other rare tumours identified are amyloidogenic pituitary adenoma, central neurocytoma, glioneuronal tumour with

Histomorphological and immunohistochemical characterization of 172 cutaneous round cell tumours in dogs

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Marina Rios Araújo

2012-08-01

Full Text Available This paper describes the use of a panel of antibodies (CD117, CD3, CD79a, CD45, cytokeratin, vimentin and E-cadherin on formalin-fixed, paraffin-embedded sections of canine cutaneous round cell tumours. Neoplastic tumours were diagnosed by histology and histochemical stains and included 107 mast cell tumours, 31 cutaneous histiocytomas, two localized histiocytic sarcomas, 21 cutaneous lymphomas, three plasma cell tumours, one transmissible venereal tumour and seven unclassified round cell tumours. The histologic diagnosis was modified in 39.5% of the total 172 neoplasms. The staining for CD45 and Ecadherin were variable, and therefore, the final diagnoses of cutaneous histiocytoma and localized histiocytic sarcoma were made based on histology in association with negative results for CD3, CD79a, CD117 and cytokeratin. The cellular origin of unclassified round cell tumours was defined in all cases. Cutaneous B-cell lymphoma and plasma cell tumours were CD79a-positive and could be distinguished from each other by the morphological characteristics. Mast cell tumours and T cell lymphoma were CD117 and CD3 positive, respectively. The positive staining for vimentin and the negative staining for CD3, CD79a, CD117 and cytokeratin favoured the diagnosis of transmissible venereal tumours. Thus, the final diagnosis of cutaneous round cell tumours should be based on the interpretation of immunohistochemical results together with the cellular morphology observed by histology. Therefore, more studies to optimize the specific markers in formalin-fixed, paraffinembedded tissues (especially for histiocytes are required for definitive diagnosis of round cell tumours in dogs.

PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia.

Science.gov (United States)

Banh, Robert S; Iorio, Caterina; Marcotte, Richard; Xu, Yang; Cojocari, Dan; Rahman, Anas Abdel; Pawling, Judy; Zhang, Wei; Sinha, Ankit; Rose, Christopher M; Isasa, Marta; Zhang, Shuang; Wu, Ronald; Virtanen, Carl; Hitomi, Toshiaki; Habu, Toshiyuki; Sidhu, Sachdev S; Koizumi, Akio; Wilkins, Sarah E; Kislinger, Thomas; Gygi, Steven P; Schofield, Christopher J; Dennis, James W; Wouters, Bradly G; Neel, Benjamin G

2016-07-01

Tumours exist in a hypoxic microenvironment and must limit excessive oxygen consumption. Hypoxia-inducible factor (HIF) controls mitochondrial oxygen consumption, but how/if tumours regulate non-mitochondrial oxygen consumption (NMOC) is unknown. Protein-tyrosine phosphatase-1B (PTP1B) is required for Her2/Neu-driven breast cancer (BC) in mice, although the underlying mechanism and human relevance remain unclear. We found that PTP1B-deficient HER2(+) xenografts have increased hypoxia, necrosis and impaired growth. In vitro, PTP1B deficiency sensitizes HER2(+) BC lines to hypoxia by increasing NMOC by α-KG-dependent dioxygenases (α-KGDDs). The moyamoya disease gene product RNF213, an E3 ligase, is negatively regulated by PTP1B in HER2(+) BC cells. RNF213 knockdown reverses the effects of PTP1B deficiency on α-KGDDs, NMOC and hypoxia-induced death of HER2(+) BC cells, and partially restores tumorigenicity. We conclude that PTP1B acts via RNF213 to suppress α-KGDD activity and NMOC. This PTP1B/RNF213/α-KGDD pathway is critical for survival of HER2(+) BC, and possibly other malignancies, in the hypoxic tumour microenvironment.

Radiological diagnosis of Klatskin's tumour; Radiologische Diagnostik von Klatskin-Tumoren

Energy Technology Data Exchange (ETDEWEB)

Pauls, S.; Juchems, M.S.; Brambs, H.-J. [Universitaetsklinikum Ulm (Germany). Abteilung Diagnostische Radiologie

2005-11-01

Patients with Klatskin's tumour present clinically unspecific symptoms such as painless jaundice and cholangitic discomfort. The only curative treatment is R0 resection of the tumour. To allow stage-specific therapy, accurate tumour staging is indispensable, the first step of which is abdominal sonography. If there is a suspect finding, cross-sectional imaging techniques like MRI or MDR-CT are used to clarify or stage the lesion, respectively. To estimate resectability, MRI together with MRC and MRI angiography are superior to MDR-CT. Biopsy using ERC is required before starting any specific treatment. If therapeutically relevant peritoneal carcinosis is clinically suspected although not radiologically confirmed, PET should also be performed. The value of PET/CT has to be evaluated in further studies. For optimal treatment, close cooperation between clinicians and radiologists is necessary. (orig.) [German] Patienten mit Klatskin-Tumoren werden klinisch durch unspezifische Symptome wie z. B. schmerzloser Ikterus oder cholangitische Beschwerden auffaellig. Eine R0-Resektion ist der einzige kurative Therapieansatz. Um eine stadiengerechte Therapie zu ermoeglichen, muss ein moeglichst exaktes Tumorstaging erfolgen. Primaer kommt die abdominelle Sonographie zum Einsatz. Zur Abklaerung eines unklaren Sonographiebefundes sowie zum Staging eines suspizierten Tumors werden Schnittbildverfahren MRT und MDR-CT benoetigt. Zur Beurteilung der lokalen Tumorresektabilitaet ist die MRT in Zusammenschau mit der MRC sowie MR-Angiographie der MDR-CT ueberlegen. Vor Einleitung einer Therapie sollte auf jeden Fall die Verdachtsdiagnose eines Klatskin-Tumors bioptisch mittels ERC gesichert werden. Wird klinisch trotz negativem Nachweis einer Peritonealkarzinose eine solche suspiziert, sollte bei Therapierelevanz (z. B. bei ansonsten fehlendem Nachweis einer Fernmetastasierung) eine PET ergaenzend durchgefuehrt werden. Der zukuenftige Stellenwert der PET/CT muss in weiteren Studien

Interaction between S100P and the anti-allergy drug cromolyn

International Nuclear Information System (INIS)

Penumutchu, Srinivasa R.; Chou, Ruey-Hwang; Yu, Chin

2014-01-01

Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by 1 H- 15 N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex

Investigating the effect of longitudinal micro-CT imaging on tumour growth in mice

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Foster, W Kyle; Ford, Nancy L, E-mail: nlford@ryerson.ca [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada)

2011-01-21

The aim of this study is to determine the impact of longitudinal micro-CT imaging on the growth of B16F1 tumours in C57BL/6 mice. Sixty mice received 2 x 10{sup 5} B16F1 cells subcutaneously in the hind flank and were divided into control (no scan), 'low-dose' (80 kVp, 70 mA, 8 s, 0.07 Gy), 'medium-dose' (80 kVp, 50 mA, 30 s, 0.18 Gy) and 'high-dose' (80 kVp, 50 mA, 50 s, 0.30 Gy) groups. All imaging was performed on a fast volumetric micro-CT scanner (GE Locus Ultra, London, Canada). Each mouse was imaged on days 4, 8, 12 and 16. After the final imaging session, each tumour was excised, weighed on an electronic balance, imaged to obtain the final tumour volume and processed for histology. Final tumour volume was used to evaluate the impact of longitudinal micro-CT imaging on the tumour growth. An ANOVA indicated no statistically significant difference in tumour volume (p = 0.331, {alpha} = {beta} = 0.1) when discriminating against a treatment-sized effect. Histological samples revealed no observable differences in apoptosis or cell proliferation. We conclude that four imaging sessions, using standard protocols, over the course of 16 days did not cause significant changes in final tumour volume for B16F1 tumours in female C57BL/6 mice (ANOVA, {alpha} = {beta} = 0.1, p = 0.331).

S100A10 protein expression is associated with oxaliplatin sensitivity in human colorectal cancer cells

Directory of Open Access Journals (Sweden)

Suzuki Sayo

2011-12-01

Full Text Available Abstract Background Individual responses to oxaliplatin (L-OHP-based chemotherapy remain unpredictable. The objective of our study was to find candidate protein markers for tumor sensitivity to L-OHP from intracellular proteins of human colorectal cancer (CRC cell lines. We performed expression difference mapping (EDM analysis of whole cell lysates from 11 human CRC cell lines with different sensitivities to L-OHP by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS, and identified a candidate protein by liquid chromatography/mass spectrometry ion trap time-of-flight (LCMS-IT-TOF. Results Of the qualified mass peaks obtained by EDM analysis, 41 proteins were differentially expressed in 11 human colorectal cancer cell lines. Among these proteins, the peak intensity of 11.1 kDa protein was strongly correlated with the L-OHP sensitivity (50% inhibitory concentrations (P R2 = 0.80. We identified this protein as Protein S100-A10 (S100A10 by MS/MS ion search using LCMS-IT-TOF. We verified its differential expression and the correlation between S100A10 protein expression levels in drug-untreated CRC cells and their L-OHP sensitivities by Western blot analyses. In addition, S100A10 protein expression levels were not correlated with sensitivity to 5-fluorouracil, suggesting that S100A10 is more specific to L-OHP than to 5-fluorouracil in CRC cells. S100A10 was detected in cell culture supernatant, suggesting secretion out of cells. Conclusions By proteomic approaches including SELDI technology, we have demonstrated that intracellular S100A10 protein expression levels in drug-untreated CRC cells differ according to cell lines and are significantly correlated with sensitivity of CRC cells to L-OHP exposure. Our findings provide a new clue to searching predictive markers of the response to L-OHP, suggesting that S100A10 is expected to be one of the candidate protein markers.

The S100A4 Oncoprotein Promotes Prostate Tumorigenesis in a Transgenic Mouse Model

DEFF Research Database (Denmark)

Siddique, Hifzur R; Adhami, Vaqar M; Parray, Aijaz

2013-01-01

earlier showed that S100A4 expression progressively increases in prostatic tissues with the advancement of prostate cancer (CaP) in TRAMP, an autochthonous mouse model. To study the functional significance of S100A4 in CaP, we generated a heterozygously deleted S100A4 (TRAMP/S100A4(+/-)) genotype...... (intracellular and extracellular) forms. We observed that 1) the growth-promoting effect of S100A4 is due to its activation of NFκB, 2) S100A4-deficient tumors exhibit reduced NFκB activity, 3) S100A4 regulates NFκB through the RAGE receptor, and 4) S100A4 and RAGE co-localize in prostatic tissues of mice......S100A4, a calcium-binding protein, is known for its role in the metastatic spread of tumor cells, a late event of cancer disease. This is the first report showing that S100A4 is not merely a metastatic protein but also an oncoprotein that plays a critical role in the development of tumors. We...

Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome

NARCIS (Netherlands)

Kaiser, T; Langhorst, J; Wittkowski, H; Becker, K; Friedrich, A W; Rueffer, A; Dobos, G J; Roth, J; Foell, D

2007-01-01

OBJECTIVE: S100A12 is a pro-inflammatory protein that is secreted by granulocytes. S100A12 serum levels increase during inflammatory bowel disease (IBD). We performed the first study analysing faecal S100A12 in adults with signs of intestinal inflammation. METHODS: Faecal S100A12 was determined by

Purification and partial characterization of canine S100A12.

Science.gov (United States)

Heilmann, Romy M; Suchodolski, Jan S; Steiner, Jörg M

2010-12-01

Canine S100A12 (cS100A12) is a calcium-binding protein of the S100 superfamily of EF-hand proteins, and its expression is restricted to neutrophils and monocytes. Interaction of S100A12 with the receptor for advanced glycation end products (RAGE) has been suggested to play a central role in inflammation. Moreover, S100A12 has been shown to represent a sensitive and specific marker for gastrointestinal inflammation in humans. Only human, porcine, bovine, and rabbit S100A12 have been purified to date, and an immunoassay for the quantification of S100A12 is available only for humans. Therefore, the aim of this study was to develop a protocol for the purification of S100A12 and to partially characterize this protein in the dog (Canis lupus familiaris) as a prelude to the development of an immunologic method for its detection and quantification in canine serum and fecal specimens. Leukocytes were isolated from canine whole blood by dextran sedimentation, and canine S100A12 was extracted from the cytosol fraction of these cells. Further purification of cS100A12 comprised of ammonium sulfate precipitation, hydrophobic interaction chromatography, and strong cation- and anion-exchange column chromatography. Canine S100A12 was successfully purified from canine whole blood. The relative molecular mass of the protein was estimated at 10,379.5 and isoelectric focusing revealed an isoelectric point of 6.0. The approximate specific absorbance of cS100A12 at 280 nm was determined to be 1.78 for a 1 mg/ml solution. The N-terminal AA sequence of the first 15 residues of cS100A12 was Thr-Lys-Leu-Glu-Asp-His-X-Glu-Gly-Ile-Val-Asp-Val-Phe-His, and revealed 100% identity with the predicted protein sequence available through the canine genome project. Sequence homology for the 14 N-terminal residues identified for cS100A12 with those of feline, bovine, porcine, and human S100A12 was 78.6%. We conclude that canine S100A12 can be successfully purified from canine whole blood using the

Feasibility of magnetic marker localisation for non-palpable breast cancer.

Science.gov (United States)

Schermers, B; van der Hage, J A; Loo, C E; Vrancken Peeters, M T F D; Winter-Warnars, H A O; van Duijnhoven, F; Ten Haken, B; Muller, S H; Ruers, T J M

2017-06-01

Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitization of interferon-γ induced apoptosis in human osteosarcoma cells by extracellular S100A4

International Nuclear Information System (INIS)

Pedersen, Kjetil Boye; Andersen, Kristin; Fodstad, Øystein; Mælandsmo, Gunhild Mari

2004-01-01

S100A4 is a small Ca 2+ -binding protein of the S100 family with metastasis-promoting properties. Recently, secreted S100A4 protein has been shown to possess a number of functions, including induction of angiogenesis, stimulation of cell motility and neurite extension. Cell cultures from two human osteosarcoma cell lines, OHS and its anti-S100A4 ribozyme transfected counterpart II-11b, was treated with IFN-γ and recombinant S100A4 in order to study the sensitizing effects of extracellular S100A4 on IFN-γ mediated apoptosis. Induction of apoptosis was demonstrated by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase and Lamin B. In the present work, we found that the S100A4-expressing human osteosarcoma cell line OHS was more sensitive to IFN-γ-mediated apoptosis than the II-11b cells. S100A4 protein was detected in conditioned medium from OHS cells, but not from II-11b cells, and addition of recombinant S100A4 to the cell medium sensitized II-11b cells to apoptosis induced by IFN-γ. The S100A4/IFN-γ-mediated induction of apoptosis was shown to be independent of caspase activation, but dependent on the formation of reactive oxygen species. Furthermore, addition of extracellular S100A4 was demonstrated to activate nuclear factor-κB (NF-κB). In conclusion, we have shown that S100A4 sensitizes osteosarcoma cells to IFN-γ-mediated induction of apoptosis. Additionally, extracellular S100A4 activates NF-κB, but whether these events are causally related remains unknown

S100A9 interaction with TLR4 promotes tumor growth.

Directory of Open Access Journals (Sweden)

Eva Källberg

Full Text Available By breeding TRAMP mice with S100A9 knock-out (S100A9(-/- animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+ S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+ macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/- and TLR4(-/-, but not in RAGE(-/- animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFβ expression in splenic CD11b(+ cells. Lastly, treatment of mice with a small molecule (ABR-215050 that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.

S100A9 Interaction with TLR4 Promotes Tumor Growth

Science.gov (United States)

Källberg, Eva; Vogl, Thomas; Liberg, David; Olsson, Anders; Björk, Per; Wikström, Pernilla; Bergh, Anders; Roth, Johannes; Ivars, Fredrik; Leanderson, Tomas

2012-01-01

By breeding TRAMP mice with S100A9 knock-out (S100A9−/−) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b+ S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68+ macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9−/− and TLR4−/−, but not in RAGE−/− animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFβ expression in splenic CD11b+ cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies. PMID:22470535

HMB-45 may be a more sensitive maker than S-100 or Melan-A for immunohistochemical diagnosis of primary oral and nasal mucosal melanomas.

Science.gov (United States)

Yu, Chuan-Hang; Chen, Huang-Hsu; Liu, Chia-Ming; Jeng, Yung-Ming; Wang, Jeng-Tzung; Wang, Yi-Ping; Liu, Bu-Yuan; Sun, Andy; Chiang, Chun-Pin

2005-10-01

Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three. This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers. Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 +/- 43%) was significantly lower than that of HMB-45 (83 +/- 28%, P = 0.0065) or of S-100 (79 +/- 33%, P = 0.0237). Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.

Interaction between S100P and the anti-allergy drug cromolyn

Energy Technology Data Exchange (ETDEWEB)

Penumutchu, Srinivasa R. [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chou, Ruey-Hwang [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China)

2014-11-21

Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex.

EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer

Science.gov (United States)

Boye, K; Nesland, J M; Sandstad, B; Haugland Haugen, M; Mælandsmo, G M; Flatmark, K

2012-01-01

Background: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. Methods: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. Results: One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. Conclusion: EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy. PMID:22782346

Neurohypophysis granular cell tumours. Upon neurohypophysis rare tumours; Les tumeurs a cellules granuleuses. Des tumeurs rares de la neurohypophyse

Energy Technology Data Exchange (ETDEWEB)

Barrande, G.; Kujas, M.; Gancel, A.; Turpin, G.; Bruckert, E.; Kuhn, J.M.; Luton, J.P. [Hopital Cochin, 75 - Paris (France)

1995-10-01

Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17 % of unselected adult autopsy cases. There are few reports of para-sellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotrophic micro-adenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyper-prolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intra-sellar and supra-sellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted-images. Trans-sphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GEAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of post operative radiation therapy on postoperative recurrences. (authors). 23 refs., 4 figs., 1 tab.

SOX10-positive cells emerge in the rat pituitary gland during late embryogenesis and start to express S100β.

Science.gov (United States)

Ueharu, Hiroki; Yoshida, Saishu; Kanno, Naoko; Horiguchi, Kotaro; Nishimura, Naoto; Kato, Takako; Kato, Yukio

2018-04-01

In the pituitary gland, S100β-positive cells localize in the neurohypophysis and adenohypophysis but the lineage of the two groups remains obscure. S100β is often observed in many neural crest-derived cell types. Therefore, in this study, we investigate the origin of pituitary S100β-positive cells by immunohistochemistry for SOX10, a potent neural crest cell marker, using S100β-green fluorescence protein-transgenic rats. On embryonic day 21.5, a SOX10-positive cell population, which was also positive for the stem/progenitor cell marker SOX2, emerged in the pituitary stalk and posterior lobe and subsequently expanded to create a rostral-caudal gradient on postnatal day 3 (P3). Thereafter, SOX10-positive cells appeared in the intermediate lobe by P15, localizing to the boundary facing the posterior lobe, the gap between the lobule structures and the marginal cell layer, a pituitary stem/progenitor cell niche. Subsequently, there was an increase in SOX10/S100β double-positive cells; some of these cells in the gap between the lobule structures showed extended cytoplasm containing F-actin, indicating a feature of migration activity. The proportion of SOX10-positive cells in the postnatal anterior lobe was lower than 0.025% but about half of them co-localized with the pituitary-specific progenitor cell marker PROP1. Collectively, the present study identified that one of the lineages of S100β-positive cells is a SOX10-positive one and that SOX10-positive cells express pituitary stem/progenitor cell marker genes.

A study on the association between parvovirus B19 infection, serum tumour necrosis factor and C-reactive protein levels among Nigerian patients with sickle cell anaemia.

Science.gov (United States)

Iwalokun, Bamidele Abiodun; Iwalokun, Senapon Olusola; Hodonu, Semande Olufunmilayo; Aina, Olugbenga Ayoola; Omilabu, Sunday

2012-11-01

Microbial burden involving parvovirus B19 infection has been recognised as a major cause of morbidity and mortality in sickle cell anaemia (SCA) patients. Given the recent reports of parvovirus B19 infection in Nigeria and the role of inflammation in sickle cell crisis, knowledge of the relationship between the two may be essential for deploying appropriate interventions in infected patients. This study determined the serum levels of tumour necrosis factor alpha (TNF-α) and C-reactive protein (CRP) as inflammatory markers in Nigerian SCA patients with and without parvovirus B19 infections. A total of 64 SCA patients aged 5-25 years and 41 age-matched apparently healthy volunteers with haemoglobin genotypes AA or AS were enrolled with consent into the study. Parvovirus B19 infection and serum levels of TNF-α and CRP were determined by the ELISA method. The overall prevalence rate of parvovirus B19 infection in the study subjects was 13.3%. This rate further showed gender variation and negative correlation with age. Significant (p Parvovirus B19 infection was found to elicit greater increases in these inflammatory markers than in infected non-SCA controls. We conclude that parvovirus B19 infection is common in this environment, and that serum TNF-α and CRP are predictors of clinical inflammatory episodes in infected SCA patients.

TU-H-BRA-09: Relationship Between B0 and the Contrast-To-Noise Ratio (CNR) of Tumour to Background for MRI/Radiotherapy Hybrids

Energy Technology Data Exchange (ETDEWEB)

Wachowicz, K; DeZanche, N; Fallone, B [Cross Cancer Institute, Edmonton, Alberta (Canada); University of Alberta, Edmonton, Alberta (Canada); Yip, E [University of Alberta, Edmonton, Alberta (Canada); Volotovskyy, V [Cross Cancer Institute, Edmonton, Alberta (Canada)

2016-06-15

Purpose: To investigate the relationship in MRI between B{sub 0} and the contrast-to-noise ratio (CNR) of various tumour/normal tissue pairs. This study is motivated by the current interest in MRI/radiotherapy hybrids, for which multiple magnetic field strengths have been proposed. CNR is the single most important parameter governing the ability of a system to identify a tumour in real time for treatment guidance. The MRI community has long since recognized that the SNR of a well-designed MR system is roughly proportional to B{sub 0}, the polarizing magnetic field. However, the CNR between two tissues is much more complicated - dependent not only on this signal behavior, but also on the different relaxation properties of the tissues. Methods: Experimentally-based models of B{sub 0}-dependant relaxation for various tumour and normal tissues from the literature were used in conjunction with signal equations for MR sequences suitable for rapid realtime imaging to develop field-dependent predictions for CNR. These CNR models were developed for liver, lung, breast, glioma, and kidney tumours for spoiled-gradient echo (SGE) and balanced steady-state free precession (bSSFP) sequences. Results: In all cases there was an improved CNR at lower fields compared to linear dependency. Further, in some tumour sites, the CNR at lower fields was found to be comparable to, or sometimes higher than those at higher fields (i.e. bSSFP CNR for glioma, kidney and liver tumours). Conclusion: Due to the variation of tissue relaxation parameters with field, lower B{sub 0} fields have been shown to perform as well or better (in terms of CNR) than higher fields for some tumour sites. In other sites this effect was less pronounced. It is the complex relationship between CNR and B{sub 0} that leads to greater CNR at 0.5 T for certain tumour types studied here for fast imaging. B. Gino Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi

Presentation for the first research co-ordination meeting on development of kits for radioimmunometric assays for tumour markers

International Nuclear Information System (INIS)

Liu Yibing

1997-01-01

Radioimmunoassay and Labeled Compound Lab. is the earliest and biggest center which supply RIA reagents in China. It started the research on RIA reagents in the middle of 1970's. Now it can produce more than 80 kinds of RIA kits including thyroid function and newborn screening, tumor markers, kidney function, diabetes-related, fertility and pregnancy monitoring and diagnosis of hepatitis B and C. There are over 1000 hospitals and research organizations using the reagents. Cancer is a disease which endanger human life. There are about 1.6 million new cancer patient and 800 thousand persons died of cancer every year in our country. The laboratory has been paying attention to development of tumor markers RIA reagents since we started the research on RIA reagents. The first kit produced was Rocket Electrophoresis Radioautograph of AFP. In 1980's it developed AFP, CEA, HCG and Ferritin RIA kits. Now RIA reagents for tumor markers have become important part of our products . Besides the products above mentioned it also can produce calcitonin RIA, thyroidglobulin RIA and CA125 IRMA. In early 1990's it established a monoclonal antibody Lab. and this Lab. have been working for the preparation of the monoclonal antibody to tumor markers

Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

Science.gov (United States)

Rofstad, E K; Fenton, B M; Sutherland, R M

1988-05-01

Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen

Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

Science.gov (United States)

Anthony, P P; Ramani, P

1991-01-01

A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver.

Binding of peanut lectin to germinal-centre cells: a marker for B-cell subsets of follicular lymphoma?

OpenAIRE

Rose, M. L.; Habeshaw, J. A.; Kennedy, R.; Sloane, J.; Wiltshaw, E.; Davies, A. J.

1981-01-01

The binding of horseradish-peroxidase-labelled peanut lectin (HRP-PNL) to cryostat sections of tonsil, lymphoma lymph nodes, reactive lymph nodes and miscellaneous tumours demonstrated that PNL binds selectively to lymphocytes in germinal centres. Lymph nodes from 21 patients with non-Hodgkin's lymphomas were phenotyped as cell suspensions for PNL binding, and the following surface markers: E rosetting, C3d, SIg, OK markers of T-cell subsets, Ig heavy-chain and light-chain classes. There was ...

Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux

Directory of Open Access Journals (Sweden)

Mélanie R. Tardif

2015-01-01

Full Text Available S100A8/A9 (calprotectin and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway. Chemotactic agents, cytokines, and particulate molecules were used to stimulate human neutrophils. MSU crystals, PMA, and H2O2 induced the release of S100A8, S100A9, and S100A12 homodimers, as well as S100A8/A9 heterodimer. High concentrations of S100A8/A9 and S100A12 were secreted in response to nanoparticles like MSU, silica, TiO2, fullerene, and single-wall carbon nanotubes as well as in response to microbe-derived molecules, such as zymosan or HKCA. However, neutrophils exposed to the chemotactic factors fMLP failed to secrete S100A8/A9 or S100A12. Secretion of S100A8/A9 was dependent on the production of reactive oxygen species and required K+ exchanges through the ATP-sensitive K+ channel. Altogether, these findings suggest that S100A12 and S100A8/A9 are secreted independently either via distinct mechanisms of secretion or following the activation of different signal transduction pathways.

RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-kB-dependent MMP-2 and bcl-2 pathway.

Science.gov (United States)

Yang, X-C; Wang, X; Luo, L; Dong, D-H; Yu, Q-C; Wang, X-S; Zhao, K

2013-06-01

S100A4 is a well established marker and mediator of metastatic disease, but the exact mechanisms responsible for the metastasis promoting effects are less well defined. We tested a hypothesis that the S100A4 gene plays a role in the proliferation and invasiveness of human renal cancer cells (RCC) and may be associated with its metastatic spread. The small interference RNA vector pcDNA3.1-S100A4 siRNA was transfected in to the human renal cancer cell lines ACHN, Ketr-3, OS-RC-2, CaKi-2 and HTB-47, then treated with ABT-737 or BB94. Cell apoptosis and cell viability was detected by flow cytometry and MTT assay. Matrigel was used for cell motility and invasion assay. MMP-2, bcl-2 and S100A4 was detected by RT-PCR and western blot assay. NF-kB subunit p65 activity was detected by confocal microscopy assay. We then determine the effect S100A4 sliencing on tumor growth, lung metastasis development in vivo. Immunohistochemistry was used to detected the expression of S100A4, bcl-2, MMP-2, p65 and CD31. S100A4 silencing in ACHN cells by RNA interference significantly inhibited NF-kB and NF-kB-mediated MMP-2 and bcl-2 activation and cellular migration, proliferation, and promoted apoptosis. Furthermore, re-expression of S100A4 in S100A4-siRNA-transfected ACHN cells by transient S100A4 cDNA transfection restored the NF-kB and NF-kB-mediated MMP-2 and bcl-2 activation and their high migratory and cellular proliferative ability. An inhibitor ABT-737 (the Bcl-2 antagonist targets Bcl-2) against Bcl-2 suppressed cellular proliferation and promoted apoptosis induced by S100A4 re-expression in S100A4-siRNA-transfected ACHN cells. A inhibitor BB94 against MMPs to neutralize MMP-2 protein suppressed cellular invasion and migration induced by S100A4 re-expression in S100A4-siRNA-transfected ACHN cells. In the prevention model, S100A4 silencing inhibited primary tumor growth by (tumor weight) (76 ± 8%) and (tumor volum) (78 ± 4%) respectively and promoted apoptosis and the formation

Proinflammatory Cytokines, Enolase and S-100 as Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy Following Perinatal Asphyxia in Newborns.

Science.gov (United States)

Chaparro-Huerta, Verónica; Flores-Soto, Mario Eduardo; Merin Sigala, Mario Ernesto; Barrera de León, Juan Carlos; Lemus-Varela, María de Lourdes; Torres-Mendoza, Blanca Miriam de Guadalupe; Beas-Zárate, Carlos

2017-02-01

Estimation of the neurological prognosis of infants suffering from perinatal asphyxia and signs of hypoxic-ischemic encephalopathy is of great clinical importance; however, it remains difficult to satisfactorily assess these signs with current standard medical practices. Prognoses are typically based on data obtained from clinical examinations and neurological tests, such as electroencephalography (EEG) and neuroimaging, but their sensitivities and specificities are far from optimal, and they do not always reliably predict future neurological sequelae. In an attempt to improve prognostic estimates, neurological research envisaged various biochemical markers detectable in the umbilical cord blood of newborns (NB). Few studies examining these biochemical factors in the whole blood of newborns exist. Thus, the aim of this study was to determine the expression and concentrations of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and specific CNS enzymes (S-100 and enolase) in infants with perinatal asphyxia. These data were compared between the affected infants and controls and were related to the degree of HIE to determine their utilities as biochemical markers for early diagnosis and prognosis. The levels of the proinflammatory cytokines and enzymes were measured by enzyme-linked immunosorbent assay (ELISA) and Reverse Transcription polymerase chain reaction (RT-PCR). The expression and serum levels of the proinflammatory cytokines, enolase and S-100 were significantly increased in the children with asphyxia compared with the controls. The role of cytokines after hypoxic-ischemic insult has been determined in studies of transgenic mice that support the use of these molecules as candidate biomarkers. Similarly, S-100 and enolase are considered promising candidates because these markers have been correlated with tissue damage in different experimental models. Copyright © 2016. Published by Elsevier B.V.

Hypoxia Mediated Release of Endothelial Microparticles and Increased Association of S100A12 with Circulating Neutrophils

Directory of Open Access Journals (Sweden)

Rebecca V. Vince

2009-01-01

Full Text Available Microparticles are released from the endothelium under normal homeostatic conditions and have been shown elevated in disease states, most notably those characterised by endothelial dysfunction. The endothelium is sensitive to oxidative stress/status and vascular cell adhesion molecule-1 (VCAM-1 expression is upregulated upon activated endothelium, furthermore the presence of VCAM-1 on microparticles is known. S100A12, a calcium binding protein part of the S100 family, is shown to be present on circulating leukocytes and is thought a sensitive marker to local inflammatory process, which may be driven by oxidative stress. Eight healthy males were subjected to breathing hypoxic air (15% O2, approximately equivalent to 3000 metres altitude for 80 minutes in a temperature controlled laboratory and venous blood samples were processed immediately for VCAM-1 microparticles (VCAM-1 MP and S100A12 association with leukocytes by flow cytometry. A pre-hypoxic blood sample was used for comparison. Both VCAM-1 MP and S100A12 association with neutrophils were significantly elevated post hypoxic breathing later declining to levels observed in the pre-test samples. A similar trend was observed in both cases and a correlation may exist between these two markers in response to hypoxia. These data offer evidence using novel markers of endothelial and circulating blood responses to hypoxia.

Role of diffusion-weighted echo-planar MRI in distinguishing between brain abscess and tumour: a preliminary report

International Nuclear Information System (INIS)

Noguchi, K.; Watanabe, N.; Nagayoshi, T.; Kanazawa, T.; Toyoshima, S.; Shimizu, M.; Seto, H.

1999-01-01

Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in differentiating between brain abscess and tumour. We examined two patients with surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two different b values (20 and 1200 s/mm 2 ). All capsule-stage brain abscesses (4 lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI as markedly high-signal areas of decreased ADC (range, 0.58-0.70 [(10-3 mm 2 /s; mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20-3.20 [(10-3 mm 2 /s; mean, 2.70)]). Solid, contrast-enhancing portions of brain tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of sightly decreased or increased ADC (range, 0.77-1.29 [(10-3 mm 2 /s; mean, 0.94)]). Our preliminary results indicate that DW echo-planar MRI be used for distinguishing between brain abscess and tumour. (orig.) (orig.)

Immunohistochemical demonstration of glial markers in retinoblastomas

DEFF Research Database (Denmark)

Schrøder, H D

1987-01-01

Twenty retinoblastomas were studied immunohistochemically in order to visualize glial cells. In the retina, the glial cells in the ganglion cell layer and the Müller cells were GFAP positive, while only the glial cells of the ganglion cell layer expressed S-100 reactivity. In the tumours S-100/GFAP...... cells reactive for both S-100 and GFAP were demonstrated. The latter findings may represent differentiation in a glial direction in the more mature parts of retinoblastoma....

Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ

DEFF Research Database (Denmark)

Rajpert-De Meyts, E; Kvist, Majbrit; Skakkebaek, N E

1996-01-01

Testicular carcinoma in situ (CIS) is the precursor of germ cell tumours in adults, except for spermatocytic seminoma. The mechanism of the progression from premalignant CIS to invasive and overt tumours is largely unknown. There are currently two main hypotheses: one is that CIS can progress dir...

Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia?

International Nuclear Information System (INIS)

Baudelet, Christine; Ansiaux, Reginald; Jordan, Benedicte F; Havaux, Xavier; Macq, Benoit; Gallez, Bernard

2004-01-01

T2*-weighted gradient-echo magnetic resonance imaging (T2*-weighted GRE MRI) was used to investigate spontaneous fluctuations in tumour vasculature non-invasively. FSa fibrosarcomas, implanted intramuscularly (i.m.) in the legs of mice, were imaged at 4.7 T, over a 30 min or 1 h sampling period. On a voxel-by-voxel basis, time courses of signal intensity were analysed using a power spectrum density (PSD) analysis to isolate voxels for which signal changes did not originate from Gaussian white noise or linear drift. Under baseline conditions, the tumours exhibited spontaneous signal fluctuations showing spatial and temporal heterogeneity over the tumour. Statistically significant fluctuations occurred at frequencies ranging from 1 cycle/3 min to 1 cycle/h. The fluctuations were independent of the scanner instabilities. Two categories of signal fluctuations were reported: (i) true fluctuations (TFV), i.e., sequential signal increase and decrease, and (ii) profound drop in signal intensity with no apparent signal recovery (SDV). No temporal correlation between tumour and contralateral muscle fluctuations was observed. Furthermore, treatments aimed at decreasing perfusion-limited hypoxia, such as carbogen combined with nicotinamide and flunarizine, decreased the incidence of tumour T2*-weighted GRE fluctuations. We also tracked dynamic changes in T2* using multiple GRE imaging. Fluctuations of T2* were observed; however, fluctuation maps using PSD analysis could not be generated reliably. An echo-time dependency of the signal fluctuations was observed, which is typical to physiological noise. Finally, at the end of T2*-weighted GRE MRI acquisition, a dynamic contrast-enhanced MRI was performed to characterize the microenvironment in which tumour signal fluctuations occurred in terms of vessel functionality, vascularity and microvascular permeability. Our data showed that TFV were predominantly located in regions with functional vessels, whereas SDV occurred in regions

Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts

DEFF Research Database (Denmark)

Tamaki, Yodo; Iwanaga, Yoshitaka; Niizuma, Shinichiro

2013-01-01

Metastasis-associated protein, S100A4 is suggested as a marker for fibrosis in several organs. It also modulates DNA binding of p53 and affects its function. However, the functional role of S100A4 in the myocardium has remained unclear. Therefore, we investigated the role of S100A4 and its relati...

Molecular characterization of c-Abl/c-Src kinase inhibitors targeted against murine tumour progenitor cells that express stem cell markers.

Directory of Open Access Journals (Sweden)

Thomas Kruewel

Full Text Available BACKGROUND: The non-receptor tyrosine kinases c-Abl and c-Src are overexpressed in various solid human tumours. Inhibition of their hyperactivity represents a molecular rationale in the combat of cancerous diseases. Here we examined the effects of a new family of pyrazolo [3,4-d] pyrimidines on a panel of 11 different murine lung tumour progenitor cell lines, that express stem cell markers, as well as on the human lung adenocarcinoma cell line A549, the human hepatoma cell line HepG2 and the human colon cancer cell line CaCo2 to obtain insight into the mode of action of these experimental drugs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with the dual kinase inhibitors blocked c-Abl and c-Src kinase activity efficiently in the nanomolar range, induced apoptosis, reduced cell viability and caused cell cycle arrest predominantly at G0/G1 phase while western blot analysis confirmed repressed protein expression of c-Abl and c-Src as well as the interacting partners p38 mitogen activated protein kinase, heterogenous ribonucleoprotein K, cyclin dependent kinase 1 and further proteins that are crucial for tumour progression. Importantly, a significant repression of the epidermal growth factor receptor was observed while whole genome gene expression analysis evidenced regulation of many cell cycle regulated genes as well integrin and focal adhesion kinase (FAK signalling to impact cytoskeleton dynamics, migration, invasion and metastasis. CONCLUSIONS/SIGNIFICANCE: Our experiments and recently published in vivo engraftment studies with various tumour cell lines revealed the dual kinase inhibitors to be efficient in their antitumour activity.

[Markers of angiogenesis in tumor growth].

Science.gov (United States)

Nefedova, N A; Kharlova, O A; Danilova, N V; Malkov, P G; Gaifullin, N M

2016-01-01

Angiogenesis is a process of new blood vessels formation. The role of angiogenesis in growth, invasion and metastasis of malignant tumours is nowdays universally recognized. Though, investigation of mechanisms of blood vessels formation and elaboration methods for assessment of tumour angiogenesis are still up-dated. Another important concern are different aspects of usage of immunohistochemical markers of blood vessels endothelium (CD31 and CD34) for assessment of tumour aggressiveness and prognosis. The problems of malignant lymphangiogenesis are also up-to-date. The focus is on methods of immunohistochemical visualization of forming lymphatic vessels, role of podoplanin, the most reliable marker of lymphatic vessels, in their identification, and formulization of the main criteria for lymphangiogenesis estimation, its correlation with metastatic activity and prognostic potential. Studying of angiogenesis and lymph angiogenesis in malignant tumors is important and challenging direction for researching tumour progression and invention of antiangiogenic therapy.

Radiation Effect on Secondary Cancerization by Tumour Cell Grafts. Take of Irradiated Tumour Cells in Irradiated and Non-Irradiated Animals

Energy Technology Data Exchange (ETDEWEB)

Costachel, O.; Sandru, Gh.; Kitzulescu, I. [Oncological Institute, Bucharest (Romania)

1969-11-15

This study was designed to determine the ability of haemocytoblastoma, SME and Jensen tumours, which had been irradiated in vitro, to take in C{sub 57}BL/6 mice or Wistar rats that were whole-body irradiated at 0.4 kR and 0.6 kR respectively. It was found-that the take of tumour cell grafts irradiated in vitro increased in whole-body irradiated mice and rats but not in non-irradiated ones. When Wistar rats, that had been whole-body irradiated with 0.7 and 0.8 kR 1 - 7 months earlier and survived after treatment, were grafted with Jensen tumour cells irradiated in vitro with 3 kR they were found to develop tumours and lung metastases (in contrast to non-irradiated rats). A cross resistance against non-irradiated Jensen tumour cells was obtained in non- irradiated Wistar rats by grafting irradiated Jensen tumour cells. Chromosomal analysis showed two supplementary giant markers in the Jensen tumour cells that had been irradiated in vitro before grafting. (author)

Low tumour cell content in a lung tumour bank: implications for molecular characterisation.

Science.gov (United States)

Goh, Felicia; Duhig, Edwina E; Clarke, Belinda E; McCaul, Elizabeth; Passmore, Linda; Courtney, Deborah; Windsor, Morgan; Naidoo, Rishendren; Franz, Louise; Parsonson, Kylie; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

2017-10-01

Lung cancer encompasses multiple malignant epithelial tumour types, each with specific targetable, potentially actionable mutations, such that precision management mandates accurate tumour typing. Molecular characterisation studies require high tumour cell content and low necrosis content, yet lung cancers are frequently a heterogeneous mixture of tumour and stromal cells. We hypothesised that there may be systematic differences in tumour cell content according to histological subtype, and that this may have implications for tumour banks as a resource for comprehensive molecular characterisation studies in lung cancer. To investigate this, we estimated tumour cell and necrosis content of 4267 samples resected from 752 primary lung tumour specimens contributed to a lung tissue bank. We found that banked lung cancer samples had low tumour cell content (33%) generally, although it was higher in carcinoids (77.5%) than other lung cancer subtypes. Tumour cells comprise a variable and often small component of banked resected tumour samples, and are accompanied by stromal reaction, inflammation, fibrosis, and normal structures. This has implications for the adequacy of unselected tumour bank samples for diagnostic and molecular investigations, and further research is needed to determine whether tumour cell content has a significant impact on analytical results in studies using tissue from tumour bank resources. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

2016-06-15

To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

Inhibin A and B as markers of menopause

DEFF Research Database (Denmark)

Overlie, Inger; Mørkrid, Lars; Andersson, Anna-Maria

2005-01-01

A more direct and precise hormonal marker of the menopause has been required for some time. The aim of this study was to identify the most accurate marker of the menopause, based on analyses of inhibin A and B, FSH, LH and estradiol (E(2)), among 59 healthy women without hormonal treatment during...

Sialyl Lewis x expression in canine malignant mammary tumours: correlation with clinicopathological features and E-Cadherin expression

International Nuclear Information System (INIS)

Pinho, Salomé S; Matos, Augusto JF; Lopes, Célia; Marcos, Nuno T; Carvalheira, Júlio; Reis, Celso A; Gärtner, Fátima

2007-01-01

Sialyl Lewis x (sLe x ) antigen is a carbohydrate antigen that is considered not only a marker for cancer but also implicated functionally in the malignant behaviour of cancer cells. Overexpression of sLe x is associated with enhanced progression and metastases of many types of cancer including those of the mammary gland. Canine mammary tumours can invade and give rise to metastases via either lymphatic or blood vessels. E-Cadherin is specifically involved in epithelial cell-to-cell adhesion. In cancer, E-Cadherin underexpression is one of the alterations that characterizes the invasive phenotype and is considered an invasion/tumour suppressor gene. Partial or complete loss of E-Cadherin expression correlates with poor prognosis in canine malignant mammary cancer. The aim of this study was to analyse the sLe x expression in canine malignant mammary tumours and to evaluate if the presence of sLe x correlates with the expression of E-Cadherin and with clinicopathological features. Fifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLe x (IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLe x tumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLe x and E-Cadherin. sLe x expression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLe x expression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLe x was reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship. In the present study we demonstrate the importance of sLe x in the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLe x as a prognostic tumour

A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

DEFF Research Database (Denmark)

Fujihara, Masashi; Bartels, Emil; Nielsen, Lars B

2009-01-01

changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear...... transgenic for a human genomic fragment encoding the full length human apoB ("apoB100" mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated......-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop...

Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

International Nuclear Information System (INIS)

Imai, Misa; Muraki, Miho; Takamatsu, Kiyoshi; Saito, Hidekazu; Seiki, Motoharu; Takahashi, Yuji

2008-01-01

Granulosa cell tumours (GCTs) are frequently seen in menopausal women and are relatively indolent. Although the physiological properties of normal granulosa cells have been studied extensively, little is known about the molecular mechanism of GCT progression. Here, we characterise the unique behavioural properties of a granulosa tumour cell line, KGN cells, for the molecular analysis of GCT progression. Population doubling was carried out to examine the proliferation capacity of KGN cells. Moreover, the invasive capacity of these cells was determined using the in vitro invasion assay. The expression level of tumour markers in KGN cells at different passages was then determined by Western blot analysis. Finally, the growth and metastasis of KGN cells injected subcutaneously (s.c.) into nude mice was observed 3 months after injection. During in vitro culture, the advanced passage KGN cells grew 2-fold faster than the early passage cells, as determined by the population doubling assay. Moreover, we found that the advanced passage cells were 2-fold more invasive than the early passage cells. The expression pattern of tumour markers, such as p53, osteopontin, BAX and BAG-1, supported the notion that with passage, KGN cells became more aggressive. Strikingly, KGN cells at both early and advanced passages metastasized to the bowel when injected s.c. into nude mice. In addition, more tumour nodules were formed when the advanced passage cells were implanted. KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo

External radioactive markers for PET data-driven respiratory gating in positron emission tomography.

Science.gov (United States)

Büther, Florian; Ernst, Iris; Hamill, James; Eich, Hans T; Schober, Otmar; Schäfers, Michael; Schäfers, Klaus P

2013-04-01

Respiratory gating is an established approach to overcoming respiration-induced image artefacts in PET. Of special interest in this respect are raw PET data-driven gating methods which do not require additional hardware to acquire respiratory signals during the scan. However, these methods rely heavily on the quality of the acquired PET data (statistical properties, data contrast, etc.). We therefore combined external radioactive markers with data-driven respiratory gating in PET/CT. The feasibility and accuracy of this approach was studied for [(18)F]FDG PET/CT imaging in patients with malignant liver and lung lesions. PET data from 30 patients with abdominal or thoracic [(18)F]FDG-positive lesions (primary tumours or metastases) were included in this prospective study. The patients underwent a 10-min list-mode PET scan with a single bed position following a standard clinical whole-body [(18)F]FDG PET/CT scan. During this scan, one to three radioactive point sources (either (22)Na or (18)F, 50-100 kBq) in a dedicated holder were attached the patient's abdomen. The list mode data acquired were retrospectively analysed for respiratory signals using established data-driven gating approaches and additionally by tracking the motion of the point sources in sinogram space. Gated reconstructions were examined qualitatively, in terms of the amount of respiratory displacement and in respect of changes in local image intensity in the gated images. The presence of the external markers did not affect whole-body PET/CT image quality. Tracking of the markers led to characteristic respiratory curves in all patients. Applying these curves for gated reconstructions resulted in images in which motion was well resolved. Quantitatively, the performance of the external marker-based approach was similar to that of the best intrinsic data-driven methods. Overall, the gain in measured tumour uptake from the nongated to the gated images indicating successful removal of respiratory motion

Image fusion analysis of 99mTc-HYNIC-Tyr3-octreotide SPECT and diagnostic CT using an immobilisation device with external markers in patients with endocrine tumours

International Nuclear Information System (INIS)

Gabriel, Michael; Hausler, Florian; Moncayo, Roy; Decristoforo, Clemens; Virgolini, Irene; Bale, Reto; Kovacs, Peter

2005-01-01

The aim of this study was to assess the value of multimodality imaging using a novel repositioning device with external markers for fusion of single-photon emission computed tomography (SPECT) and computed tomography (CT) images. The additional benefit derived from this methodological approach was analysed in comparison with SPECT and diagnostic CT alone in terms of detection rate, reliability and anatomical assignment of abnormal findings with SPECT. Fifty-three patients (30 males, 23 females) with known or suspected endocrine tumours were studied. Clinical indications for somatostatin receptor (SSTR) scintigraphy (SPECT/CT image fusion) included staging of newly diagnosed tumours (n=14) and detection of unknown primary tumour in the presence of clinical and/or biochemical suspicion of neuroendocrine malignancy (n=20). Follow-up studies after therapy were performed in 19 patients. A mean activity of 400 MBq of 99m Tc-EDDA/HYNIC-Tyr 3 -octreotide was given intravenously. SPECT using a dual-detector scintillation camera and diagnostic multi-detector CT were sequentially performed. To ensure reproducible positioning, patients were fixed in an individualised vacuum mattress with modality-specific external markers for co-registration. SPECT and CT data were initially interpreted separately and the fused images were interpreted jointly in consensus by nuclear medicine and diagnostic radiology physicians. SPECT was true-positive (TP) in 18 patients, true-negative (TN) in 16, false-negative (FN) in ten and false-positive (FP) in nine; CT was TP in 18 patients, TN in 21, FP in ten and FN in four. With image fusion (SPECT and CT), the scan result was TP in 27 patients (50.9%), TN in 25 patients (47.2%) and FN in one patient, this FN result being caused by multiple small liver metastases; sensitivity was 95% and specificity, 100%. The difference between SPECT and SPECT/CT was statistically as significant as the difference between CT and SPECT/CT image fusion (P<0

Initial experience with TPA as a tumour marker in ovarian malignancy

International Nuclear Information System (INIS)

Dalen, A. van; Favier, J.; Eastham, W.N.

1984-01-01

The Tissue Polypeptide Antigen (TPA) and Carcinoembryonic Antigen (CEA) content of serum were estimated in samples taken from 21 patients with malignant ovarian tumours. The patients were followed for variable period ranging from 6 to 22 months and the TPA and CEA levels were estimated after debulking operations and courses of CHAP-5 therapy. The relative success of the operation and/or treatment was reflected in an appropriate alteration of the serum TPA level. CEA levels remained more or less stationary. The serum TPA levels of 13 of the 21 patients, irrespective of the tumour type, differentiation or stage of tumour growth, exhibited a good concordance with the clinical observations at second look operations. The one patient with a disseminated form of adenoacanthoma failed to show an elevation of the TPA levels and 7 patients continue to have a constantly elevated TPA levels but as yet no clinical evidence of recurrent or metastatic disease. (orig.) [de

Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell carcinoma of the bladder can distinguish between residual tumour and post-chemotherapy effect

International Nuclear Information System (INIS)

Donaldson, Stephanie B.; Bonington, Suzanne C.; Kershaw, Lucy E.; Cowan, Richard; Lyons, Jeanette; Elliott, Tony; Carrington, Bernadette M.

2013-01-01

Introduction: Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff). Methods and materials: Twenty-one patients underwent DCE-MRI scans with 2.5 s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T 2 -weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI 80s ) and plasma perfusion (F p ) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Student's t-test. Results: Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI 80s and F p were significantly higher in areas of residual tumour than Tr-Eff (rSI 80s = 2.9 vs 1.7, p < 0.001; F p = 20.7 vs 9.1 ml/100 ml/min, p = 0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI 80s ), 60% and 86% (F p ), and 75% and 100% when combined. Conclusion: DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy

Effect of combined irradiation and EGFR/Erb-B inhibition with BIBW 2992 on proliferation and tumour cure in cell lines and xenografts

International Nuclear Information System (INIS)

Gurtner, Kristin; Ebert, Nadja; Pfitzmann, Dorothee; Eicheler, Wolfgang; Zips, Daniel; Baumann, Michael; Krause, Mechthild

2014-01-01

In previous experiments an enhanced anti-proliterative effect of the EGFR/ErbB tyrosine kinase inhibitor (TKI) BIBW 2992 with single dose irradiation was observed in FaDu tumour xenografts. Aim of the present experiment was to determine if this effect can also be seen in combination with a fractionated radiotherapy. Secondly we investigate the efficacy of BIBW 2992 on local tumour control for UT-SCC-15. Tumour pieces of FaDu, UT-SCC-14, A431, UT-SCC-15 (squamous cell carcinomas) and A7 (glioma) tumour models were transplanted onto the right hind leg of NMRI (nu/nu) nude mice. For evaluation of tumour growth mice were either treated daily orally with BIBW 2992 (30 mg/kg body weight), or carrier up to a final tumour size of 15 mm or with a fractionated radiotherapy (15f/15d, 30 Gy) with simultaneous application of BIBW 2992 or carrier. For local tumour control UT-SCC-15 tumours were treated with a fractionated radiotherapy (30f/6weeks) or received 30f/6 weeks in combination with daily orally BIBW 2992 (22.5 mg/kg b.w.) during RT. A significant effect on tumour growth time was observed in all tumour models for BIBW 2992 application alone. However, substantial intertumoural heterogeneity could be seen. In the UT-SCC-14, UT-SCC-15 and A431 tumour models a total regression of the tumours and no recurrence during treatment time (73 days) were determined where as for the A7 tumour only a slight effect was noticeable. For the combined treatment of fractionated radiotherapy (15f/15d) and BIBW 2992 administration a significant effect on tumour growth time was seen compared to irradiation alone for A7, UT-SCC-15 and A431 (ER 1.2 – 3.7), this advantage could not be demonstrated for FaDu and UT-SCC-14. However, the local tumour control was not altered for the UT-SCC-15 tumour model when adding BIBW 2992 to fractionated irradiation (30f/6weeks). A heterogeneous effect on tumour growth time of BIBW 2992 alone as well as in combination with fractionated irradiation could be

Correlation of plasma B-type natriuretic peptide levels with metabolic risk markers.

Science.gov (United States)

Ahued-Ortega, José Armando; León-García, Plácido Enrique; Hernández-Pérez, Elizabeth

2018-04-17

Natriuretic peptide type B (BNP) is a marker of myocardium injury. This peptide has been associated with metabolic risk markers, although controversy exists in this regard. The aim of the present study was to determine the correlation of plasma BNP levels with metabolic risk parameters. A retrospective, observational study that included 152 patients, who were classified according to their clinical diagnosis as patients with metabolic syndrome. Plasma BNP levels and clinical metabolic parameters were assessed by using Spearmańs rank correlation coefficient. A significant inverse association with weight (r=-.408; p<.0001) and BMI (r=-.443; p<.001) was obtained. While a positive significant association with systolic pressure (r=.324; p<.001) was observed. A significant decrease was found in BNP levels and components of metabolic syndrome. (p<.05). Based on the results from this study, we can conclude that BNP determination could be an adequate metabolic marker. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

Science.gov (United States)

Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

2012-01-01

Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Madhuranthakam, Ananth J. [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Margulis, Vitaly; Cadeddu, Jeffrey A. [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); Brugarolas, James [UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Internal Medicine, Dallas, TX (United States); Kapur, Payal [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Pathology, Dallas, Texas (United States); Pedrosa, Ivan [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States)

2018-01-15

To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K{sup trans}), rate constant (K{sub ep}) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

International Nuclear Information System (INIS)

Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael; Madhuranthakam, Ananth J.; Margulis, Vitaly; Cadeddu, Jeffrey A.; Brugarolas, James; Kapur, Payal; Pedrosa, Ivan

2018-01-01

To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K trans ), rate constant (K ep ) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

MR first pass perfusion of benign and malignant cardiac tumours - significant differences and diagnostic accuracy

International Nuclear Information System (INIS)

Bauner, K.U.; Picciolo, M.; Theisen, D.; Sandner, T.A.; Reiser, M.F.; Huber, A.M.; Sourbron, S.; Schmitz, C.

2012-01-01

To determine the diagnostic value of magnetic resonance (MR) first pass perfusion in the differentiation of benign and malignant cardiac tumours. 24 patients with cardiac tumours (11 malignant, histopathological correlation present in all cases) were examined using MRI. In addition to morphological sequences a saturation-recovery T1w-GRE technique was implemented for tumour perfusion. The maximum relative signal enhancement (RSE[%]) and the slope of the RSE t -curve (slopeRSE[%/s]) of tumour tissue were assessed. A t-test was used to identify significant differences between benign and malignant tumours. Sensitivities and specificities were calculated for detection of malignant lesions and were compared with the sensitivity and specificity based on solely morphological image assessment. The RSE and slopeRSE of malignant cardiac tumours were significantly higher compared with benign lesions (p < 0.001 and p < 0.001). The calculated sensitivities and specificities of RSE and slopeRSE for identification of malignant lesions were 100% and 84.6% and 100% and 92.3%, respectively with cut-off values of 80% and 6%/s. The sensitivity and specificity for identification of malignant lesions on the basis of morphological imaging alone were 90.9% and 69.2%. With first pass perfusion, malignant cardiac masses can be identified with higher sensitivity and specificity compared with morphological image assessment alone. (orig.)

Indicators of inappropriate tumour marker use through the mining of electronic health records.

Science.gov (United States)

Gion, Massimo; Cardinali, Giulia; Trevisiol, Chiara; Zappa, Marco; Rainato, Giulia; Fabricio, Aline S C

2017-08-01

Although the issue of monitoring appropriateness of tumour markers (TMs) request in outpatients remains crucial, proper indicators are still demanding. The present study developed and explored indicators of inappropriate TM ordering in outpatients through the data mining of electronic health records (EHRs). Carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific antigen (PSA) ordered in outpatients during a year were examined by mining EHRs of a Local Health Authority in Italy. Evidence-based criteria were used to develop performance indicators. Demographic and clinical information associated with TM orders were examined. A total of 80 813 TMs were ordered in 52 536 outpatients (1.54 markers/patient). Indicators related to disease codes, gender, age, and TM repetitions were developed, and their application showed that (1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and 65.6%) whereas the other TMs are largely requested also in patients without cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are negligible; (3) although requests in people older than 80 years are relevant (16.4% of total), the highest rate of request of all markers occurs in patients aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69 years; (5) associated with cancer code for all age intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA are prevalent in cancer patients or benign diseases to which TMs are appropriate, whereas PSA repetitions occur mainly in patients without cancer. The developed indicators resulted suitable to monitor TM overordering in outpatients through the mining of EHRs. The present study is a first approach towards the use of big-data mining for TM appropriateness evaluation purposes. © 2017 John Wiley & Sons, Ltd.

Hsp100/ClpB Chaperone Function and Mechanism

Energy Technology Data Exchange (ETDEWEB)

Vierling, Elizabeth [Univ. of Massachusetts, Amherst, MA (United States). Dept. of Biochemistry and Molecular Biology

2015-01-27

The supported research investigated the mechanism of action of a unique class of molecular chaperones in higher plants, the Hsp100/ClpB proteins, with the ultimate goal of defining how these chaperones influence plant growth, development, stress tolerance and productivity. Molecular chaperones are essential effectors of cellular “protein quality control”, which comprises processes that ensure the proper folding, localization, activation and turnover of proteins. Hsp100/ClpB proteins are required for temperature acclimation in plants, optimal seed yield, and proper chloroplast development. The model plant Arabidopsis thaliana and genetic and molecular approaches were used to investigate two of the three members of the Hsp100/ClpB proteins in plants, cytosolic AtHsp101 and chloroplast-localized AtClpB-p. Investigating the chaperone activity of the Hsp100/ClpB proteins addresses DOE goals in that this activity impacts how “plants generate and assemble components” as well as “allowing for their self repair”. Additionally, Hsp100/ClpB protein function in plants is directly required for optimal “utilization of biological energy” and is involved in “mechanisms that control the architecture of energy transduction systems”.

An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

LENUS (Irish Health Repository)

Donatello, Simona

2011-04-26

Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.

Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

Science.gov (United States)

Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

2006-05-01

The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

Tumour exosome integrins determine organotropic metastasis.

Science.gov (United States)

Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

2015-11-19

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

A novel role for autologous tumour cell vaccination in the immunotherapy of the poorly immunogenic B16-BL6 melanoma.

Science.gov (United States)

Geiger, J D; Wagner, P D; Shu, S; Chang, A E

1992-06-01

The growth of immunogenic tumours stimulates the generation of tumour-sensitized, but not functional, pre-effector T cells in the draining lymph nodes. These pre-effector cells can mature into effector cells upon in-vitro stimulation with anti-CD3 and IL-2. In the current study, using a defined, poorly immunogenic tumour, B16-BL6 melanoma, the pre-effector cell response was not evident during progressive tumour growth but was elicited by vaccination with irradiated tumour cells admixed with Corynebacterium parvum. After anti-CD3/IL-2 activation, these cells were capable of mediating the regression of established pulmonary metastases. The efficacy of the vaccine depended on the doses of both tumour cells and the adjuvant. While higher numbers of tumour cells were more effective, an optimal dose (12.5 micrograms) of C. parvum was required. The dose of irradiation was not a critical factor. After vaccination, kinetic studies revealed that the pre-effector cell response was evident 4 days later and declined after 14 days. These observations illustrate the potential role of active immunization in the cellular therapy of cancer.

Discrimination of paediatric brain tumours using apparent diffusion coefficient histograms

International Nuclear Information System (INIS)

Bull, Jonathan G.; Clark, Christopher A.; Saunders, Dawn E.

2012-01-01

To determine if histograms of apparent diffusion coefficients (ADC) can be used to differentiate paediatric brain tumours. Imaging of histologically confirmed tumours with pre-operative ADC maps were reviewed (54 cases, 32 male, mean age 6.1 years; range 0.1-15.8 years) comprising 6 groups. Whole tumour ADC histograms were calculated; normalised for volume. Stepwise logistic regression analysis was used to differentiate tumour types using histogram metrics, initially for all groups and then for specific subsets. All 6 groups (5 dysembryoplastic neuroectodermal tumours, 22 primitive neuroectodermal tumours (PNET), 5 ependymomas, 7 choroid plexus papillomas, 4 atypical teratoid rhabdoid tumours (ATRT) and 9 juvenile pilocytic astrocytomas (JPA)) were compared. 74% (40/54) were correctly classified using logistic regression of ADC histogram parameters. In the analysis of posterior fossa tumours, 80% of ependymomas, 100% of astrocytomas and 94% of PNET-medulloblastoma were classified correctly. All PNETs were discriminated from ATRTs (22 PNET and 4 supratentorial ATRTs) (100%). ADC histograms are useful in differentiating paediatric brain tumours, in particular, the common posterior fossa tumours of childhood. PNETs were differentiated from supratentorial ATRTs, in all cases, which has important implications in terms of clinical management. (orig.)

Correlation of expressions of S100A8 and S100A9 and its ...

African Journals Online (AJOL)

(S100A9) in nasopharyngeal carcinoma (NPC) tissues and their correlation with clinical pathological characteristics and ..... receptor (RAGE), a process which also activates .... S100A8 and S100A9 between Prostate Cancer and. BPH.

In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

Science.gov (United States)

Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

2016-09-01

During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery.

IL-17B Can Impact on Endothelial Cellular Traits Linked to Tumour Angiogenesis

Directory of Open Access Journals (Sweden)

Andrew J. Sanders

2010-01-01

Full Text Available IL-17B is a member of the IL-17 cytokine family which have been implicated in inflammatory response and autoimmune diseases such as rheumatoid arthritis. The founding member of this family, IL-17 (or IL-17A, has also been implicated in promoting tumour angiogenesis through the induction of other proangiogenic factors. Here we examine the potential of recombinant human IL-17B to contribute to the angiogenic process. In vitro rhIL-17B was able to inhibit HECV endothelial cell-matrix adhesion and cellular migration and also, at higher concentrations, could substantially reduce tubule formation compared to untreated HECV cells in a Matrigel tubule formation assay. This data suggests that IL-17B may act in an antiangiogenic manner.

Wilms tumour: prognostic factors, staging, therapy and late effects

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Kaste, Sue C. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Dome, Jeffrey S. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Babyn, Paul S. [Hospital for Sick Children, Department of Radiology, Toronto (Canada); Graf, Norbert M. [University Hospital of the Saarland, Clinic for Pediatric Oncology and Hematology, Homburg (Germany); Grundy, Paul [University of Alberta, Division of Pediatric Hematology, Oncology and Palliative Care, and Northern Alberta Children' s Cancer Program, Edmonton (Canada); Godzinski, Jan [Mother and Child Institute, Department of Oncological Surgery for Children and Adolescents, Warsaw (Poland); Levitt, Gill A. [Great Ormond Street Hospital for Sick Children NHS Trust, Paediatric Oncology, London (United Kingdom); Jenkinson, Helen [Birmingham Children' s Hospital NHS Trust, Oncology Department, Birmingham (United Kingdom)

2008-01-15

Wilms tumour is the most common malignant renal tumour in children. Dramatic improvements in survival have occurred as the result of advances in anaesthetic and surgical management, irradiation and chemotherapy. Current therapies are based on trials and studies primarily conducted by large multi-institutional cooperatives including the Societe Internationale d'Oncologie Pediatrique (SIOP) and the Children's Oncology Group (COG). The primary goals are to treat patients according to well-defined risk groups in order to achieve the highest cure rates, to decrease the frequency and intensity of acute and late toxicity and to minimize the cost of therapy. The SIOP trials and studies largely focus on the issue of preoperative therapy, whereas the COG trials and studies start with primary surgery. This paper reviews prognostic factors and staging systems for Wilms tumour and its current treatment with surgery and chemotherapy. Surgery remains a crucial part of treatment for nephroblastoma, providing local primary tumour control and adequate staging and possibly controlling the metastatic spread and central vascular extension of the disease. Partial nephrectomy, when technically feasible, seems reasonable not only in those with bilateral disease but also in those with unilateral disease where the patient has urological disorders or syndromes predisposing to malignancy. Partial nephrectomy, however, is frequently not sufficient for an anaplastic variant of tumour. The late effects for Wilms tumour and its treatment are also reviewed. The treatment of Wilms tumour has been a success story, and currently in excess of 80% of children diagnosed with Wilms tumour can look forward to long-term survival, with less than 20% experiencing serious morbidity at 20 years from diagnosis. The late complications are a consequence of the type and intensity of treatment required, which in turn reflects the nature and extent of the original tumour. Continual international trial

Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma.

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Tiveron, Rogério Costa; de Freitas, Luiz Carlos Conti; Figueiredo, David L; Serafini, Luciano N; Mamede, Rui Celso Martins; Zago, Marco A

2012-01-01

Many studies have reported increased expression of S100 A7 (psoriasin) in neoplastic lesions. Among them are studies on breast carcinoma, bladder squamous cell carcinoma, skin tumors and oral cavity squamous cell carcinoma. The expression of S100 A7 has not been described for laryngeal cancer. This study aims to identify the expression of the calcium-binding protein S100 A7 and its correlation with squamous cell carcinomas of the larynx. Specimens from 63 patients were submitted to immunohistochemistry testing with antibody S100 A7. Results were classified and compared. The group with highly differentiated tumors had the highest treatment failure scores. Moderately differentiated tumors had higher treatment failure scores than poorly differentiated tumors. Higher scores were predominantly seen on stages I and II in moderately differentiated tumors, whereas score distribution was more homogeneous in advanced stage disease (III and IV). Regarding failure in treatment, the group scoring zero (3/4 complications: 75%) differed significantly from the remaining groups (13/59: 22%). S100 A7 marker was expressed in 93.7% of laryngeal cancer cases, with higher positive correlation rates in more differentiated tumors and significantly lower rates of treatment failure. Scores had no impact on survival rates.

HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

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Linge, Annett; Lohaus, Fabian; Löck, Steffen

2016-01-01

OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell...

Immunosuppressive mediators of oral squamous cell carcinoma in tumour samples and saliva.

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Gonçalves, Andréia Souza; Arantes, Diego Antonio Costa; Bernardes, Vanessa Fátima; Jaeger, Filipe; Silva, Janine Mayra; Silva, Tarcília Aparecida; Aguiar, Maria Cássia Ferreira; Batista, Aline Carvalho

2015-01-01

The goal of this study was to compare the salivary concentrations of IL-10, TGF-β1 and soluble HLA-G (sHLA-G) in patients with oral squamous cell carcinoma (OSCC) to those in healthy individuals (control group), and to correlate the expression of these mediators in saliva with that in the tumour microenvironment. Neoplastic tissue and saliva samples from patients with OSCC (n=22) were analysed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) respectively. We detected high expression of IL-10 and HLA-G in the tumour microenvironment when compared to healthy oral mucosa samples. Determination of IL-10 salivary concentration enabled us to distinguish patients with OSCC from healthy individuals (P=0.038), which showed correlation with tissue expression of this cytokine. HLA-G salivary release was similar in both groups (P=0.17) and no correlation with tumour expression was observed. TGF-β1 expression was low or absent in tumours, and salivary concentration was similar between groups. Our results suggest that of the three markers analysed, IL-10 is a potential salivary biomarker. Furthermore, the elevated expression of HLA-G and IL-10 in tumour sites could favour the escape of tumour cells from immune defense mechanisms. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation.

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Hansen, Fernanda; Battú, Cíntia Eickhoff; Dutra, Márcio Ferreira; Galland, Fabiana; Lirio, Franciane; Broetto, Núbia; Nardin, Patrícia; Gonçalves, Carlos-Alberto

2016-02-01

Diabetes is a metabolic disease characterized by high fasting-glucose levels. Diabetic complications have been associated with hyperglycemia and high levels of reactive compounds, such as methylglyoxal (MG) and advanced glycation endproducts (AGEs) formation derived from glucose. Diabetic patients have a higher risk of developing neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease. Herein, we examined the effect of high glucose, MG and carboxyethyllysine (CEL), a MG-derived AGE of lysine, on oxidative, metabolic and astrocyte-specific parameters in acute hippocampal slices, and investigated some of the mechanisms that could mediate these effects. Glucose, MG and CEL did not alter reactive oxygen species (ROS) formation, glucose uptake or glutamine synthetase activity. However, glutamate uptake and S100B secretion were decreased after MG and CEL exposure. RAGE activation and glycation reactions, examined by aminoguanidine and L-lysine co-incubation, did not mediate these changes. Acute MG and CEL exposure, but not glucose, were able to induce similar effects on hippocampal slices, suggesting that conditions of high glucose concentrations are primarily toxic by elevating the rates of these glycation compounds, such as MG, and by generation of protein cross-links. Alterations in the secretion of S100B and the glutamatergic activity mediated by MG and AGEs can contribute to the brain dysfunction observed in diabetic patients.

Seroprevalence of hepatitis B and hepatitis C markers among children and adolescents in the south brazilian region: metropolitan area of Florianópolis, Santa Catarina

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Andréia Royer Voigt

Full Text Available Hepatitis B and C are important causes of morbidity and mortality worldwide. In Brazil, according to the Ministry of Health, about 15% of population is infected by hepatitis B virus (HBV and less than 1% by hepatitis C virus (HCV. Nevertheless, the age-specific prevalence of HBV and HCV markers remains unknown. This study aimed to determine the seroprevalence of HBV and HCV markers of infection and immunity in children and adolescents between 10 to 16 years old who live in the metropolitan area of Florianópolis, state of Santa Catarina, South of Brazil. Three hundred and eighty four individuals were enrolled in this study. Serological markers for HBV and HCV (HBsAg, total anti-HBc, anti-HBc IgM, anti-HBs and anti-HCV were determined through Microparticle Enzyme Immunosorbant Assay (MEIA - AxSYM System® - by using commercial diagnostic kits (Abbott Laboratories, Abbott Park, Illinois, USA. All 384 adolescents (100% were negative for HBsAg and anti-HBc IgM. Only two (0.52% were positive for total anti-HBc. Among the studied individuals, 226 (58.85% presented titers of anti-HBs > 10.0mIU/mL, 121 (31.51% presented anti HBs < 10.0mIU/mL, and 37 (9.64% did not present titers of anti-HBs. Regarding to anti-HCV, all 384 adolescents (100% presented negative results for this marker. In conclusion, this study showed a low prevalence of HBV and HCV infections. In addition, it was verified a great number of children and adolescents (89.84% who were positive for the immunity marker anti-HBs, implying that the National Immunization Program Protocol for hepatitis B has been effective in the studied region.

Blood-brain barrier dysfunction following traumatic brain injury: correlation of K(trans) (DCE-MRI) and SUVR (99mTc-DTPA SPECT) but not serum S100B.

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Winter, Craig; Bell, Christopher; Whyte, Timothy; Cardinal, John; Macfarlane, David; Rose, Stephen

2015-07-01

Damage to the blood-brain barrier (BBB) is an important secondary mechanism that occurs following traumatic brain injury (TBI) and may provide a potential therapeutic target to improve patient outcome. For such a progress to be realised, an accurate assessment of BBB compromise needs to be established. Fourteen patients with TBI were prospectively recruited. Post-traumatic BBB dysfunction was assessed using dynamic contrast-enhanced MRI (DCE-MRI), single-photon emission computerised tomography (SPECT) and serum S100B levels. A statistically significant correlation between standardised uptake value ratio (SUVR) calculated from 99mTc-DTPA SPECT and K(trans) (a volume transfer constant) from DCE-MRI was found for those eight patients who had concurrent scans. The positive correlation persisted when the data were corrected for patient age, number of days following trauma and both parameters combined. We found no statistically significant correlation between either of the imaging modalities and concurrent serum S100B levels. The correlation of SPECT with DCE-MRI suggests that either scan may be used to assess post-traumatic BBB damage. We could not support serum S100B to be an accurate measure of BBB damage when sampled a number of days following injury but the small number of patients, the heterogeneity in TBI patients and the delay following injury makes any firm conclusions regarding S100B and BBB difficult.

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study

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Ana Luiza de Castro Conde Toscano

Full Text Available ABSTRACT OBJECTIVE To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS Among 2,242 HIV positive patients, we identified 105 (4.7% patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B “e” antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105 of patients with chronic hepatitis B, and 50% (8/16 of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B “e” antigen positive patients, 57% (35/61 presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35 of those who initially cleared hepatitis B “e” antigen presented seroreversion or reactivation of this marker. CONCLUSIONS Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

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Miroslava Bilecova-Rabajdova

2014-01-01

Full Text Available Background. In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma. Materials and Methods. We compared expression of genes related to apoptosis (DR6 and Gpm6B in the blood of patients suffering from stage I of breast cancer in different grades (I–IV, with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot.Results. In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1 and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower.Conclusion. This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours.

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

International Nuclear Information System (INIS)

Oliveira, Soraya I de; Andrade, Luciana NS; Onuchic, Ana C; Nonogaki, Sueli; Fernandes, Patrícia D; Pinheiro, Mônica C; Rohde, Ciro BS; Chammas, Roger; Jancar, Sonia

2010-01-01

Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma. Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry. Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the

Sero markers of hepatitis B and C in patients with cirrhosis

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Khan, A.A.; Khalil-ur-Rehman; Haider, Z.; Shafqat, F.

2002-01-01

Objective: To assess the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in pathogenesis of liver cirrhosis. Design: It was a prospective study. Place and duration of study: This study was done at two centers, Sheikh Zayed Hospital, Lahore and Jinnah Hospital, over a period of six months from June to December, 1997. Subjects and Methods: Ninety-four patients with liver cirrhosis were evaluated for sero markers of hepatitis B and C virus at two teaching hospitals in Lahore. Viral markers studied were anti-HCV, HBSAG, anti-HBclgG, anti-HBs, and HbeAg. Anti-HDV was done in HbsAg positive cases. Results: Twenty-two out of 94 (23%) patients were positive and 72(77%) negative for HbsAg. Anti-HCV was positive in 64 (68%) and no major sero markers for HBV or HCV were seen in 16 patients. Conclusion: It was evident from sero markers that exposure to hepatitis B and C had occurred but which one was responsible for cirrhosis, was hard to determine. Inasmuch as vaccine against hepatitis B virus is available, mass vaccination in the population may be a consideration to prevent cirrhosis due to hepatitis B virus. (author)

Immunoradiometric assay of a novel proliferation marker: tumour polypeptide specific antigen in breast cancer management in north India

International Nuclear Information System (INIS)

Phanna-Hazra, P.; Sharma, U.; Gupta, K.K.; Bhatnagar, V.; Idnani, R.; Gangwar, P.K.; Hazra, D.K.

2004-01-01

Tissue Polypeptide Specific Antigen (TPS) is a novel tumour marker defined by the monoclonal antibody M3 ,discovered by Bjorklund,which is claimed to be a proliferation marker, and belonging to the cytokeratin 8-18 family. M3 defines this antigen in particular out of a group of Tissue Polypeptide antigens (TPA) charecterised by the same Swedish group and was claimed to be a pancarcinoma antigen reportedly being elevated in several different cancers in the European literature.Pancarcinoma markers are of interest in relation to cancer detection as well as for assessing therapy and prognosis.Pancarcinoma antigens are also of interest for radiobioconjugate immunotargetting both for diagnosis as well as for therapy. There were no reports on this marker in an Indian population and therefore this study was initiated at two institutions in Meerut and Agra, both in the northern state of Uttar Pradesh. In addition to 250 healthy controls, 288 cases of breast cancer were studied .In addituion benign disorders were studied: breast fibroadenosis 16, breast fibro adenoma 5, breast abscess 4. TPS levels were determined by an immunoradiometric assay. In controls all but 4 had values less than 80 Units/1,the upper normal level quoted by Bjorklund.The relationship of the serum levels of the markers to histological grade and anatomical stage of the tumour were studied. In addition several of the cases underwent therapy with chemotherapy /radiotherapy/surgery or combinations thereof. The response to treatment during follow up was categorized as Complete emission(CR),Partial Remission (PR)Stable Disease(SD), Progressive Disease(PD)and recurrence (R) by the respective clinicians using standard criteria. In the cancer subjects there was a close correlation of TPS elevation with anatomical stage. 10 cases belonged to stage 1 with TPS levels 176.1+-103.94 Units/L ,61 to stage II(TPS levels 206.45 +-168.23).,79 to stage Ilia (TPS 251.5+-168.53),83 to stage IIIB (TPS 537.35+- 691.71),and 55

DNA methylation-based classification of central nervous system tumours

DEFF Research Database (Denmark)

Capper, David; Jones, David T.W.; Sill, Martin

2018-01-01

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter-observer variabil......Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging - with substantial inter......-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show...

Correlation of human S100A12 (EN-RAGE) and high-sensitivity C-reactive protein as gingival crevicular fluid and serum markers of inflammation in chronic periodontitis and type 2 diabetes.

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Pradeep, A R; Martande, Santosh S; Singh, Sonender Pal; Suke, Deepak Kumar; Raju, Arjun P; Naik, Savitha B

2014-04-01

The aim of the present study was to evaluate the levels and correlation of human S100A12 and high-sensitivity C-reactive protein (hs-CRP) in gingival crevicular fluid (GCF) and serum in chronic periodontitis (CP) subjects with and without type 2 diabetes mellitus (DM). A total of 44 subjects were divided into three groups: group 1 had 10 periodontally healthy subjects, group 2 consisted of 17 CP subjects and group 3 had 17 type 2 DM subjects with CP. GCF and serum levels of human S100A12 and hs-CRP were quantified using enzyme-linked immunosorbent assay and immunoturbidimetric analysis, respectively. The clinical outcomes evaluated were gingival index, probing depth and clinical attachment level and the correlations of the two inflammatory mediators with clinical parameters were evaluated. Both human S100A12 and hs-CRP levels increased from group 1 to group 2 to group 3. The GCF and serum values of both these inflammatory mediators correlated positively with each other and with the periodontal parameters evaluated (p < 0.05). Human S100A12 and hs-CRP can be considered as possible GCF and serum markers of inflammatory activity in CP and DM.

Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100

International Nuclear Information System (INIS)

Soria, L.F.; Ludwig, E.H.; Clarke, H.R.G.; McCarthy, B.J.; Vega, G.L.; Grundy, S.M.

1989-01-01

Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG → CAG), a CG mutational hot spot, defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia

S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression.

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Prieto, Daniel; Sotelo, Natalia; Seija, Noé; Sernbo, Sandra; Abreu, Cecilia; Durán, Rosario; Gil, Magdalena; Sicco, Estefanía; Irigoin, Victoria; Oliver, Carolina; Landoni, Ana Inés; Gabus, Raúl; Dighiero, Guillermo; Oppezzo, Pablo

2017-08-10

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL. © 2017 by The American Society of Hematology.

Biochemical Markers of Brain Injury: An Integrated Proteomics-Based Approach

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2006-02-01

some variability between protein assay measurements. Using densitometric analysis after 1D-PAGE, microfiltration alone showed an 11 ( 5% sample reduction...KOPETSCH, O., WOSZCZYK, A., et al. (2003). Serum S-100B protein as a molecular marker in severe trau- matic brain injury. Restor . Neurol. Neurosci. 21...proteomics. Implications in the search for preventive initiatives to slow the clinical progression of Alzheimer’s disease dementia. Restor . Neurol. Neurosci

Reconstructive options in pelvic tumours

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Mayilvahanan N

2005-01-01

Full Text Available Background: Pelvic tumours present a complex problem. It is difficult to choose between limb salvage and hemipelvectomy. Method: Forty three patients of tumours of pelvis underwent limb salvage resection with reconstruction in 32 patients. The majority were chondrosarcomas (20 cases followed by Ewing sarcoma. Stage II B was the most common stage in malignant lesions and all the seven benign lesions were aggressive (B3. Surgical margins achieved were wide in 31 and marginal in 12 cases. Ilium was involved in 51% of cases and periacetabular involvement was seen in 12 patients. The resections done were mostly of types I &II of Enneking′s classification of pelvic resection. Arthrodesis was attempted in 24 patients. Customized Saddle prosthesis was used in seven patients and no reconstruction in 12 patients. Adjuvant chemotherapy was given to all high-grade malignant tumours, combined with radiotherapy in 7 patients. Results: With a mean follow up of 48.5 months and one patient lost to follow up, the recurrence rate among the evaluated cases was 16.6%. Oncologically, 30 patients were continuously disease free with 7 local recurrences and 4 deaths due to disseminated disease and 2 patients died of other causes. During the initial years, satisfactory functional results were achieved with prosthetic replacement. Long-term functional result of 36 patients who were alive at the time of latest follow up was satisfactory in 75% who underwent arthrodesis and in those where no reconstruction was used. We also describe a method of new classification of pelvic resections that clarifies certain shortcomings of the previous systems of classification. Conclusion: Selection of a procedure depends largely on the patient factors, the tumour grade, the resultant defect and the tissue factors. Resection with proper margins gives better functional and oncological results

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

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Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

2013-03-05

Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

The germacranolide sesquiterpene lactone neurolenin B of the medicinal plant Neurolaena lobata (L.) R.Br. ex Cass inhibits NPM/ALK-driven cell expansion and NF-κB-driven tumour intravasation.

Science.gov (United States)

Unger, Christine; Kiss, Izabella; Vasas, Andrea; Lajter, Ildikó; Kramer, Nina; Atanasov, Atanas Georgiev; Nguyen, Chi Huu; Chatuphonprasert, Waranya; Brenner, Stefan; Krieger, Sigurd; McKinnon, Ruxandra; Peschel, Andrea; Kain, Renate; Saiko, Philipp; Szekeres, Thomas; Kenner, Lukas; Hassler, Melanie R; Diaz, Rene; Frisch, Richard; Dirsch, Verena M; Jäger, Walter; de Martin, Rainer; Bochkov, Valery N; Passreiter, Claus M; Peter-Vörösmarty, Barbara; Mader, Robert M; Grusch, Michael; Dolznig, Helmut; Kopp, Brigitte; Zupko, Istvan; Hohmann, Judit; Krupitza, Georg

2015-08-15

The t(2;5)(p23;q35) chromosomal translocation results in the expression of the fusion protein NPM/ALK that when expressed in T-lymphocytes gives rise to anaplastic large cell lymphomas (ALCL). In search of new therapy options the dichloromethane extract of the ethnomedicinal plant Neurolaena lobata (L.) R.Br. ex Cass was shown to inhibit NPM/ALK expression. Therefore, we analysed whether the active principles that were recently isolated and found to inhibit inflammatory responses specifically inhibit growth of NPM/ALK+ ALCL, leukaemia and breast cancer cells, but not of normal cells, and the intravasation through the lymphendothelial barrier. ALCL, leukaemia and breast cancer cells, and normal peripheral blood mononuclear cells (PBMCs) were treated with isolated sesquiterpene lactones and analysed for cell cycle progression, proliferation, mitochondrial activity, apoptosis, protein and mRNA expression, NF-κB and cytochrome P450 activity, 12(S)-HETE production and lymphendothelial intravasation. In vitro treatment of ALCL by neurolenin B suppressed NPM/ALK, JunB and PDGF-Rβ expression, inhibited the growth of ALCL cells late in M phase, and induced apoptosis via caspase 3 without compromising mitochondrial activity (as a measure of general exogenic toxicity). Moreover, neurolenin B attenuated tumour spheroid intravasation probably through inhibition of NF-κB and CYP1A1. Neurolenin B specifically decreased pro-carcinogenic NPM/ALK expression in ALK+ ALCL cells and, via the inhibition of NF-kB signalling, attenuated tumour intra/extravasation into the lymphatics. Hence, neurolenin B may open new options to treat ALCL and to manage early metastatic processes to which no other therapies exist. Copyright © 2015 Elsevier GmbH. All rights reserved.

Design of compounds having enhanced tumour uptake, using serum albumin as a carrier. Pt. 2

International Nuclear Information System (INIS)

Schilling, U.; Friedrich, E.A.; Sinn, H.; Schrenk, H.H.; Clorius, J.H.; Maier-Borst, W.

1992-01-01

In the present in vivo study the uptake kinetics of radioiodinated albumin were determined in normal organs, and tumours of rats using sequential scintigraphy. Results indicate that cellular uptake of the marker takes place. Fluorescence was not observed in muscle tissue. This appears to suggest that the albumin uptake is greater in tumours than in normal tissue, and that it is metabolized in the tumour cells. (Author)

[S100A7 promotes the metastasis and epithelial-mesenchymal transition on HeLa and CaSki cells].

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Tian, T; Hua, Z; Wang, L Z; Wang, X Y; Chen, H Y; Liu, Z H; Cui, Z M

2018-02-25

Objective: To elucidate the impact of over-expression of S100A7 on migration, invasion, proliferation, cell cycle, and epithelial-mesenchymal transition (EMT) in human cervical cancer HeLa and CaSki cells. Methods: (1) Immunohistochemistry of SP was used to examine the expression of S100A7 in 40 cases of squamous cervical cancer tissues and 20 cases of normal cervical tissues. (2) The vectors of pLVX-IRES-Neo-S100A7 and pLVX-IRES-Neo were used to transfect human cervical cancer HeLa and CaSki cells, and the positive clones were screened and identified. Next, transwell migration assay, cell counting kit-8 (CCK-8) assay and fluorescence activating cell sorter (FACS) were used to detect the effect of S100A7-overexpression on the migration, invasion, proliferation and cell cycle of cervical cancer cells. Furthermore, western blot was performed to observe the expression of epithelial marker (E-cadherin) and mesenchymal markers (N-cadherin, vimentin, and fibronectin) of EMT. Results: (1) S100A7 expression was significantly higher in cervical squamous cancer tissues (median 91.6) than that in normal cervical tissues (median 52.1; Z=- 2.948, P= 0.003) . (2) Stable S100A7-overexpressed cells were established using lentiviral-mediated gene delivery in HeLa and CaSki cells. S100A7 was detected by real-time quantitative reverse transcription PCR, S100A7 mRNA of S100A7-overexpressed cells were 119±3 and 177±16, increased significantly compared with control groups of median ( Pcells, the number of S100A7-overexpressed HeLa and CaSki cells that passed the transwell membrane assay were increased significanatly (572±51 vs 337±25, PHeLa and CaSki cells that passed the transwell membrane were respectively 441±15 and 110±14, elevated significantly compared with control cells (156±21 and 59±7; Pcell cycle progression of HeLa and CaSki cells ( P> 0.05) . Expression of E-cadherin was dramatically decreased, while N-cadherin, vimentin, and fibronectin increased in S100A7

Gene expression and protein secretion of apolipoprotein B100 (ApoB100 in transition dairy cows under hot or thermoneutral environments

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Alessandro Nardone

2010-01-01

Full Text Available The aim of the study was to investigate the effects of hot season on gene expression and protein secretion of ApoB100 in transition dairy cows. Hot season strongly down-regulated ApoB100 gene and protein expression. This condition and the higher circulating NEFA were responsible for the higher lipid accumulation in liver of heat-stressed transition cows.

Structural and functional diversification in the teleost S100 family of calcium-binding proteins

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Korsching Sigrun I

2008-02-01

level the teleost S100 proteins can serve as precise markers for several different cell types. At least some of their functions may be related to those of their counterparts in mammals. Accordingly, our findings provide an excellent basis for future studies of the functions and interaction partners of s100 genes and finally their role in diseases, using the zebrafish as a model organism.

Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

LENUS (Irish Health Repository)

Whelan, M C

2012-01-31

Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.

Optical LDPC decoders for beyond 100 Gbits/s optical transmission.

Science.gov (United States)

Djordjevic, Ivan B; Xu, Lei; Wang, Ting

2009-05-01

We present an optical low-density parity-check (LDPC) decoder suitable for implementation above 100 Gbits/s, which provides large coding gains when based on large-girth LDPC codes. We show that a basic building block, the probabilities multiplier circuit, can be implemented using a Mach-Zehnder interferometer, and we propose corresponding probabilistic-domain sum-product algorithm (SPA). We perform simulations of a fully parallel implementation employing girth-10 LDPC codes and proposed SPA. The girth-10 LDPC(24015,19212) code of the rate of 0.8 outperforms the BCH(128,113)xBCH(256,239) turbo-product code of the rate of 0.82 by 0.91 dB (for binary phase-shift keying at 100 Gbits/s and a bit error rate of 10(-9)), and provides a net effective coding gain of 10.09 dB.

Biomolecular Markers in Cancer of the Tongue

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Daris Ferrari

2009-01-01

Full Text Available The incidence of tongue cancer is increasing worldwide, and its aggressiveness remains high regardless of treatment. Genetic changes and the expression of abnormal proteins have been frequently reported in the case of head and neck cancers, but the little information that has been published concerning tongue tumours is often contradictory. This review will concentrate on the immunohistochemical expression of biomolecular markers and their relationships with clinical behaviour and prognosis. Most of these proteins are associated with nodal stage, tumour progression and metastases, but there is still controversy concerning their impact on disease-free and overall survival, and treatment response. More extensive clinical studies are needed to identify the patterns of molecular alterations and the most reliable predictors in order to develop tailored anti-tumour strategies based on the targeting of hypoxia markers, vascular and lymphangiogenic factors, epidermal growth factor receptors, intracytoplasmatic signalling and apoptosis.

SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

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Pasupuleti Prathima

2016-11-01

Full Text Available BACKGROUND Neuroendocrine tumours occur at various sites in the human body. They are considered as one of the close differentials for many tumours. Various benign and malignant tumours undergo neuroendocrine differentiation. Its incidence is slightly increasing due to advanced imaging modalities. Although rare, they can be seen in breast, gallbladder and skin. The aim of the study is to study the spectrum of neuroendocrine tumours from various sites, their clinical presentation, histomorphological features with immunohistochemistry and review of literature. MATERIALS AND METHODS This is a retrospective study for a period of 3 years (June 2013-June 2016. Surgical resection specimens were included in the study. Out of the total specimens received, 24 cases were of neuroendocrine tumours. Differential diagnosis of small round cell tumours also was considered and a panel of immunohistochemical markers were included to rule out them. Biopsy specimens were excluded from the study. RESULTS Out of the 24 cases, 18 cases were benign lesions. 6 cases were malignant lesions. Female preponderance was noted. Peak incidence was seen in 20-30 years of age group. CONCLUSION Neuroendocrine tumours can occur anywhere in the body and it should be considered in one of the differential diagnosis. Diagnosis must be accurately made.

Purification, crystallization and preliminary X-ray diffraction of human S100A15

Energy Technology Data Exchange (ETDEWEB)

Boeshans, Karen M. [X-ray Crystallography Facility, NIAMS, National Institutes of Health, Bethesda, MD 20892 (United States); Wolf, Ronald; Voscopoulos, Christopher [Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Gillette, William; Esposito, Dominic [Protein Expression Laboratory, Research Technology Program, National Cancer Institute, SAIC-Frederick Inc., Frederick, MD 21702 (United States); Mueser, Timothy C. [Department of Chemistry, University of Toledo, Toledo, OH 43606 (United States); Yuspa, Stuart H. [Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Ahvazi, Bijan, E-mail: ahvazib@mail.nih.gov [X-ray Crystallography Facility, NIAMS, National Institutes of Health, Bethesda, MD 20892 (United States)

2006-05-01

S100 proteins are differentially expressed during epithelial cell maturation, tumorigenesis and inflammation. The novel human S100A15 protein has been cloned, expressed, purified and crystallized in two crystal forms, a triclinic and a monoclinic form, which diffract to 1.7 and 2.0 Å, respectively. Human S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. The protein is implicated as an effector in calcium-mediated signal transduction pathways. Although its biological function is unclear, the association of the 11.2 kDa S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for therapy. To provide insight into the function of S100A15, the protein was crystallized to visualize its structure and to further the understanding of how the many similar calcium-binding mediator proteins in the cell distinguish their cognate target molecules. The S100A15 protein has been cloned, expressed and purified to homogeneity and produced two crystal forms. Crystals of form I are triclinic, with unit-cell parameters a = 33.5, b = 44.3, c = 44.8 Å, α = 71.2, β = 68.1, γ = 67.8° and an estimated two molecules in the asymmetric unit, and diffract to 1.7 Å resolution. Crystals of form II are monoclinic, with unit-cell parameters a = 82.1, b = 33.6, c = 52.2 Å, β = 128.2° and an estimated one molecule in the asymmetric unit, and diffract to 2.0 Å resolution. This structural analysis of the human S100A15 will further aid in the phylogenic comparison between the other members of the S100 protein family, especially the highly homologous paralog S100A7.

Prediction of occult hepatitis B virus infection in liver transplant donors through hepatitis B virus blood markers.

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Tandoi, Francesco; Caviglia, Gian Paolo; Pittaluga, Fabrizia; Abate, Maria Lorena; Smedile, Antonina; Romagnoli, Renato; Salizzoni, Mauro

2014-11-01

Occult hepatitis B virus infection is defined as detectable HBV-DNA in liver of HBsAg-negative individuals, with or without detectable serum HBV-DNA. In deceased liver donors, results of tissue analysis cannot be obtained prior to allocation for liver transplantation. we investigated prevalence and predictability of occult hepatitis B using blood markers of viral exposure/infection in deceased liver donors. In 50 consecutive HBsAg-negative/anti-HBc-positive and 20 age-matched HBsAg-negative/anti-HBc-negative donors, a nested-PCR assay was employed in liver biopsies for diagnosis of occult hepatitis B according to Taormina criteria. All donors were characterized for plasma HBV-DNA and serum anti-HBs/anti-HBe. In liver tissue, occult hepatitis B was present in 30/50 anti-HBc-positive (60%) and in 0/20 anti-HBc-negative donors (pdonors with detectable HBV-DNA in plasma (n=5) or anti-HBs>1,000 mIU/mL (n=5) eventually showed occult infection, i.e, 10/30 occult hepatitis B-positive donors which could have been identified prior to transplantation. In the remaining 40 anti-HBc-positive donors, probability of occult infection was 62% for anti-HBe-positive and/or anti-HBs ≥ 58 mIU/mL; 29% for anti-HBe-negative and anti-HBsdonors, combining anti-HBc with other blood markers of hepatitis B exposure/infection allows to predict occult hepatitis B with certainty and speed in one third of cases. These findings might help refine the allocation of livers from anti-HBc-positive donors. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Tumour bed delineation for partial breast/breast boost radiotherapy: What is the optimal number of implanted markers?

International Nuclear Information System (INIS)

Kirby, Anna NM.; Jena, Rajesh; Harris, Emma J.; Evans, Phil M.; Crowley, Clare; Gregory, Deborah L.; Coles, Charlotte E.

2013-01-01

Purpose: International consensus has not been reached regarding the optimal number of implanted tumour bed (TB) markers for partial breast/breast boost radiotherapy target volume delineation. Four common methods are: insertion of 6 clips (4 radial, 1 deep and 1 superficial), 5 clips (4 radial and 1 deep), 1 clip at the chest wall, and no clips. We compared TB volumes delineated using 6, 5, 1 and 0 clips in women who have undergone wide-local excision (WLE) of breast cancer (BC) with full-thickness closure of the excision cavity, in order to determine the additional margin required for breast boost or partial breast irradiation (PBI) when fewer than 6 clips are used. Methods: Ten patients with invasive ductal BC who had undergone WLE followed by implantation of six fiducial markers (titanium clips) each underwent CT imaging for radiotherapy planning purposes. Retrospective processing of the DICOM image datasets was performed to remove markers and associated imaging artefacts, using an in-house software algorithm. Four observers outlined TB volumes on four different datasets for each case: (1) all markers present (CT 6M ); (2) the superficial marker removed (CT 5M ); (3) all but the chest wall marker removed (CT CW ); (4) all markers removed (CT 0M ). For each observer, the additional margin required around each of TB 0M , TB CW , and TB 5M in order to encompass TB 6M was calculated. The conformity level index (CLI) and differences in centre-of-mass (COM) between observers were quantified for CT 0M , CT CW , CT 5M , CT 6M . Results: The overall median additional margins required to encompass TB 6M were 8 mm (range 0–28 mm) for TB 0M , 5 mm (range 1–13 mm) for TB CW , and 2 mm (range 0–7 mm) for TB 5M . CLI were higher for TB volumes delineated using CT 6M (0.31) CT 5M (0.32) than for CT CW (0.19) and CT 0M (0.15). Conclusions: In women who have undergone WLE of breast cancer with full-thickness closure of the excision cavity and who are proceeding to PBI or

{sup 18}F-FDG PET/CT for detection of malignant peripheral nerve sheath tumours in neurofibromatosis type 1: tumour-to-liver ratio is superior to an SUV{sub max} cut-off

Energy Technology Data Exchange (ETDEWEB)

Salamon, Johannes [University Medical Centre Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); University Hospital Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Centre Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); University Medical Centre Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Bannas, Peter; Yamamura, Jin; Herrmann, Jochen; Adam, Gerhard; Derlin, Thorsten [University Medical Centre Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Friedrich, Reinhard E. [University Medical Centre Hamburg-Eppendorf, Department of Oral and Maxillofacial Surgery, Hamburg (Germany); Mautner, Victor F. [University Medical Centre Hamburg-Eppendorf, Department of Neurology, Hamburg (Germany)

2014-02-15

To evaluate the usefulness of normalising intra-tumour tracer accumulation on {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to reference tissue uptake for characterisation of peripheral nerve sheath tumours (PNSTs) in neurofibromatosis type 1 (NF1) compared with the established maximum standardised uptake value (SUVmax) cut-off of >3.5. Forty-nine patients underwent FDG PET/CT. Intra-tumour tracer uptake (SUVmax) was normalised to three different reference tissues (tumour-to-liver, tumour-to-muscle and tumour-to-fat ratios). Receiver operating characteristic (ROC) analyses were used out to assess the diagnostic performance. Histopathology and follow-up served as the reference standard. Intra-tumour tracer uptake correlated significantly with liver uptake (r{sub s} = 0.58, P = 0.016). On ROC analysis, the optimum threshold for tumour-to-liver ratio was >2.6 (AUC = 0.9735). Both the SUVmax cut-off value of >3.5 and a tumour-to-liver ratio >2.6 provided a sensitivity of 100 %, but specificity was significantly higher for the latter (90.3 % vs 79.8 %; P = 0.013). In patients with NF1, quantitative {sup 18}F-FDG PET imaging may identify malignant change in neurofibromas with high accuracy. Specificity could be significantly increased by using the tumour-to-liver ratio. The authors recommend further evaluation of a tumour-to-liver ratio cut-off value of >2.6 for diagnostic intervention planning. (orig.)

Tracking errors in a prototype real-time tumour tracking system

International Nuclear Information System (INIS)

Sharp, Gregory C; Jiang, Steve B; Shimizu, Shinichi; Shirato, Hiroki

2004-01-01

In motion-compensated radiation therapy, radio-opaque markers can be implanted in or near a tumour and tracked in real-time using fluoroscopic imaging. Tracking these implanted markers gives highly accurate position information, except when tracking fails due to poor or ambiguous imaging conditions. This study investigates methods for automatic detection of tracking errors, and assesses the frequency and impact of tracking errors on treatments using the prototype real-time tumour tracking system. We investigated four indicators for automatic detection of tracking errors, and found that the distance between corresponding rays was most effective. We also found that tracking errors cause a loss of gating efficiency of between 7.6 and 10.2%. The incidence of treatment beam delivery during tracking errors was estimated at between 0.8% and 1.25%

Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

Science.gov (United States)

Borges, Ana; Sousa, Inês; Castro, Luis

2017-06-01

This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of

Evaluation of tumour necrosis during chemotherapy with diffusion-weighted MR imaging: preliminary results in osteosarcomas

International Nuclear Information System (INIS)

Uhl, Markus; Saueressig, Ulrich; Bley, Thorsten; Langer, Mathias; Koehler, Gabriele; Kontny, Udo; Niemeyer, Charlotte; Reichardt, Wilfried; Ilyasof, Kamil

2006-01-01

During successful chemotherapy of osteosarcomas tumour size does not diminish significantly because the therapy has limited impact on the mineralized matrix of the tumour. Treatment response is considered successful if, histologically, more than 90% of tumour cells show necrosis. To determine if osteosarcomas change their water diffusion during preoperative chemotherapy in relation to the amount of tumour necrosis. Eight patients (age 11-19 years) with histologically proven limb osteosarcoma underwent T1-weighted, fat-suppressed T2-weighted and contrast-enhanced T1-weighted spin-echo imaging together with diffusion-weighted EPI sequences (b = 700) at 1.5 T before and after five cycles of standard chemotherapy. Tumour volume and apparent diffusion coefficient (ADC) maps were calculated before and after chemotherapy. The degree of tumour necrosis after chemotherapy was assessed using the histological Salzer-Kuntschik classification (grades 1-6). During chemotherapy, the ADC values of osteosarcomas changed significantly. The ADC of untreated tumour was 2.1 ± 0.4 x 10 -3 mm 2 /s (mean ± SD) (95% CI 1.6-2.0). The ADC of chemotherapy-treated sarcomas was 2.5 ± 0.4 x 10 -3 mm 2 /s (95% CI 1.8-2.2). Necrotic areas, which were confirmed by macroscopic examination, showed ADC values up to 2.7 x 10 -3 mm 2 /s. Four patients with little viable tumour tissue within the neoplasm (Salzer-Kuntschik grades 1-2) had an increase in ADC of 0.4 up to 0.7 x 10 -3 mm 2 /s. Four patients with larger areas of viable tumour (Salzer-Kuntschik grade 4) showed a lesser increase in ADC of 0.0 up to 0.3 x 10 -3 mm 2 /s. The differences in ADC values in tumour tissue before and after chemotherapy were highly significant (P = 0.01). During chemotherapy of osteosarcomas, tumour ADC changes are related to the degree of tumour necrosis. (orig.)

Intrafractional tracking accuracy in infrared marker-based hybrid dynamic tumour-tracking irradiation with a gimballed linac

International Nuclear Information System (INIS)

Mukumoto, Nobutaka; Nakamura, Mitsuhiro; Yamada, Masahiro; Takahashi, Kunio; Tanabe, Hiroaki; Yano, Shinsuke; Miyabe, Yuki; Ueki, Nami; Kaneko, Shuji; Matsuo, Yukinori; Mizowaki, Takashi; Sawada, Akira; Kokubo, Masaki; Hiraoka, Masahiro

2014-01-01

Purpose: To verify the intrafractional tracking accuracy in infrared (IR) marker-based hybrid dynamic tumour tracking irradiation (“IR Tracking”) with the Vero4DRT. Materials and methods: The gimballed X-ray head tracks a moving target by predicting its future position from displacements of IR markers in real-time. Ten lung cancer patients who underwent IR Tracking were enrolled. The 95th percentiles of intrafractional mechanical (iE M 95 ), prediction (iE P 95 ), and overall targeting errors (iE T 95 ) were calculated from orthogonal fluoroscopy images acquired during tracking irradiation and from the synchronously acquired log files. Results: Averaged intrafractional errors were (left–right, cranio-caudal [CC], anterior–posterior [AP]) = (0.1 mm, 0.4 mm, 0.1 mm) for iE M 95 , (1.2 mm, 2.7 mm, 2.1 mm) for iE P 95 , and (1.3 mm, 2.4 mm, 1.4 mm) for iE T 95 . By correcting systematic prediction errors in the previous field, the iE P 95 was reduced significantly, by an average of 0.4 mm in the CC (p < 0.05) and by 0.3 mm in the AP (p < 0.01) directions. Conclusions: Prediction errors were the primary cause of overall targeting errors, whereas mechanical errors were negligible. Furthermore, improvement of the prediction accuracy could be achieved by correcting systematic prediction errors in the previous field

Gene expression of circulating tumour cells in breast cancer patients

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Bölke E

2009-09-01

Full Text Available Abstract Background The diagnostic tools to predict the prognosis in patients suffering from breast cancer (BC need further improvements. New technological achievements like the gene profiling of circulating tumour cells (CTC could help identify new prognostic markers in the clinical setting. Furthermore, gene expression patterns of CTC might provide important informations on the mechanisms of tumour cell metastasation. Materials and methods We performed realtime-PCR and multiplex-PCR analyses following immunomagnetic separation of CTC. Peripheral blood (PB samples of 63 patients with breast cancer of various stages were analyzed and compared to a control group of 14 healthy individuals. After reverse-transcription, we performed multiplex PCR using primers for the genes ga733.3, muc-1 and c-erbB2. Mammaglobin1, spdef and c-erbB2 were analyzed applying realtime-PCR. Results ga733.2 overexpression was found in 12.7% of breast cancer cases, muc-1 in 15.9%, mgb1 in 9.1% and spdef in 12.1%. In this study, c-erbB2 did not show any significant correlation to BC, possibly due to a highly ambient expression. Besides single gene analyses, gene profiles were additionally evaluated. Highly significant correlations to BC were found in single gene analyses of ga733.2 and muc-1 and in gene profile analyses of ga733.3*muc-1 and GA7 ga733.3*muc-1*mgb1*spdef. Conclusion Our study reveals that the single genes ga733.3, muc-1 and the gene profiles ga733.3*muc-1 and ga733.3*3muc-1*mgb1*spdef can serve as markers for the detection of CTC in BC. The multigene analyses found highly positive levels in BC patients. Our study indicates that not single gene analyses but subtle patterns of multiple genes lead to rising accuracy and low loss of specificity in detection of breast cancer cases.

Genetic variation of rs438601 marker in the Iranian Population: An informative marker for molecular diagnosis of hemophilia B

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P Dorri

2014-12-01

Conclusion: The study findings demonstrated that rs438601 marker due to high heterozygosity could be suggested as an appropriate diagnostic marker in linkage analysis and carrier detection of hemophilia B in regard with a sample of Iranian population.

In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.

Science.gov (United States)

Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

2016-02-25

The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody (99m)Tc-D10 for visualizing small tumour lesions with volumes below 100 mm(3) by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody (99m)Tc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm(3) ± 21.2 and 26.6 mm(3) ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of (99m)Tc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody (99m)Tc-D10.

In vivo detection of small tumour lesions by multi-pinhole SPECT applying a 99mTc-labelled nanobody targeting the Epidermal Growth Factor Receptor

Science.gov (United States)

Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

2016-01-01

The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10. PMID:26912069

Procalcitonin and C-reactive protein as markers of bacterial infection in patients with solid tumours

DEFF Research Database (Denmark)

Diness, Laura V; Maraldo, Maja V; Mortensen, Christiane E

2014-01-01

INTRODUCTION: The diagnosis of bacterial infections in patients with solid tumours can be difficult as both the tumour and its treatment can cause symptoms and signs similar to those of infections. Many patients with solid tumours therefore receive antibiotic treatment without having a bacterial......, but with no signs of infection. RESULTS: Of the 41 admitted patients, 25 were classified as having an infection (either microbiologically or radioo-gically verified). Among the 25 cases with infection, PCT was within the normal range in 11 cases and only elevated in 14. As nearly half of the patients with infection...... had PCT within the normal range, PCT is not suited to exclude an infection. CRP was elevated in 20 patients out of the 25. CONCLUSION: PCT within the normal range cannot exclude an infection and does not appear to be superior to CRP to exclude an infection in patients with solid tumours. FUNDING...

Comparison of tumour age response to radiation for cells derived from tissue culture or solid tumours

International Nuclear Information System (INIS)

Keng, P.C.; Siemann, D.W.; Rochester Univ., NY; Rochester Univ., NY; Wheeler, K.T.

1984-01-01

Direct comparison of the cell age response of 9L and KHT tumour cells derived either from tissue culture or solid tumours was achieved. Cells from dissociated KHT and 9L tumours (the latter implanted either subcutaneously or intracerebrally) and cells from tissue culture were separated into homogenous sized populations by centrifugal elutriation. In both tumour models these homogeneous sized populations correspond to populations enriched at different stages of the cell cycle. The survival of these elutriated cell populations was measured after a single dose of Cs-137 gamma rays. For cells isolated from 9L solid tumours, there was little variation in radiosensitivity throughout the cell cycle; however, a very small but significant increase in resistance was found in late G 1 cells. This lack of a large variation in radiosensitivity through the cell cycle for 9L cells from solid tumours also was seen in 9L cells growing in monolayer tissue culture. When similar experiments were performed using the KHT sarcoma tumour model, the results showed that KHT cells in vitro exhibited a fairly conventional increase in radioresistance in both mid G 1 and late S. However, the cell age response of KHT cells from solid tumours was different; particularly in the late S and G 2 + M phases. (author)

Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma?

Science.gov (United States)

Kucher, Cynthia; Zhang, Paul J; Acs, Geza; Roberts, Shelley; Xu, Xiaowei

2006-09-01

The sentinel lymph node (SLN) biopsy has become an increasingly important procedure used in the primary staging of malignant melanoma. However, micrometastases in a lymph node can be easily missed on routine H&E-stained sections. Therefore, S-100 and HMB-45 IHC stains are standardly performed on grossly negative SLNs for detection of metastatic melanoma. Each of these IHC markers, however, is not ideal. The authors investigated whether the newer IHC marker Melan-A would improve the detection of metastatic melanoma in SLN biopsies. Forty lymph nodes previously diagnosed with metastatic melanoma were retrospectively evaluated for S-100, HMB-45, and Melan-A expression. In addition, 42 SLN biopsies for metastatic melanoma detection were prospectively collected and evaluated for S-100, HMB-45, and Melan-A expression. All lymph nodes with metastatic melanoma from the retrospective study demonstrated S-100 reactivity. Five of the lymph nodes with metastatic melanoma from the retrospective study failed to express either HMB-45 or Melan-A, all of which displayed a desmoplastic morphology. One of the metastases positive for S-100 and HMB-45 failed to show reactivity with Melan-A (3%). The prospective study found 10 lymph nodes from 42 cases to be positive for metastatic melanoma, which were positive for S-100 (100%). Nine of the involved lymph nodes were positive for HMB-45(90%), and nine were positive for Melan-A (90%). Melan-A, although very specific, cannot replace the use of S-100 and HMB-45 for the detection of metastatic melanoma in SLNs. It can, however, substitute for HMB-45 with equally good results.

Tetracycline is back. Three-step tetracycline-biotin tumour targeting

International Nuclear Information System (INIS)

Salehi, N.; Lichtenstein, M.

1998-01-01

Full text: In the 1960s, investigators attempted to use radiolabelled tetracycline for the detection of tumours. This was limited by bone and gastrointestinal uptake. The monoclonal antibody Avidin Biotin technology has been used for 10 years to target tumours. We have improved a novel mechanism using three step targeting, to demonstrate tumour cells in (C57B1/6X balb-c) F1 mice with subcutaneously implanted E-3 thymoma. The three steps were (1) i.p. injection of Biotin Tetracycline conjugate (t:1) ratio, (2) 96 h later Avidin was injected, and (3) 24 h after (2) 99m Tc-CDTPA-Biotin was injected. Avidin has four high affinity (Km 10-15) Biotin binding sites, hence step (2) couples the Avidin to Tetracycline-Biotin in the tumour. The Avidin then provides a high affinity target for the otherwise rapidly urinary excreted 99m Tc-CDTPA-Biotin. Mice were sacrificed 16-24h after (3) by cervical dislocation. Biodistribution of radioactivity tumour to blood, liver, bone and stomach were: T:BL= 7.2, T:LI= 3.35, TBO= 9.65, T:ST= 0.93. The percentage of injected dose/g was T = 4.49%, BL = 0.62%. E-3 Thymoma is a rapid growing tumour. At day 1 (step 1) the tumour size was 0.45 cm, six days later (step 3) each dimension was doubled. Hence, percentage of injected dose per gram is artefactually reduced eight-fold. With a slowly growing tumour using the same method the results may be better. The conclusions reached are that Tetracycline-Biotin 3-stage method of tumour targeting is worthy of further development

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

International Nuclear Information System (INIS)

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

2005-01-01

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

100-B/C Target Analyte List Development for Soil

Energy Technology Data Exchange (ETDEWEB)

R.W. Ovink

2010-03-18

This report documents the process used to identify source area target analytes in support of the 100-B/C remedial investigation/feasibility study addendum to DOE/RL-2008-46. This report also establishes the analyte exclusion criteria applicable for 100-B/C use and the analytical methods needed to analyze the target analytes.

The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

Science.gov (United States)

Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C

2015-02-27

ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

Science.gov (United States)

Tang, Ke; Zhang, Yi; Zhang, Huafeng; Xu, Pingwei; Liu, Jing; Ma, Jingwei; Lv, Meng; Li, Dapeng; Katirai, Foad; Shen, Guan-Xin; Zhang, Guimei; Feng, Zuo-Hua; Ye, Duyun; Huang, Bo

2012-01-01

Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

Clinical multi-colour fluorescence imaging of malignant tumours - initial experience

International Nuclear Information System (INIS)

Svanberg, K.; Wang, I.; Montan, S.; Andersson-Engels, S.; Svanberg, S.; Lund Inst. of Technology

1998-01-01

The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation, ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s was mixed with a normal colour video image of the tissue. A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in vitro investigations of resected breast cancer. (orig./MG)

Polysaccharides from Sargassum thunbergii: Monthly variations and anti-complement and anti-tumour activities.

Science.gov (United States)

Jin, Weihua; Liu, Ge; Zhong, Weihong; Sun, Chaomin; Zhang, Quanbin

2017-12-01

Monthly variations of polysaccharides from Sargassum thunbergii and their anti-complement and anti-tumour activities were investigated. It was observed that an increase in fucose and total sugar contents occurred during the growth period (from early April to mid-June), accompanied by a decrease in molar ratios of other monosaccharides to fucose. The highest yields were obtained from early July to early September, which was in accordance with the significant increase in molar ratio of glucose to fucose and decrease in molar ratio of other monosaccharides to fucose. And the above results suggested that S. Thunbergii synthesized large amount of laminaran, the storage substance of brown algae, during the senescence period. However, sulfate contents were relatively stable in the life cycle of S. thunbergii. These results suggested that S. thunbergii synthesized complex sulfated heteropolysacchairdes during inactive period, while during other periods, it synthesized more sulfated galactofucan. All polysaccharides showed anti-complement activity, suggesting that the harvesting time did not influence the anti-complement activities. In the anti-tumour assay in vitro, the polysaccharides taken during the senescence period had much lower anti-tumour activity, suggesting that fucoidan, but not laminaran, determined the anti-tumour activities. Therefore, polysaccharides from S. thunbergii might have great potential in anti-complement and anti-tumour application. Copyright © 2017 Elsevier B.V. All rights reserved.

Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling.

Science.gov (United States)

Findeisen, Peter; Zapatka, Marc; Peccerella, Teresa; Matzk, Heike; Neumaier, Michael; Schadendorf, Dirk; Ugurel, Selma

2009-05-01

Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

HisB as novel selection marker for gene targeting approaches in Aspergillus niger.

Science.gov (United States)

Fiedler, Markus R M; Gensheimer, Tarek; Kubisch, Christin; Meyer, Vera

2017-03-08

For Aspergillus niger, a broad set of auxotrophic and dominant resistance markers is available. However, only few offer targeted modification of a gene of interest into or at a genomic locus of choice, which hampers functional genomics studies. We thus aimed to extend the available set by generating a histidine auxotrophic strain with a characterized hisB locus for targeted gene integration and deletion in A. niger. A histidine-auxotrophic strain was established via disruption of the A. niger hisB gene by using the counterselectable pyrG marker. After curing, a hisB - , pyrG - strain was obtained, which served as recipient strain for further studies. We show here that both hisB orthologs from A. nidulans and A. niger can be used to reestablish histidine prototrophy in this recipient strain. Whereas the hisB gene from A. nidulans was suitable for efficient gene targeting at different loci in A. niger, the hisB gene from A. niger allowed efficient integration of a Tet-on driven luciferase reporter construct at the endogenous non-functional hisB locus. Subsequent analysis of the luciferase activity revealed that the hisB locus is tight under non-inducing conditions and allows even higher luciferase expression levels compared to the pyrG integration locus. Taken together, we provide here an alternative selection marker for A. niger, hisB, which allows efficient homologous integration rates as well as high expression levels which compare favorably to the well-established pyrG selection marker.

Genome-wide DNA polymorphism in the indica rice varieties RGD-7S and Taifeng B as revealed by whole genome re-sequencing.

Science.gov (United States)

Fu, Chong-Yun; Liu, Wu-Ge; Liu, Di-Lin; Li, Ji-Hua; Zhu, Man-Shan; Liao, Yi-Long; Liu, Zhen-Rong; Zeng, Xue-Qin; Wang, Feng

2016-03-01

Next-generation sequencing technologies provide opportunities to further understand genetic variation, even within closely related cultivars. We performed whole genome resequencing of two elite indica rice varieties, RGD-7S and Taifeng B, whose F1 progeny showed hybrid weakness and hybrid vigor when grown in the early- and late-cropping seasons, respectively. Approximately 150 million 100-bp pair-end reads were generated, which covered ∼86% of the rice (Oryza sativa L. japonica 'Nipponbare') reference genome. A total of 2,758,740 polymorphic sites including 2,408,845 SNPs and 349,895 InDels were detected in RGD-7S and Taifeng B, respectively. Applying stringent parameters, we identified 961,791 SNPs and 46,640 InDels between RGD-7S and Taifeng B (RGD-7S/Taifeng B). The density of DNA polymorphisms was 256.8 SNPs and 12.5 InDels per 100 kb for RGD-7S/Taifeng B. Copy number variations (CNVs) were also investigated. In RGD-7S, 1989 of 2727 CNVs were overlapped in 218 genes, and 1231 of 2010 CNVs were annotated in 175 genes in Taifeng B. In addition, we verified a subset of InDels in the interval of hybrid weakness genes, Hw3 and Hw4, and obtained some polymorphic InDel markers, which will provide a sound foundation for cloning hybrid weakness genes. Analysis of genomic variations will also contribute to understanding the genetic basis of hybrid weakness and heterosis.