Expression of tumour necrosis factor alpha and accumulation of fibronectin in coronary artery restenotic lesions retrieved by atherectomy.

Science.gov (United States)

Clausell, N.; de Lima, V. C.; Molossi, S.; Liu, P.; Turley, E.; Gotlieb, A. I.; Adelman, A. G.; Rabinovitch, M.

1995-01-01

BACKGROUND--The formation of coronary artery neointima experimentally induced in piglets after cardiac transplantation is related to an immune-inflammatory reaction associated with increased expression of T cells and inflammatory mediators (tumour necrosis factor alpha and interleukin 1 beta) and upregulation of fibronectin. In vivo blockade of tumour necrosis factor alpha in rabbits after cardiac transplantation results in reduced neointimal formation. The objective of this study was to investigate the hypothesis that coronary restenosis after atherectomy or percutaneous balloon angioplasty is associated with a similar inflammatory cascade initiated by mechanical injury. METHODS--Specimens taken at coronary atherectomy were analysed from 16 patients. Nine had had the procedure performed twice, firstly, to remove a primary lesion, and secondly, to remove a restenotic lesion. Seven had percutaneous balloon angioplasty after removal of restenotic tissue. Coronary atherectomy specimens were analysed by immunohistochemistry for the presence of T cells, macrophages, major histocompatibility complex II, interleukin 1 beta, tumour necrosis factor alpha, fibronectin, and the receptor for hyaluronan mediated motility. RESULTS--The groups were clinically and angiographically similar with equivalent lumens before and after atherectomy. Restenotic lesions had increased expression of tumour necrosis factor alpha and fibronectin compared with the primary lesions (P < 0.05 for both). There was also a trend towards a greater number of T cells and increased expression of interleukin 1 beta. CONCLUSIONS--Restenosis is associated with increased expression of tumour necrosis factor alpha and fibronectin, suggesting that an immune-inflammatory reaction probably contributes to neointimal formation and may represent a form of wound healing and repair secondary to mechanical injury. Images PMID:7626352

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.

Therapeutic responses in systematic targeted alpha therapy trial for melanoma

International Nuclear Information System (INIS)

Raja, C.; Rizvi, S.M.A.; Song, E.Y.; Graham, P.; Kearsley, J.H.; Goldsmith, H.; Bosserhoff, A.; Morgenstern, A.; Apostolidis, C.; Reisfeld, R.

2006-01-01

Full text: The therapeutic response of melanoma patients after systemic alpha therapy has been investigated in an open-labeled Phase 1 dose escalation study to establish the effective dose of alpha-immunoconjugate 2l3 Bi-cDTPA-9.2.27 mAb (AIC). The tools used to investigate the effects were physical examination; the images of the tumours, pathology comparisons over 12 weeks; CT comparisons and changes in tumour marker over 8 weeks. The physical examination indicated varied tumour responses. One patient showed complete response at 12 weeks post-TAT, with 20 of 21 tumours completely regressing, the last reduced by 80%. The tumour beds were biopsied for staining; S l OO was negative and no viable cells were observed. Most patients showed stable disease at 2 weeks. In one patient the CT comparison of 8 weeks with baseline showed marked reduction in three lung lesions. At least 4/21 patients showed partial response at 4 to 8 weeks and the same number showed stable disease. The disease progressed in 7 patients. The tumour marker melanoma inhibitory activity protein (MIA) showed reductions over 8 weeks, and was consistent with observations in most patients. Complete and partial responses were observed in systemic TAT for stage IV melanoma, but there was no dose-response relationship

The polymorphism -863C/A in tumour necrosis factor-alpha gene contributes an independent association to gout.

Science.gov (United States)

Chang, S-J; Tsai, P-C; Chen, C-J; Lai, H-M; Ko, Y-C

2007-11-01

To investigate the associations between polymorphisms in the promoter of the tumour necrosis factor-alpha (TNF-alpha) gene and gout. The polymorphisms -308G/A and -863C/A in the TNF-alpha gene were determined in 106 gout patients and 159 healthy controls among male Taiwanese using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The biochemical markers, including Glutamic-oxaloacetic transaminase (GOT), Glutamic-pyruvic transaminase (GPT), uric acid, creatinine, total cholesterol (TC), triglycerides (TG), body mass index (BMI) and hypertension, as well as alcohol consumption were measured. The gout patients had 9.43% (10/106) with genotype AA at polymorphism -863C/A showing a significantly higher fraction than controls (0.63%; 1/159, P gout patients had significantly higher portions of abnormal GOT, GPT, creatinine, TC, TG, alcohol consumption, hypertension and hyperuricaemia than controls (P 0.05). After adjustment by a stepwise logistic regression method, the hyperuricaemia, creatinine, GPT, TG and alcohol consumption as well as genotype AA at polymorphism -863C/A were found to be significantly associated with gout. The genotype AA at polymorphism -863C/A in a recessive model showed a significant association with developing gout independent of hyperuricaemia, abnormal creatinine, higher TG, GPT and alcohol consumption.

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. 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.

Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.

LENUS (Irish Health Repository)

Caiazza, F

2012-02-01

BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)alpha expression correlated with EGFR\\/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)alpha activity in clinical breast cancer was established by relating the expression of cPLA(2)alpha in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)alpha mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)alpha expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)alpha expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)alpha in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.

The average number of alpha-particle hits to the cell nucleus required to eradicate a tumour cell population

International Nuclear Information System (INIS)

Roeske, John C; Stinchcomb, Thomas G

2006-01-01

Alpha-particle emitters are currently being considered for the treatment of micrometastatic disease. Based on in vitro studies, it has been speculated that only a few alpha-particle hits to the cell nucleus are considered lethal. However, such estimates do not consider the stochastic variations in the number of alpha-particle hits, energy deposited, or in the cell survival process itself. Using a tumour control probability (TCP) model for alpha-particle emitters, we derive an estimate of the average number of hits to the cell nucleus required to provide a high probability of eradicating a tumour cell population. In simulation studies, our results demonstrate that the average number of hits required to achieve a 90% TCP for 10 4 clonogenic cells ranges from 18 to 108. Those cells that have large cell nuclei, high radiosensitivities and alpha-particle emissions occurring primarily in the nuclei tended to require more hits. As the clinical implementation of alpha-particle emitters is considered, this type of analysis may be useful in interpreting clinical results and in designing treatment strategies to achieve a favourable therapeutic outcome. (note)

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

Science.gov (United States)

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.

Development of a sensitive ELISA for the quantification of human tumour necrosis factor-alpha using 4 polyclonal antibodies.

NARCIS (Netherlands)

Grebenchtchikov, N.J.; Ven-Jongekrijg, J. van der; Pesman, G.J.; Geurts-Moespot, A.; Meer, J.W.M. van der; Sweep, C.G.J.

2005-01-01

Despite the availability of many assays to measure concentrations of tumour necrosis factor alpha (TNF-alpha) in body fluids, these assays often lack specificity or sensitivity and are often of questionable reliability, resulting in inconsistent results. Therefore, we have developed an ELISA that is

IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes

DEFF Research Database (Denmark)

Falkencrone, Sidsel; Poulsen, Lars K.; Bindslev-Jensen, Carsten

2013-01-01

IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-α), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have...

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

Energy Technology Data Exchange (ETDEWEB)

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.

Science.gov (United States)

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.

Clinical value of imaging using antibody to alpha fetoprotein in germ cell tumours

International Nuclear Information System (INIS)

Hitchins, R.N.; Begent, R.H.J.; Green, A.J.; Searle, F.; Bagshawe, K.D.; Charing Cross Group of Hospitals, London; Van Heyningen, V.

1989-01-01

Germ cell tumours (GCT) producing alpha fetoprotein (aFP) can be imaged by external scintigraphy after intraveneous administration of radiolabelled antibody directed against aFP. Antibody imaging (AI) by this method was used in an attempt to guide surgical resection of deposits of drug-resistant or recurrent GCT. 30 patients with GCT and raised aFP in whom site of tumour was not known were investigated by AI and conventional imaging methods. All but one were heavily pretreated. Where tumour appeared localised, resection was attempted. Tumour was found in all sites positive by both AI and conventional imaging. AI produced false-positive results in one of 30 patients and false-negative results in 9 patients. Computerised tomography was false-positive in one case and false-negative in three. In these patients, AI gave true-negative and true-positive results, respectively. Of 11 patients with positive AI in whom resection was attempted, 6 achieved sustained complete response with up to 5 years follow-up. We conclude AI and conventional imaging methods to be complementary in selection for surgery of patients with drug-resistant or recurrent GCT. (orig.) [de

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

Directory of Open Access Journals (Sweden)

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.

A study of serum levels of leptin, ghrelin and tumour necrosis factor-alpha in child patients with cyanotic and acyanotic, congenital heart disease

International Nuclear Information System (INIS)

Shahramian, I.; Noori, N.M.

2013-01-01

Objective: To investigate the serum levels of leptin, ghrelin and tumour necrosis factor-alpha in children with cyanotic and acyanotic congenital heart disease. Methods: The prospective cohort study, was conducted at imam Ali Hospital, Zahedan University of Medical Sciences, Iran, in 2009-10 and comprised 64 subjects, including patients and controls. Using enzyme-linked immunosorpent assay kits, serum levels of ghrelin, leptin and tumour necrosis factor-alpha were measured and compared among patients (both cyanotic and acyanotic) and the controls, SPSS version 20 was used for statistical analysis. Results: Of the 64 subjects, 24 (37.5%) were cyanotic, 21(32.8%) were acynotic and 19(29.68%) were healthy controls. The three groups were homogenous in terms of age and gender characteristics. There was no significant difference among the groups leptin, ghrelin and tumour necrosis factor-alpha serum levels (p>0.05). There were also no significant differences in terms of weight, height and body mass index (P>0.05). Conclusion: Serum levels of ghrelin, leptin and tumour necrosis factor-alpha did not change in acyanotic and cyanotic patients with congenital heart disease, suggesting that other crucial factors may regulate individuals' nutrient intake, growth, weight and energy intake and output. (author)

Serum alpha fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance

NARCIS (Netherlands)

de Wit, R; Collette, L; Sylvester, R; de Mulder, PHM; Sleijfer, DT; Huinink, WWT; Kaye, SB; van Oosterom, AT; Boven, E; Stoter, G

It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a

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.

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

Science.gov (United States)

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

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.

Tumor necrosis factor-alpha and interleukin -6 as diagnostic markers of diabetic complications in children with type I diabetes mellitus

International Nuclear Information System (INIS)

El-Nashar, N.A.; Moawad, A.T.; Nassar, E.M.

2010-01-01

This study aimed to determine the role of cellular auto immunity and its humoral mediators in pathogenesis and following up of type I diabetes mellitus (TIDM). Therefore, serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), glycemic control, body mass index, duration of the disease and microalbuminuria in children with TIDM were evaluated. This study was conducted on 30 patients suffered from type I diabetes mellitus (TIDM), 14 males and 16 females with mean age of 11.40 ±3.67 years and 20 apparently healthy children served as control (10 male and 10 female). Children with TIDM were classified according to duration: diabetic children for 5 years or less duration (n= 15, duration means: 2.74 ± 1.34 years) and diabetic children > 5 years (n=15, duration means: 7.35 ± 1.49 years); according to glycemic control: children with good glycemic control (n=16, HbAIc: 7.82 ± 2.70) and diabetic children with poor glycemic control (n=14, HbAIc: 10.49 ± 2.72) and according to complication: diabetic children without complications (n= 20) and diabetic children with microvascular or neurological complications (n= 10, nephritic, retinal or neurological complications). Patients and controls were subjected to careful history, clinical examination and laboratory investigations. The following investigations were done for all children; random blood glucose, Glycated hemoglobin (HbAIc %), microalbuminuria and kidney function tests. Serum tumour necrosis factor-alpha (TNF-alpha) and serum interleukin-6 (IL-6) were measured using immuno-enzymometric assay (ELISA). Patients with TIDM with duration more than 5 years, with poor glycemic control and with complications had higher serum glucose levels, higher HbAIc%, higher level of blood urea nitrogen (BUN), serum creatinine, microalbuminuria and elevated serum TNF-alpha (p<0.0001) and IL-6 (p<0.0001) in comparison to the same diabetic patients with 5 years duration or less, with good glycemic control

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

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

Science.gov (United States)

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

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.

PET imaging of {alpha}{sub v}{beta}{sub 3} integrin expression in tumours with {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides

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Dijkgraaf, Ingrid; Franssen, Gerben M.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Yim, Cheng-Bin [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Utrecht University, Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht (Netherlands); Schuit, Robert C. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); Luurtsema, Gert [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Hanzeplein 1, P.O. Box 30.001, Groningen (Netherlands); Liu, Shuang [Purdue University, School of Health Sciences, West Lafayette, IN (United States)

2011-01-15

Due to the restricted expression of {alpha}{sub v}{beta}{sub 3} in tumours, {alpha}{sub v}{beta}{sub 3} is considered a suitable receptor for tumour targeting. In this study the {alpha}{sub v}{beta}{sub 3}-binding characteristics of {sup 68}Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their {sup 111}In-labelled counterparts. A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)]{sub 2}) and a tetrameric (E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2}) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with {sup 68}Ga. In vitro {alpha}{sub v}{beta}{sub 3}-binding characteristics were determined in a competitive binding assay. In vivo {alpha}{sub v}{beta}{sub 3}-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. The IC{sub 50} values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)]{sub 2} and DOTA-E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2} were 23.9 {+-} 1.22, 8.99 {+-} 1.20 and 1.74 {+-} 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 {+-} 1.15, 3.34 {+-} 1.16 and 1.80 {+-} 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 {+-} 0.30, 5.24 {+-} 0.27 and 7.11 {+-} 0.67%ID/g, respectively) was comparable to that of their {sup 111}In-labelled counterparts (2.70 {+-} 0.29, 5.61 {+-} 0.85 and 7.32 {+-} 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The {sup 68}Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of {alpha}{sub v} {beta}{sub 3} expression with PET. (orig.)

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

Directory of Open Access Journals (Sweden)

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.

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

NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Ryder, L P

1989-01-01

The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5...

Generation of tumour-necrosis-factor-alpha-specific affibody molecules capable of blocking receptor binding in vitro.

Science.gov (United States)

Jonsson, Andreas; Wållberg, Helena; Herne, Nina; Ståhl, Stefan; Frejd, Fredrik Y

2009-08-17

Affibody molecules specific for human TNF-alpha (tumour necrosis factor-alpha) were selected by phage-display technology from a library based on the 58-residue Protein A-derived Z domain. TNF-alpha is a proinflammatory cytokine involved in several inflammatory diseases and, to this day, four TNF-alpha-blocking protein pharmaceuticals have been approved for clinical use. The phage selection generated 18 unique cysteine-free affibody sequences of which 12 were chosen, after sequence cluster analysis, for characterization as proteins. Biosensor binding studies of the 12 Escherichia coli-produced and IMAC (immobilized-metal-ion affinity chromatography)-purified affibody molecules revealed three variants that demonstrated the strongest binding to human TNF-alpha. These three affibody molecules were subjected to kinetic binding analysis and also tested for their binding to mouse, rat and pig TNF-alpha. For ZTNF-alpha:185, subnanomolar affinity (KD=0.1-0.5 nM) for human TNF-alpha was demonstrated, as well as significant binding to TNF-alpha from the other species. Furthermore, the binding site was found to overlap with the binding site for the TNF-alpha receptor, since this interaction could be efficiently blocked by the ZTNF-alpha:185 affibody. When investigating six dimeric affibody constructs with different linker lengths, and one trimeric construct, it was found that the inhibition of the TNF-alpha binding to its receptor could be further improved by using dimers with extended linkers and/or a trimeric affibody construct. The potential implication of the results for the future design of affibody-based reagents for the diagnosis of inflammation is discussed.

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

International Nuclear Information System (INIS)

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

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

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

Directory of Open Access Journals (Sweden)

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 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.

Science.gov (United States)

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.

Osteopontin as a marker for response to pegylated interferon Alpha ...

African Journals Online (AJOL)

Osteopontin as a marker for response to pegylated interferon Alpha-2b treatment in Chronic HCV Saudi patients. Yousri Mostafa Hussein1,2, Ayman Alhazmi1, Saad Alzahrani3, Ahmad El-Askary1,4,. Abdulrahman Alghamdy5, Eman Bayomy4, Assmaa Selim6, Mohammed Alghamdy1. 1. Medical Laboratories Department ...

Plasmodium vivax merozoite surface protein-3 alpha: a high-resolution marker for genetic diversity studies.

Science.gov (United States)

Prajapati, Surendra Kumar; Joshi, Hema; Valecha, Neena

2010-06-01

Malaria, an ancient human infectious disease caused by five species of Plasmodium, among them Plasmodium vivax is the most widespread human malaria species and causes huge morbidity to its host. Identification of genetic marker to resolve higher genetic diversity for an ancient origin organism is a crucial task. We have analyzed genetic diversity of P. vivax field isolates using highly polymorphic antigen gene merozoite surface protein-3 alpha (msp-3 alpha) and assessed its suitability as high-resolution genetic marker for population genetic studies. 27 P. vivax field isolates collected during chloroquine therapeutic efficacy study at Chennai were analyzed for genetic diversity. PCR-RFLP was employed to assess the genetic variations using highly polymorphic antigen gene msp-3 alpha. We observed three distinct PCR alleles at msp-3 alpha, and among them allele A showed significantly high frequency (53%, chi2 = 8.22, p = 0.001). PCR-RFLP analysis revealed 14 and 17 distinct RFLP patterns for Hha1 and Alu1 enzymes respectively. Further, RFLP analysis revealed that allele A at msp-3 alpha is more diverse in the population compared with allele B and C. Combining Hha1 and Alu1 RFLP patterns revealed 21 distinct genotypes among 22 isolates reflects higher diversity resolution power of msp-3 alpha in the field isolates. P. vivax isolates from Chennai region revealed substantial amount of genetic diversity and comparison of allelic diversity with other antigen genes and microsatellites suggesting that msp-3 alpha could be a high-resolution marker for genetic diversity studies among P. vivax field isolates.

Tumour necrosis factor-alpha blockers: potential limitations in the management of advanced endometriosis? A case report.

Science.gov (United States)

Shakiba, Khashayar; Falcone, Tommaso

2006-09-01

Several studies have shown that tumour necrosis factor (TNF)-alpha levels are increased in the peritoneal fluid of women with endometriosis, with correlation between TNF-alpha concentrations and the degree of disease. It is also likely that elevation of peritoneal fluids' TNF-alpha levels may play a role in the pathogenesis of infertility associated with endometriosis. Use of drugs such as etanercept, a TNF-alpha receptor immunoglobulin fusion protein which inhibits TNF-alpha activity, showed in an animal study to reduce the severity of the disease, and the size of endometriotic foci. TNF-alpha blockers were recommended as a possible new line of therapy for endometriosis. Our case involved a 35-year-old Para 0, with rheumatic arthritis and stage 4 endometriosis. After 6 years of constant use of etanercept, she showed no improvement of endometriosis as demonstrated at laparoscopy. However, she underwent a successful IVF after the first attempt. TNF-alpha-blocker medications might not be beneficial for patients with advanced endometriosis. However, we cannot exclude the possible effect of these medications on early-stage endometriosis, and further study is required. Some of the immunologic abnormalities in the pelvis of patients with endometriosis could be the consequence of the disease and not the cause, and possibly suppression of immune cells and their products may not have a major effect on endometriotic lesions at an advanced stage. This also could explain why suppression of TNF-alpha showed no effect on infertility. However, use of TNF-alpha-blockers before IVF might increase the success rate in advanced endometriosis.

Primary pleuro-pulmonary malignant germ cell tumours.

Directory of Open Access Journals (Sweden)

Vaideeswar P

2002-01-01

Full Text Available Lungs and pleura are rare sites for malignant germ-cell tumours. Two cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma are described in young males who presented with rapid progression of respiratory symptoms. The malignant mixed germ cell tumour occurred in the right lung, while the yolk-sac tumour had a pseudomesotheliomatous growth pattern suggesting a pleural origin. Alpha-foetoprotein was immunohistochemically demonstrated in both.

Influence of tumour size on the efficacy of targeted alpha therapy with (213)Bi-[DOTA(0),Tyr(3)]-octreotate.

Science.gov (United States)

Chan, Ho Sze; Konijnenberg, Mark W; de Blois, Erik; Koelewijn, Stuart; Baum, Richard P; Morgenstern, Alfred; Bruchertseifer, Frank; Breeman, Wouter A; de Jong, Marion

2016-12-01

Targeted alpha therapy has been postulated to have great potential for the treatment of small clusters of tumour cells as well as small metastases. (213)Bismuth, an α-emitter with a half-life of 46 min, has shown to be effective in preclinical as well as in clinical applications. In this study, we evaluated whether (213)Bi-[DOTA(0), Tyr(3)]-octreotate ((213)Bi-DOTATATE), a (213)Bi-labelled somatostatin analogue with high affinity for somatostatin receptor subtype 2 (SSTR2), is suitable for the treatment of larger neuroendocrine tumours overexpressing SSTR2 in comparison to its effectiveness for smaller tumours. We performed a preclinical targeted radionuclide therapy study with (213)Bi-DOTATATE in animals bearing tumours of different sizes (50 and 200 mm(3)) using two tumour models: H69 (human small cell lung carcinoma) and CA20948 (rat pancreatic tumour). Pharmacokinetics was determined for calculation of dosimetry in organs and tumours. H69- or CA20948-xenografted mice with tumour volumes of approximately 120 mm(3) were euthanized at 10, 30, 60 and 120 min post injection of a single dose of (213)Bi-DOTATATE (1.5-4.8 MBq). To investigate the therapeutic efficacy of (213)Bi-DOTATATE, xenografted H69 and CA20948 tumour-bearing mice with tumour sizes of 50 and 200 mm(3) were administered daily with a therapeutic dose of (213)Bi-DOTATATE (0.3 nmol, 2-4 MBq) for three consecutive days. The animals were followed for 90 days after treatment. At day 90, mice were injected with 25 MBq (99m)Tc-DMSA and imaged by SPECT/CT to investigate possible renal dysfunction due to (213)Bi-DOTATATE treatment. Higher tumour uptakes were found in CA20948 tumour-bearing animals compared to those in H69 tumour-bearing mice with the highest tumour uptake of 19.6 ± 6.6 %IA/g in CA20948 tumour-bearing animals, while for H69 tumour-bearing mice, the highest tumour uptake was found to be 9.8 ± 2.4 %IA/g. Nevertheless, as the anti-tumour effect was more pronounced in H69

Single-hit mechanism of tumour cell killing by radiation.

Science.gov (United States)

Chapman, J D

2003-02-01

To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells

Peak alpha frequency is a neural marker of cognitive function across the autism spectrum.

Science.gov (United States)

Dickinson, Abigail; DiStefano, Charlotte; Senturk, Damla; Jeste, Shafali Spurling

2018-03-01

Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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.

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.

Cancer progression: is inhibin alpha from Venus or Mars?

Science.gov (United States)

Ball, Emma M A; Mellor, Sally L; Risbridger, Gail P

2004-10-01

The inhibin field has been perplexed by the information that inhibin alpha is a tumour suppressor in mice yet is elevated in women with ovarian cancer. Furthermore, we have consistently observed a down-regulation or loss of inhibin alpha in prostate cancer patient samples and cell lines. However, our latest data have prompted us to re-evaluate the role of inhibin alpha in prostate and other cancers. Using the analogy of TGF-beta as a springboard for our hypothesis, we offer a unifying model whereby the previously conflicting observations in mice, men and women can be explained. We propose that initially inhibin alpha is tumour-suppressive and is expressed in benign and early-stage primary cancers. Tumour-suppressive inhibin alpha is then silenced as the tumour progresses but is reactivated as a pro-metastatic factor in advanced, aggressive cancers.

Differential risk assessments from five hypoxia specific assays: The basis for biologically adapted individualized radiotherapy in advanced head and neck cancer patients

DEFF Research Database (Denmark)

Nordsmark, Marianne; Eriksen, Jesper Grau; Gebski, Val

2007-01-01

osteopontin measured by ELISA, tumour oxygenation status using pO(2) needle electrodes and tumour osteopontin, hypoxia inducible factor 1alpha (HIF-1alpha) and carboxyanhydrase 9 (CA9) by immunohistochemistry. The primary treatment was radiotherapy and the hypoxic radiosensitizer nimorazole. Loco......-regional tumour control was evaluated at 5 years. RESULTS: All five markers showed inter-tumour variability. Inter-marker correlations were inconsistent. Only plasma osteopontin inversely correlated with median tumour pO(2), (p=0.02, r=0.28) and CA9 correlated with HIF-1alpha (p...-Meier analysis high plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9 and tumour osteopontin failed to predict loco-regional control in this set dataset. When analyzing Hb, stage, and the five markers...

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

Ovarian yolk sac tumour in a girl - case report.

Science.gov (United States)

Sharma, Charu; Shah, Hemanshi; Sisodiya Shenoy, Neha; Makhija, Deepa; Waghmare, Mukta

2017-01-01

Yolk sac tumours are rare ovarian malignancies accounting for less than 1% of malignant ovarian germ cell tumours. They are mostly seen in adolescents and young women and are usually unilateral making fertility preservation imperative. Raised alpha-feto protein level is the hallmark of this tumour. We describe stage III yolk sac tumour in a girl child.

Improved targeting of the alpha(v)beta (3) integrin by multimerisation of RGD peptides.

NARCIS (Netherlands)

Dijkgraaf, I.; Kruijtzer, J.A.; Liu, S.; Soede, A.C.; Oyen, W.J.G.; Corstens, F.H.M.; Liskamp, R.M.; Boerman, O.C.

2007-01-01

PURPOSE: The integrin alpha(v)beta(3) is expressed on sprouting endothelial cells and on various tumour cell types. Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3) binding

Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1{alpha}

Energy Technology Data Exchange (ETDEWEB)

Ueda, Masashi [Kyoto University, Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto (Japan); Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kudo, Takashi; Konishi, Hiroaki; Miyano, Azusa; Ono, Masahiro; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kuge, Yuji [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Mukai, Takahiro [Kyushu University, Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Fukuoka (Japan); Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Masahiro [Kyoto University, Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto (Japan)

2010-08-15

Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-{sup 123}I-iodobenzoyl)norbiotinamide ({sup 123}I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and {sup 123}I-IBB for rapid imaging of HIF-1-active tumours. Tumour-implanted mice were pretargeted with POS. After 24 h, {sup 125}I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between {sup 125}I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of {sup 125}I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1{alpha} immunohistochemistry. {sup 125}I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from {sup 125}I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of {sup 125}I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of {sup 125}I-IBB was heterogeneous and was significantly correlated with HIF-1{alpha}-positive regions (R=0.58, p<0.0001). POS pretargeting with {sup 123}I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours. (orig.)

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.

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.)

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.

Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

Directory of Open Access Journals (Sweden)

Ruqaya AL Darwish

2015-01-01

Full Text Available There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB, with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

Diffusion-weighted magnetic resonance imaging: a potential non-invasive marker of tumour aggressiveness in localized prostate cancer

International Nuclear Information System (INIS)

Souza, N.M. de; Riches, S.F.; Van As, N.J.; Morgan, V.A.; Ashley, S.A.; Fisher, C.; Payne, G.S.; Parker, C.

2008-01-01

Aim: To evaluate diffusion-weighted magnetic resonance imaging (DW-MRI) as a marker for disease aggressiveness by comparing tumour apparent diffusion coefficients (ADCs) between patients with low- versus higher-risk localized prostate cancer. Method: Forty-four consecutive patients classified as low- [n = 26, stageT1/T2a, Gleason score ≤ 6, prostate-specific antigen (PSA) 10 (group 2)] risk, who subsequently were monitored with active surveillance or started neoadjuvant hormone and radiotherapy, respectively, underwent endorectal MRI. T2-weighted (T2W) and DW images (5 b values, 0-800 s/mm 2 ) were acquired and isotropic ADC maps generated. Regions of interest (ROIs) on T2W axial images [around whole prostate, central gland (CG), and tumour] were transferred to ADC maps. Tumour, CG, and peripheral zone (PZ = whole prostate minus CG and tumour) ADCs (fast component from b = 0-100 s/mm 2 , slow component from b = 100-800 s/mm 2 ) were compared. Results: T2W-defined tumour volume medians, and quartiles were 1.2 cm 3 , 0.7 and 3.3 cm 3 (group 1); and 6 cm 3 , 1.3 and 16.5 cm 3 (group 2). There were significant differences in both ADC fast (1778 ± 264 x 10 -6 versus 1583 ± 283 x 10 -6 mm 2 /s, p = 0.03) and ADC slow (1379 ± 321 x 10 -6 versus 1196 ± 158 x 10 -6 mm 2 /s, p = 0.001) between groups. Tumour volume (p = 0.002) and ADC slow (p = 0.005) were significant differentiators of risk group. Conclusion: Significant differences in tumour ADCs exist between patients with low-risk, and those with higher-risk localized prostate cancer. DW-MRI merits further study with respect to clinical outcomes

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.

Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients.

Science.gov (United States)

Warren, Mikako; Matsuno, Ryosuke; Tran, Henry; Shimada, Hiroyuki

2018-03-01

This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase (TH) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity. Phox2b immunohistochemistry (IHC) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours (pNT)]: 15 neuroblastoma undifferentiated (NB-UD), 10 NB poorly differentiated (NB-PD), 10 NB differentiating (NB-D), 10 ganglioneuroblastoma intermixed (GNBi), 10 GNB nodular (GNBn) and 10 ganglioneuroma (GN); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma/paraganglioma (PCC/PG)]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma/neuroblastoma; and (group 4) 44 non-neural crest tumours. TH IHC was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in pNT (n = 65 of 65), strongly in NB-UD and NB-PD and with less intensity in NB-D, GNB and GN. Diffuse TH was seen in all NB-PD, NB-D, GNB and GN, but nine of 15 NB-UD and a nodule in GNBn did not express TH (n = 55 of 65). PCC/PG expressed diffuse Phox2b (n = 23 of 23) and diffuse TH, except for one tumour (n = 22 of 23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b (n = none of 44). Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacking TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin. © 2017 John Wiley & Sons Ltd.

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

FIRST-TRIMESTER MATERNAL SERUM ALPHA-FETOPROTEIN AS A MARKER FOR FETAL CHROMOSOMAL DISORDERS

NARCIS (Netherlands)

VANLITH, JMM

1994-01-01

We evaluated first-trimester maternal serum alpha-fetoprotein (MS-AFP) as a marker for fetal chromosomal disorders. The multicentre study was performed under the auspices of the Dutch Working Party on Prenatal Diagnosis. MS-AFP was measured in 2404 normal pregnancies and 72 chromosomally abnormal

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)

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

International Nuclear Information System (INIS)

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)

Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours.

Science.gov (United States)

Saidak, Zuzana; Morisse, Mony Chenda; Chatelain, Denis; Sauzay, Chloé; Houessinon, Aline; Guilain, Nelly; Soyez, Marion; Chauffert, Bruno; Dakpé, Stéphanie; Galmiche, Antoine

2018-03-01

The squamous cell carcinoma antigen (SCCA), encoded by the genes SERPINB3/B4, is a tumour marker produced by head and neck squamous cell carcinoma (HNSCC). We aimed to examine SERPINB3/B4 mRNA levels and its clinical significance in the therapeutic context. We retrieved mRNA expression levels, clinical, pathological and genomic data for 520 HNSCC from The Cancer Genome Atlas (TCGA). HNSCC tumours express high levels of SERPINB3/B4 mRNA. SERPINB3 expression differs depending on Human papillomavirus (HPV) infection status, primary tumour location, grade and differentiation, extension to lymph nodes and extracapsular spread. Interestingly, we observed an association between SERPINB3/B4 and the presence of tumour immune infiltrate as well as the expression of the immune checkpoint regulators PD-L1/PD-L2 that depended on HPV status. Our findings point to potential interest of SERPINB3/B4 for the stratification of HNSCC patients in the therapeutic context. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

PET imaging of alphavbeta integrin expression in tumours with Ga-labelled mono-, di- and tetrameric RGD peptides

NARCIS (Netherlands)

Dijkgraaf, I.; Yim, C.B.; Franssen, G.M.; Schuit, R.C.; Luurtsema, G.; Liu, S.; Oyen, W.J.G.; Boerman, O.C.

2011-01-01

PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared

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.

[Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha].

Science.gov (United States)

Landeros-Olvera, Erick; López-Alvarenga, Juan Carlos; Nava-González, Edna J; Gallegos-Cabriales, Esther; Lavalle-González, Fernando; Bastarrachea, Raúl A; Salazar González, Bertha Cecilia

2014-01-01

The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n=17, controls n=17) with a body mass index>27kg/m(2). Molecular analysis was performed by immune-fluorescence. Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2μ/ml (P=.008); leptin 20.0 vs. 28.0μ/L (P=.02); and tumour necrosis factor-alpha 4.7 vs. 5.1pg/ml (P=.05). The established exercise (5 sessions a week of exercise of 40min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Alpha-interferon does not increase the efficacy of 5-fluorouracil in advanced colorectal cancer.

LENUS (Irish Health Repository)

Thirion, P

2001-03-02

Two meta-analyses were conducted to quantify the benefit of combining alpha-IFN to 5FU in advanced colorectal cancer in terms of tumour response and survival. Analyses were based on a total of 3254 individual patient data provided by principal investigators of each trial. The meta-analysis of 5FU +\\/- LV vs. 5FU +\\/- LV + alpha-IFN combined 12 trials and 1766 patients. The meta-analysis failed to show any statistically significant difference between the two treatment groups in terms of tumour response or survival. Overall tumour response rates were 25% for patients receiving no alpha-IFN vs. 24% for patients receiving alpha-IFN (relative risk, RR = 1.02), and median survivals were 11.4 months for patients receiving no alpha-IFN vs. 11.5 months for patients receiving alpha-IFN (hazard ratio, HR = 0.95). The meta-analysis of 5FU + LV vs. 5FU + alpha-IFN combined 7 trials, and 1488 patients. This meta-analysis showed an advantage for 5FU + LV over 5FU + alpha-IFN which was statistically significant in terms of tumour response (23% vs. 18%; RR = 1.26;P = 0.042), and of a borderline significance for overall survival (HR = 1.11;P = 0.066). Metastases confined to the liver and primary rectal tumours were independent favourable prognostic factors for tumour response, whereas good performance status, metastases confined to the liver or confined to the lung, and primary tumour in the rectum were independent favourable prognostic factors for survival. We conclude that alpha-IFN does not increase the efficacy of 5FU or of 5FU + LV, and that 5FU + alpha-IFN is significantly inferior to 5FU + LV, for patients with advanced colorectal cancer.

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)

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)

Alpha Emitting Radionuclides and Radiopharmaceuticals for Therapy

International Nuclear Information System (INIS)

Chérel, Michel; Barbet, Jacques

2013-01-01

Today, cancer treatments mainly rely on surgery or external beam radiation to remove or destroy bulky tumors. Chemotherapy is given when tumours cannot be removed or when dissemination is suspected. However, these approaches cannot permanently treat all cancers and relapse occurs in up to 50% of the patients’ population. Radioimmunotherapy (RIT) and peptide receptor radionuclide therapy (PRRT) are effective against some disseminated and metastatic diseases, although they are rarely curative. Most preclinical and clinical developments in this field have involved electron-emitting radionuclides, particularly iodine-131, yttrium-90 and lutetium-177. The large range of the electrons emitted by these radionuclides reduces their efficacy against very small tumour cell clusters or isolated tumour cells present in residual disease and in many haematological tumours (leukaemia, myeloma). The range of alpha particles in biological tissues is very short, less than 0.1 mm, which makes alpha emitters theoretically ideal for treatment of such isolated tumour cells or micro-clusters of malignant cells. Thus, over the last decade, a growing interest for the use of alpha-emitting radionuclides has emerged. Research on targeted alpha therapy (TAT) began years ago in Nantes through cooperation between Subatech, a nuclear physics laboratory, CRCNA, a cancer research centre with a nuclear oncology team and ITU (Karlsruhe, Germany). CD138 was demonstrated as a potential target antigen for Multiple Myeloma, which is a target of huge clinical interest particularly suited for TAT because of the disseminated nature of the disease consisting primarily of isolated cells and small clusters of tumour cells mainly localized in the bone marrow. Thus anti-CD138 antibodies were labelled with bismuth-213 from actinium-225/bismuth-213 generators provided by ITU and used to target multiple myeloma cells. In vitro studies showed cell cycle arrest, synergism with chemotherapy and very little induction

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

overall survival. The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis. (orig.)

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

Energy Technology Data Exchange (ETDEWEB)

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

overall survival. The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis. (orig.)

Analysis of the local kinetics and localization of interleukin-1 alpha, tumour necrosis factor-alpha and transforming growth factor-beta, during the course of experimental pulmonary tuberculosis.

Science.gov (United States)

Hernandez-Pando, R; Orozco, H; Arriaga, K; Sampieri, A; Larriva-Sahd, J; Madrid-Marina, V

1997-01-01

A mouse model of pulmonary tuberculosis induced by the intratracheal instillation of live and virulent mycobacteria strain H37-Rv was used to examine the relationship of the histopathological findings with the local kinetics production and cellular distribution of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and transforming growth factor-beta (TGF-beta). The histopathological and immunological studies showed two phases of the disease: acute or early and chronic or advanced. The acute phase was characterized by inflammatory infiltrate in the alveolar-capillary interstitium, blood vessels and bronchial wall with formation of granulomas. During this acute phase, which lasted from 1 to 28 days, high percentages of TNF-alpha and IL-1 alpha immunostained activated macrophages were observed principally in the interstium-intralveolar inflammatory infiltrate and in granulomas. Electron microscopy studies of these cells, showed extensive rough endoplasmic reticulum, numerous lysosomes and occasional mycobacteria. Double labelling with colloid gold showed that TNF-alpha and IL-1 alpha were present in the same cells, but were confined to separate vacuoles near the Golgi area, and mixed in larger vacuoles near to cell membrane. The concentration of TNF-alpha and IL-1 alpha as well as their respective mRNAs were elevated in the early phase, particularly at day 3 when the bacillary count decreased. A second peak was seen at days 14 and 21-28 when granulomas appeared and evolved to full maturation. In contrast, TGF-beta production and numbers of immunoreactive cells were low in comparison with the advanced phase of the disease. The chronic phase was characterized by histopathological changes indicative of more severity (i.e. pneumonia, focal necrosis and extensive interstitial fibrosis) with a decrease in the TNF-alpha and IL-1 alpha production that coincided with the highest level of TGF-beta. The bacillary counts were highest as the macrophages

Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus.

Science.gov (United States)

Garcia, J A; Ferreira, H L; Vieira, F V; Gameiro, R; Andrade, A L; Eugênio, F R; Flores, E F; Cardoso, T C

2017-06-01

Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication-induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy. © 2015 John Wiley & Sons Ltd.

Targeted Alpha Therapy: From Alpha to Omega

International Nuclear Information System (INIS)

Allen, Barry J; Clarke, Raymond; Huang Chenyu

2013-01-01

This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial

NARCIS (Netherlands)

Smolen, Josef S.; Kay, Jonathan; Doyle, Mittie K.; Landewé, Robert; Matteson, Eric L.; Wollenhaupt, Jürgen; Gaylis, Norman; Murphy, Frederick T.; Neal, Jeffrey S.; Zhou, Yiying; Visvanathan, Sudha; Hsia, Elizabeth C.; Rahman, Mahboob U.; Ahern, Michael John; Hall, Stephen; Nash, Peter Thomas; Graninger, Winfried; Ebner, Wolfgang; Machold, Klaus; Zamani, Omid; Atkins, Christopher; Beaulieu, André; Bell, Mary; Fitzcharles, Mary Ann; Keystone, Edward; Khraishi, Majed; McKendry, Robert J. R.; Rahman, Proton; Thomason, Glen T. D.; Thorne, J. Carter; Bookman, Arthur; Faraawi, Rafat; Hannonen, Pekka; Leirisalo-Repo, Marjetta; Järvinen, Pentti; Braun, Jürgen; Burmester, Gerd; Fiehn, Christoph; Gruenke, Mathias; Bäuerle, Michael; Hauer, Rolf-Walter; Kellner, Herbert; Rubbert, Andrea; Schewe, Stefan; Sieper, Joachim; Tony, Hans-Peter; Kekow, Jörn; Ching, Daniel Wai Tho; Jones, Peter Brian Barrie; Singh, Gagrath Pradeep

2009-01-01

Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid

Alpha-fetoprotein as a prognostic marker in acute liver failure: a pilot study.

Science.gov (United States)

Varshney, Anshul; Gupta, Rohit; Verma, Sanjiv K; Ahmad, Sohaib

2017-07-01

Prognostic markers of acute liver failure (ALF) are based on clinical, laboratory or radiological parameters. Most of the biochemical markers are based on hepatic degeneration. We studied the impact of serial serum alpha-fetoprotein (AFP) levels, a marker of liver regeneration, on the outcome of the patients with ALF. AFP levels were estimated on days 1 and 3 of hospitalisation of 32 patients with ALF and the ratio (AFP day3/day1) was calculated. All subjects were categorised as group A (expired) or group B (survived). The AFP ratio was 0.84  +  0.15 in group A (n = 20) versus 1.55  +  0.70 in group B (n = 10); P < 0.001. However, the absolute initial AFP values were not associated with the outcome, favourable or unfavourable. We conclude that AFP levels change dynamically during ALF and have the potential to be used as a predictor of outcome in isolation or in combination with well-established prognostic markers.

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

Directory of Open Access Journals (Sweden)

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

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.

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

Directory of Open Access Journals (Sweden)

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.

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

ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor.

Directory of Open Access Journals (Sweden)

Elton Zeqiraj

2009-06-01

Full Text Available Pseudokinases lack essential residues for kinase activity, yet are emerging as important regulators of signal transduction networks. The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25. Here, we describe the structure of STRADalpha in complex with MO25alpha. The structure reveals an intricate web of interactions between STRADalpha and MO25alpha involving the alphaC-helix of STRADalpha, reminiscent of the mechanism by which CDK2 interacts with cyclin A. Surprisingly, STRADalpha binds ATP and displays a closed conformation and an ordered activation loop, typical of active protein kinases. Inactivity is accounted for by nonconservative substitution of almost all essential catalytic residues. We demonstrate that binding of ATP enhances the affinity of STRADalpha for MO25alpha, and conversely, binding of MO25alpha promotes interaction of STRADalpha with ATP. Mutagenesis studies reveal that association of STRADalpha with either ATP or MO25alpha is essential for LKB1 activation. We conclude that ATP and MO25alpha cooperate to maintain STRADalpha in an "active" closed conformation required for LKB1 activation. It has recently been demonstrated that a mutation in human STRADalpha that truncates a C-terminal region of the pseudokinase domain leads to the polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE syndrome. We demonstrate this mutation destabilizes STRADalpha and prevents association with LKB1. In summary, our findings describe one of the first structures of a genuinely inactive pseudokinase. The ability of STRADalpha to activate LKB1 is dependent on a closed "active" conformation, aided by ATP and MO25alpha binding. Thus, the function of STRADalpha is mediated through an active kinase conformation rather than kinase activity. It is possible that other pseudokinases exert their function through nucleotide binding and active conformations.

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.

Index of alpha/theta ratio of the electroencephalogram: a new marker for Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Magali eSchmidt

2013-10-01

Full Text Available Objective: We evaluated quantitative EEG measures to determine a screening index to discriminate AD patients from normal individuals. Methods: Two groups of individuals older than 50 years, comprising a control group of 57 normal volunteers and a study group of 50 patients with probable AD, were compared. EEG recordings were obtained from subjects in a wake state with eyes closed at rest for 30 min. Logistic regression analysis was conducted. Results: Spectral potentials of the alpha and theta bands were computed for all electrodes and the alpha/theta ratio calculated. Logistic regression of alpha/theta of the mean potential of the C3 and O1 electrodes was carried out. A formula was calculated to aid the diagnosis of AD yielding 76.4 % sensitivity and 84.6 specificity for AD with an area under the ROC curve of 0.92. Conclusions: Logistic regression of alpha/theta of the spectrum of the mean potential of EEG represents a good marker discriminating AD patients from normal controls.

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.

Chlorpromazine inhibits tumour necrosis factor synthesis and cytotoxicity in vitro.

Science.gov (United States)

Zinetti, M; Galli, G; Demitri, M T; Fantuzzi, G; Minto, M; Ghezzi, P; Alzani, R; Cozzi, E; Fratelli, M

1995-11-01

Chlorpromazine (CPZ) has been previously shown to protect against endotoxin [lipopolysaccharide (LPS)] lethality and inhibit the release of tumour necrosis factor in vivo. We investigated at the cellular level whether this was due to direct inhibition of tumour necrosis factor-alpha (TNF-alpha) synthesis, using LPS-stimulated THP-1 human monocytic leukemia cells. We also studied the effect of CPZ on human TNF-alpha action by assessing TNF-alpha cytotoxicity on mouse fibrosarcoma L929 cells. CPZ (1-100 microM) inhibited TNF-alpha production in THP-1 cells in a dose dependent manner by a maximum of 80%. This effect was comparable to that of two well-known inhibitory drugs, dexamethasone and cyclicAMP. Inhibition was also evident at the mRNA level. On the other hand CPZ (10-25 microM) also inhibited TNF-alpha activity: in fact it reduced the cytotoxicity of TNF-alpha on L929 cells (EC50 was increased four times) and could provide protection even as a post-treatment. CPZ inhibited TNF-induced apoptosis in L929 cells, as detected by analysis of nuclear morphology. However, since we showed that apoptosis was very limited, and was not the main mode of cell death in our conditions, this could not explain the overall protection. Since CPZ did not interfere with either the oligomerization state of TNF-alpha or its receptor binding, our data suggest that it reduced cytotoxicity by inhibiting some steps in the TNF-alpha signalling pathways.

Tumour alpha/beta ratios and dose-rate selection in brachytherapy

International Nuclear Information System (INIS)

Duchesne, G.M.

2003-01-01

Traditionally brachytherapy employed low dose rate (LDR) techniques. Recent adoption of high dose rate (HDR) applications, addressing radiation protection concerns, has sparked debate over possible reductions in therapeutic ratio. The radiobiological characteristics of two contrasting examples, prostate cancer and cervical cancer, are examined. Both in-vitro and clinical observations of prostate cancer suggest a low α/β ratio. Labelling indices are below 2.5%, translating into long potential doubling times (Tpot ) of 16 to 61 days or more. Clinical PSA doubling times are in the order of years. Analysis of clinical endpoints in prostate cancer treated with either LDR or HDR techniques indicates that its α/β ratio may lie between 1 - 4 Gy, similar to slowly proliferating late reacting tissues. As such, therapeutic gain may arise from the use of hypofractionated HDR treatments, exploiting the sensitivity to large fraction sizes, effectively escalating dose. The slow proliferative rate also gives credence to the use of LDR, although several tumour doublings may occur during the effective treatment time, and analysis of the clinical data using a low α/β ratio suggests that LDR doses are only equivalent to 70 Gy with conventional fractionation. Cervical carcinoma is a rapidly proliferating tumour with Tpot values of 3-6 days. LDR implants were delivered over relatively short treatment times, negating repopulation effects, and the 'hyperfractionation' effect of LDR was suited to the high α/β ratio. HDR, although also preventing significant repopulation, has the potential to decrease the therapeutic ratio if low α/β , late-reacting tissues are not protected. Clinical data however show improved outcomes and reduced morbidity with HDR through reduced doses to normal tissues. Choosing the optimal dose rate in brachytherapy depends on tumour behaviour and achievable accuracy. HDR offers some advantages even for high α/β ratio tumours, and may be the technique of

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

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)

Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to the tumour necrosis factor alpha inhibitor etanercept.

Science.gov (United States)

Kamarashev, J; Lor, P; Forster, A; Heinzerling, L; Burg, G; Nestle, F O

2002-01-01

We report a 50-year-old male patient with a 15-year history of psoriasis including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A induced a generalised pustular exacerbation and a aggravation of the joint condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as well as regression of the pustular eruption, while residual erythema was still present. The clinical response was reflected by an increase in circulating interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during treatment. We conclude that etanercept may be a safe and effective therapy not only in severe psoriatic arthritis, but also in cases of pustular rebound after withdrawal of immunosuppressive agents. Copyright 2002 S. Karger AG, Basel

Flow cytometric applications to tumour biology: prospects and pitfalls

International Nuclear Information System (INIS)

Raju, M.R.; Johnson, T.S.; Tokita, N.; Gillette, E.L.

1980-01-01

A brief review of cytometry instrumentation and its potential applications in tumour biology is presented. DNA distribution measurements of cells from spontaneous dog tumours and cultured cells after exposure to X-rays, alpha particles or adriamycin are shown. The data show that DNA fluorescence measurements have application in the study of cell kinetics after either radiation or drug treatment. Extensive and careful experimentation is needed, however, to utilize the sophisticated developments in flow cytometry instrumentation. (author)

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.

Inflammatory cardiovascular risk markers in obstructive sleep apnoea syndrome.

LENUS (Irish Health Repository)

Ryan, Silke

2012-02-01

Obstructive sleep apnoea syndrome (OSAS) represents a highly prevalent disease and is recognized as a major public health burden. Large-scale epidemiological studies have demonstrated an independent relationship between OSAS and various cardiovascular disorders. The pathogenesis of cardiovascular complications in OSAS is not completely understood, but given the complexity of the disorder, a multifactorial etiology is likely. Inflammatory processes have emerged as critical in the pathogenesis of atherosclerosis in general and they mediate many of the stages of atheroma formation. Circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These markers include cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and selectins, cytokines such as tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), chemokines such as IL-8, and C-reactive protein (CRP). There is increasing evidence that inflammatory processes also play a central role in the cardiovascular pathophysiology of OSAS. This is supported by cell culture and animal studies identifying a preferential activation of inflammatory pathways by intermittent hypoxia (IH), the hallmark of OSAS. A number of studies have selectively examined the expression of inflammatory factors in OSAS patients with different conclusions. These different findings may have been contributed to by a number of methodological factors such as small subject numbers, inadequately matched study populations, particularly in terms of body mass index (BMI), and inclusion of patients with pre-existing cardiovascular or metabolic diseases. This review will focus on the potential role of various inflammatory markers in OSAS with a critical analysis of the current literature.

Comparison of interferon {gamma} release assays and conventional screening tests before tumour necrosis factor {alpha} blockade in patients with inflammatory arthritis.

LENUS (Irish Health Repository)

Martin, J

2012-02-01

OBJECTIVE: To compare the performance of two interferon gamma release assays (IGRAs) and conventional screening tests in patients with inflammatory arthritis undergoing screening for latent tuberculosis infection (LTBI) before treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) compounds. METHODS: Successive patients were subjected to conventional LTBI screening, including a tuberculin skin test (TST). The T-SPOT.TB test was performed on all patients and the QuantiFERON-TB Gold test was performed on a large subset. The results of the IGRAs were compared with the results of conventional screening tests. RESULTS: A total 150 patients were evaluated. The majority (57.9%) had rheumatoid arthritis. Previous vaccination with Bacille Calmette-Guerin was confirmed in 82% of patients. No patient had received prior anti-TB treatment. A total of 57 patients (38.0%) had at least one positive conventional risk factor. In contrast, an unequivocally positive T-SPOT.TB test was seen in only 14\\/143 (9.8%). There was 98.2% agreement between the two IGRAs. Statistically significant associations were found between each of the IGRAs and both TST and risk history, but not chest x-ray (CXR). A positive IGRA result was significantly associated with increased age. TB was not reactivated in any patient during the follow-up period. Interpretation: This study suggests that IGRAs may be useful when screening for LTBI before anti-TNFalpha therapy in patients with immune-mediated inflammatory diseases. The observations reported here also highlight the inadequate performance of CXR as a marker of LTBI.

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

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).

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.

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.

Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.

Science.gov (United States)

Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana

2007-01-01

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

In vitro and preclinical targeted alpha therapy for cancer

International Nuclear Information System (INIS)

Allen, B.J.; Rizvi, S.; Li, Y.; Tian, Z.; University of Wollongong, NSW; Ranson, M.; Russell, P.J.

2000-01-01

Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotope Bi-213 is produced by generator and chelated to a cancer affined monoclonal antibody or protein to form the alpha-conjugate (AC) against melanoma, leukaemia, colorectal, bladder, breast and prostate cancers. These ACs are tested for stability, specificity and cytotoxicity. Subcutaneous inoculation of 1.5 million cells into the flanks of nude mice causes tumours to grow in all mice. The tumour growth is compared between untreated controls, nonspecific RIC and specific RIC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Results: Stable alpha-ACs can be produced which are highly specific and cytotoxic in vitro. Local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Local TAT can also completely regress (11/12) sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts. These results point to the potential application of local TAT and systemic TAT in the management of these cancers. A phase 1 and 2 clinical trial is planned for local TAT of sc recurrent melanoma. Copyright (2000) Australasian College of Physical Scientists and Engineers in Medicine

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)

DEFF Research Database (Denmark)

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...

Research on the comparative value of radio-immunoanalyses of three embryonic antigens: alpha 1 foeto-protein ''α1FP'' alpha 2H-isoferritine ''α2HF'' and carcino-embryonnic antigen ''CEA'' for diagnonis and post-therapy observation

International Nuclear Information System (INIS)

Rimbaut, C.; Rudant, C.; Buffe, D.

Alpha 1 foeto-protein, specific for 2 kinds of tumour (hepatoblastemo, teratoma), is useful in radio-immunoanalysis for the very early diagnosis of a tumour revival. Alpha 2 HF isoferritine and carcino-embryonic antigen, proteins non-specific to cancer, nevertheless possess in common the property of increasing in cases of tumours with liver metastases, though one is more specific to widespread secreting tumours while the other seems to be connected rather with an early reactivity of a tumour whatever its nature or origin. Finally a wide variation in these protein fractions is observed from one individual to another and it is therefore extremely important to make comparative determinations within a given series, the tendency of the evolution curve to rise or not being the important element in post-treatment supervision [fr

Evaluation of Fibroblast Activation Protein-Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer

Science.gov (United States)

2009-12-01

low molecular weight recombinant human gelatin: development of a substitute for animal- derived gelatin with superior features, Protein Expr. Purif...by the honey - bee , could be modified to a form that was no longer hydro- lyzed by the native activator protease DPP4 but, instead, was hydrolyzed by...TITLE: Evaluation of Fibroblast Activation Protein -Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer PRINCIPAL

PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours.

Science.gov (United States)

Hung, Yin P; Lee, John P; Bellizzi, Andrew M; Hornick, Jason L

2017-11-01

Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours. Immunohistochemistry for PHOX2B was performed with a rabbit monoclonal antibody. PHOX2B positivity was defined as the presence of nuclear immunoreactivity in ≥5% of cells. PHOX2B was positive in 70 (92%) peripheral neuroblastic tumours, including 68 of 72 (94%) paediatric and two of four (50%) adult cases. Furthermore, PHOX2B was consistently negative in all non-peripheral neuroblastic tumours, with staining being absent in 160 cases and limited in four cases. PHOX2B is a highly sensitive and specific immunohistochemical marker for peripheral neuroblastic tumours, including neuroblastoma. PHOX2B reliably distinguishes neuroblastoma from histological mimics such as Wilms tumour, Ewing sarcoma, and CIC-rearranged round cell sarcoma. PHOX2B negativity in two of four adult neuroblastoma cases raises the possibility that some adult neuroblastomas are of a different lineage than paediatric cases. © 2017 John Wiley & Sons Ltd.

Preoperative Alpha-Fetoprotein Slope is Predictive of Hepatocellular Carcinoma Recurrence after Liver Transplantation

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Kathy Han

2007-01-01

Full Text Available BACKGROUND: Liver transplantation (LT offers a possible cure for patients with hepatocellular carcinoma (HCC and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP levels.

Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release.

Science.gov (United States)

Formica, S; Roach, T I; Blackwell, J M

1994-05-01

The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

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.

Use of molecular markers aids in the development of diverse inbred backcross lines in Beit Alpha cucumber (Cucumis sativus L.)

Science.gov (United States)

Beit Alpha cucumber (Cucumis sativus L.) is a Mediterranean fresh-market type with a relatively narrow genetic base. To broaden its base for plant improvement, 42 diverse accessions were compared employing a previously defined standard marker array to choose wide-based parental lines for use in bac...

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

Science.gov (United States)

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.

T-cell receptor V sub. alpha. and C sub. alpha. alleles associated with multiple sclerosis and myasthenia gravis

Energy Technology Data Exchange (ETDEWEB)

Oksenberg, J.R.; Cavalli-Sforza, L.L.; Steinman, L. (Stanford Univ., CA (USA)); Sherritt, M.; Bernard, C.C. (LaTrobe Univ., Victoria (Australia)); Begovich, A.B.; Erlich, H.A. (Cetus Corporation, Emeryville, CA (USA))

1989-02-01

Polymorphic markers in genes encoding the {alpha} chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, the authors amplified selected sequences derived from the full-length TcR {alpha} cDNA probe. These PcR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of the polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, the authors have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic V{sub {alpha}} and C{sub {alpha}} markers were identified between patients and healthy individuals.

Mitochondria: An intriguing target for killing tumour-initiating cells

Czech Academy of Sciences Publication Activity Database

Yan, B.; Dong, L.; Neužil, Jiří

2016-01-01

Roč. 26, JAN 2016 (2016), s. 86-93 ISSN 1567-7249 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * ALPHA-TOCOPHERYL SUCCINATE * Therapeutic resistance * Mitochondria Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.704, year: 2016

Transforming growth factor alpha and epidermal growth factor in laryngeal carcinomas demonstrated by immunohistochemistry

DEFF Research Database (Denmark)

Christensen, M E; Therkildsen, M H; Poulsen, Steen Seier

1993-01-01

the basal cell layer. The present investigation and our previous results confirm the existence of EGF receptors, TGF-alpha and EGF in laryngeal carcinomas. In addition, we conclude that the conditions do exist for growth factors to act through an autocrine system in poorly differentiated tumours and through......Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF...... receptors) which were confined predominantly to the undifferentiated cells. The expression of this growth factor system in malignant cells may play a role in carcinogenesis and/or tumour growth. All carcinomas were positive for TGF-alpha and 12 were positive for EGF. In moderately-to-well differentiated...

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)

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.

213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

International Nuclear Information System (INIS)

Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U.; Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A.; Boll, R.; Murphy, K.

2014-01-01

Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as 90 Y/ 177 Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with 213 Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with 90 Y/ 177 Lu-DOTATOC were treated with an intraarterial infusion of 213 Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of 213 Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and 68 Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of 213 Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)

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

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

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

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.)

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...

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.

Adenomyoepithelial tumours and myoepithelial carcinomas of the breast – a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells

Directory of Open Access Journals (Sweden)

Herbst Hermann

2005-07-01

Full Text Available Abstract Background Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic. Methods A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH was performed. Results Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH. Conclusion Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present

{sup 213}Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

Energy Technology Data Exchange (ETDEWEB)

Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Boll, R.; Murphy, K. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)

2014-11-15

Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as {sup 90}Y/{sup 177}Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with {sup 213}Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with {sup 90}Y/{sup 177}Lu-DOTATOC were treated with an intraarterial infusion of {sup 213}Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of {sup 213}Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and {sup 68}Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of {sup 213}Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)

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

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)

Behandlingseffekten på reumatoid artritis for de tre eksisterende tumornekrosefaktor-alpha-haemmende behandlinger. Metaanalytisk litteraturstudie--sekundaerpublikation

DEFF Research Database (Denmark)

Christensen, Robin; Kristensen, Lars Erik; Geborek, Pierre

2009-01-01

Absolute treatment efficacy (via number needed to treat) of rheumatoid arthritis for each of the three available anti tumour necrosis factor alpha inhibiting therapies. Our aim was to indirectly compare the long-term efficacy of the available anti-tumour necrosis factor (TNF) therapies in patient...

Flow cytometric techniques for detection of candidate cancer stem cell subpopulations in canine tumour models.

Science.gov (United States)

Blacking, T M; Waterfall, M; Samuel, K; Argyle, D J

2012-12-01

The cancer stem cell (CSC) hypothesis proposes that tumour growth is maintained by a distinct subpopulation of 'CSC'. This study applied flow cytometric methods, reported to detect CSC in both primary and cultured cancer cells of other species, to identify candidate canine subpopulations. Cell lines representing diverse canine malignancies, and cells derived from spontaneous canine tumours, were evaluated for expression of stem cell-associated surface markers (CD34, CD44, CD117 and CD133) and functional properties [Hoecsht 33342 efflux, aldehyde dehydrogenase (ALDH) activity]. No discrete marker-defined subsets were identified within established cell lines; cells derived directly from spontaneous tumours demonstrated more heterogeneity, although this diminished upon in vitro culture. Functional assays produced variable results, suggesting context-dependency. Flow cytometric methods may be adopted to identify putative canine CSC. Whilst cell lines are valuable in assay development, primary cells may provide a more rewarding model for studying tumour heterogeneity in the context of CSC. However, it will be essential to fully characterize any candidate subpopulations to ensure that they meet CSC criteria. © 2011 Blackwell Publishing 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.

Impact of renal failure on the tumor markers of mesothelioma, N-ERC/mesothelin and osteopontin.

Science.gov (United States)

Shiomi, Kazu; Shiomi, Satoko; Ishinaga, Yuji; Sakuraba, Motoki; Hagiwara, Yoshiaki; Miyashita, Kazuya; Maeda, Masahiro; Suzuki, Kenji; Takahashi, Kazuhisa; Hino, Okio

2011-04-01

Knowledge of the characteristics and effective use of tumour markers for mesothelioma is essential for early-stage diagnosis of mesothelioma. We examined whether renal dysfunction influences blood concentrations of promising new tumour markers, N-ERC/mesothelin (N-ERC) and osteopontin (OPN), to an important degree. Levels of serum N-ERC and plasma OPN in 32 patients with chronic renal dysfunction, 22 of whom were on hemodialysis (CKD group), and 102 healthy volunteers were measured. Serum concentrations of N-ERC and plasma concentrations of OPN in the CKD group were significantly higher than those in volunteers, regardless of diabetes status and age. Blood concentrations of these markers increased as renal function decreased. N-ERC and OPN concentrations are significantly influenced by renal function. Therefore, the extent of renal failure must be considered when inferring the existence of tumours and chemotherapeutic response from the values of these markers in routine practice.

Targeted alpha therapy for melanoma : from bench to bedside

International Nuclear Information System (INIS)

Allen, B.J.; Rizvi, S.M.A.; Li, Y.; Tsui, W.; Douglas, S.; Raja, C.; Graham, P.; Smart, R.; Butler, P.; Kearsley, J.; Thompson, J.

2001-01-01

Full text: The control of metastatic melanoma remains an elusive objective. Targeted alpha therapy (TAT) offers a new approach to the control of micrometastases and regression of tumours. The alpha emitting immunoconjugate (AIC) against malignant melanoma has been prepared by chelating Bi-213 to the anti-melanoma antibody 9.2.27, and injected locally at 2 d post-inoculation of 1.5 million melanoma cells, or intralesionally into skin tumours. Human subjects receive 50μCi intralesional dose, escalating to 1 mCi. The clearances from the tumour, kidneys and bladder are monitored by a NaI detector that detects the 440 keV gamma ray. Blood samples and tumour photographs are taken at O. 2 and 4 weeks; tumours are excised at 4 weeks. Isolated cancer cells and preangiogenic cell clusters in mice can be eliminated with 25 μCi local AIC injection, and intra-lesional injections of 100 μCi are sufficient to completely regress melanomas with volumes up to 300 mm 3 without side-effects. Systemic TAT with a single administration is less effective with 100% growth delay of tumours observed, and ∼20% complete inhibition. The clinical TAT trial for recurrent subcutaneous melanoma has been approved by the NSW Radiation Advisory Committee and the SES Human Ethics Committee. In a world first phase 1 study, the first 5 subjects have been treated by intralesional injection, 3 at 50 μCi, and 2 at 150 μCi. All subjects having unchanged blood profiles at 2 and 4 weeks post-therapy. Tumour volumes appear little changed. However, histology of a 3 cm melanoma shows that almost complete cell kill occurred at 150 μCi, with only a few small cell clusters surviving. Local TAT inhibits tumourogenesis and intralesional TAT completely regresses melanoma in mice. Intralesional TAT for melanoma in human subjects is non-toxic so far and appears to be a promising modality. The ultimate objective is to apply systemic TAT for the control of melanoma micrometastases. Copyright (2001) Australasian

Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

International Nuclear Information System (INIS)

Neuzil, Jiri; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Prochazka, Lubomir; Dong, Lanfeng; Andera, Ladislav; Ralph, Stephen J.

2007-01-01

Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133 + cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well

lmmunohistochemical study of effect of ionizing radiation on human malignant tumours

International Nuclear Information System (INIS)

Adomaitiene, D. I.; Aleknavicius, E.; Valuckas, K. and others

2000-01-01

Cell proliferation-associated tumour markers are considered to have a valuable clinical significance. The current study was designed to investigate changes in immunohistochemical (IH) expression of proliferating cell nuclear antigen PCNA in human malignant tumour tissue samples obtained before and after preoperative radiotherapy. Tumour tissue samples were obtained from 26 patients with rectal carcinoma, from 22 patients with carcinoma corporis uteri and from 82 patients with breast cancer. Tumour samples were processed for IH examination by using monoclonal antibodies (MoAbs) PC10 against PCNA. IH analysis of histological specimens of carcinoma corporis uteri and rectal carcinoma obtained before and after preoperative radiotherapy has revealed heterogeneity of biological response to irradiation. The great majority of tumour specimens after irradiation showed a high PCNA expression level in cell population. Only minority of tumour specimens (15-20%) exhibited reduced immunoreactivity with MoAbs PC10. PCNA positivity rate in breast cancer specimens obtained during surgery from 55 patients after preoperative radiotherapy in comparison to biomarker expression pattern in tumour specimens from 27 unirradiated patients (control group) was found to be tended to decrease. These in vivo findings are discussed in terms of radiation-induced cell death, followed after proliferation, and PCNA role in DNA repair. (author)

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

Tumour necrosis factor-alpha impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: Role of Hes1.

Science.gov (United States)

Keohane, Aoife; Ryan, Sinead; Maloney, Eimer; Sullivan, Aideen M; Nolan, Yvonne M

2010-01-01

Tumour necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine, which influences neuronal survival and function yet there is limited information available on its effects on hippocampal neural precursor cells (NPCs). We show that TNFalpha treatment during proliferation had no effect on the percentage of proliferating cells prepared from embryonic rat hippocampal neurosphere cultures, nor did it affect cell fate towards either an astrocytic or neuronal lineage when cells were then allowed to differentiate. However, when cells were differentiated in the presence of TNFalpha, significantly reduced percentages of newly born and post-mitotic neurons, significantly increased percentages of astrocytes and increased expression of TNFalpha receptors, TNF-R1 and TNF-R2, as well as expression of the anti-neurogenic Hes1 gene, were observed. These data indicate that exposure of hippocampal NPCs to TNFalpha when they are undergoing differentiation but not proliferation has a detrimental effect on their neuronal lineage fate, which may be mediated through increased expression of Hes1. Copyright 2009 Elsevier Inc. All rights reserved.

Preclinical studies and clinical trial of targeted alpha therapy for cancer

International Nuclear Information System (INIS)

Allen, B.J.

2002-01-01

Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukemia, colorectal, breast and prostate cancers. Materials and Methods: The alpha-emitting radioisotope is Bi-213, which is produced by the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (eg plasmmogen activator inhibitor PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukemia (WM60 mab), colorectal (C30.6 mab), breast (PAI2) and prostate (PAI2, J591 mab) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Results: In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than nonspecific ACs, specific beta emitting conjugates or free isotope. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can also completely regress advanced sc melanomas but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Conclusions: These results point to the application of local and systemic TAT in the management of secondary cancer. A phase 1 and 2 clinical trial of TAT of subcutaneous, secondary melanoma has commenced at St George Hospital, and 10/30 subjects have been treated by intralesional injection

Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of germline mismatch repair gene mutation status: a literature review.

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Metcalf, Alexander M; Spurdle, Amanda B

2014-03-01

Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can be caused by either germline mutations in mismatch repair (MMR) genes, or non-inherited transcriptional silencing of the MLH1 promoter. A correlation between MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has been reported in CRC studies. Germline MMR mutations also greatly increase risk of endometrial cancer (EC), but no systematic review has been undertaken to determine if these tumour markers may be useful predictors of MMR mutation status in EC patients. Endometrial cancer cohorts meeting review inclusion criteria encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11 studies for MLH1 methylation testing. BRAF V600E mutations were reported in 4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were 7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15. Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in 48/51 (94%) of tumours. We have also detailed specific examples that show the importance of MLH1 promoter region, assay design, and quantification of methylation. This review shows that BRAF mutations occurs so infrequently in endometrial tumours they can be discounted as a useful marker for predicting MMR-negative mutation status, and further studies of endometrial cohorts with known MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter methylation as a marker of negative germline MMR mutation status in EC patients.

C595 antibody: A potential vector for targeted alpha therapy

International Nuclear Information System (INIS)

Perkins, A.C.; Allen, B.J.

2005-01-01

Full text: Mucins are high molecular-weight heavily glycosylated glycoproteins with many oligosaccharide side-chains, linked to a protein backbone called apomucin. A total of 19 different mucin genes (MUC1-MUC4, MUC5B, MUC5AC, MUC6-MUC18) have been identified to date. Mucins are present on the surface of most epithelial cells and play a role in their protection and lubrication. In cancer cells the mucin molecule becomes altered, thus representing an important target for diagnosis and therapy. Urinary epithelial mucin1 (MUC1) is found to be frequently up-regulated and abnormally glycosylated in a number of common malignancies, including breast, bladder, colon, ovarian and gastric cancer. The monoclonal antibody C595 is an IgG3 murine MAb raised against the protein core of human MUC1. Epitope mapping has shown that C595 recognizes a tetrapeptide motif (RPAP) within the protein core of MUC1 mucin that contains a large domain of multiples of a highly conserved 20-amino-acid-repeat sequence (PDTRPAPGSTAPPAHGVTSA). This antibody has previously been radiolabelled with 99m Tc and 111 In and used for imaging a range of tumour types including ovary, breast and bladder. The antibody has also been radiolabelled with 67 Cu and 188 Re for the therapy of superficial bladder cancer. More recently we have investigated the pre-clinical use of the C595 antibody for targeted alpha therapy using 213 Bi which emits alpha particles with high linear energy transfer (LET), short range (80 m) radiation and has a short physical half-life of 45.6 minutes. Alpha particles are some 7300 times heavier than beta particles and in theory, following binding of an alpha immunocongugates to the target, a large fraction of the alpha particle energy is delivered to cancer cells, with minimal concomitant radiation of normal tissues. 213 Bi was produced from the 225 Ac/ 213 Bi generator. For antibody conjugation the chelator, cyclic diethylenetriaminepentacetic acid anhydride (DTPA) was used. Initial

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.

National survey on internal quality control for tumour markers in clinical laboratories in China.

Science.gov (United States)

Wang, Wei; Zhong, Kun; Yuan, Shuai; He, Falin; Du, Yuxuan; Hu, Zhehui; Wang, Zhiguo

2018-06-15

This survey was initiated to obtain knowledge on the current situation of internal quality control (IQC) practice for tumour markers (TMs) in China. Additionally, we tried to acquire the most appropriate quality specifications. This survey was a current status survey. The IQC information had been collected via online questionnaires. All of 1821 clinical laboratories which participated in the 2016 TMs external quality assessment (EQA) programme had been enrolled. The imprecision evaluation criteria were the minimal, desirable, and optimal allowable imprecisions based on biological variations, and 1/3 total allowable error (TEa) and 1/4 TEa. A total of 1628 laboratories answered the questionnaires (89%). The coefficients of variation (CVs) of the IQC of participant laboratories varied greatly from 1% (5 th percentile) to 13% (95 th percentile). More than 82% (82 - 91%) of participant laboratories two types of CVs met 1/3 TEa except for CA 19-9. The percentiles of current CVs were smaller than cumulative CVs. A number of 1240 laboratories (76%) reported their principles and systems used. The electrochemiluminescence was the most used principle (45%) and had the smallest CVs. The performance of laboratories for TMs IQC has yet to be improved. On the basis of the obtained results, 1/3 TEa would be realistic and attainable quality specification for TMs IQC for clinical laboratories in China.

Probing the limits of alpha power lateralisation as a neural marker of selective attention in middle-aged and older listeners.

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Tune, Sarah; Wöstmann, Malte; Obleser, Jonas

2018-02-11

In recent years, hemispheric lateralisation of alpha power has emerged as a neural mechanism thought to underpin spatial attention across sensory modalities. Yet, how healthy ageing, beginning in middle adulthood, impacts the modulation of lateralised alpha power supporting auditory attention remains poorly understood. In the current electroencephalography study, middle-aged and older adults (N = 29; ~40-70 years) performed a dichotic listening task that simulates a challenging, multitalker scenario. We examined the extent to which the modulation of 8-12 Hz alpha power would serve as neural marker of listening success across age. With respect to the increase in interindividual variability with age, we examined an extensive battery of behavioural, perceptual and neural measures. Similar to findings on younger adults, middle-aged and older listeners' auditory spatial attention induced robust lateralisation of alpha power, which synchronised with the speech rate. Notably, the observed relationship between this alpha lateralisation and task performance did not co-vary with age. Instead, task performance was strongly related to an individual's attentional and working memory capacity. Multivariate analyses revealed a separation of neural and behavioural variables independent of age. Our results suggest that in age-varying samples as the present one, the lateralisation of alpha power is neither a sufficient nor necessary neural strategy for an individual's auditory spatial attention, as higher age might come with increased use of alternative, compensatory mechanisms. Our findings emphasise that explaining interindividual variability will be key to understanding the role of alpha oscillations in auditory attention in the ageing listener. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Diagnostic markers for germ cell neoplasms

DEFF Research Database (Denmark)

Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E

2015-01-01

This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCTs), with focus on the most common testicular GCTs (TGCTs). GCTs are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic diff...... of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up....

Characterization of a canine tetranucleotide microsatellite marker located in the first intron of the tumor necrosis factor alpha gene.

Science.gov (United States)

Watanabe, Masashi; Tanaka, Kazuaki; Takizawa, Tatsuya; Segawa, Kazuhito; Neo, Sakurako; Tsuchiya, Ryo; Murata, Michiko; Murakami, Masaru; Hisasue, Masaharu

2014-01-01

A polymorphic tetranucleotide (GAAT)n microsatellite in the first intron of the canine tumor necrosis factor alpha (TNFA) gene was characterized in this study; 139 dogs were analyzed: 22 Beagles, 26 Chihuahuas, 20 Miniature Dachshunds, 24 Miniature Poodles, 22 Pembroke Welsh Corgis and 25 Shiba Inus. We detected the presence of the 4 alleles (GAAT)5, (GAAT)6, (GAAT)7 and (GAAT)8, including 9 of the 10 expected genotypes. The expected heterozygosity (He) and the polymorphic information content (PIC) value of this microsatellite locus varied from 0.389 to 0.749 and from 0.333 to 0.682, respectively, among the 6 breeds. The allelic frequency differed greatly among breeds, but this microsatellite marker was highly polymorphic and could be a useful marker for the canine TNFA gene.

Unsuccessful mitosis in multicellular tumour spheroids.

Science.gov (United States)

Molla, Annie; Couvet, Morgane; Coll, Jean-Luc

2017-04-25

Multicellular spheroids are very attractive models in oncology because they mimic the 3D organization of the tumour cells with their microenvironment. We show here using 3 different cell types (mammary TSA/pc, embryonic kidney Hek293 and cervical cancer HeLa), that when the cells are growing as spheroids the frequency of binucleated cells is augmented as occurs in some human tumours.We therefore describe mitosis in multicellular spheroids by following mitotic markers and by time-lapse experiments. Chromosomes alignment appears to be correct on the metaphasic plate and the passenger complex is well localized on centromere. Moreover aurora kinases are fully active and histone H3 is phosphorylated on Ser 10. Consequently, the mitotic spindle checkpoint is satisfied and, anaphase proceeds as illustrated by the transfer of survivin on the spindle and by the segregation of the two lots of chromosomes. However, the segregation plane is not well defined and oscillations of the dividing cells are observed. Finally, cytokinesis fails and the absence of separation of the two daughter cells gives rise to binucleated cells.Division orientation is specified during interphase and persists throughout mitosis. Our data indicate that the cancer cells, in multicellular spheroids, lose their ability to regulate their orientation, a feature commonly encountered in tumours.Moreover, multicellular spheroid expansion is still sensitive to mitotic drugs as pactlitaxel and aurora kinase inhibitors. The spheroids thus represent a highly relevant model for studying drug efficiency in tumours.

Increased FOXP3 expression in tumour-associated tissues of horses affected with equine sarcoid disease.

Science.gov (United States)

Mählmann, K; Hamza, E; Marti, E; Dolf, G; Klukowska, J; Gerber, V; Koch, C

2014-12-01

Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleukin 4 (IL4) and interferon gamma (IFNG) mRNA in lesional and tumour-distant samples from ES-affected horses, as well as in dermal samples of healthy control horses were measured using quantitative reverse transcription polymerase chain reaction (PCR). Expression levels were compared between lesional and tumour-distant as well as between tumour-distant and control samples. Furthermore, BPV-1 E5 DNA in samples of ES-affected horses was quantified using quantitative PCR, and possible associations of viral load, disease severity and gene expression levels were evaluated. Expression levels of FOXP3, IL10 and IFNG mRNA and BPV-1 E5 copy numbers were significantly increased in lesional compared to tumour-distant samples. There was no difference in FOXP3 and cytokine expression in tumour-distant samples from ES- compared with control horses. In tumour-distant samples viral load was positively correlated with IL10 expression and severity score. The increased expression of Treg markers in tumour-associated tissues of ES-affected equids indicates a local, Treg-induced immune suppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Memory decline in Down syndrome and its relationship to iPF2alpha, a urinary marker of oxidative stress.

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Panagiotis Zis

Full Text Available Lipid peroxidation may be a marker of free-radical-mediated injury associated with Alzheimer's disease (AD. We aimed to investigate whether changes in lipid peroxidation is associated with cognitive decline in individuals with Down syndrome over a 4-year period.Thirty-two adults with DS participated in a longitudinal study with urinary isoprostane 8,12-iso-iPF2alpha (iPF2alpha assays at baseline and four years follow-up. Informants rated their functional ability and memory function and the adults with DS attempted assessments of language skills and memory. Twenty-six individuals completed assessments of memory (Modified Memory Object Task, MOMT, adaptive behavior (ABAS, and receptive vocabulary (British Picture vocabulary, BPVS at both time-points.Overall change in iPF2alpha level was negatively correlated with change in the MOMT score (Spearman's Rho =  -0.576, p = 0.006, i.e., increased lipid peroxidation was correlated with worse memory functioning over time. An increase of ≥ 0.02 ng/mg creatinine iPF2α had good sensitivity (85.7%, positive predictive value (75%,, specificity (85.7% and negative predictive value (92.3% for memory decline.Change in iPF2alpha over time may have potential as a biomarker for memory decline in Down syndrome and potentially also help to track progression of MCI to AD in the general population.

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

Science.gov (United States)

Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

The prevalence of the HPV 16 genome, integrated viral status and p53 genotype in cervical cancer population of north-eastern Hungary, the correlation with the established markers of tumour progression.

Science.gov (United States)

Hernádi, Zoltán; Sápy, Tamás; Krasznai, Zoárd T

2004-03-15

To evaluate the prevalence of the HPV 16 integrated status and the p53 genotype in cervical cancer in north-eastern Hungary and their correlation with the established prognostic factors. Parallel with the routine histological examination, Southern blot hybridisation and multiplex PCRs were used to detect type/physical state of HPV DNA in primary tumours and in regional lymph nodes combined with p53 genotyping of 83 patients. 46.9% (39/83) prevalence rate of HPV 16 genome was found. The frequency of viral integration (76.9% in primary tumours and 95.2% in regional lymph nodes) and that of the p53Arg homozygous genotype (64.1%) proved to be higher than reported from other parts of the world. The HPV 16 integration and the p53 genotype, failed to correlate with the FIGO stage and lymphatic spread. The prevalence of the integrated status of the HPV 16 genome combined with homozygous p53Arg genotype is relatively high in Hungary. These factors however failed to show a strong correlation with the established markers of tumour progression.

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

Liquid fiducial marker performance during radiotherapy of locally advanced non small cell lung cancer

DEFF Research Database (Denmark)

Rydhög, Jonas Scherman; Mortensen, Steen Riisgaard; Larsen, Klaus Richter

2016-01-01

We analysed the positional and structural stability of a long-term biodegradable liquid fiducial marker (BioXmark) for radiotherapy in patients with locally advanced lung cancer. Markers were injected via endoscopic- or endobronchial ultrasound in lymph nodes and reachable primary tumours. Marker...

The Z-isomer of 11{beta}-methoxy-17{alpha}-[{sup 123}I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

Energy Technology Data Exchange (ETDEWEB)

Rijks, Leonie J. M.; Boer, Gerard J.; Endert, Erik; Bruin, Kora de; Janssen, Anton G. M.; Royen, Eric A. van

1997-01-01

The potential of both stereoisomers of 11{beta}-methoxy-17{alpha}-[{sup 123}I]iodovinylestradiol (E- and Z-[{sup 123}I]MIVE) as suitable radioligands for imaging of estrogen receptor(ER)-positive human breast tumours was studied. The 17{alpha}-[{sup 123}I]iodovinylestradiol derivatives were prepared stereospecifically by oxidative radioiododestannylation of the corresponding 17{alpha}-tri-n-butylstannylvinylestradiol precursors. Both isomers of MIVE showed high in vitro affinity for dimethylbenzanthracene-induced rat and fresh human mammary tumour ER, that of Z-MIVE however being manyfold higher than that of E-MIVE. In vivo distribution studies with E- and Z-[{sup 123}I]MIVE in normal and tumour-bearing female rats showed ER-mediated uptake and retention in uterus, ovaries, pituitary, hypothalamus and mammary tumours, again the highest for Z-[{sup 123}I]MIVE. The uterus- and tumour-to-nontarget tissue (fat, muscle) uptake ratios were also highest for Z-[{sup 123}I]MIVE. Additionally, planar whole body imaging of two breast cancer patients 1-2 h after injection of Z-[{sup 123}I]MIVE showed increased focal uptake at known tumour sites. Therefore, we conclude that Z-[{sup 123}I]MIVE is a promising radioligand for the diagnostic imaging of ER in human breast cancer.

Integrated radiotherapy imaging system (IRIS): design considerations of tumour tracking with linac gantry-mounted diagnostic x-ray systems with flat-panel detectors.

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Berbeco, Ross I; Jiang, Steve B; Sharp, Gregory C; Chen, George T; Mostafavi, Hassan; Shirato, Hiroki

2004-01-21

The design of an integrated radiotherapy imaging system (IRIS), consisting of gantry mounted diagnostic (kV) x-ray tubes and fast read-out flat-panel amorphous-silicon detectors, has been studied. The system is meant to be capable of three main functions: radiographs for three-dimensional (3D) patient set-up, cone-beam CT and real-time tumour/marker tracking. The goal of the current study is to determine whether one source/panel pair is sufficient for real-time tumour/marker tracking and, if two are needed, the optimal position of each relative to other components and the isocentre. A single gantry-mounted source/imager pair is certainly capable of the first two of the three functions listed above and may also be useful for the third, if combined with prior knowledge of the target's trajectory. This would be necessary because only motion in two dimensions is visible with a single imager/source system. However, with previously collected information about the trajectory, the third coordinate may be derived from the other two with sufficient accuracy to facilitate tracking. This deduction of the third coordinate can only be made if the 3D tumour/marker trajectory is consistent from fraction to fraction. The feasibility of tumour tracking with one source/imager pair has been theoretically examined here using measured lung marker trajectory data for seven patients from multiple treatment fractions. The patients' selection criteria include minimum mean amplitudes of the tumour motions greater than 1 cm peak-to-peak. The marker trajectory for each patient was modelled using the first fraction data. Then for the rest of the data, marker positions were derived from the imager projections at various gantry angles and compared with the measured tumour positions. Our results show that, due to the three dimensionality and irregular trajectory characteristics of tumour motion, on a fraction-to-fraction basis, a 'monoscopic' system (single source/imager) is inadequate for

Two cases of breast carcinoma with osteoclastic giant cells: Are the osteoclastic giant cells pro-tumoural differentiation of macrophages?

Directory of Open Access Journals (Sweden)

Shishido-Hara Yukiko

2010-08-01

Full Text Available Abstract Breast carcinoma with osteoclastic giant cells (OGCs is characterized by multinucleated OGCs, and usually displays inflammatory hypervascular stroma. OGCs may derive from tumor-associated macrophages, but their nature remains controversial. We report two cases, in which OGCs appear in common microenvironment despite different tumoural histology. A 44-year-old woman (Case 1 had OGCs accompanying invasive ductal carcinoma, and an 83-year-old woman (Case 2 with carcinosarcoma. Immunohistochemically, in both cases, tumoural and non-tumoural cells strongly expressed VEGF and MMP12, which promote macrophage migration and angiogenesis. The Chalkley count on CD-31-stained sections revealed elevated angiogenesis in both cases. The OGCs expressed bone-osteoclast markers (MMP9, TRAP, cathepsin K and a histiocyte marker (CD68, but not an MHC class II antigen, HLA-DR. The results indicate a pathogenesis: regardless of tumoural histology, OGCs derive from macrophages, likely in response to hypervascular microenvironments with secretion of common cytokines. The OGCs have acquired bone-osteoclast-like characteristics, but lost antigen presentation abilities as an anti-cancer defense. Appearance of OGCs may not be anti-tumoural immunological reactions, but rather pro-tumoural differentiation of macrophage responding to hypervascular microenvironments induced by breast cancer.

Therapy strategy for intracranial germ-cell tumours and initial results of the GPO therapy study MAKEI 86

International Nuclear Information System (INIS)

Goebel, U.; Calaminus, G.; Haasenritter, N.

1988-01-01

Pineal tumours are increasingly identified histologically since the introduction of the surgical microscope and microsurgical techniques. A major biological characteristic of germ-cell tumours is the fact that they produce tumour markers. Meaningful therapy planning is determined by the biological behaviour of the individual tumour entity which is strongly influenced by its intracranial localization. Important risk factors need to be identified and weighted according to previous treatment in order to arrive at an adequate therapy with improved curative prospects. Three risk areas can be defined for tumour extension. Therapy planning is also determined by the metastatic spread behaviour of germ-cell tumours. Within the two therapy studies for nontesticular germ-cell tumours MAKEI 83 and 86, a total of 180 germ-cell tumours, 24 of which were localized intercranially, were reported from 46 different clinics. All patients have a survival probability according to Kaplan and Meier of 67 ± 10% at an observation duration of 48 months. (orig./MG) [de

Tumour heterogeneity in oesophageal cancer assessed by CT texture analysis: Preliminary evidence of an association with tumour metabolism, stage, and survival

International Nuclear Information System (INIS)

Ganeshan, B.; Skogen, K.; Pressney, I.; Coutroubis, D.; Miles, K.

2012-01-01

Aim: To undertake a pilot study assessing whether tumour heterogeneity evaluated using computed tomography texture analysis (CTTA) has the potential to provide a marker of tumour aggression and prognosis in oesophageal cancer. Materials and methods: In 21 patients, unenhanced CT images of the primary oesophageal lesion obtained using positron-emission tomography (PET)-CT examinations underwent CTTA. CTTA was carried out using a software algorithm that selectively filters and extracts textures at different anatomical scales between filter values 1.0 (fine detail) and 2.5 (coarse features) with quantification as entropy and uniformity (measures image heterogeneity). Texture parameters were correlated with average tumour 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG) uptake [standardized uptake values (SUV mean and SUV max )] and clinical staging as determined by endoscopic ultrasound (nodal involvement) and PET-CT (distant metastases). The relationship between tumour stage, FDG uptake, and texture with survival was assessed using Kaplan–Meier analysis. Results: Tumour heterogeneity correlated with SUV max and SUV mean . The closest correlations were found for SUV mean measured as uniformity and entropy with coarse filtration (r = –0.754, p < 0.0001; and r = 0.748, p = 0.0001 respectively). Heterogeneity was also significantly greater in patients with clinical stage III or IV for filter values between 1.0 and 2.0 (maximum difference at filter value 1.5: entropy: p = 0.027; uniformity p = 0.032). The median (range) survival was 21 (4–34) months. Tumour heterogeneity assessed by CTTA (coarse uniformity) was an independent predictor of survival [odds ratio (OR)=4.45 (95% CI: 1.08, 18.37); p = 0.039]. Conclusion: CTTA assessment of tumour heterogeneity has the potential to identify oesophageal cancers with adverse biological features and provide a prognostic indicator of survival.

Radiolabelled aptamers for tumour imaging and therapy

International Nuclear Information System (INIS)

Perkins, A.C.; Missailidis, S.

2005-01-01

Full text: The growth in biotechnology has led to new techniques for the design, selection and production of ligands capable of molecular recognition. One promising approach is the production of specific receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers. The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). We have used combinatorial chemistry techniques coupled with polymerase chain reaction (PCR) to rapidly select aptamers from degenerate libraries that bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy. MUC1 is widely expressed by normal glandular epithelial cells, however this expression is dramatically increased when the cells become malignant. This has been well documented for breast and ovarian cancer, as well as some lung, pancreatic and prostate cancers. Recently it has also been shown that MUC1 is a valuable marker for bladder and has been used for the imaging and targeted therapy of bladder cancer. The aptamer selection process was performed on affinity chromatography matrices. After ten rounds of selection and amplification, aptamers were cloned and sequenced. Post SELEX amino modifications have been used to confer nuclease resistance and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by fluorescent microscopy on MUC1-expressing tumour cells. Using peptide coupling reactions, we have successfully attached chelators for Tc-99m radiolabelling. Two of the constructs tested were based on mono-aptamer chelator complexes, one with commercially available MAG3 and one with a novel designed cyclen-based chelator. The other two constructs were based on the use of multi-aptamer complexes

The prognostic value of pimonidazole and tumour pO2 in human cervix carcinomas after radiation therapy: a prospective international multi-center study

DEFF Research Database (Denmark)

Nordsmark, Marianne; Loncaster, Julie; Aquino-Parsons, Christina

2006-01-01

BACKGROUND AND PURPOSE: Hypoxia adversely affects treatment outcome in human uterine cervical cancer. Here, we present the results of a prospective international multi-centre study evaluating the prognostic value of pre-treatment tumour oxygen partial pressure (pO(2)) and the hypoxia marker pimon...... pimonidazole (pimo). MATERIALS AND METHODS: One hundred and twenty-seven patients with primary cervix cancer were entered. Pre-treatment tumour pO(2) measurements were obtained, and reported by the median tumour pO(2), the fraction of pO(2) values......BACKGROUND AND PURPOSE: Hypoxia adversely affects treatment outcome in human uterine cervical cancer. Here, we present the results of a prospective international multi-centre study evaluating the prognostic value of pre-treatment tumour oxygen partial pressure (pO(2)) and the hypoxia marker...

Tumour cell–derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth

Directory of Open Access Journals (Sweden)

Hiroaki Haga

2015-01-01

Full Text Available The contributions of mesenchymal stem cells (MSCs to tumour growth and stroma formation are poorly understood. Tumour cells can transfer genetic information and modulate cell signalling in other cells through the release of extracellular vesicles (EVs. We examined the contribution of EV-mediated inter-cellular signalling between bone marrow MSCs and tumour cells in human cholangiocarcinoma, highly desmoplastic cancers that are characterized by tumour cells closely intertwined within a dense fibrous stroma. Exposure of MSCs to tumour cell–derived EVs enhanced MSC migratory capability and expression of alpha-smooth muscle actin mRNA, in addition to mRNA expression and release of CXCL-1, CCL2 and IL-6. Conditioned media from MSCs exposed to tumour cell–derived EVs increased STAT-3 phosphorylation and proliferation in tumour cells. These effects were completely blocked by anti-IL-6R antibody. In conclusion, tumour cell–derived EVs can contribute to the generation of tumour stroma through fibroblastic differentiation of MSCs, and can also selectively modulate the cellular release of soluble factors such as IL-6 by MSCs that can, in turn, alter tumour cell proliferation. Thus, malignant cells can “educate” MSCs to induce local microenvironmental changes that enhance tumour cell growth.

Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

International Nuclear Information System (INIS)

Hendry, Jolyon H.

2001-01-01

Purpose: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. Results: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. Conclusions: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability

Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers.

Science.gov (United States)

Cleary, Allison S; Leonard, Travis L; Gestl, Shelley A; Gunther, Edward J

2014-04-03

Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones. As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors. Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models, definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy. Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.

Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review).

Science.gov (United States)

Andergassen, Ulrich; Kölbl, Alexandra C; Mahner, Sven; Jeschke, Udo

2016-04-01

Cells, which detach from a primary epithelial tumour and migrate through lymphatic vessels and blood stream are called 'circulating tumour cells'. These cells are considered to be the main root of remote metastasis and are correlated to a worse prognosis concerning progression-free and overall survival of the patients. Therefore, the detection of the minimal residual disease is of great importance regarding therapeutic decisions. Many different detection strategies are already available, but only one method, the CellSearch® system, reached FDA approval. The present review focusses on the detection of circulating tumour cells by means of real-time PCR, a highly sensitive method based on differences in gene expression between normal and malignant cells. Strategies for an enrichment of tumour cells are mentioned, as well as a large panel of potential marker genes. Drawbacks and advantages of the technique are elucidated, whereas, the greatest advantage might be, that by selection of appropriate marker genes, also tumour cells, which have already undergone epithelial to mesenchymal transition can be detected. Finally, the application of real-time PCR in different gynaecological malignancies is described, with breast cancer being the most studied cancer entity.

A comparative study of tissue inhibitor of metalloproteinases-1 levels in plasma and tumour tissue from patients with primary breast cancer and in plasma from patients with metastatic breast cancer

DEFF Research Database (Denmark)

Rasmussen, Anne-Sofie Schrohl; Mueller, Volkmar; Christensen, Ib Jarle

2008-01-01

OBJECTIVE: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been investigated as a potential tumour marker in breast cancer. Here we investigated the correlation between TIMP-1 in tumour tissue and plasma to evaluate whether TIMP-1 in plasma is actually a surrogate marker for TIMP-1 in prima...

The future role of anti-tumour necrosis factor (TNF) products in the treatment of rheumatoid arthritis.

Science.gov (United States)

Camussi, G; Lupia, E

1998-05-01

Tumour necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potential pathogenic role in the establishment of rheumatoid synovitis, in the formation of pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNF alpha a potential target for anticytokine therapy. Experimental studies have shown that TNF alpha blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis both in collagen-induced arthritis in mice and in transgenic mice overexpressing TNF alpha, which develop a rheumatoid-like destructive arthritis. Clinical studies based on the use of anti-TNF alpha antibodies or soluble receptors have suggested a potential beneficial effect of TNF alpha-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNF alpha therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated with an improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNF alpha therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNF alpha production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNF alpha

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

International Nuclear Information System (INIS)

Kaste, Sue C.; Dome, Jeffrey S.; Babyn, Paul S.; Graf, Norbert M.; Grundy, Paul; Godzinski, Jan; Levitt, Gill A.; Jenkinson, Helen

2008-01-01

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 development

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

Energy Technology Data Exchange (ETDEWEB)

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

MOLECULAR MARKERS FOR METASTATIC PROSTATE ADENOCARCINOMA

Directory of Open Access Journals (Sweden)

I. S. Kunin

2012-01-01

Full Text Available The search of molecular markers of metastasing and prognosis in prostate cancer remains an urgent task. In this study, we investigated the relationship of gene expression heparanase-1 (HPSE1 and D-glucuronil C5-epimerase (GLCE with early disease relapse and metastasis of a 2,5−3 years after diagnosis. It was shown that the ratio of the expression levels of genes HPSE1/GLCE > 1 may serve as a prognostic relapse marker and trends of the tumour to metastasis. The data obtained suggest to use this option as a molecular marker for the diagnostics of metastatic process and the disease prognosis.

Expression pattern of clinically relevant markers in paediatric germ cell- and sex-cord stromal tumours is similar to adult testicular tumours

DEFF Research Database (Denmark)

Mosbech, Christiane Hammershaimb; Svingen, Terje; Nielsen, John Erik

2014-01-01

Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of childhood cancers. Like adult GCTs, they probably originate from primordial germ cells, but the pattern of histopathological types is different, and they occur predominantly in extragonadal sites along the body midline....

Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer.

Science.gov (United States)

Tölle, Angelika; Jung, Monika; Rabenhorst, Silke; Kilic, Ergin; Jung, Klaus; Weikert, Steffen

2013-10-01

Since differential expression of microRNAs (miRNAs) has been found to be highly associated with several types of cancer, the goal of the present study was to identify an miRNA fingerprint as a non‑invasive diagnostic tool to detect urinary bladder cancer using the easily accessible samples of whole blood and urine. Blood and urine samples from 4 controls and from patients suffering from superficial and invasive bladder cancer were analyzed using miRNA microarray consisting of 754 human miRNAs from the Sanger database v14. Using RT‑qPCR technique, 6 of the differentially expressed miRNAs were validated in the controls (20 blood, 19 urine samples) and patients with superficial (18 blood, 16 urine samples) or invasive (20 blood and urine samples each) tumours. Three blood miRNAs (miR‑26b‑5p, miR‑144‑5p, miR‑374‑5p) were found to be significantly upregulated in invasive bladder tumour patients (Pbladder tumours with 94% specificity and 65% sensitivity. The urine miR‑1255b‑5p reached 68% specificity and 85% sensitivity in the diagnosis of invasive tumours. This pilot study represents the first characterization of an miRNA profile for urinary bladder tumours in whole blood samples. In addition, it was shown that invasive bladder tumours could be identified by differentially expressed urine miRNAs. Further studies are needed to test the clinical usefulness for bladder cancer detection and surveillance.

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

Preclinical targeted alpha therapy for melanoma, leukaemia, breast, prostate and colorectal cancers

International Nuclear Information System (INIS)

Allen, B.J.; Rizvi, S.; Li, Y.; Tian, Z.; University of Wollongong, NSW; Ranson, M.

2000-01-01

Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micro-metastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 are produced by accelerator and generator respectively and are chelated to a cancer specific monoclonal antibody, peptide or protein to form the alpha-conjugates (AC) against melanoma, leukaemia, breast, prostate and colorectal cancers. These ACs are tested for stability, specificity and cytotoxicity in vitro and in vivo using several nude mouse models. The Australian TAT program began some 7 years at ANSTO but was still-born. Later, TAT had a second wind at St George Hospital, where collaborative research led to the investigation of Tb-149 as a new alpha emitting radionuclide. Subsequently, increased emphasis was placed on the Ac-225 generator to produce Bi-213. Although in-house funding was terminated in 1998, the project received its third wind with local fund raising in the Shire and a US grant in 1999, and continues to break new ground in the control of the above cancers. Stable alpha-ACs are produced which are highly specific and cytotoxic in vitro against melanoma, leukaemia, colorectal, breast and prostate cancers. Subcutaneous inoculation of 11.5 million cells into the flanks of nude mice causes tumours to grow in all mice. The tumour growth is compared with untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of melanoma xenografts and gives almost complete control of breast cancer tumour growth in the primary site and metastatic invasion of the lymph nodes. These results point to the application of local

Effect of tamoxifen pre-treatment on the retention of tritiated oestradiol and 5. cap alpha. -dihydrotestosterone and on glucose metabolism in human breast carcinomas

Energy Technology Data Exchange (ETDEWEB)

Deshpande, N; Mitchell, I [Imperial Cancer Research Fund, London (UK). Labs.; Hughes, D

1978-05-01

The effect of pre-treatment with tamoxifen on glucose metabolism and retention of injected oestradiol-17B and 5..cap alpha..-dihydrotestosterone by human breast carcinomas were studied in patients undergoing mastectomy. The following effects were observed: the pretreatment reduced retention of oestradiol-17B whereas a small but statistically significant rise in 5..cap alpha..-dihydrotestosterone accumulation was observed. There was an increase in both phosphofructokinase (PFK) and glucose-6-phosphate dehydrogenase (G6PDH) activities in tumours from treated patients whereas ..cap alpha..-glycerolphosphate dehydrogenase (..cap alpha..-GPDH) activity was significantly reduced in the same tumours. The significance of these findings is discussed and it is argued that these changes in carbohydrate metabolism may not be due to the blocking of hormone receptors.

Stroma-regulated HMGA2 is an independent prognostic marker in PDAC and AAC

DEFF Research Database (Denmark)

Strell, Carina; Norberg, Karin Jessica; Mezheyeuski, Artur

2017-01-01

was more frequent in patients with PDAC than with AAC. The HMGA2 status in tumour cells significantly correlated with the abundance of PDGFRβ-defined stroma cells. In vivo co-injection of Panc-1 cancer cells with pancreatic stellate cells increased tumour growth in a manner associated with increased HMGA2...... expression. Furthermore, in vitro treatment of Panc-1 with conditioned media from PDGF-BB-activated stellate cells increased their ability to form tumour spheroids.Conclusions:This study identifies HMGA2 expression in tumour cells as an independent prognostic marker in PDAC and AAC. Correlative data analysis...

Prostate alpha/beta revisited - an analysis of clinical results from 14 168 patients

Energy Technology Data Exchange (ETDEWEB)

Dasu, Alexandru [Dept. of Radiation Physics UHL, County Council of Oestergoetland, Linkoeping (Sweden); Radiation Physics, Dept. of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping Univ., Linkoeping (Sweden); Toma-Dasu, Iuliana [Medical Radiation Physics, Stockholm Univ. and Karolinska Institutet, Stockholm (Sweden)

2012-11-15

Purpose. To determine the dose response parameters and the fractionation sensitivity of prostate tumours from clinical results of patients treated with external beam radiotherapy. Material and methods. The study was based on five-year biochemical results from 14 168 patients treated with external beam radiotherapy. Treatment data from 11 330 patients treated with conventional fractionation have been corrected for overall treatment time and fitted with a logit equation. The results have been used to determine the optimum {alpha}/{beta} values that minimise differences in predictions from 2838 patients treated with hypofractionated schedules. Results. Conventional fractionation data yielded logit dose response parameters for all risk groups and for all definitions of biochemical failures. The analysis of hypofractionation data led to very low {alpha}/{beta} values (1-1.7 Gy) in all mentioned cases. Neglecting the correction for overall treatment time has little impact on the derivation of {alpha}/{beta} values for prostate cancers. Conclusions. These results indicate that the high fractionation sensitivity is an intrinsic property of prostate carcinomas and they support the use of hypofractionation to increase the therapeutic gain for these tumours.

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

Hepatic tumours in children with biliary atresia: Single-centre experience in 13 cases and review of the literature

International Nuclear Information System (INIS)

Yoon, H.J.; Jeon, T.Y.; Yoo, S.-Y.; Kim, J.H.; Eo, H.; Lee, S.-K.; Kim, J.S.

2014-01-01

Aim: To establish the risks of developing of hepatic tumours and to investigate their clinical and imaging findings in children with biliary atresia (BA) after Kasai portoenterostomy (Kasai). Materials and methods: Among 157 children who had undergone Kasai for BA over an 18 year period, patients who had newly developed hepatic tumours were identified. Patient demographics, clinical features, and imaging findings were retrospectively reviewed. Results: Three male and 10 female patients (mean age 3.9 years) all (8%, of 157) had single hepatic tumours, which were confirmed in 10 explanted and three non-explanted livers. Ten (77%) were benign and three (23%) were malignant. Of the benign hepatic tumours, focal nodular hyperplasia (FNH; n = 6) was the most common, followed by regenerative nodules (n = 3) and adenoma (n = 1). All FNH appeared in young children <1 year of age and showed a subcapsular location, bulging contour, and lack of central scar. Malignant tumours included two hepatocellular carcinomas and one cholangiocarcinoma. Conclusion: Hepatic tumours developed in approximately 8% of children with BA after Kasai. Although benign tumours, including FNHs and regenerative nodules, were more common than malignant tumours, screening with alpha-foetoprotein (AFP) levels and regular imaging studies are the mainstay of malignant tumour detection

Tumour location within the breast: Does tumour site have prognostic ability?

Science.gov (United States)

Rummel, Seth; Hueman, Matthew T; Costantino, Nick; Shriver, Craig D; Ellsworth, Rachel E

2015-01-01

Tumour location within the breast varies with the highest frequency in the upper outer quadrant (UOQ) and lowest frequency in the lower inner quadrant (LIQ). Whether tumour location is prognostic is unclear. To determine whether tumour location is prognostic, associations between tumour site and clinicopathological characteristics were evaluated. All patients enrolled in the Clinical Breast Care Project whose tumour site-UOQ, upper inner quadrant (UIQ), central, LIQ, lower outer quadrant (LOQ)-was determined by a single, dedicated breast pathologist were included in this study. Patients with multicentric disease (n = 122) or tumours spanning multiple quadrants (n = 381) were excluded from further analysis. Clinicopathological characteristics were analysed using chi-square tests for univariate analysis with multivariate analysis performed using principal components analysis (PCA) and multiple logistic regression. Significance was defined as P location, 30 had bilateral disease. Tumour location in the UOQ (51.5%) was significantly higher than in the UIQ (15.6%), LOQ (14.2%), central (10.6%), or LIQ (8.1%). Tumours in the central quadrant were significantly more likely to have higher tumour stage (P = 0.003) and size (P location as a prognostic factor revealed that although tumours in the central region are associated with less favourable outcome, these associations are not independent of location but rather driven by larger tumour size. Tumours in the central region are more difficult to detect mammographically, resulting in larger tumour size at diagnosis and thus less favourable prognosis. Together, these data demonstrate that tumour location is not an independent prognostic factor.

CA 15–3 cell lines and tissue expression in canine mammary cancer and the correlation between serum levels and tumour histological grade

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Manuali Elisabetta

2012-06-01

Full Text Available Abstract Background Mammary tumours are the most common malignancy diagnosed in female dogs and a significant cause of mortality and morbidity in this species. Carbohydrate antigen (CA 15–3 is a mucinous glycoprotein aberrantly over-expressed in human mammary neoplasms and one of the most widely used serum tumour markers in women with breast cancer. The aim of this study was to investigate the antigenic analogies of human and canine CA 15–3 and to assess its expression in canine mammary cancer tissues and cell lines. Immunohistochemical expression of CA 15–3 was evaluated in 7 canine mammary cancer cell lines and 50 malignant mammary tumours. As a positive control, the human breast carcinoma cell line MCF7 and tissue were used. To assess CA 15–3 staining, a semi-quantitative method was applied. To confirm the specificity and cross-reactivity of an anti-human CA 15–3 antibody to canine tissues, an immunoblot analysis was performed. We also investigated serum CA 15–3 activity to establish whether its expression could be assigned to several tumour characteristics to evaluate its potential use as a serum tumour marker in the canine mammary oncology field. Results Immunocytochemical analysis revealed CA 15–3 expression in all examined canine mammary cancer cell lines, whereas its expression was confirmed by immunoblot only in the most invasive cells (CMT-W1, CMT-W1M, CMT-W2 and CMT-W2M. In the tissue, an immunohistochemical staining pattern was observed in 34 (68% of the malignant tumours. A high statistical correlation (p = 0.0019 between serum CA 15–3 levels and the degree of tumour proliferation and differentiation was shown, which indicates that the values of this serum marker increase as the tumour stage progresses. Conclusions The results of this study reveal that CA 15–3 is expressed in both canine mammary tumour cell lines and tissues and that serum levels significantly correlate with the histological grade of the

Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study

International Nuclear Information System (INIS)

Albrethsen, Jakob; Bøgebo, Rikke; Gammeltoft, Steen; Olsen, Jesper; Winther, Benny; Raskov, Hans

2005-01-01

Molecular markers for localized colon tumours and for prognosis following therapy are needed. Proteomics research is currently producing numerous biomarker studies with clinical potential. We investigate the protein composition of plasma and of tumour extracts with the aim of identifying biomarkers for colon cancer. By Surface Enhanced Laser Desorption/Ionisation – Time Of Flight / Mass spectrometry (SELDI-TOF/MS) we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue. By size exclusion chromatography, we investigate the binding of HNP 1-3 to high mass plasma proteins. By microflow we investigate the effect of HNP 1-3 on mammalian cells. Human Neutrophil Peptides -1, -2 and -3 (HNP 1-3), also known as alfa-defensin-1, -2 and -3, are present in elevated concentrations in serum from colon cancer patients and in protein extracts from colon tumours. A fraction of HNP 1-3 in serum is bound to unidentified high mass plasma proteins. HNP 1-3 purified from colon tumours are lethal to mammalian cells. HNP 1-3 may serve as blood markers for colon cancer in combination with other diagnostic tools. We propose that HNP 1-3 are carried into the bloodstream by attaching to high mass plasma proteins in the tumour microenvironment. We discuss the effect of HNP 1-3 on tumour progression

Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells).

Science.gov (United States)

Puthia, Manoj; Storm, Petter; Nadeem, Aftab; Hsiung, Sabrina; Svanborg, Catharina

2014-01-01

Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. To investigate if HAMLET can be used for colon cancer treatment and prevention. Apc(Min)(/+) mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Peroral HAMLET administration reduced tumour progression and mortality in Apc(Min)(/+) mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.

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

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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.

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

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study.

Science.gov (United States)

Farrelly, Cormac; Lal, Priti; Trerotola, Scott O; Nadolski, Gregory J; Watts, Micah M; Gorrian, Catherine Mc; Guzzo, Thomas J

2016-05-01

To correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA. In this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1-7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens. Mean PVS PSA was 4.29, range 2.3-6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left-sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events. fPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

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

Science.gov (United States)

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.

Clinical evaluation of anti-alpha-fetoprotein radioimmunodetection

International Nuclear Information System (INIS)

Chapman, C.E.; Keeling, A.A.; Bradwell, A.R.; Chandler, S.T.; Dykes, P.W.

1986-01-01

Anti-alpha-fetoprotein (AFP) radioimmunodetection was performed in response to clinical requests in 16 patients. In two patients, assessment of a known tumour was required; the anti-AFP scans were accurate and provided useful clinical information in both cases. In the remaining 14 patients the request was for localisation of suspected recurrent tumour. Accurate information was provided in four of these patients. In this latter group, various conventional methods of investigation had failed to disclose the site of recurrence. However, of a total of 21 sites reported as positive in these 14 patients, eight proved to be false positives. Two false negative results also occurred in this group and nine could not be evaluated. Although occasionally patients were usefully scanned, improvements are necessary before consistently reliable information can be obtained using this technique. (author)

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

Age related association of her-2/neu with prognostic markers in female breast carcinoma

International Nuclear Information System (INIS)

Sharif, M.A.; Mamoon, N.; Mushtaq, S.; Khadim, M.T.

2010-01-01

To determine age-related association of Her-2/neu expression with histological and immunohistochemical prognostic markers in female breast carcinoma. Study Design: Cross sectional, observational study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from January 2004 to December 2007. Methodology: Patients of primary operable female breast carcinoma were categorised as 50 years (post-menopausal) age groups. Histological type, tumour size, tumour grade and lymph node status were determined while estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu expression were evaluated immunohistochemically. Association of Her-2/neu with histological and immunohistochemical prognostic markers was determined in pre-menopausal, peri-menopausal and post- menopausal age groups using the x2 test for uni- and multivariate analysis. Results: Out of the 722 patients, 230 (31.9%) were in pre-menopuasal, 221 (30.6%) in peri-menopausal and 271 (37.5%) in post-menopausal age group. Infiltrating ductal carcinoma was the pre-dominant subtype in all the age groups. Mean tumour size was 4.3 +- 2.3 cm (range 0.4-17 cm) and lymph node metastasis was seen in 310 (70.8%) cases. Her-2/neu showed association with ER in the all the age groups while PR only showed association in the peri-menopausal and postmenopausal women. Her-2/neu showed no association with tumour size, tumor grade and lymph node metastases in pre-menopausal and peri-menopausal women while it showed positive association with tumour size and lymph node metastasis in the post-menopausal women (p < 0.05). Conclusion: Majority (62%) patients were under 50 years as against the Western epidemiology. Association of Her-2/neu with ER, PR, tumour size and lymph node metastasis was age related as pre-menopausal, peri-menopausal and postmenopausal had variable expression of these prognostic markers with therapeutic and prognostic implications. (author)

Diagnostic value of different tumor markers, our experience

International Nuclear Information System (INIS)

Pervez, T.; Anwar, S.

2000-01-01

Variety of tumor markers with varying sensitivity and specificity are used for diagnosis of different malignancies. This study was done to determine the diagnostic value of different tumor markers in our patients with various malignancies. Out of 235 patients studied, 162 were suffering from malignant and 73 from benign diseases. Among these 84 were positive for tumor markers. Out of these positive tumor markers, 75 were suffering from malignancy. Tumor marker analyzed were ca-15-3, ca-125, BETA-HCG, CEA, PSA and alpha-FP depending upon the type of the disease these cases presented. Analysis of the results revealed that different tumor markers had sensitivity varying from 76.9-95.8% and specificity varying form 75-90.9%. CA-125 was observed to be the most specific and sensitive tumor marker for ovarian tumors followed by alpha-FP for hepatocellular tumors and CEA for gastrointestinal tumors. Similarly, PSA for prostate cancers, beta-HCG for choriocarcinoma and CA-15-3 for breast cancer. It is concluded that all the tumor markers have a variable diagnostic value, which cannot be relied upon independently, without other tests added to increase diagnostic value. (author)

Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients

Directory of Open Access Journals (Sweden)

Rino A Gani

2016-05-01

Full Text Available Aim: to evaluate the use of alpha-1-acid glycoprotein (AAG for diagnosing hepatocellular carcinoma (HCC, and to combine with alpha fetoprotein (AFP as part of routine examination in liver cirrhosis patients. Methods: this is a diagnostic study using cross-sectional design. A hundred and six patients were included in this study. Baseline data such as age, gender, AFP, AAG, peripheral blood count, AST and ALT were consecutively collected from liver cirrhosis patients with or without HCC. Serum AAG were measured quantitatively using immunoturboditimetric assay and AFP with enzyme immune assay (EIA. Statistical analysis were done using SPSS 13.0. Data comparisons between group were done using Mann-Whitney test. Diagnostic performance for each marker alone was compared to the surrogate use of both markers (combined parallel approach in HCC cases. Results: receiver operating characteristic (ROC analysis showed that area under the curve for AFP AAG combination was 88.1% and higher than AFP only (86.2% or AAG only (76.5% with sensitivity of 83%, 73% and 44%, respectively, at specificity of >80%. Conclusion: our study showed that combination of AFP and AAG is superior than either marker alone in diagnosing HCC in liver cirrhosis patients. Combination of AFP and AAG may be used to prompt early diagnosis screening of HCC. Key words: alpha fetoprotein, alpha-1-acid glycoprotein, biomarker, liver cancer

MRI of pineal region tumours: relationship between tumours and adjacent structures

International Nuclear Information System (INIS)

Satoh, H.; Kurisu, K.

1995-01-01

A variety of tumours may arise in the pineal region; accurate diagnosis is important in the selection of treatment and prognosis. A retrospective analysis of the MRI studies of 25 patients with pathologically proven pineal region tumours was performed, focused on the relationship between the tumour and neighbouring structures. Compression of the tectal plate was classified as expansive or invasive, and compression of the corpus callosum as inferior, anterior or posterior. In 10 of the 14 patients (71 %) with germ cell tumours tectal compression was of the invasive type; 8 patients (57 %) had multiple tumours and in 13 (93 %) the tumour margins were irregular. Teratomas were readily diagnosed because of characteristic heterogeneous signal intensity. Pineal cell tumours were differentiated from germ cell tumours by their rounded shape, solid nature, sharp margins, and expansive type of tectal compression. Meningiomas were characterised by their falcotentorial attachments, posterior callosal compression, and a low-intensity rim on T2-weighted images. Gd-DTPA injection enabled clear demonstration of the site and extent of tumour spread and was useful in differentiating cystic and solid components. The appearances described, while not pathognomonic, are helpful in the differential diagnosis of pineal region tumours, and valuable in planning appropriate treatment. (orig.). With 4 figs., 6 tabs

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study

Energy Technology Data Exchange (ETDEWEB)

Farrelly, Cormac, E-mail: farrellycormac@gmail.com [Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Lal, Priti [University of Pennsylvania Perelman School of Medicine, Department of Pathology and Laboratory Medicine (United States); Trerotola, Scott O.; Nadolski, Gregory J.; Watts, Micah M. [Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Gorrian, Catherine Mc. [Mater Misericordiae University Hospital, University College Dublin School of Medicine & Medical Science (Ireland); Guzzo, Thomas J. [University of Pennsylvania Perelman School of Medicine, Department of Urology and Surgery (United States)

2016-05-15

PurposeTo correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA.Materials and MethodsIn this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1–7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens.ResultsMean PVS PSA was 4.29, range 2.3–6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left–sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events.ConclusionfPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study

International Nuclear Information System (INIS)

Farrelly, Cormac; Lal, Priti; Trerotola, Scott O.; Nadolski, Gregory J.; Watts, Micah M.; Gorrian, Catherine Mc.; Guzzo, Thomas J.

2016-01-01

PurposeTo correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA.Materials and MethodsIn this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1–7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens.ResultsMean PVS PSA was 4.29, range 2.3–6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left–sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events.ConclusionfPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

TUMOUR VACCINE

NARCIS (Netherlands)

Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

1999-01-01

The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumour radioresponsiveness

International Nuclear Information System (INIS)

Britten, R.A.; Evans, A.J.; Allalunis-Turner, M.J.; Franko, A.J.; Pearcey, R.G.

1996-01-01

The level of intra-tumoral heterogeneity of cellular radiosensitivity within primary cultures of three carcinomas of the cervix has been established. All three cultures contained clones that varied by as much as 3-fold in their clinically relevant radiosensitivity (SF 2 ). The level of intra-tumoral heterogeneity observed in these cervical tumour cultures was sufficient to be a major confounding factor to the use of pre-treatment assessments of radiosensitivity to predict for clinical radioresponsiveness. Mathematical modeling of the relative elimination of the tumour clones during fractionated radiotherapy indicates that, in two of the three biopsy samples, the use of pre-treatment derived SF 2 values from the heterogeneous tumour sample would significantly overestimate radioresponsiveness. We conclude that assays of cellular radiosensitivity that identify the radiosensitivity of the most radioresistant clones and measure their relative abundance could potentially increase the effectiveness of SF 2 values as a predictive marker of radioresponsiveness

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.

Tumour auto-antibody screening: performance of protein microarrays using SEREX derived antigens

International Nuclear Information System (INIS)

Stempfer, René; Weinhäusel, Andreas; Syed, Parvez; Vierlinger, Klemens; Pichler, Rudolf; Meese, Eckart; Leidinger, Petra; Ludwig, Nicole; Kriegner, Albert; Nöhammer, Christa

2010-01-01

The simplicity and potential of minimal invasive testing using serum from patients make auto-antibody based biomarkers a very promising tool for use in diagnostics of cancer and auto-immune disease. Although several methods exist for elucidating candidate-protein markers, immobilizing these onto membranes and generating so called macroarrays is of limited use for marker validation. Especially when several hundred samples have to be analysed, microarrays could serve as a good alternative since processing macro membranes is cumbersome and reproducibility of results is moderate. Candidate markers identified by SEREX (serological identification of antigens by recombinant expression cloning) screenings of brain and lung tumour were used for macroarray and microarray production. For microarray production recombinant proteins were expressed in E. coli by autoinduction and purified His-tag (histidine-tagged) proteins were then used for the production of protein microarrays. Protein arrays were hybridized with the serum samples from brain and lung tumour patients. Methods for the generation of microarrays were successfully established when using antigens derived from membrane-based selection. Signal patterns obtained by microarrays analysis of brain and lung tumour patients' sera were highly reproducible (R = 0.92-0.96). This provides the technical foundation for diagnostic applications on the basis of auto-antibody patterns. In this limited test set, the assay provided high reproducibility and a broad dynamic range to classify all brain and lung samples correctly. Protein microarray is an efficient means for auto-antibody-based detection when using SEREX-derived clones expressing antigenic proteins. Protein microarrays are preferred to macroarrays due to the easier handling and the high reproducibility of auto-antibody testing. Especially when using only a few microliters of patient samples protein microarrays are ideally suited for validation of auto

Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

DEFF Research Database (Denmark)

Andreassen, B. U.; Pærregaard, Anders; Michaelsen, Kim F.

2008-01-01

To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels...... during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days -3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy...... intake was below recommended levels. There was a loss of lean body mass (arm muscle area)(median, 2031 mm(2) (day -3) vs 1477 mm(2) (day 31); p = 0.04), and of fat mass (arm fat area) (791 mm(2) (day -3) vs 648 mm(2) (day +31); p = 0.04). sTNFRI was elevated throughout the course of transplantation...

Immunity to tumour antigens.

Science.gov (United States)

Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

2005-01-01

During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

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

Science.gov (United States)

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.

Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial.

Science.gov (United States)

Amanullah, Muhammad M; Hamid, Mohammad; Hanif, Hashim M; Muzaffar, Marium; Siddiqui, Maria T; Adhi, Fatima; Ahmad, Khabir; Khan, Shahjahan; Hasan, Zahra

2016-03-01

Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters. To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery. A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010-2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines - Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha - were measured. Clinical parameters were also assessed. Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups. Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease.

Science.gov (United States)

Schwiertz, Andreas; Spiegel, Jörg; Dillmann, Ulrich; Grundmann, David; Bürmann, Jan; Faßbender, Klaus; Schäfer, Karl-Herbert; Unger, Marcus M

2018-02-12

Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD. In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors. Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation. Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD. Copyright © 2018 Elsevier Ltd. All rights reserved.

The combined effects of plutonium and cigarette smoke on the production of lung tumours

International Nuclear Information System (INIS)

Priest, N.D.; Moores, S.R.; Black, A.; Talbot, R.; Morgan, A.

1989-01-01

An experiment was conducted to determine the effect of exposure to cigarette smoke on the incidence of plutonium induced lung tumours in mice. Approximately 130 female CBA/H mice were used. These were exposed to plutonium-239 dioxide to give an initial alveolar deposit of 100 Bq, then treated in one of three ways. One third received no further treatment and were held for a period of 18 months. The remainder were either sham-exposed or exposed to mainstream cigarette smoke for one year then held for a further 6 months. After this all the animals were killed. The control mice - that had received only plutonium -contained more tumours than mice that were also either sham-exposed or exposed to cigarette smoke. The lowest number of tumours was found in the group exposed to smoke. These results indicate that, under some circumstances, the effects of cigarette smoke and of alpha-irradiation of the lung can be antagonistic, contrasting with a common expectation of synergy. (author)

Established and emerging biological activity markers of inflammatory bowel disease

DEFF Research Database (Denmark)

Nielsen, O H; Vainer, B; Madsen, S M

2000-01-01

Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder......, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially...... orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion...

Established and emerging biological activity markers of inflammatory bowel disease

DEFF Research Database (Denmark)

Nielsen, O H; Vainer, B; Madsen, S M

2000-01-01

orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion......Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder......, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially...

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

Electrochemotherapy of tumours

International Nuclear Information System (INIS)

Sersa, G.; Cemazar, M.; Rudolf, Z.; Miklavcic, D.

2006-01-01

Electrochemotherapy consists of chemotherapy followed by local application of electric pulses to the tumour to increase drug delivery into cells. Drug uptake can be increased by electroporation for only those drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, only bleomycin and cisplatin found their way from preclinical testing to clinical trials. In vitro studies demonstrated several fold increase of their cytotoxicity after electroporation of cells. In vivo, electroporation of tumours after local or systemic administration of either of the drugs, i.e. electrochemotherapy, proved to be an effective antitumour treatment. In preclinical studies on several tumour models, electrochemotherapy either with bleomycin or cisplatin was elaborated and parameters for effective local tumour control were determined. In veterinary medicine, electrochemotherapy also proved to be effective in the treatment of primary tumours in cats, dogs and horses. In human clinical studies, electrochemotherapy was performed on the patients with progressive disease and accessible tumour nodules of different malignancies. All clinical studies demonstrated that electrochemotherapy is an effective treatment for local tumour control in cancer patients. (author)

Gastric Calcifying Fibrous Tumour

Directory of Open Access Journals (Sweden)

Tan Attila

2006-01-01

Full Text Available Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours; however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases.

Calretinin expression in the differential diagnosis of ameloblastoma and keratocystic odontogenic tumour

International Nuclear Information System (INIS)

Kalsoom, F.; Atique, M.; Ahmed, S.

2015-01-01

To determine calretinin expression by immunohistochemistry in ameloblastoma and keratocystic odontogenic tumors (KCOT) and to document the use of calretinin as a differentiating marker between the two lesions. Study Design: A cross sectional study conducted on previously diagnosed cases of ameloblastoma and Keratocystic odontogenic tumour. Place and Duration of Study: Armed forces Institute of Pathology, Rawalpindi Pakistan and duration was one year. (Sep 2009- Aug 2010). Materials and Methods: Twenty cases each of Ameloblastoma and KCOT were retrieved from the record files along with their paraffin embedded blocks. Histological features of all the cases were reviewed on freshly prepared slides and a fresh diagnosis made regardless of the previous diagnosis. The immunohistochemical marker, Calretinin, was applied on both types of cases using the avidin-biotinylated peroxidase complex method. The results were interpreted. Results: In the cases of Ameloblastoma the epithelial tumour nests showed positivity for Calretinin expression. In 85% cases; intense and diffuse staining was observed in more than 80% of the stellate reticulum like cells while 15% cases showed focal and moderate staining patterns. On the other hand KCOT showed contrary results as none of epithelial lining expressed positive staining for Calretinin, (p<0.001). Conclusion: Calretinin can be used as a useful marker for Ameloblastoma and can be used to differentiate KCOT from Ameloblastoma. (author)

Molecular markers derived from bombesin for tumor diagnosis by SPECT and PET

International Nuclear Information System (INIS)

Pujatti, Priscilla Brunelli

2012-01-01

A high number of molecules have already been identified to have high affinity to some receptors overexpressed on tumour cells and the radiolabelling of those molecules offers the possibility of new compounds for tumour diagnosis and therapy by nuclear medicine. Among of those molecules, bombesin (BBN) has become focus of interest, as its BB 2 receptors are known to be overexpressed in prostate, breast, colon, pancreatic and lung tumour, as long as glioblastomas and neuroblastomas. BBN agonists and antagonists have already been described for this purpose and promising results were obtained in preclinical studies. However, most of them exhibited high abdominal accumulation, especially in pancreas and intestines, which can compromise diagnosis accuracy and cause serious adverse effects in therapy. In this context, the goal of the present work to radiolabel new BBN derivatives with 11 1In and 68 Ga and to evaluate their potential for BB 2 positive tumors diagnosis by single photon emission tomography (SPECT) and positron emission tomography (PET). The structure of studied peptides was Q-YG n -BBN(6-14), where Q is the chelator, n is the number of glycine aminoacids in the spacer YG n and BBN(6-14) is the original bombesin sequence from the aminoacid 6 to 14. The derivative in which the last aminoacid (methionine, Met) was replaced by norleucine (Nle) was also evaluated. The experimental evaluation of the bombesin derivatives was divided into four steps: computational studies, molecular markers for SPECT, molecular markers for PET and toxicological studies. The theoretical partition (log P) and distribution (log D) coefficients were calculated for all bombesin derivatives conjugated to DTPA (diethylenetriaminepentaacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelators applying computational programmes. Bombesin derivatives for SPECT were developed by radiolabelling DTPA-conjugated bombesin derivatives with 111 In to determine the best

Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours

Energy Technology Data Exchange (ETDEWEB)

Bortolussi, S., E-mail: silva.bortolussi@pv.infn.i [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Ballarini, F. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Gadan, M.A. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Protti, N.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Clerici, A.; Ferrari, C.; Cansolino, L.; Zonta, C.; Zonta, A. [Department of Surgery, University of Pavia, via Ferrata 27100 Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, via Ferrata 27100 Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy)

2011-02-15

Lung carcinoma is the leading cause of cancer mortality in the Western countries. Despite the introduction over the last few years of new therapeutic agents, survival from lung cancer has shown no discernible improvement in the last 20 years. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely. The selective boron uptake in the tumour with respect to healthy tissues makes Boron Neutron Capture Therapy a potentially advantageous option in the treatment of tumours that affect whole vital organs, and that are surgically inoperable. To study the possibility of applying BNCT to the treatment of diffuse pulmonary tumours, an animal model for boron uptake measurements in lung metastases was developed. Both healthy and tumour-bearing rats were infused with Boronophenylalanine (BPA) and sacrificed at different time intervals after drug administration. The lungs were extracted, and prepared for boron analysis by neutron autoradiography and {alpha}-spectroscopy. The boron concentrations in tumour and normal lung were plotted as a function of the time elapsed after BPA administration. The concentration in tumour is almost constant within the error bars for all the time intervals of the experiment (1-8 h), while the curve in normal lung decreases after 4 h from BPA infusion. At 4 h, the ratio of boron concentration in tumour to boron concentration in healthy lung is higher than 3, and it stays above this level up to 8 h. Also the images of boron distribution in the samples, obtained by neutron autoradiography, show a selective absorption in the metastases.

Tumour-induced osteomalacia.

Science.gov (United States)

Minisola, Salvatore; Peacock, Munro; Fukumoto, Seijii; Cipriani, Cristiana; Pepe, Jessica; Tella, Sri Harsha; Collins, Michael T

2017-07-13

Tumour-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic disorder caused by tumours that secrete fibroblast growth factor 23 (FGF23). Owing to the role of FGF23 in renal phosphate handling and vitamin D synthesis, TIO is characterized by decreased renal tubular reabsorption of phosphate, by hypophosphataemia and by low levels of active vitamin D. Chronic hypophosphataemia ultimately results in osteomalacia (that is, inadequate bone mineralization). The diagnosis of TIO is usually suspected when serum phosphate levels are chronically low in the setting of bone pain, fragility fractures and muscle weakness. Locating the offending tumour can be very difficult, as the tumour is often very small and can be anywhere in the body. Surgical removal of the tumour is the only definitive treatment. When the tumour cannot be located or when complete resection is not possible, medical treatment with phosphate salts or active vitamin D is necessary. One of the most promising emerging treatments for unresectable tumours that cause TIO is the anti-FGF23 monoclonal antibody KRN23. The recent identification of a fusion of fibronectin and fibroblast growth factor receptor 1 (FGFR1) as a molecular driver in some tumours not only sheds light on the pathophysiology of TIO but also opens the door to a better understanding of the transcription, translocation, post-translational modification and secretion of FGF23, as well as suggesting approaches to targeted therapy. Further study will reveal if the FGFR1 pathway is also involved in tumours that do not harbour the translocation.

Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

Energy Technology Data Exchange (ETDEWEB)

Vordermark, D. [Dept. of Radiation Oncology, Univ. of Wuerzburg (Germany); Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States); Brown, J.M. [Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States)

2003-12-01

Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1{alpha} responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1{alpha} overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a

Tumour sleuths

International Nuclear Information System (INIS)

Beyers, M.; Springolo, E.; Conradie, J.D.

1986-01-01

Hepatocellular carcinoma is a common disease in South Africa and its identification difficult. Methods for the diagnosis of this disease includes the production of hybridoma cell lines by inoculating laboratory mice with a purified human tumour-associated antigen or the antigen-containing surface membranes or the intact cells. In the diagnosis of hepatocellular carcinoma, high concentrations of serum alpha fetoprotein (AFP) can be measured by means of radioimmunoassay techniques. The need for specific methods of diagnosis and treatment of hepatocellular carcinoma led to the investigation by the Isotope Production Centre at Pelindaba into the possibility of using radiolabelled monoclonal anti-AFP for diagnosis, and later, therapy of hepatocellular carcinoma. The monoclonal antibodies can also be labelled with 131 I. Recently the Department of Nuclear Medicine of the University of the Witwatersrand is conducting diagnostic trials on patients who have given their informed consent, to assess the specificity of 131 I radiolabelled anti-AFP monoclonal antibodies to hepatocellular carcinoma cells in humans. Although the investigation is still in its infancy, monoclonal antibodies may prove to be successful non-invasive agents for detecting tumors in early stages

Adnexal Tumours Of Skin

Directory of Open Access Journals (Sweden)

Parate Sanjay N

1998-01-01

Full Text Available A total 120 cases of epidermal appendage tumours of skin were analysed and classified according to the classification provided by WHO’. Epidermal appendage tumours accounted for 12.87% of all skin tumours, of which 29.17% were benign and 70.83% were malignant. Most of the tumours (75.83% were in the head and face region. The most common tumour was basal cell epithelioma (55%.

Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy

Energy Technology Data Exchange (ETDEWEB)

Kao, W.-Y. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Chiou, Y.-Y., E-mail: yychiou@vghtpe.gov.tw [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hung, H.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Su, C.-W., E-mail: cwsu2@vghtpe.gov.tw [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Chou, Y.-H. [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, J.-C. [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China); Huo, T.-I. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Huang, Y.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, W.-C. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China)

2012-05-15

Aims: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and methods: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of {>=}100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results: After a median follow-up of 26.7 {+-} 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and {>=}100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of {>=}100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count {<=}10{sup 5}/mm{sup 3} (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

A potent and selective p38 inhibitor protects against bone damage in murine collagen-induced arthritis : a comparison with neutralization of mouse TNF alpha

NARCIS (Netherlands)

Mihara, K.; Almansa, C.; Smeets, R. L.; Loomans, E. E. M. G.; Dulos, J.; Vink, P. M. F.; Rooseboom, M.; Kreutzer, H.; Cavalcanti, F.; Boots, A. M.; Nelissen, R. L.

Background and purpose: The p38 kinase regulates the release of proinflammatory cytokines including tumour-necrosis factor-alpha (TNF alpha) and is regarded as a potential therapeutic target in rheumatoid arthritis (RA). Using the novel p38 inhibitor Org 48762-0, we investigated the therapeutic

The Z-isomer of 11 beta-methoxy-17 alpha-[123I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

NARCIS (Netherlands)

Rijks, L. J.; Boer, G. J.; Endert, E.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

1997-01-01

The potential of both stereoisomers of 11 beta-methoxy-17 alpha-[123I] iodovinylestradiol (E- and Z-[123I]MIVE) as suitable radioligands for imaging of estrogen receptor (ER)-positive human breast tumours was studied. The 17 alpha-[123I]iodovinylestradiol derivatives were prepared stereospecifically

Investigation of pancreas tumour movements and of their potential markers by four-dimensional scanography: implication for image-guided radiotherapy; etude des mouvements des tumeurs du pancreas et de leurs marqueurs potentiels par scanographie quadridimensionnelle: implication pour la radiotherapie guidee par l'image

Energy Technology Data Exchange (ETDEWEB)

Huguet, F. [Hopital Tenon, Paris (France); Yorke, E.; Davidson, M.; Zhang, Z.; Jackson, A.; Mageras, G.; Wu, A.; Goodman, K. [Memorial Sloan-Kettering Cancer Center, New York (United States)

2011-10-15

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

Limited value of 18F-FDG PET/CT and S-100B tumour marker in the detection of liver metastases from uveal melanoma compared to liver metastases from cutaneous melanoma

International Nuclear Information System (INIS)

Strobel, K.; Veit-Haibach, P.; Fischer, D.R.; Steinert, Hans C.; Schulthess, G.K. von; Bode, B.; Dummer, R.; Imhof, L.; Goldinger, S.

2009-01-01

The objective of this study was to evaluate the value of 18 F-FDG PET/CT and S-100B tumour marker for the detection of liver metastases from uveal melanoma in comparison to liver metastases from cutaneous melanoma. A retrospective evaluation was conducted of 27 liver metastases in 13 patients with uveal melanoma (UM) (mean age: 56.8, range: 30-77) and 43 liver metastases in 14 patients (mean age: 57.9, range: 40-82) with cutaneous melanoma (CM) regarding size and FDG uptake by measuring the maximum standardized uptake value (SUV max ). S-100B serum tumour markers were available in 20 patients. Cytology, histology, additional morphological imaging and follow-up served as reference standard. In nine patients liver metastases were further evaluated histologically regarding GLUT-1 and S-100 receptor expression and regarding epithelial or spindle cell growth pattern. Of 27 liver metastases in 6 of 13 patients (46%) with UM, 16 (59%) were FDG negative, whereas all liver metastases from CM were positive. Liver metastases from UM showed significantly (p max (mean: 3.5, range: 1.5-13.4) compared with liver metastases from CM (mean: 6.6, range: 2.3-15.3). In four of six (66.7%) patients with UM and liver metastases S-100B was normal and in two (33.3%) increased. All PET-negative liver metastases were detectable by morphological imaging (CT or MRI). S-100B was abnormal in 13 of 14 patients with liver metastases from CM. S-100B values were significantly higher (p = 0.007) in the CM patient group (mean S-100B: 10.9 μg/l, range: 0.1-115 μg/l) compared with the UM patients (mean: 0.2 μg/l, range: 0.0-0.5 μg/l). Histological work-up of the liver metastases showed no obvious difference in GLUT-1 or S-100 expression between UM and CM liver metastases. The minority (36%) of patients with UM had extrahepatic metastases and the majority (86%) of patients with CM had extrahepatic metastases, respectively. There was a close to significant trend to better survival of UM patients

Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition

International Nuclear Information System (INIS)

Gorges, Tobias M; Tinhofer, Ingeborg; Drosch, Michael; Röse, Lars; Zollner, Thomas M; Krahn, Thomas

2012-01-01

Circulating tumour cells (CTCs) have shown prognostic relevance in metastatic breast, prostate, colon and pancreatic cancer. For further development of CTCs as a biomarker, we compared the performance of different protocols for CTC detection in murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468 and KPL-4). Blood samples were taken from tumour bearing animals (20 to 200 mm 2 ) and analysed for CTCs using 1. an epithelial marker based enrichment method (AdnaTest), 2. an antibody independent technique, targeting human gene transcripts (qualitative PCR), and 3. an antibody-independent approach, targeting human DNA-sequences (quantitative PCR). Further, gene expression changes associated with epithelial-to-mesenchymal transition (EMT) were determined with an EMT-specific PCR assay. We used the commercially available Adna Test, RT-PCR on human housekeeping genes and a PCR on AluJ sequences to detect CTCs in xenografts models. Phenotypic changes in CTCs were tested with the commercially available “Human Epithelial to Mesenchymal Transition RT-Profiler PCR Array”. Although the AdnaTest detects as few as 1 tumour cell in 1 ml of mouse blood spiking experiments, no CTCs were detectable with this approach in vivo despite visible metastasis formation. The presence of CTCs could, however, be demonstrated by PCR targeting human transcripts or DNA-sequences - without epithelial pre-enrichment. The failure of CTC detection by the AdnaTest resulted from downregulation of EpCAM, whereas mesenchymal markers like Twist and EGFR were upregulated on CTCs. Such a change in the expression profile during metastatic spread of tumour cells has already been reported and was linked to a biological program termed epithelial-mesenchymal transition (EMT). The use of EpCAM-based enrichment techniques leads to the failure to detect CTC populations that have undergone EMT. Our findings may explain clinical results where low CTC numbers have been reported even in patients with late

Pasteurization of bone for tumour eradication prior to reimplantation – An in vitro & pre-clinical efficacy study

Science.gov (United States)

Kode, Jyoti; Taur, Prasad; Gulia, Ashish; Jambhekar, Nirmala; Agarwal, Manish; Puri, Ajay

2014-01-01

Background & objectives: In current era of limb-salvage therapy, pasteurization of bone sarcomas is receiving growing attention as a potential extracorporeal treatment and cost-effective alternative to allografts and radiation before surgical reimplantation. Detailed in vitro and in vivo pre-clinical study to evaluate efficacy of pasteurization to eradicate malignant cells has not been reported yet. The present study was carried out to assess the efficacy of pasteurization to kill tumour cells both in vitro and in vivo. Methods: Surgically resected specimens of osteosarcomas (n=4) were cut into equal halves and one section was pasteurized by heating at 60°C to 65°C for 40 min. Paired samples before and after pasteurization were studied in vitro for DNA ploidy, evaluation of histological change and elimination of mitotic activity. These tissues were transplanted in immune-deficient NOD-SCID mice to evaluate effect on tumour-generating ability, presence of human nuclei, osteopontin and cytokine/chemokines released in tumour-transplanted mice. Results: Non-pasteurized tumour samples had viable tumour cells which exhibited significant growth in culture, increased proliferative ability and clonogenic potential while respective pasteurized tumour tissues did not grow in culture and did not exhibit clonogenicity. Flow cytometry revealed that propidium iodide positive dead cells increased significantly (Ppasteurization. Seven of 12 non-pasteurized tumour transplanted mice demonstrated tumour-forming ability as against 0 of 12 in pasteurized tumour transplanted mice. Solid tumour xenografts exhibited strong expression of anti-human nuclei and osteopontin by immunohistochemistry as well as secretary human interluekin-6 (IL-6) while pasteurized mice failed to express these markers. Interpretation & conclusions: This study has provided a basis to establish pasteurization as being efficacious in ensuring tumour eradication from resected bone tumour specimens. Pasteurized

Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis-associated tumorigenesis in mice.

Science.gov (United States)

Jauch, Dominik; Martin, Maria; Schiechl, Gabriela; Kesselring, Rebecca; Schlitt, Hans Jürgen; Geissler, Edward K; Fichtner-Feigl, Stefan

2011-12-01

Colitis-associated tumorigenesis is a balance between proliferation of tumour cells and tumour immunosurveillance. The role of T-helper-cell-derived cytokines in tumour growth is not fully understood. In this study the authors investigated the influence of interleukin (IL) 21 on intestinal tumorigenesis. Chronic colitis was induced in IL-21(-/-) and littermate control wild-type mice with three cycles of 1.5% dextran sulphate sodium (DSS) over 7 days followed by 7 days of drinking water. Mice received an azoxymethane injection on day 0 of DSS-colitis to induce tumorigenesis. Immunohistochemistry was performed on inflamed and tumour-bearing areas of colons. Cytokine expression of isolated colonic CD4 T cells was determined by ELISA. Cytotoxic capacity of isolated colonic CD8 T cells targeting tumour cells was evaluated by flow cytometry and quantitative cytotoxicity assay. Apoptosis of tumour cells was determined by TUNEL assay of colonic sections. Increasing expression of IL-21 was observed in chronic colitis, which showed functional importance, since IL-21 deficiency prevented chronic DSS-colitis development. Further, in the absence of IL-21, significantly fewer tumour nodules were detected, despite a similar extent of intestinal inflammation. In wild-type mice, 8.6±1.9 tumour nodules were found compared with 1.0±1.2 in IL-21-deficient mice. In tumour-bearing IL-21-deficient mice, intestinal inflammation was restored and partly dependent on interferon (IFN)-γ, whereas the inflammation in wild-type mice showed high IL-17A concentrations. In these rare tumours in IL-21-deficient mice, tumour cell proliferation (Ki-67) was decreased, while cell apoptosis was increased, compared with wild-type mice. Increased IFNγ expression in tumour-bearing IL-21-deficient mice led to increased tumour immunosurveillance mediated by cytotoxic CD8CD103 T cells targeting E-cadherin(+) colonic tumour cells and therefore limited tumour growth. These results indicate that IL-21

Monte Carlo Simulations of Necrotic Cell Targeted Alpha Therapy

International Nuclear Information System (INIS)

Penfold, S.N.; Brown, M.P.; Bezak, E.

2011-01-01

Full text: Hypoxic tumour cells are radioresistant and are significant contributors to the locoregional recurrences and distant metastases that mark treatment failure. Due to restricted circulatory supply, hypoxic tumor cells frequently become necrotic and thus necrotic areas often lie near hypoxic tumour areas. In this study we investigate the feasibility of binding an alpha-emitting conjugate to necrotic cells located in the proximity of hypoxic, viable tumour cells. Monte Carlo radiation transport simulations were performed to investigate the dose distribution resulting from the thorium 227 (Th227) decay chain in a representative tumour geometry. The Geant4 software toolkit was used to simulate the decay and interactions of the Th227 decay chain. The distribution of Th227 was based on a study by Thomlinson and Gray of human lung cancer histological samples (Thomlinson RH, Gray LH. Br J Cancer 1955; 9:539). The normalized dose distribution obtained with Geant4 from a cylindrical Th227 source in water is illustrated in Fig. I. The relative contribution of the different decay channels is displayed, together with a profile through the centre of the accumulated dose map. The results support the hypothesis that significant α-particle doses will be deposited in the hypoxic tumor tissue immediately surrounding the necrotic core (where the majority of Th227 will be located). As an internal a-particle generator, the Th227-radioimmunoconjugate shows potential as an efficient hypoxic tumour sterilizer.

A Mononucleotide Markers Panel to Identify hMLH1/hMSH2 Germline Mutations

Directory of Open Access Journals (Sweden)

M. Pedroni

2007-01-01

Full Text Available Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI. MSI is present in 85–90% of colorectal cancers that occur in Lynch Syndrome. To standardize the molecular diagnosis of MSI, a panel of 5 microsatellite markers was proposed (known as the “Bethesda panel”. Aim of our study is to evaluate if MSI testing with two mononucleotide markers, such as BAT25 and BAT26, was sufficient to identify patients with hMLH1/hMSH2 germline mutations. We tested 105 tumours for MSI using both the Bethesda markers and the two mononucleotide markers BAT25 and BAT26. Moreover, immunohistochemical evaluation of MLH1 and MSH2 proteins was executed on the tumours with at least one unstable microsatellite, whereas germline hMLH1/hMSH2 mutations were searched for all cases showing two or more unstable microsatellites.

Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

Science.gov (United States)

Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

2015-03-01

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. © 2015 The authors.

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

TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia.

Directory of Open Access Journals (Sweden)

Mariana Maschietto

Full Text Available The presence of diffuse anaplasia in Wilms tumours (DAWT is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information.We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32 and gene expression (n = 36 arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling.From the 40 cases, 22 (55% had TP53 mutations (2 detected only after deep-sequencing, 20 of which also had 17p loss (91%; 18 (45% cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25 had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR, 3.89; 95% confidence interval (CI, 1.26-16.0 and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7 compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03. These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes.This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.

TP53 mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia.

Science.gov (United States)

Maschietto, Mariana; Williams, Richard D; Chagtai, Tasnim; Popov, Sergey D; Sebire, Neil J; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R; Grundy, Paul; Dome, Jeffrey S; Pritchard-Jones, Kathy

2014-01-01

The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.

GROWTH HORMONE-, ALPHA-SUBUNIT AND THYROTROPIN-COSECRETING PITUITARY-ADENOMA IN FAMILIAL SETTING OF PITUITARY-TUMOR

NARCIS (Netherlands)

LINKS, TP; MONKELBAAN, JF; DULLAART, RPF; VANHAEFTEN, TW

1993-01-01

A patient with acromegaly and hyperthyroidism due to a growth hormone-, thyrotrophin- and alpha-subunit-secreting pituitary adenoma is described. His deceased father had suffered from a pituitary tumour, and was likely to have had acromegaly as well. Plasma growth hormone and insulin-like growth

Use of the micronucleus assay for the selective detection of radiosensitivity in BUdR-unincorporated cells after pulse-labelling of exponentially growing tumour cells

Energy Technology Data Exchange (ETDEWEB)

Masunaga, S.; Ono, K.; Fushiki, M.; Abe, M. (Kyoto Univ. (Japan). Faculty of Medicine); Wandl, E.O. (Vienna Univ. (Austria). Klinik fuer Strahlentherapie und Strahlenbiologie)

1990-08-01

To determine the radiosensitivity of non S-phase tumour cells in vitro, survival curves of SCC VII tumour cells were obtained after a short block with hydroxyurea. Dose-response curves of micronucleus (MN) frequency appearing in non-S-phase cells were also determined by excluding S-phase cells with immunofluorescence staining to 5-bromo-2'-deoxyuridine (BUdR). Both the dose response curves of MN frequency and survival curves were analysed by a linear-quadratic model (surviving fraction =exp (-{alpha}D-{beta}D{sup 2}), MN frequency =aD+bD{sup 2}+c). A good correlation between the {alpha}/{beta} and a/b ratios was observed. In both BUdR-unincorporated and asynchronous cell cultures, the regression lines between the surviving fraction and micronucleus frequency were statistically identical. (author).

Imaging of sacral tumours

International Nuclear Information System (INIS)

Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S.; Leclere, J.; Vanel, D.; Missenard, G.; Pinieux, G. de

2008-01-01

All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

Imaging of sacral tumours

Energy Technology Data Exchange (ETDEWEB)

Gerber, S.; Ollivier, L.; Brisse, H.; Neuenschwander, S. [Institut Curie, Department of Radiology, Paris (France); Leclere, J. [Institut Gustave Roussy, Department of Radiology, Villejuif (France); Vanel, D. [The Rizzoli Institute, Department of Radiology, Bologna (Italy); Missenard, G. [Institut Gustave Roussy, Comite de pathologie tumorale de l' appareil locomoteur, Villejuif (France); Pinieux, G. de [CHRU de Tours, Department of Pathology, Hopital Trousseau, Tours (France)

2008-04-15

All components of the sacrum (bone, cartilage, bone marrow, meninges, nerves, notochord remnants, etc.) can give rise to benign or malignant tumours. Bone metastases and intraosseous sites of haematological malignancies, lymphoma and multiple myeloma are the most frequent aetiologies, while primary bone tumours and meningeal or nerve tumours are less common. Some histological types have a predilection for the sacrum, especially chordoma and giant cell tumour. Clinical signs are usually minor, and sacral tumours are often discovered in the context of nerve root or pelvic organ compression. The roles of conventional radiology, CT and MRI are described and compared with the histological features of the main tumours. The impact of imaging on treatment decisions and follow-up is also reviewed. (orig.)

An efficient marker-free vector for clean gene transfer into plants

African Journals Online (AJOL)

Yomi

2012-02-23

Feb 23, 2012 ... vector sequences inserted into plant genomes. Transformation ..... Thymosin Alpha 1 (Tα1) in Marker-free Transgenic Lettuce (Lactuca sativa). ... obtaining marker-free plants of a cross-pollinating and vegetatively propagated ...

Traditional and emerging molecular markers in neuroblastoma prognosis: the good, the bad and the ugly.

Science.gov (United States)

Poremba, C; Hero, B; Goertz, H G; Scheel, C; Wai, D; Schaefer, K L; Christiansen, H; Berthold, F; Juergens, H; Boecker, W; Dockhorn-Dworniczak, B

2001-01-01

Neuroblastomas (NB) are a heterogeneous group of childhood tumours with a wide range of likelihood for tumour progression. As traditional parameters do not ensure completely accurate prognostic grouping, new molecular markers are needed for assessing the individual patient's prognosis more precisely. 133 NB of all stages were analysed in blind-trial fashion for telomerase activity (TA), expression of surviving, and MYCN status. These data were correlated with other traditional prognostic indicators and disease outcome. TA is a powerful independent prognostic marker for all stages and is capable of differentiating between good and poor outcome in putative "favourable" clinical or biological subgroups of NB patients. High surviving expression is associated with an adverse outcome, but is more difficult to interprete than TA because survivin expression needs to be accurately quantified to be of predictive value. We propose an extended progression model for NB including emerging prognostic markers, with emphasis on telomerase activity.

Influence of G308A polymorphism of tumor necrosis factor-alpha gene on inflammatory markers in postsurgical head and neck cancer patients with early enteral nutrition.

Science.gov (United States)

de Luis, Daniel Antonio; Sagrado, Manue Gonzalez; Vallejo, Luis Angel; Carcedo, Luis María Gil; Izaola, Olatz; Cuellar, Luis; Terroba, María Concepción; Aller, Rocío

2007-01-01

Although immune dysfunction in patients with cancer could be multifactorial, the immune system may be modulated by nutritional substrates and genetic background. Our study evaluated the effect of G308A polymorphism of the tumor necrosis factor-alpha (TNF-alpha) gene on inflammatory markers in patients after surgery for head and neck cancer who received early enteral nutrition. A population of 60 patients with oral and laryngeal cancer was enrolled. At surgery patients were treated with a hyperproteic enteral diet. Perioperatively and on postoperative day 6 the following parameters were evaluated: serum values of prealbumin, transferrin, total number of lymphocytes, interleukin-6, TNF-alpha, and C-reactive protein. In addition, genotyping of G308A gene polymorphism was assessed. Patients' mean age was 61.1 +/- 14.6 y (four women, 56 men) with a body mass index of 25.4 +/- 5.2 kg/m(2) and a previous weight loss of 0.35 +/- 0.2 kg. Forty patients (37 men, 3 women; 66.6%) had the genotype G308/G308 (wild group) and 20 patients (19 men, 1 woman; 23.4%) had the genotype G308/A308 (mutant group). A significant increase in prealbumin and transferrin levels was detected in both groups. C-reactive protein decreased in both groups (wild group: 105.1 +/- 60 versus 53.8 +/- 62.3 mg/dL, P < 0.05; mutant group: 99.5 +/- 46 versus 43.9 +/- 51.9 mg/dL, P < 0.05). Interleukin-6 decreased in both groups (wild group: 20.1 +/- 22 versus 6.2 +/- 4.1 pg/mL, P < 0.05; mutant group: 22.3 +/- 38 versus 9.2 +/- 7.4 pg/mL, P = NS). Lymphocytes increased in both groups (wild group: 1102 +/- 468 versus 1600 +/- 537 10(3)/mL, P = NS; mutant group: 1441 +/- 739 10(3)/mL versus 1669 +/- 614 10(6)/mL, P = NS). TNF-alpha showed no changes. The G308A polymorphism of the TNF-alpha gene did not affect levels of inflammatory markers in patients after surgery for head and neck cancer who were treated with early enteral nutrition.

Elevated levels of tumor necrosis factor alpha and mortality in centenarians

DEFF Research Database (Denmark)

Bruunsgaard, Helle; Andersen-Ranberg, Karen; Hjelmborg, Jacob v B

2003-01-01

BACKGROUND: Aging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) alpha initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-alpha was also a prognostic marker for all......-cause mortality in these persons. METHODS: We enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-alpha, interleukin (IL)-6, IL-8, and C-reactive protein were measured at baseline, and we determined the associations between the markers of inflammation and mortality during...... the subsequent 5 years. RESULTS: Only 9 subjects were alive after 5 years. Elevated levels of TNF-alpha were associated with mortality in both men and women (hazard ratio = 1.34 per SD of 2.81 pg/mL; 95% confidence interval: 1.12 to 1.60, P = 0.001). Levels of IL-6 and IL-8 did not affect survival; levels of C...

L-lactate transport in Ehrlich ascites-tumour cells.

Science.gov (United States)

Spencer, T L; Lehninger, A L

1976-01-01

Ehrlich ascites-tumour cells were investigated with regard to their stability to transport L-lactate by measuring either the distribution of [14C]lactate or concomitant H+ ion movements. The movement of lactate was dependent on the pH difference across the cell membrane and was electroneutral, as evidenced by an observed 1:1 antiport for OH- ions or 1:1 symport with H+ ions. 2. Kinetic experiments showed that lactate transport was saturable, with an apparent Km of approx. 4.68 mM and a Vmax. as high as 680 nmol/min per mg of protein at pH 6.2 and 37 degrees C. 3. Lactate transport exhibited a high temperature dependence (activation energy = 139 kJ/mol). 4. Lactate transport was inhibited competitively by (a) a variety of other substituted monocarboxylic acids (e.g. pyruvate, Ki = 6.3 mM), which were themselves transported, (b) the non-transportable analogues alpha-cyano-4-hydroxycinnamate (Ki = 0.5 mM), alpha-cyano-3-hydroxycinnamate (Ki = 2mM) and DL-p-hydroxyphenyl-lactate (Ki = 3.6 mM) and (c) the thiol-group reagent mersalyl (Ki = 125 muM). 5. Transport of simple monocarboxylic acids, including acetate and propionate, was insensitive to these inhibitors; they presumably cross the membrane by means of a different mechanism. 6. Experiments using saturating amounts of mersalyl as an "inhibitor stop" allowed measurements of the initial rates of net influx and of net efflux of [14C]lactate. Influx and efflux of lactate were judged to be symmetrical reactions in that they exhibited similar concentration dependence. 7. It is concluded that lactate transport in Ehrlich ascites-tumour cells is mediated by a carrier capable of transporting a number of other substituted monocarboxylic acids, but not unsubstituted short-chain aliphatic acids. PMID:7237

The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas.

Science.gov (United States)

Kannan, K; Munirajan, A K; Krishnamurthy, J; Bhuvarahamurthy, V; Mohanprasad, B K; Panishankar, K H; Tsuchida, N; Shanmugam, G

2000-03-01

Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associated with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16INK4alpha/p19ARF genes. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations. SSCP analysis indicated that only 9% (8/87) of the tumours had mutation in p16INK4alpha/p19ARF genes. Seventy-two tumours studied here were previously analysed for p53 mutations and 21% (15/72) of them were found to have mutations in p53 gene. Only one tumour was found to have mutation at both p53 and p16INK4alpha/p19ARF genes. Thus, the mutation rates observed were 21% for p53, 9% for p16INK4alpha/p19ARF, and 1% for both. Sequencing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) transversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine to a termination codon at p16INK4alpha gene codon 80 and the same mutation will alter codon 94 of p19ARF gene from CCG to CTG (proline to leucine). These results suggest that p16INK4alpha/p19ARF mutations are less frequent than p53 mutations in Indian oral SCCs. The p53 and p16INK4alpha/p19ARF mutational events are independent and are mutually exclusive suggesting that mutational inactivation of either p53 or p16INK4alpha/p19ARF may alleviate the need for the inactivation of the other gene.

Tumour necrosis factor-alpha (TNF-alpha) transcription and translation in the CD4+ T cell-transplanted scid mouse model of colitis

DEFF Research Database (Denmark)

Williams, A M; Whiting, C V; Bonhagen, K

1999-01-01

The adoptive transfer of activated CD4+ alpha/beta T cell blasts from the spleens of immunocompetent C.B-17+/+ or BALB/cdm2 mice into C.B-17scid/scid (scid) mice induces a colitis in the scid recipient within 8 weeks, which progresses to severe disease within 16 weeks. T cells isolated from......-labelled riboprobes were used. The prominent myeloid cell infiltrate in diseased tissues comprised F4/80+, Mac-l+ macrophages, neutrophils, dendritic cells and activated macrophages. TNF-alpha transcription and translation were associated with activated macrophages in the lamina propria. Activated macrophages...

Oxygen tension in human tumours measured with polarographic needle electrodes and its relationship to vascular density, necrosis and hypoxia

International Nuclear Information System (INIS)

Lyng, Heidi; Sundfoer, Kolbein; Rofstad, Einar K.

1997-01-01

Background and purpose: The use of polarographic needle electrodes for measurement of oxygen tension (pO 2 ) in tumours requires documentation of the validity of the method. In the present work the pO 2 values measured polarographically with the Eppendorf pO 2 histograph in human tumours were compared with the histological appearance of the tumour tissue, i.e. vascular density, fraction of necrosis and fraction of hypoxic tissue, to investigate whether the measurements reflected the expected pO 2 . Materials and methods: The pO 2 was measured in cervix tumours in patients and in human melanoma xenografted tumours in athymic mice. Vascular density was determined in the cervix tumours by histological analysis of biopsies from the pO 2 measurement tracks. Fraction of necrosis and fraction of hypoxic tissue, i.e. tissue binding the hypoxia marker pimonidazole, were determined in the melanomas by analysis of histological sections from the tumour planes in which the pO 2 measurements were performed. Results: The pO 2 distributions showed large intratumour heterogeneity. In cervix tumours, tumour regions with vascular density (vascular length per unit tissue volume) in the range of 47-77 mm/mm 3 showed higher pO 2 than tumour regions with vascular density in the range of 20-47 mm/mm 3 , which in turn showed higher pO 2 than tumour regions with vascular density in the range of 0-20 mm/mm 3 . In melanomas, tumour regions in which necrosis and hypoxia constituted more than 50% of the tissue showed lower pO 2 than other tumour regions. Conclusions: The pO 2 measured in the tumours was consistent with the histological appearance of the tissue in which the measurements were performed, suggesting that reliable pO 2 distributions of tumours can be obtained with polarographic needle electrodes

The Askin tumour. Neuroactodermic tumour of the thoracic wall

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Velazquez, P.; Nicolas, A. I.; Vivas, I.; Damaso Aquerreta, J.; Martinez-Cuesta, A.

1999-01-01

The Askin tumours is an extremely rare and malignant process in the thoracic pulmonary region during infancy and youth. The differential diagnosis has to be considered with other thoracic wall tumours that are more common in pediatrics like the undifferentiated neuroblastoma, the embionic rabdomiosarcoma, the Ewing sarcoma and the linfoma. A retrospective examination was carried out on 473 thoracic wall tumours from 1994 to 1997 at our centre, resulting in 4 patients with an anatomopathologically tested Askin tumour (ages from 13-21). All the cases were studied using simple radiography and CT. In two cases MRI was also used. The most common clinical manifestation was a palpable painful mass in the thoracic wall. In the simple radiograph the main finding was a large mass of extrapleural soft material, with costal destruction ( n=3) and a pleural effusion (n=2). In the CT study the mass was heterogeneous, with internal calcifications in one case. CT and MRI showed invasion in the mediastinum (n=1), medular channel (n=1) and phrenic and sulphrenic extension (n=1). The Askin tumour should be included in the differential diagnosis of thoracic wall masses in infant-youth ages. There are no specific morphological characteristics. Both CT and MRI are useful for the diagnosis, staging and follow up. (Author) 11 refs

Detection of respiratory tumour motion using intrinsic list mode-driven gating in positron emission tomography.

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Büther, Florian; Ernst, Iris; Dawood, Mohammad; Kraxner, Peter; Schäfers, Michael; Schober, Otmar; Schäfers, Klaus P

2010-12-01

Respiratory motion of organs during PET scans is known to degrade PET image quality, potentially resulting in blurred images, attenuation artefacts and erroneous tracer quantification. List mode-based gating has been shown to reduce these pitfalls in cardiac PET. This study evaluates these intrinsic gating methods for tumour PET scans. A total of 34 patients with liver or lung tumours (14 liver tumours and 27 lung tumours in all) underwent a 15-min single-bed list mode PET scan of the tumour region. Of these, 15 patients (8 liver and 11 lung tumours in total) were monitored by a video camera registering a marker on the patient's abdomen, thus capturing the respiratory motion for PET gating (video method). Further gating information was deduced by dividing the list mode stream into 200-ms frames, determining the number of coincidences (sensitivity method) and computing the axial centre of mass of the measured count rates in the same frames (centre of mass method). Additionally, these list mode-based methods were evaluated using only coincidences originating from the tumour region by segmenting the tumour in sinogram space (segmented sensitivity/centre of mass method). Measured displacement of the tumours between end-expiration and end-inspiration and the increase in apparent uptake in the gated images served as a measure for the exactness of gating. To estimate the accuracy, a thorax phantom study with moved activity sources simulating small tumours was also performed. All methods resolved the respiratory motion with varying success. The best results were seen in the segmented centre of mass method, on average leading to larger displacements and uptake values than the other methods. The simple centre of mass method performed worse in terms of displacements due to activities moving into the field of view during the respiratory cycle. Both sensitivity- and video-based methods lead to similar results. List mode-driven PET gating, especially the segmented centre of mass

Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin.

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Little, D; Said, J W; Siegel, R J; Fealy, M; Fishbein, M C

1986-06-01

Markers for endothelial cells including Ulex europaeus 1 lectin, blood group A, B, and H, and the prostaglandin metabolite 6-keto-PGF1 alpha were evaluated in paraffin secretions from formalin-fixed benign and malignant vascular neoplasms using a variety of immunohistochemical techniques, and results compared with staining for factor VIII-related antigen. Staining for Ulex appeared more sensitive than factor VIII-related antigen in identifying poorly differentiated neoplasms including haemangiosarcomas and spindle cell proliferations in Kaposi's sarcoma. Staining for blood group related antigens correlated with blood group in all cases. Ulex europaeus 1 lectin was the only marker for endothelial cells in lymphangiomas.

HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

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Mark O Kitchen

2018-01-01

Full Text Available Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease.

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.)

Hepatocellular carcinoma (HCC) and diagnostic significance of alpha-fetoprotein (AFP)

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Baig, J.A.; Alam, J.M.; Baig, M.; Mahmood, S.R.; Shaheen, R.; Waheed, A.

2009-01-01

Alpha-fetoprotein (alpha-fetoprotein, AFP) is a Glycoprotein, belonging to the intriguing class of onco-development protein. Generally designated as tumour marker, AFP is recognized as an important blood component, having specific diagnostic utilities Elevation of its level up to pathological range in adults correlate with the appearance of several malignant and chronic conditions, such as hepatocellular carcinoma (HCC) and chronic liver disease, respectively. To evaluate the diagnostic significance of AFP in HCC, a study was carried out for a period of two years (Jan. 2004 to Dec. 2005) A brief history of Patients was taken with clinical symptoms and signs and initial diagnosis. Patients admitted in wards or visiting OPDs with diagnosis or suspicions of HCC and additional conditions of Chronic Liver disease (CLDs), hepatitis C (HCV) and hepatitis B viral (HBV) infections, were selected and classified according to gender. When confirmed, their HCC status was evaluated and classified according to clinical condition. In 1012 adults including, males 762 (75.3%) and females 250 (24.7%) patients suspected of or diagnosed with HCC and presence of HBV and HCV infections. Out of 480 males, who depicted elevated AFP levels, 39 (8.13%) were diagnosed with HCC. Similarly, 7 (5.34%) females out of 131 with elevated levels of AFP were diagnosed with HCC. Mean elevated AFP levels in all HCC patients were, 421+-59 mu g/ml (range 157-4019 mu g/ml) in males and 163+-32 mu g/ml (range 101-2341 mu g/ml) in females. In males, the overall estimated mean AFP elevated values were analyzed to be 514 mu g/ml (range 67-4019+-59 mu g/ml), whereas in females it was 396+-42 mu g/ml (range 21-2341 mu g/ml). It was also noted that 43 (8.96%) males and 7 (5.34%) female patients, exhibited elevated levels of AFP, however, found negative for HCV and HBV infections. It is concluded that AFP is a significant markers for Hepatocellular carcinoma, helpful in assessing problems in management of HCC and

On-chip integrated labelling, transport and detection of tumour cells.

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Woods, Jane; Docker, Peter T; Dyer, Charlotte E; Haswell, Stephen J; Greenman, John

2011-11-01

Microflow cytometry represents a promising tool for the investigation of diagnostic and prognostic cellular cancer markers, particularly if integrated within a device that allows primary cells to be freshly isolated from the solid tumour biopsies that more accurately reflect patient-specific in vivo tissue microenvironments at the time of staining. However, current tissue processing techniques involve several sequential stages with concomitant cell losses, and as such are inappropriate for use with small biopsies. Accordingly, we present a simple method for combined antibody-labelling and dissociation of heterogeneous cells from a tumour mass, which reduces the number of processing steps. Perfusion of ex vivo tissue at 4°C with antibodies and enzymes slows cellular activity while allowing sufficient time for the diffusion of minimally active enzymes. In situ antibody-labelled cells are then dissociated at 37°C from the tumour mass, whereupon hydrogel-filled channels allow the release of relatively low cell numbers (<1000) into a biomimetic microenvironment. This novel approach to sample processing is then further integrated with hydrogel-based electrokinetic transport of the freshly liberated fluorescent cells for downstream detection. It is anticipated that this integrated microfluidic methodology will have wide-ranging biomedical and clinical applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radiological diagnosis of liver tumours

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Lundstedt, C.

1987-01-01

Sixty patients treated with an intra-arterial cytostatic drug for metastases from colo-rectal carcinoma were evaluated with angiography to determine prognostic parameters. The extent of tumour in the liver and an unchanged or diminished tumour volume following treatment, as demonstrated with angiography, were associated with significant prolongation of survival. Patients who developed occlusion of the hepatic artery or of branches of the portal vein, also survived longer. 189 patients examined with angiography, 161 with computed tomography (CT), 95 with computed tomographic arteriography (CTA) and 71 with ultrasound (US) were subjected to liver evaluation at laparotomy consisting of inspection and palpation. The result of this surgical liver evaluation was for the purpose of the study regarded as completely accurate and was used to assess the accuracy of the different radiological methods. The location of tumour in the liver lobes or segments was analysed, with a separate evaluation of the right and left liver lobes. The rate of detection of individual tumour nodules was also determined. Angiography detected 55% of liver areas affected by tumour and 47% of individual tumour nodules. CT detected 83% of liver lobes or segments containing tumour, and 70% of the tumour nodules. US detected 69% of the portions of liver holding tumour, and also 69% of the tumour nodules. CTA detected 85% of tumours areas and 74% of separate tumour nodules. Some lesions detected with CT were not seen with CTA and vice versa. More false-positive results were recorded with CTA than with CT using intravenous contrast enhancement. (orig.)

Inhibition of systemic inflammation by central action of the neuropeptide alpha-melanocyte- stimulating hormone.

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Delgado Hernàndez, R; Demitri, M T; Carlin, A; Meazza, C; Villa, P; Ghezzi, P; Lipton, J M; Catania, A

1999-01-01

The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) reduces fever and acute inflammation in the skin when administered centrally. The aim of the present research was to determine whether central alpha-MSH can also reduce signs of systemic inflammation in mice with endotoxemia. Increases in serum tumor necrosis factor-alpha and nitric oxide, induced by intraperitoneal administration of endotoxin, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Lung myeloperoxidase activity, a marker of neutrophil infiltration, was increased in endotoxemic mice; the increase was significantly less in lungs of mice treated with central alpha-MSH. Intraperitoneal administration of the small dose of alpha-MSH that was effective centrally did not alter any of the markers of inflammation. In experiments using immunoneutralization of central alpha-MSH, we tested the idea that endogenous peptide induced within the brain during systemic inflammation modulates host responses to endotoxic challenge in peripheral tissues. The data showed that proinflammatory agents induced by endotoxin in the circulation, lungs, and liver were significantly greater after blockade of central alpha-MSH. The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation.

Immunological Characterization of Whole Tumour Lysate-Loaded Dendritic Cells for Cancer Immunotherapy

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Ottobrini, Luisa; Biasin, Mara; Borelli, Manuela; Lucignani, Giovanni; Trabattoni, Daria; Clerici, Mario

2016-01-01

Introduction Dendritic cells play a key role as initiators of T-cell responses, and even if tumour antigen-loaded dendritic cells can induce anti-tumour responses, their efficacy has been questioned, suggesting a need to enhance immunization strategies. Matherials & Methods We focused on the characterization of bone marrow-derived dendritic cells pulsed with whole tumour lysate (TAA-DC), as a source of known and unknown antigens, in a mouse model of breast cancer (MMTV-Ras). Dendritic cells were evaluated for antigen uptake and for the expression of MHC class I/II and costimulatory molecules and markers associated with maturation. Results Results showed that antigen-loaded dendritic cells are characterized by a phenotypically semi-mature/mature profile and by the upregulation of genes involved in antigen presentation and T-cell priming. Activated dendritic cells stimulated T-cell proliferation and induced the production of high concentrations of IL-12p70 and IFN-γ but only low levels of IL-10, indicating their ability to elicit a TH1-immune response. Furthermore, administration of Antigen loaded-Dendritic Cells in MMTV-Ras mice evoked a strong anti-tumour response in vivo as demonstrated by a general activation of immunocompetent cells and the release of TH1 cytokines. Conclusion Data herein could be useful in the design of antitumoral DC-based therapies, showing a specific activation of immune system against breast cancer. PMID:26795765

Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition

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Gorges Tobias M

2012-05-01

Full Text Available Abstract Background Circulating tumour cells (CTCs have shown prognostic relevance in metastatic breast, prostate, colon and pancreatic cancer. For further development of CTCs as a biomarker, we compared the performance of different protocols for CTC detection in murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468 and KPL-4. Blood samples were taken from tumour bearing animals (20 to 200 mm2 and analysed for CTCs using 1. an epithelial marker based enrichment method (AdnaTest, 2. an antibody independent technique, targeting human gene transcripts (qualitative PCR, and 3. an antibody-independent approach, targeting human DNA-sequences (quantitative PCR. Further, gene expression changes associated with epithelial-to-mesenchymal transition (EMT were determined with an EMT-specific PCR assay. Methods We used the commercially available Adna Test, RT-PCR on human housekeeping genes and a PCR on AluJ sequences to detect CTCs in xenografts models. Phenotypic changes in CTCs were tested with the commercially available “Human Epithelial to Mesenchymal Transition RT-Profiler PCR Array”. Results Although the AdnaTest detects as few as 1 tumour cell in 1 ml of mouse blood spiking experiments, no CTCs were detectable with this approach in vivo despite visible metastasis formation. The presence of CTCs could, however, be demonstrated by PCR targeting human transcripts or DNA-sequences - without epithelial pre-enrichment. The failure of CTC detection by the AdnaTest resulted from downregulation of EpCAM, whereas mesenchymal markers like Twist and EGFR were upregulated on CTCs. Such a change in the expression profile during metastatic spread of tumour cells has already been reported and was linked to a biological program termed epithelial-mesenchymal transition (EMT. Conclusions The use of EpCAM-based enrichment techniques leads to the failure to detect CTC populations that have undergone EMT. Our findings may explain clinical results where low

Radiation-induced brain tumours: potential late complications of radiation therapy for brain tumours

International Nuclear Information System (INIS)

Nishio, S.; Morioka, T.; Inamura, T.; Takeshita, I.; Fukui, M.; Sasaki, M.; Nakamura, K.; Wakisaka, S.

1998-01-01

The development of neoplasms subsequent to therapeutic cranial irradiation is a rare but serious and potentially fatal complication. In this study, we retrospectively reviewed the clinical and pathological aspects of 11 patients who underwent cranial irradiation (range, 24-110 cGy) to treat their primary disease and thereafter developed secondary tumours within a span of 13 years. All tumours arose within the previous radiation fields, and satisfied the widely used criteria for the definition of radiation-induced neoplasms. There was no sex predominance (M: 5, F: 6) and the patients tended to be young at irradiation (1.3 - 42 years; median age: 22 years). The median latency period before the detection of the secondary tumour was 14.5 years (range: 6.5 - 24 years). Meningiomas developed in 5 patients, sarcomas in 4, and malignant gliomas in 2. A pre-operative diagnosis of a secondary tumour was correctly obtained in 10 patients based on the neuro-imaging as well as nuclear medicine findings. All patients underwent a surgical removal of the secondary tumour, 3 underwent additional chemotherapy, and one received stereotactic secondary irradiation therapy. During a median of 2 years of follow-up review after the diagnosis of a secondary tumour, 3 patients died related to the secondary tumours (2 sarcomas, 1 glioblastoma), one died of a recurrent primary glioma, while the remaining 7 have been alive for from 10 months to 12 years after being treated for the secondary tumours (median: 3 years). Based on these data, the clinicopathological characteristics and possible role of treatment for secondary tumours are briefly discussed. (author)

Boron uptake measurements in metastatic tumours in rat lung

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Bortolussi, S.; Altieri, S.; Bruschi, P.

2006-01-01

Lung carcinoma is the leading cause of cancer mortality worldwide; despite the introduction over the last few years of new therapeutic agents, very little progress has been made in terms of survival, and the overall prognosis for these patients remains poor. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely and essential. To study the possibility to apply BNCT in the cure of diffuse pulmonary tumours, we created a BNCT Lung Project in Pavia, supported by Ministry of Education, University and Research (MIUR), in which Physicists, Medical Doctors and Biologists are involved. The first steps were; 1. development of an animal model for Boron uptake measurements in healthy and tumour lung tissues; 2. evaluation of the possibility to treat patients with epithermal neutron beams (See S. Altieri et al., this Conference); 3. in-vitro study of BNCT efficacy (see A. Zonta et al.). Spatial Boron distribution by neutron radiography in lung metastases from Colon Adenocarcinoma is reported; furthermore we present preliminary results of Boron concentration measures in rat lung tissues. The measures were performed using alpha spectrometry in thin tissue samples. (author)

Is the gene encoding Chibby implicated as a tumour suppressor in colorectal cancer ?

International Nuclear Information System (INIS)

Gad, Sophie; Teboul, David; Lièvre, Astrid; Goasguen, Nicolas; Berger, Anne; Beaune, Philippe; Laurent-Puig, Pierre

2004-01-01

A novel member of the Wnt signalling pathway, Chibby, was recently identified. This protein inhibits Wnt/β-catenin mediated transcriptional activation by competing with Lef-1 (the transcription factor and target of β-catenin) to bind to β-catenin. This suggests that Chibby could be a tumour suppressor protein. The C22orf2 gene coding Chibby is located on chromosome 22, a region recurrently lost in colorectal cancer. Activation of the Wnt pathway is a major feature of colorectal cancer and occurs through inactivation of APC or activation of β-catenin. All of this led us to analyse the possible implication of Chibby in colorectal carcinogenesis. First, 36 tumour and matched normal colonic mucosa DNA were genotyped with five microsatellite markers located on chromosome 22 to search for loss of heterozygosity. Then, mutation screening of the C22orf2 coding sequence and splice sites was performed in the 36 tumour DNA. Finally, expression of Chibby was analysed by quantitative RT-PCR on 10 patients, 4 with loss of heterozygosity (LOH) on chromosome 22. Loss of heterozygosity involving the C22orf2 region was detected in 11 out of 36 patients (30%). Sequencing analysis revealed a known variant, rs3747174, in exon 5: T321C leading to a silent amino acid polymorphism A107A. Allelic frequencies were 0.69 and 0.31 for T and C variants respectively. No other mutation was detected. Among the 10 patients studied, expression analysis revealed that Chibby is overexpressed in 2 tumours and underexpressed in 1. No correlations were found with 22q LOH status. As no somatic mutation was detected in C22orf2 in 36 colorectal tumour DNA, our results do not support the implication of Chibby as a tumour suppressor in colorectal carcinogenesis. This was supported by the absence of underexpression of Chibby among the tumour samples with 22q LOH. The implication of other Wnt pathway members remains to be identified to explain the part of colorectal tumours without mutation in APC and β-catenin

Experimental tumour treatment

International Nuclear Information System (INIS)

1985-08-01

This report of 1984 is the seventh in a series and presents that year's results of continuous studies in the domain of experimental tumour radiotherapy. In the year under review, more personnel has been available for the studies, and the scientific programmes for the assessment of acute and chronic side effects of radiotherapies have been extended. New models have been developed, among them a first system based on animal experiments, for quantifying the mucositis of the oral and pharyngeal mucosa, a limiting condition in the radiotherapy of head and throat tumours. Another significant advancement is a model for quantification of chronical damage to the ureter, which still is a serious problem in the radiotherapy of gynaecological tumours. The 1984 experimental tumour studies have been mainly devoted to the repopulation and split-dose recovery in various tumours, concentrating on dose fractionation as one of the major problems studies. Particular interest has been attached to the processes involved in treatments over several weeks with a daily effective dose of 2 Gy. (orig./MG) [de

Slow-neutron capture therapy for malignant tumours: its history and recent development

International Nuclear Information System (INIS)

Hatanaka, H.

1975-01-01

Slow-neutron capture therapy was first suggested in 1936. The early clinical trials were performed at Brookhaven National Laboratory and Massachusetts Institute of Technology reactors. In the last series of treatments in 1960 and 1961, none of the 17 glioblastoma patients lived longer than a year and the clinical trial was discontinued, particularly because the was pathological evidence that normal tissue had been seriously damaged. Hatanaka, who worked first with Sweet between 1964 and 1967, continued intensive basic research and organized a collaborating team of chemists, physicists and physicians in Japan where he resumed treatment of brain tumour patients in 1968. The rationale of the revised therapy included: (1) use of promising compounds such as mercaptoundecahydrododecaborate, which has a high tumour binding property, (2) use of adrenocorticoid to minimize vascular damage, (3) intra-arterial infusion of boron to obtain a higher concentration in the tumour, (4) restriction of excessive neutron intensity, (5) and some technical improvements. New research techniques were also introduced, such as alpha autoradiography, electron microscopy, and immunotherapy. With the mercaptoundecahydrododecaborate compound an absolute concentration of 30 μg per gram of tumour is easily attainable, while the blood level of the isotope can be lowered to at least half of the tumour concentration. Normal dog brains were able to tolerate this therapy. Among the 15 patients so far treated, 13 were treated at the Hitachi Training Reactor. Patients, who had undergone repeated surgery as well as excessive irradiation before they came for the therapy, could not recover their full activities, but proved they could enjoy a significant prolongation of their lives. The only two fresh cases of glioblastoma responded so well to the therapy that one has been working as an engineer and the other as a farmer for 3 years without neurological deficits. Recent progress and future potentials of the

Response of tumour necrosis factor alpha (TNF ) in blood and spleen mice that vaccinated with P.berghei radiation

International Nuclear Information System (INIS)

Darlina; Tur R; Teja K

2015-01-01

Tumor necrosis factor is a glycoprotein derived from helper T lymphocytes that play an important role in the body's response against malaria infection. However, TNF-α has double play that is on appropriate levels will provide protection and healing, while at excessive levels which may be a response to hyperparasitemia. Thus investigated the expression of TNF alpha secreted blood lymphocytes and spleen cells the mice that's infected with 1 x 10 7 P.berghei infectious or inactivated by radiation. Levels of TNF alpha serum and spleen cell culture medium was monitored on days 2, 7, 14 post infection. Monitoring of parasite growth every two days for 60 days. Determination of TNF alpha levels were measure using ELISA. The results showed parasitaemia mice infected with 175 Gy irradiated parasites have pre patent period of 16 days longer than the control (non-irradiated parasites) with low parasitaemia. TNF alpha concentration that secreted spleen cells of mice vaccinated higher than control mice. Concentration of TNF alpha that secreted blood lymphocyte of mice vaccinated lower than control mice. It was concluded that the secretion of TNF alpha by blood lymphocytes caused more pathogenic factors of the parasite, while the secretion of TNF alpha in spleen due to an immune response against the parasite. (author)

FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

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Abasolo, Ibane [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Pujal, Judit; Navarro, Pilar [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Rabanal, Rosa M.; Serafin, Anna [Universitat Autonoma de Barcelona, Departament de Medicina i Cirurgia Animals, Barcelona (Spain); Millan, Olga [Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Real, Francisco X. [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid (Spain)

2009-07-15

The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

International Nuclear Information System (INIS)

Abasolo, Ibane; Pujal, Judit; Navarro, Pilar; Rabanal, Rosa M.; Serafin, Anna; Millan, Olga; Real, Francisco X.

2009-01-01

The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours

NARCIS (Netherlands)

M.J. Murray (Matthew); E. Bell (Emma); K.L. Raby (Katie L.); M.A. Rijlaarsdam (Martin); A.J.M. Gillis (Ad); L.H.J. Looijenga (Leendert); H. Brown (Helen); B. Destenaves (Benoit); J.C. Nicholson (James); N. Coleman (Nicholas)

2016-01-01

textabstractBackground:The current biomarkers alpha-fetoprotein and human chorionic gonadotropin have limited sensitivity and specificity for diagnosing malignant germ-cell tumours (GCTs). MicroRNAs (miRNAs) from the miR-371-373 and miR-302/367 clusters are overexpressed in all malignant GCTs, and

Adapting radiotherapy to hypoxic tumours

International Nuclear Information System (INIS)

Malinen, Eirik; Soevik, Aste; Hristov, Dimitre; Bruland, Oeyvind S; Olsen, Dag Rune

2006-01-01

In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO 2 -related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO 2 -related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO 2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO 2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure

Adapting radiotherapy to hypoxic tumours

Science.gov (United States)

Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

2006-10-01

In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

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

Extract of corn silk (stigma of Zea mays) inhibits the tumour necrosis factor-alpha- and bacterial lipopolysaccharide-induced cell adhesion and ICAM-1 expression.

Science.gov (United States)

Habtemariam, S

1998-05-01

Treatment of human endothelial cells with cytokines such as tumour necrosis factor-alpha (TNF) or E. coli lipopolysaccharide (LPS) induces the expression of several adhesion molecules and enhances leukocyte adhesion to endothelial cell surface. Interfering with this leukocyte adhesion or adhesion molecules upregulation is an important therapeutic target for the treatment of bacterial sepsis and various inflammatory diseases. In the course of screening marketed European anti-inflammatory herbal drugs for TNF antagonistic activity, a crude ethanolic extract of corn silk (stigma of Zea mays) exhibited significant activity. The extract at concentrations of 9-250 micrograms/ml effectively inhibited the TNF- and LPS-induced adhesiveness of EAhy 926 endothelial cells to monocytic U937 cells. Similar concentration ranges of corn silk extract did also block the TNF and LPS but not the phorbol 12-myristate 13-acetate-induced ICAM-1 expression on EAhy 926 endothelial cell surface. The extract did not alter the production of TNF by LPS-activated macrophages and failed to inhibit the cytotoxic activity of TNF. It is concluded that corn silk possesses important therapeutic potential for TNF- and LPS-mediated leukocyte adhesion and trafficking.

Tumour targeting with systemically administered bacteria.

LENUS (Irish Health Repository)

Morrissey, David

2012-01-31

Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

Tumour and tumour-like lesions of the patella - a multicentre experience

International Nuclear Information System (INIS)

Singh, J.; James, S.L.; Davies, A.M.; Kroon, H.M.; Woertler, K.; Anderson, S.E.

2009-01-01

Fifty-nine cases of lesions presenting in the patella were identified after review of the databases of four European bone tumour registries. Of the 59 cases, 46% were non neoplastic, 39% were benign and 15% were malignant. The commonest benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were more likely to have a benign neoplasm. Lesions in patients less than 40 years of age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC), osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40 years, the following were common lesions: intra-osseous gout, metastasis and intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen more commonly in GCT and brown tumour in hyperparathyroidism. There was associated soft tissue extension in gout and malignant lesions. (orig.)

Tumour and tumour-like lesions of the patella - a multicentre experience

Energy Technology Data Exchange (ETDEWEB)

Singh, J.; James, S.L.; Davies, A.M. [The Royal Orthopaedic Hospital, Department of Radiology, Birmingham (United Kingdom); Kroon, H.M. [Leiden University Medical Centre, Department of Radiology, C-2-S, P. O Box 9600, Leiden (Netherlands); Woertler, K. [Technische Universitaet Muenchen, Department of Radiology, Munich (Germany); Anderson, S.E. [Knochentumor- Referenzzentrum der Schweizerischen Gesellschaft fuer Pathologie, Basel (Switzerland)

2009-03-15

Fifty-nine cases of lesions presenting in the patella were identified after review of the databases of four European bone tumour registries. Of the 59 cases, 46% were non neoplastic, 39% were benign and 15% were malignant. The commonest benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were more likely to have a benign neoplasm. Lesions in patients less than 40 years of age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC), osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40 years, the following were common lesions: intra-osseous gout, metastasis and intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen more commonly in GCT and brown tumour in hyperparathyroidism. There was associated soft tissue extension in gout and malignant lesions. (orig.)

[Surgical Management of Peritoneal Surface Malignancy with Respect to Tumour Type, Tumour Stage and Individual Tumour Biology].

Science.gov (United States)

Beckert, S; Struller, F; Grischke, E-M; Glatzle, J; Zieker, D; Königsrainer, A; Königsrainer, I

2016-08-01

Peritoneal tumour dissemination is still considered as a terminal disease. For the last two decades, cytoreductive surgery (CRS) combined with intraoperative hyperthermic chemotherapy (HIPEC) has been popularised by Paul Sugarbaker almost doubling survival in selected patients compared with systemic chemotherapy alone. Nowadays, this particular treatment protocol is available in comprehensive cancer centres with reasonable mortality and morbidity. However, patient selection is still challenging. In general, CRS and HIPEC is indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei as well as in peritoneal metastases derived from gastrointestinal malignancies and ovarian cancers. Since systemic tumour spread is uncommon in patients with peritoneal metastases, peritoneal tumour dissemination was defined as localised disease within the "compartment abdomen". However, CRS and HIPEC are only beneficial as long as complete cytoreduction is achieved (CC-0 or CC-1). Histopathological parameters, the Sugarbaker peritoneal carcinomatosis index (PCI) and general condition of the patient have been established as patient selection criteria. In primary peritoneal cancers, individual tumour biology is the predominant criterium for patient selection as opposed to intraabdominal tumour load in peritoneal metastases derived from gastrointestinal cancers. In gastric cancer, CRS and HIPEC should be restricted to synchronous limited disease because of its biological aggressiveness. In patients with free floating cancer cells without macroscopic signs of peritoneal spread, however, CRS and HIPEC following preoperative "neoadjuvant" chemotherapy preserves chances for cure. So far, there is no general recommendation for CRS and HIPEC by clinical practice guidelines. In the recent S3 guideline for treatment of colorectal cancer, however, CRS and HIPEC have been included as possible treatment options. Georg Thieme Verlag KG Stuttgart · New York.

The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas.

Science.gov (United States)

Rogers, Te Whiti; Toor, Gurvinder; Drummond, Katharine; Love, Craig; Field, Kathryn; Asher, Rebecca; Tsui, Alpha; Buckland, Michael; Gonzales, Michael

2018-03-01

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

Vaginal haemangioendothelioma: an unusual tumour.

LENUS (Irish Health Repository)

Mohan, H

2012-02-01

Vaginal tumours are uncommon and this is a particularly rare case of a vaginal haemangioendothelioma in a 38-year-old woman. Initial presentation consisted of symptoms similar to uterovaginal prolapse with "something coming down". Examination under anaesthesia demonstrated a necrotic anterior vaginal wall tumour. Histology of the lesion revealed a haemangioendothelioma which had some features of haemangiopericytoma. While the natural history of vaginal haemangioendothelioma is uncertain, as a group, they have a propensity for local recurrence. To our knowledge this is the third reported case of a vaginal haemangioendothelioma. Management of this tumour is challenging given the paucity of literature on this tumour. There is a need to add rare tumours to our "knowledge bank" to guide management of these unusual tumours.

of brain tumours

African Journals Online (AJOL)

outline of the important clinical issues related to brain tumours and psychiatry. ... Left-sided, frontal tumours also seem to be associated with higher rates of depression, while those in the frontal lobe of the right .... Oxford: Blackwell Science,.

Gender impact on first trimester markers in Down syndrome screening

DEFF Research Database (Denmark)

Larsen, Severin Olesen; Wøjdemann, Karen R; Shalmi, Anne-Cathrine

2002-01-01

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with nor......The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies...... with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male...

Value of skeletal scintiscanning in cases of primary bone tumours and tumourous alterations

International Nuclear Information System (INIS)

Sokolowski, U.

1982-01-01

In the course of an investigation on the storage behaviour of primary bone tumours and tumourous bone alterations the skeletal scintigrams of a total of 26 patients were evaluated. Bone scintiscanning was done according to current practice after injection of an average amount of 10mCi sup(99m)Tc-MDP, followed by a semiquantitative evaluation. In all cases of malignant bone tumours there was fond to be increased storage of radionuclide; with benign bone alterations this was so in 70 per cent of cases. To differentiate between benign and malignant tumours respectively inflammatory bone diseases was not as a rule possible; however, the investigation yielded additional information completing the X-ray findings essentially. Thus very high storage of radioactivity was established for all osteosarcomas, whereas benign bone growths exhibited more circumscribed accumulations of activity. Skeletal scintiscanning for diagnostical purposes is particularly informative as to the early detection of bone foci evading X-ray diagnosis, more accurate delimitation of tumourous processes, and course control of tumours tending to degenerate. (orig./MG) [de

Management of parapharyngeal space tumours

International Nuclear Information System (INIS)

Ahmad, F.; Waqar-Uddin; Khan, M.S.; Khawar, A.; Bangush, W.; Aslam, J.

2006-01-01

Objective: To determine the role of clinical features, fine needle aspiration cytology (FNAC) and computed tomography (CT) scan in diagnosing Para pharyngeal space (PPS) tumours and treatment options. Design: A descriptive study. Place and Duration of Study: From July 2000 to July 2002 at Pakistan Institute of Medical Sciences, Islamabad. Patients and Methods: Patients diagnosed as having PPS tumours were studied. The medical record of patients was reviewed for their age, gender, clinical features, investigations (FNAC and CT scan) and treatment. The mean age, percentage of different clinical features and the sensitivity and specificity of FNAC was determined. Results: The mean age of patients presenting with PPS tumours was 33.6 years. The most common clinical features were neck mass (93%) and bulge in lateral pharyngeal wall (80%). The CT scan showed exact location and extent of tumour in 11 out of 15 cases. The sensitivity and specificity of FNAC was 70% and 85% respectively. The most common tumours were neurogenic tumours and salivary gland tumours. Surgery was performed in all except 2 patients with lymphoma in whom radiation and chemotherapy was recommended. Conclusion: This study indicates that PPS tumours are usually benign neurosurgeon and salivary gland tumours presenting with neck mass and bulge in or oropharynx. FNAC and CT scan are important in diagnostic work up and treatment planning. Surgery has the best results in most cases. (author)

GATA transcription factors in testicular adrenal rest tumours

Directory of Open Access Journals (Sweden)

Manon Engels

2017-11-01

Full Text Available Testicular adrenal rest tumours (TARTs are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16, Leydig cell tumours (LCTs; n = 7, adrenal (foetal (n = 6 + adult (n = 10 and testis (foetal (n = 13 + adult (n = 8. We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively, while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes. Incubation of adrenocortical cells (H295RA with ACTH, however, did not induce GATA expression in vitro. Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation.

[Neonatal tumours and congenital malformations].

Science.gov (United States)

Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L

2008-06-01

The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data

Plasma alpha-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients

DEFF Research Database (Denmark)

Joseph, G.; Tarnow, L.; Astrup, A.S.

2008-01-01

CONTEXT: alpha-Defensins are antimicrobial peptides of the innate immune system. In addition, experimental evidence suggests that alpha-defensins are proatherogenic. OBJECTIVE: The objective of the study was to examine the predictive value of plasma alpha-defensin as a clinical marker of cardiova...... to the development of CVD or an innocent bystander Udgivelsesdato: 2008/4...

Comparison of metastatic disease after local tumour treatment with radiotherapy or surgery in various tumour models

International Nuclear Information System (INIS)

Ruiter, J. de; Cramer, S.J.; Lelieveld, P.; Putten, L.M. van

1982-01-01

Spontaneous metastases in lymph nodes and/or the lung were obtained after tumour cell inoculation of four mouse tumours and one rat tumour into the foot-pads of syngeneic animals or their F 1 hybrids. Following local radiotherapy with doses of 45-80 Gy, significantly more mice died with metastases than following local amputation of the tumour-bearing foot when the 2661 carcinoma was involved. No significant difference was observed after these treatments for the other tumours. The enhancement of metastatic growth after local radiotherapy in the 2661 carcinoma seems not to be due to incomplete killing of tumour cells in the foot. The presence of irradiated normal structures and tumour tissue after radiotherapy promoted the outgrowth of 2661 carcinoma cells which were outside the radiation field at the time of treatment. Evidently, even under similar experimental conditions, radiotherapy may enhance the growth of metastases from some tumours and not from others. (author)

Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

Science.gov (United States)

Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

2015-04-29

A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer

International Nuclear Information System (INIS)

Noetzel, Erik; Veeck, Jürgen; Niederacher, Dieter; Galm, Oliver; Horn, Felicitas; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

2008-01-01

Inhibitor of DNA binding/Inhibitor of differentiation 4 (ID4) is a critical factor for cell proliferation and differentiation in normal vertebrate development. ID4 has regulative functions for differentiation and growth of the developing brain. The role of ID1, ID2 and ID3 are expected to be oncogenic due to their overexpression in pancreatic cancer and colorectal adenocarcinomas, respectively. Aside from these findings, loss of ID3 expression was demonstrated in ovarian cancer. The aim of the present study was to reveal the factual role of ID4 in carcinogenesis in more detail, since its role for the pathogenesis of human breast cancer has been discussed controversially, assigning both oncogenic and tumour suppressive functions. ID4 promoter methylation, ID4 mRNA expression and ID4 protein expression were analysed in primary human breast cancer specimens using methylation-specific PCR (MSP) (n=170), semiquantitative realtime RT-PCR (n=46) and immunhistochemistry (n=3), respectively. In order to demonstrate a functional association of ID4 promoter methylation with its gene silencing, we performed DNA demethylation analysis with four human breast cell lines using MSP and semiquantitative realtime RT-PCR. In addition, we performed correlations of ID4 promoter methylation with ID4 mRNA and ID4 protein expression in matched samples of breast tumour and corresponding normal tissue. We carried out statistical analyses in order to find correlations between ID4 promoter methylation and clinicopathological parameters. Frequent ID4 promoter methylation was observed in primary breast cancer samples (69%, 117/170). We found a tight correlation (P<0.0001) between ID4 promoter methylation and loss of ID4 expression in primary breast cancer 3 specimens. Demethylating treatment with breast cancer cell lines was associated with clear ID4 mRNA re-expression. Tumours with ID4 promoter methylation showed distinct loss of ID4 expression on both transcription and protein level

An Original Approach for Quantification of Blood Vessels on the Whole Tumour Section

Directory of Open Access Journals (Sweden)

Nga Tran Kim

2003-01-01

Full Text Available Relative abundance of tumour angiogenesis has been shown to be of clinical relevance in cancers of various locations such as the ovary. Nevertheless, several problems are encountered when quantifying tumour microvessels: (i as many other tumour markers, vascularity pattern is often heterogeneous within the tumour mass and even within the same histological section. As a consequence, an adequate acquisition method must be developed for accurate field sampling. (ii Manual microvessel counting is long, tedious and subject to poor reproducibility. Introduction in routine practice requires a fast, reproducible and reliable automatic image processing. In this study we present an original procedure combining a slide scanner image acquisition and a fully automatic image analysis sequence. The slide scanner offers the advantage of recording an image of the whole histological section for subsequent automatic blood vessel detection and hot spot area location. Microvessel density and surface fraction were measured for the whole section as well as within hot spots. Different immunostaining methods were tested in order to optimise the procedure. Moreover, the method proposed was submitted to a quality control procedure, with reference to interactive identification of microvessels at scanner level. This experiment showed that 93 to 97% of blood vessels were detected, according to the staining protocol used. Colour figures can be viewed on http://www.esacp.org/acp/2003/25‐2/kim.htm.

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.)

Diagnostic utility of Wilms′ tumour-1 protein (WT-1 immunostaining in paediatric renal tumours

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Surbhi Goyal

2016-01-01

Interpretation & conclusions: WT1 helps to differentiate Wilms′ tumour from other paediatric renal tumours. It may help in differentiating the two subgroups of Wilms′ tumour which have distinct molecular pathogenesis and biological behaviour, however, further prospective studies are required for validation of this hypothesis.

In vivo assay of the radiation sensitivity of hypoxic tumour cells. Influence of radiation quality and hypoxic sensitization

International Nuclear Information System (INIS)

Porschen, W.; Bosiljanoff, P.; Gewehr, K.; Muehlensiepen, H.; Feinendegen, L.E.

1977-01-01

In order to measure quantitatively tumour cell kinetics in living mice, tumour bearing animals (sarcoma-180) received intravenously 5-iodo-2'-deoxyuridine (IUdR), a thymidine analogue, which was labelled with 125 I or with 131 I, both of which can be easily externally counted by their gamma emission. IUdR is stably bound to DNA, reutilization is minimal and the measured activity loss from the tumour later than 50 hours after injection signals cell loss or cell death. The effect of irradiation on euoxic and average tumour cells was studied by sequentially labelling the tumour bearing animals first with 125 IUdR and, 70 hours later, with 131 IUdR. At the time of the second injection the average tumour cell population is labelled by the first injection of 125 IUdR, and the second injection of 131 IUdR nearly exclusively tags the perivascular tumour cells; these are euoxic in contrast to the average tumour cell, a large proportion of which is hypoxic. The radiation-induced activity loss rates from the two labelled tumour cell populations indicate the sensitivities of the two populations. At dose levels that cause identical effects on euoxic cells, the ratio of radiation-induced enhancement of cell loss rates for euoxic cells to average cells was 2.6 for 60 Co gamma radiation, 1.4 for 15MeV neutron irradiation, and 1.0 for alpha irradiation (1.5.MeV). The effect of five hypoxic cell sensitizers was analysed. The sensitization was limited to hypoxic cells, and the most effective drug was Ro-07-0582, showing at the 50% level of maximum effect a dose modifying factor of 1.5. Sensitization was highest when the drug was given 15 min prior to irradiation. Hyperthermia affected nearly exclusively hypoxic cells and showed a dose modifying factor of about 2 when the tumours were heated at 42 0 C for 30 min immediately after irradiation. The resulting enhancement of effect was reduced when hyperthermia was applied prior to irradiation. (author)

A case of alpha-fetoprotein-producing esophageal adenocarcinoma.

Science.gov (United States)

Chen, Yi-Yu; Hsu, Wen-Hung; Hu, Huang-Ming; Wu, Deng-Chyang; Lin, Wen-Yi

2013-02-01

Alpha-fetoprotein is a well-known tumor marker in the screening and follow-up of hepatocellular carcinoma. In Taiwanese society, a high prevalence of hepatitis and hepatoma and elevation of alpha-fetoprotein associated with liver function impairment usually suggested clinics undertake further examination for liver or genital tumor. We report the case of 45-year-old man who was found to have an alpha-fetoprotein-producing esophageal adenocarcinoma with an initial presentation of liver function impairment and rapid elevation of alpha-fetoprotein. Esophageal cancer was diagnosed via endoscope and a biopsy proved the presence of adenocarcinoma. A small endoscopic biopsy specimen failed to identify the alpha-fetoprotein positive tumor cell. Esophagectomy was performed and histopathological study of surgical specimen revealed grade II adenocarcinoma with regional metastatic lymphadenopathy. Immunohistochemical study was focal positive for alpha-fetoprotein. Serum alpha-fetoprotein declined transiently after esophagectomy and fluctuation of alpha-fetoprotein level was noted during the treatment with adjuvant chemotherapy. Finally, 19 months after the operation, the patient died due to multiple organ metastases with multiple organ failure. Thus, a small specimen for upper endoscopy may not be sufficient in the presence of alpha-fetoprotein-producing adenocarcinoma. Monitoring of serum alpha-fetoprotein may be useful in the evaluation and follow-up of esophageal alpha-fetoprotein-producing adenocarcinoma. Copyright © 2012. Published by Elsevier B.V.

Novel biochemical markers of psychosocial stress in women.

Directory of Open Access Journals (Sweden)

Marie Asberg

Full Text Available BACKGROUND: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women. METHODS: Plasma concentrations of interleukin (IL 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma, tumor necrosis factor-alpha (TNF-alpha, monocyte chemotactic protein-1 (MCP-1, epidermal growth factor (EGF, vascular endothelial growth factor (VEGF, thyroid stimulating hormone (TSH, total tri-iodothyronine (TT3, total thyroxine (TT4, prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women. RESULTS: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill. CONCLUSIONS: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

PET/MR in invasive ductal breast cancer: correlation between imaging markers and histological phenotype.

Science.gov (United States)

Catalano, Onofrio Antonio; Horn, Gary Lloyd; Signore, Alberto; Iannace, Carlo; Lepore, Maria; Vangel, Mark; Luongo, Angelo; Catalano, Marco; Lehman, Constance; Salvatore, Marco; Soricelli, Andrea; Catana, Ciprian; Mahmood, Umar; Rosen, Bruce Robert

2017-03-28

Differences in genetics and receptor expression (phenotypes) of invasive ductal breast cancer (IDC) impact on prognosis and treatment response. Immunohistochemistry (IHC), the most used technique for IDC phenotyping, has some limitations including its invasiveness. We explored the possibility of contrast-enhanced positron emission tomography magnetic resonance (CE-FDG PET/MR) to discriminate IDC phenotypes. 21 IDC patients with IHC assessment of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and antigen Ki-67 (Ki67) underwent CE-FDG PET/MR. Magnetic resonance-perfusion biomarkers, apparent diffusion coefficient (ADC), and standard uptake value (SUV) were compared with IHC markers and phenotypes, using a Student's t-test and one-way ANOVA. ER/PR- tumours demonstrated higher Kep mean and SUV max than ER or PR+ tumours. HER2- tumours displayed higher ADC mean , Kep mean , and SUV max than HER2+tumours. Only ADC mean discriminated Ki67⩽14% tumours (lower ADC mean ) from Ki67>14% tumours. PET/MR biomarkers correlated with IHC phenotype in 13 out of 21 patients (62%; P=0.001). Positron emission tomography magnetic resonance might non-invasively help discriminate IDC phenotypes, helping to optimise individual therapy options.

NANOG priming before full reprogramming may generate germ cell tumours

Directory of Open Access Journals (Sweden)

I Grad

2011-11-01

Full Text Available Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

Radiodiagnosis of tumours of gastrointestinal tract

International Nuclear Information System (INIS)

Sokolov, Yu.N.; Antonovich, V.B.

1981-01-01

Systematic description of X-ray picture of tumours of gastrointestinal tract organs is given. The possibilities of contemporary methods of X-ray examination in their revealing are shown. Clinical and X-ray trend of tumour diagnosis is underlined. The basic and accessory symptoms are analyzed from which X-ray semiotics of tumours is turned out. The expressiveness of X-ray symptoms is shown in relation to morphological forms and localization of the tumours. Much attention is given to radiodiagnosis of early tumours of stomach. Differential diagnosis of tumours with non-tumoural diseases is given. X-ray semiotics of lesions of gastrointestinal tract organs in malignant diseases of blood system is presented [ru

Malignant thyroid tumours

International Nuclear Information System (INIS)

Boerner, W.; Reiners, C.

1987-01-01

The subjects dealt with at the symposium cover all topical aspects of pathology, epidemiology, diagnosis, therapy, and aftercare of the malignant thyroid tumours. A survey of the histological classification of the thyroid tumours and a review of the latest findings concerning the radiocarcinogenesis are followed by a detailed discussion of the most significant tumours. There are also papers dealing with controversial aspects of the histological classification, the value of diagnostic methods, radicality of the therapy, or after care. For five conference papers, separate records are available in the database. (orig./ECB) With 59 figs.; 57 tabs [de

Cyclin D1 in well differentiated thyroid tumour of uncertain malignant potential.

Science.gov (United States)

Lamba Saini, Monika; Weynand, Birgit; Rahier, Jacques; Mourad, Michel; Hamoir, Marc; Marbaix, Etienne

2015-04-18

Encapsulated follicular tumours with equivocal papillary thyroid carcinoma (PTC) type nuclear features continue to remain a challenge despite the recent attempts to classify these borderline lesions. The term 'well differentiated tumour of uncertain malignant potential (WDT-UMP)' was introduced to classify these tumours. The present study aimed to evaluate the role of a cell cycle regulator like cyclin D1 in these tumours along with assessment of other well established PTC markers like galectin-3, HBME-1, CK19. Thirteen cases of metastatic PTC, papillary microcarcinoma and follicular variant of PTC (FVPTC) were identified from a histological review of 510 cases. In addition, 13 cases of a subset of follicular adenomatoid nodules with focal areas showing nuclear features characteristic of PTC, identified as WDT-UMP, were also analyzed. Immunohistochemical analysis of galectin-3, HBME-1, CK19 and the proliferation markers Ki67 and cyclin D1 was performed. Lesions were analyzed for cyclin D1 gene amplification by fluorescent in-situ hybridization. All WDT-UMP lesions showed immunolabelling of cyclin D1, Ki67; 11/ 13 cases showed immunolabelling of CK19; 10/13 cases showed immunolabelling of HBME-1 and 4/13 cases showed immunolabelling of galectin-3. Surrounding benign adenomatoid areas showed no to faint focal staining in all thirteen cases of cyclin D1, HBME-1 and galectin-3. A low rate of cyclin D1 gene amplification was identified in a significant proportion of cells in the WDT-UMP lesions as compared to surrounding benign adenomatoid areas. Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in WDT-UMP lesions showing cytological features of papillary thyroid carcinoma within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of PTC. Overexpression of cyclin D1, associated with the amplification of the gene suggests that these WDT-UMP lesions are an

Nuclear relocation of STAT6 reliably predicts NAB2-STAT6 fusion for the diagnosis of solitary fibrous tumour.

Science.gov (United States)

Koelsche, Christian; Schweizer, Leonille; Renner, Marcus; Warth, Arne; Jones, David T W; Sahm, Felix; Reuss, David E; Capper, David; Knösel, Thomas; Schulz, Birte; Petersen, Iver; Ulrich, Alexis; Renker, Eva Kristin; Lehner, Burkhard; Pfister, Stefan M; Schirmacher, Peter; von Deimling, Andreas; Mechtersheimer, Gunhild

2014-11-01

Nuclear relocation of STAT6 has been shown in tumours with NAB2-STAT6 fusion, and has been proposed as an ancillary marker for the diagnosis of solitary fibrous tumours (SFTs). The aim of this study was to verify the utility of STAT6 immunohistology in diagnosing SFT. A total of 689 formalin-fixed paraffin-embedded tumours comprising 35 pleural SFTs and 654 other mesenchymal tumours were investigated for STAT6 expression using immunohistochemistry. Nine dedifferentiated liposarcomas (DDLSs) and five SFTs were also examined for the presence of NAB2-STAT6 fusion at the protein level using the proximity ligation assay (PLA), and for copy number variants (CNVs) with the Illumina Infinium Human Methylation450 array. Thirty-four of 35 SFTs showed strong nuclear STAT6 expression. Furthermore, five of 68 DDLSs, two of 130 undifferentiated pleomorphic sarcomas and one of 63 cases of nodular fasciitis showed moderate to strong nuclear STAT6 expression. The PLA indicated the presence of NAB2-STAT6 fusion protein in SFTs, but signal was also detected in some DDLSs. Copy number analysis showed an overall low frequency of chromosomal imbalances in SFTs, but complex karyotypes in DDLSs, including amplification of STAT6 and MDM2 loci. The detection of nuclear relocation of STAT6 with immunohistochemistry is a characteristic of SFTs, and may serve as a diagnostic marker that indicates NAB2-STAT6 fusion and helps to discriminate SFTs from histological mimics. © 2014 John Wiley & Sons Ltd.

Diagnostic value of alpha-fetoprotein in liver cancer

International Nuclear Information System (INIS)

Pervez, T.; Anwar, S.M.

2001-01-01

Objective: To determine diagnostic value of alpha-fetoproteins (alpha-FP) in liver cancer. Design: Prospective study. Place and duration of study: Department of clinical oncology services Hospital Lahore, during the period from February 1998 to February 2001. Subjects and Methods: Among 200 persons studied, 100 presented with liver mass, jaundice and other symptoms directing toward liver pathology, later confirmed histopathologically, as suffering from hepatocellular carcinoma (HCC) while the other 100 healthy subject came to the department for blood donation and were HBs Ag pasitive on blood screening. All these subjects under went blood test for alpha-FP. This tumor marker was analyzed by using enzyme immunoassay-based kit. Results: The alpha-FP positivity was statistically evaluated. In HCC this test was statistically significant with p value of <0.001. In this study sensitivity of alpha-FP was 72% specificity 89%, positive predictive value 86.7% and negative predictive value of 76.1%. Conclusion: This study showed that alpha-FP was a useful diagnostic tool in the diagnosis of HCC. (author)

Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers.

Science.gov (United States)

Nielsen, Signe Tellerup; Lehrskov-Schmidt, Louise; Krogh-Madsen, Rikke; Solomon, Thomas P J; Lehrskov-Schmidt, Lars; Holst, Jens Juul; Møller, Kirsten

2013-11-01

Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown. We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated. TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged. In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect. Copyright © 2013 John Wiley & Sons, Ltd.

Failure of isolated rat tibial periosteal cells to 5 alpha reduce testosterone to 5 alpha-dihydrotestosterone

International Nuclear Information System (INIS)

Turner, R.T.; Bleiberg, B.; Colvard, D.S.; Keeting, P.E.; Evans, G.; Spelsberg, T.C.

1990-01-01

Periosteal cells were isolated from tibiae of adult male rats after collagenase treatment. Northern blot analysis of total cytoplasmic RNA extracted from the isolated periosteal cells was positive for expression of genes encoding the osteoblast marker proteins osteocalcin (BGP) and pre-pro-alpha 2(I) chain of type 1 precollagen. The isolated periosteal cells were incubated with 1 nM [3H]testosterone [( 3 H]T) for up to 240 minutes and the reaction products separated by high-performance liquid chromatography. [ 3 H]5 alpha-dihydrotestosterone [( 3 H]DHT) was not detected in extracts of periosteal cell incubations. In contrast, [ 3 H]DHT was produced in a time-dependent manner by cells from seminal vesicles. These results suggest that testosterone 5 alpha-reductase activity is not expressed by osteoblasts in rat tibial periosteum and that the anabolic effects of androgens in this tissue are not mediated by locally produced DHT

Teratoid Wilms tumour with chemotherapy resistance

Directory of Open Access Journals (Sweden)

Renuka Gahine

2015-01-01

Full Text Available We present a case of Teratoid Wilms tumour (a rare histologic variant in a 4 year old male who presented with an abdominal lump. Wilms Tumour with paracaval lymphadenopathy and tumour thrombi in right renal vein and inferior vena cava was made radiologically. FNAC report was suggestive of Wilms tumour and patient was subjected to 6 cycles of chemotherapy with not much reduction in size. Post nephrectomy histological diagnosis of Teratoid Wilms tumour was established. Resistance to chemotherapy and radiotherapy is thought to be due to presence of well differentiated histologic appearance. Teratoid Wilms tumour is usually not an aggressive neoplasm and prognosis is comparatively neoplasm and prognosis is comparatively good if the tumour is excised completely thus surgery being the best treatment.

Clinical Introduction of a Novel Liquid Fiducial Marker for Breathing Adapted Radiotherapy of Non-Small Cell Lung Cancer

DEFF Research Database (Denmark)

Rydhog, Jonas Scherman

delivery, e.g. breathing related tumour motion and anatomical changes during treatment. To ensure dose delivery to the target, a safety margin is added to the tumour. A large treatment volume, however, can be problematic due to the proximity of vital anatomical structures in the chest region, e...... for the tumour position in lung cancer patients. Furthermore, we evaluated the potential benefit of a breathing adaptation technique, where patients hold their breath during treatment delivery. We found that this technique reduced both tumour motion and doses to risk organs. Finally, we investigated...... the potential of measuring radiation doses from an activated liquid silver marker, via photon-nuclear reactions in-situ, using positron emission-tomography and proved a clear correlation between delivered radiation dose and measured induced activity....

Long-term effects of intravenous 1 alpha (OH)D3 combined with CaCO3 and low-calcium dialysis on secondary hyperparathyroidism and biochemical bone markers in patients on chronic hemodialysis

DEFF Research Database (Denmark)

Brandi, L; Daugaard, H; Nielsen, P K

1996-01-01

doses of CaCO3 and to reduce the doses of an aluminium-containing oral phosphate binder. A decrease in p-Ca2+ during dialysis was induced, and special care had to focus on the compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism. (2) The combination of 'low......The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l) on plasma (p) parathyroid hormone (PTH) and biochemical bone markers (osteocalcin, alkaline phosphatase, procollagen type 1 c......-terminal extension peptide) were examined in 54 patients on chronic hemodialysis with either normal or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood samples were obtained 1 week before the start of treatment...

CpG island methylation phenotype (CIMP) in oral cancer: associated with a marked inflammatory response and less aggressive tumour biology.

Science.gov (United States)

Shaw, Richard J; Hall, Gillian L; Lowe, Derek; Bowers, Naomi L; Liloglou, Triantafillos; Field, John K; Woolgar, Julia A; Risk, Janet M

2007-10-01

Studies in several tumour sites highlight the significance of the CpG island methylation phenotype (CIMP), with distinct features of histology, biological aggression and outcome. We utilise pyrosequencing techniques of quantitative methylation analysis to investigate the presence of CIMP in oral squamous cell carcinoma (OSCC) for the first time, and evaluate its correlation with allelic imbalance, pathology and clinical behaviour. Tumour tissue, control tissue and PBLs were obtained from 74 patients with oral squamous cell carcinoma. Pyrosequencing was used to analyse methylation patterns in 75-200 bp regions of the CpG rich gene promoters of 10 genes with a broad range of cellular functions. Allelic imbalance was investigated using a multiplexed panel of 11 microsatellite markers. Corresponding variables, histopathological staging and grading were correlated with these genetic and epigenetic aberrations. A cluster of tumours with a greater degree of promoter methylation than would be predicted by chance alone (P=0.001) were designated CIMP+ve. This group had less aggressive tumour biology in terms of tumour thickness (p=0.015) and nodal metastasis (P=0.012), this being apparently independent of tumour diameter. Further, it seems that these CIMP+ve tumours excited a greater host inflammatory response (P=0.019). The exact mechanisms underlying CIMP remain obscure but the association with a greater inflammatory host response supports existing theories relating these features in other tumour sites. As CIMP has significant associations with other well documented prognostic indicators, it may prove beneficial to include methylation analyses in molecular risk modelling of tumours.

A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer.

Science.gov (United States)

Perán, Macarena; López-Ruiz, Elena; García, María Ángel; Nadaraia-Hoke, Shorena; Brandt, Ralf; Marchal, Juan A; Kenyon, Julian

2017-10-25

Proteolytic enzymes have shown efficacy in cancer therapy. We present a combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP) using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed by matrigel-based tube formation and by fibrous capsule formation assays. Furthermore, cell invasion and wound healing assays together with qRT-PCR determination of epithelial-to-mesenchymal transition (EMT) markers were performed on human cancer cells treated with PRP. Additionally, in vivo pharmacokinetic studies were implemented and the PRP's anti-tumour efficacy was explored against orthotopic pancreatic and ovarian cancer tumours. PRP formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer cell migration and invasiveness; and to be an effective and well tolerated in vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository formulation containing both pancreatic pro-enzymes in the context of a UK Pharmaceuticals Special Scheme was evaluated in advanced cancer patients. Consequently, PRP could have relevant oncological clinical applications for the treatment of advanced or metastatic pancreatic adenocarcinoma and advanced epithelial ovarian cancer.

Molecular profiling of tumour budding implicates TGFβ-mediated epithelial-mesenchymal transition as a therapeutic target in oral squamous cell carcinoma.

Science.gov (United States)

Jensen, D H; Dabelsteen, E; Specht, L; Fiehn, A M K; Therkildsen, M H; Jønson, L; Vikesaa, J; Nielsen, F C; von Buchwald, C

2015-08-01

Although tumour budding is an adverse prognostic factor for many cancer types, the molecular mechanisms governing this phenomenon are incompletely understood. Therefore, understanding the molecular basis of tumour budding may provide new therapeutic and diagnostic options. We employ digital image analysis to demonstrate that the number of tumour buds in cytokeratin-stained sections correlates with patients having lymph node metastases at diagnosis. The tumour bud count was also a predictor of overall survival, independent of TNM stage. Tumour buds and paired central tumour areas were subsequently collected from oral squamous cell carcinoma (OSCC) specimens, using laser capture microdissection, and examined with RNA sequencing and miRNA-qPCR arrays. Compared with cells from the central parts of the tumours, budding cells exhibited a particular gene expression signature, comprising factors involved in epithelial-mesenchymal transition (EMT) and activated TGFβ signalling. Transcription factors ZEB1 and PRRX1 were up-regulated concomitantly with the decreased expression of mesenchymal-epithelial (MET) transcription factors (eg OVOL1) in addition to Krüppel-like factors and Grainyhead-like factors. Moreover, miR-200 family members were down-regulated in budding tumour cells. We used immunohistochemistry to validate five markers of the EMT/MET process in 199 OSCC tumours, as well as in situ hybridization in 20 OSCC samples. Given the strong relationship between tumour budding and the development of lymph node metastases and an adverse prognosis, therapeutics based on inhibiting the activation of TGFβ signalling may prove useful in the treatment of OSCC. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Wilms' tumour (nephroblastoma)

African Journals Online (AJOL)

Wilms' tumour or nephroblastoma is a cancer of the kidney that ... It may be noticed by parents or it may be an incidental finding ... patients. It may lead to iron deficiency anaemia. Rarely Wilms' tumour may present with acquired von Willebrand's ... the best treatment approach. ... with multimodality therapy in paediatric.

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.)

Evaluation of a second trimester triple marker screening test for fetal status using alpha-fetoprotein (aFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3)

International Nuclear Information System (INIS)

Mi, Seong Young; Kim, Jong Ho; Choi, Seung Hun

1997-01-01

Our purpose was to assess the utility of maternal serum triple-marker screening test using alpha-fetoprotein (aFP), human Chorionic Gonadotropin (hCG) and unconjugated Estriol (uE 3 ) for fetal chromosomal abnormalities. 1,767 venous blood samples (4ml) between 15 and 20 week's gestation for maternal serum screening from January to October 1996, were tested with Kodak Amerix-M triple marker radioimmunoassay kits. Risk analysis was achieved with interpretive software such as Alpha (LMS, Kodak Clinical Diagnostics). Marker levels are transformed into multiples of median (MOM), which represent an interpretation of (weight regressed) patient marker levels relative to regressed median levels for stated gestation. By multivariate anaysis, the three MOM values are combined to generate a liklihood ratio. Calculation of a patient, risk is the product of liklihood ratio and age-related risk. Risk assessment is weight for maternal age. The median values of aFP, hCG and uE 3 were well correlated with gestational age, respectively (r=0.94, p=0.003; r=-0.97, p=0.029; r=0.99, p 3 weren't (r=-0.17, p=0.22; r=0.36, p=0.09, respectively). The values of aFP, CG and uE 3 between pregnancy younger than 35 years-old (n=87) and older than that (n=1640) were 51.67±27.44, vs 54.65±126.36, 46.45±30.08 vs 51.33±38.50 and 8.01±11.01 vs 6.68±7.23, respectively but all of them failed to show significant differences. A second-trimester risk for trisomy 21 > or = 1:270 was considered screen positive. Patients were screen positive for trisomy 21 if aFP or 2.1 MOM and E 3 2.5 MOM. The initial screen-positive rate for both Down' syndrome and neural tube defect were 1.46% (26/1767); 0.73% (13/1767) with each other. Among screen positive 26 patients, three and nine were normal karyotype and normal phenotype, respectively and five patients had still births. Reamining 9 patients underwent terminations. In conclusion, compared with the other group's data even in Koreans (Whang et al, and Song et al

{alpha}{sub v}{beta}{sub 3} imaging can accurately distinguish between mature teratoma and necrosis in {sup 18}F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

Energy Technology Data Exchange (ETDEWEB)

Aide, Nicolas [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Centre Francois Baclesse, Service de Medecine Nucleaire, Caen (France); Briand, Melanie; Dutoit, Soizic; Deslandes, Edwiges; Poulain, Laurent [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Bohn, Pierre; Rouvet, Jean; Modzelewski, Romain; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Department of Nuclear Medicine, Rouen (France); Lasnon, Charline [Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Chasle, Jacques [Francois Baclesse Cancer Centre and Caen University, Pathology Department, Caen (France); Vela, Antony [Francois Baclesse Cancer Centre and Caen University, Radiophysics Unit, Caen (France); Carreiras, Franck [Universite de Cergy Pontoise, UFR Sciences et Techniques, ERRMECe, EA 1391, Institut des materiaux, Cergy-Pontoise (France)

2011-02-15

We assessed whether imaging {alpha}{sub v}{beta}{sub 3} integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).{sup 18}F-Fluorodeoxyglucose ({sup 18}F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of {alpha}{sub v}{beta}{sub 3} expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [{sup 99m}Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse {alpha}{sub v}{beta}{sub 3} expression were performed. Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for {sup 18}F-FDG [mean standardised uptake value (SUV{sub mean}) = 0.48 {+-} 0.05] compared to untreated embryonal carcinoma (SUV{sub mean} = 0.92 {+-} 0.13) (p = 0.005). {alpha}{sub v}{beta}{sub 3} imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 {+-} 1.57) from necrosis (tumour to muscle ratio = 1.3 {+-} 0.26) (p = 0.0002). Immunohistochemistry studies showed that {alpha}{sub v}{beta}{sub 3} integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. Imaging {alpha}{sub v}{beta}{sub 3} integrin accurately distinguished mature teratoma from

Tumours and tumour-like conditions of the jaw seen in Zaria, Nigeria ...

African Journals Online (AJOL)

%) ameloblastomas; 33 (23.4%) fibrous dysplasia; 31 (22.0%) cemento-osseous dysplasia; 9 (6.4%) myxomas; 8 (5.7%) ameloblastic fibroma; and 3 (2.1%) adenomatoid odontogenic tumours; and 9 (6.4%) unclassified tumours. The benign ...

A viscoelastic model of the correlation between respiratory lung tumour motion and an external abdominal signal

International Nuclear Information System (INIS)

Cavan, A.E.; Wilson, P.L.; Meyer, J.; Berbeco, R.I.

2010-01-01

Full text: Accuracy of radiotherapy treatment of lung cancer is limited by respiratory induced tumour motion. Compensation for this motion is required to increase treatment efficacy. The lung tumour motion is related to motion of an external abdominal marker, but a reliable model of this correlation is essential. Three viscoelastic systems were developed, in order to determine the best model and analyse its effectiveness on clinical data. Three 1D viscoelastic systems (a spring and dash pot in parallel, series and a combination) were developed and compared using a simulated breathing pattern. The most effective model was applied to 60 clinical data sets (consisting of co-ordinates of tumour and abdominal motion) from multiple treatment fractions of ten patients. The model was optimised for each data set, and efficacy determined by calculating the root mean square (RMS) error between the mo elled position and the actual tumour motion. Upon application to clinical data the parallel configuration achieved an average RMS error of 0.95 mm (superior-inferior direction). The model had patient specific parameters, and displayed good consistency over extended treatment periods. The model ha dled amplitude, frequency and baseline variations of the input signal, and phase shifts between tumour and abdominal motions. This study has shown that a viscoelastic model can be used to cor relate internal lung tumour motion with an external abdominal signal. The ability to handle breathing pattern in'egularities is comparable or better than previous models. Extending the model to a full 3D, pr dictive system could allow clinical implementation for radiotherapy.

Primary bone tumours of the hand

International Nuclear Information System (INIS)

Kozlowski, K.; Azouz, E.M.; Campbell, J.; Marton, D.; Morris, L.; Padovani, J.; Sprague, P.; Beluffi, G.; Berzero, G.F.; Cherubino, P.; Adelaide Children's Hospital; Hospital for Children, Perth; Montreal Children's Hospital, Quebec; Saint Justine Hospital, Montreal, Quebec; Children's Hospital, Denver, CO; Hopital des Enfants, 13 - Marseille; Pavia Univ.; Pavia Univ.

1988-01-01

Twenty-one primary bone tumours of the hand in children from 8 paediatric hospitals are reported. Osteochondromas and enchondromas were not included. Our material consisted of 16 patients with common tumours (3 Ewing's sarcoma, 5 aneurysmal bone cyst, 6 osteoid osteoma and 2 epithelioma) and 5 patients with uncommon tumours (osteoma, simple bone cyst, haemangiopericytoma, capillary angiomatous tumour and benign ossifying fibroma or osteoblastoma). The X-ray diagnosis of the common tumours should have high concordance with histology, whereas that of uncommon tumours in much more difficult and uncertain. The characteristic features of Ewing's sarcoma are stressed as all our children with this tumour had a delayed diagnosis and a fatal outcome. Differential diagnosis with other short tubular bone lesions of the hand - specifically osteomyelitis - is discussed and the posibilities of microscopic diagnosis are stressed. (orig.)

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

Science.gov (United States)

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Biological effects of alpha particles in lung tissue

International Nuclear Information System (INIS)

Hofmann, W.; Daschil, F.

1985-01-01

Allowing for concomitant cellular inactivation, the tumour incidence function can be written as the product of two probabilities, for malignant transformation and for not being killed. Cell survival of mammalian cells in culture after heavy ion irradiation has been described successfully by the formalism of track structure theory for cellular inactivation. Thus a transformation function is derived by extracting cellular radiosensitivity parameters from experimental data on mutation to thioguanine resistance. For defined conditions of radon daughter inhalation, from the fraction of inhaled radionuclides deposited and retained on bronchial airway surfaces are calculated. The LET distribution in sensitive bronchial stem cells hit by alpha particles depends on initial alpha particle energy, airway diameter, and stem cell depth. Applying the methodology of track structure theory and using cellular radiosensitivity parameters for cell killing and mutation, the radiation risk at a given stem cell depth is expressed by the probabilities for cellular survival, for mutation or transformation, and the joint probability for cancer induction. (author)

Marker chromosome 21 identified by microdissection and FISH

Energy Technology Data Exchange (ETDEWEB)

Sun, Y.; Palmer, C.G. [Indiana Univ. School of Medicine, Indianapolis, IN (United States); Rubinstein, J. [Univ. Affiliated Cincinnati Center for Developmental Disorders, OH (United States)] [and others

1995-03-27

A child without Down`s syndrome but with developmental delay, short stature, and autistic behavior was found to be mosaic 46,XX/47,XX,+mar(21) de novo. The marker was a small ring or dot-like chromosome. Microdissection of the marker was performed. The dissected fragments were biotinylated with sequence-independent PCR as a probe pool for fluorescence in situ hybridization (FISH). FISH results suggested an acrocentric origin of the marker. Subsequent FISH with {alpha}-satellite DNA probes for acrocentric chromosomes and chromosome-specific 21 and 22 painting probes confirmed its origin from chromosome 21. 14 refs., 3 figs.

Evaluation of Cucurbita maxima extract against scopolamine-induced amnesia in rats: implication of tumour necrosis factor alpha.

Science.gov (United States)

Jawaid, Talha; Shakya, Ashok K; Siddiqui, Hefazat Hussain; Kamal, Mehnaz

2014-01-01

Cucurbita maxima (CM) seed oil is commonly used in Indian folk medicine to treat various ailments. We have investigated the effect of CM seed oil on memory impairment induced by scopolamine in rats. Male adult Wistar rats were administered scopolamine 1 mg/kg body weight, i.p. or 1.25 mg/kg body weight, s.c. to induce memory impairment. The nootropic agent piracetam 100 mg/kg body weight, i.p. and CM seed oil 100 and 200 mg/kg body weight, p.o. were administered daily for five consecutive days. The memory function was evaluated in the Morris water maze (MWM) test, the social recognition test (SRT), the elevated plus maze (EPM) test, and the pole climbing test (PCT). Acetylcholinesterase (AChE) activity and oxidative stress parameters were estimated in the cortex, hippocampus, and cerebellum of the brains after completion of the behavioural studies. The effects of scopolamine on the levels of the tumour necrosis factor alpha (TNF-α) transcript were also investigated. Scopolamine caused memory impairment in all the behavioural paradigms along with a significant increase in the AChE activity and oxidative stress in the brain. Scopolamine also caused a significant increase in the expression of TNF-α in the hippocampus. CM seed oil exhibited antiamnesic activity as indicated by a significant reduction in the latency time in the MWM test and decreased social interaction during trial 2 in the SRT. Further, treatment with CM seed oil significantly decreased the AChE activity and malondialdehyde levels and increased the glutathione level in brain regions. CM seed oil also significantly decreased the expression of TNF-α in the hippocampus. The effect of CM seed oil on behavioural and biochemical parameters was comparable to that observed in rats treated with piracetam. These results indicate that CM seed oil may exert antiamnesic activity which may be attributed to the inhibition of AChE and inflammation as well as its antioxidant activity in the brain.

Alpha radioactivity in tobacco leaves: Effect of fertilizers

Energy Technology Data Exchange (ETDEWEB)

Nain, Mahabir [Department of Physics, Government College Karnal, Haryana 132001 (India)], E-mail: mnain@rediffmail.com; Chauhan, R.P. [Department of Physics, National Institute of Technology, Kurukshetra 136119 (India); Chakarvarti, S.K. [Department of Applied Physics, NIT, Kurukshetra 136119 (India)

2008-08-15

The link between cigarette smoke and cancer has long been established. Smokers are 10 times at a greater risk of developing lung cancer than that of non-smokers. The toxicity in tobacco is considered mainly due to the presence of chemi-toxins like nicotine, tar, aromatic hydrocarbons, sterols and many other materials leading to mutagenicity and carcinogenicity. There are many reports on the presence of naturally occurring radionuclides viz., {sup 210}Po and {sup 210}Pb in tobacco. Investigations on alpha-emitting radionuclides, especially on {sup 210}Po have gained significant importance as alpha interactions with chromosomes of cells may contribute to early arteriosclerosis developments in tobacco smokers. Due to relatively high activity concentration of {sup 210}Po and {sup 210}Pb that are found in tobacco and its product cigarette can increase the internal intake of both the radionuclides and their concentrations in lung tissues. This causes an increase in the internal radiation dose which enhances the instances of lung cancer. Many workers have tried to explain the role of {sup 210}Po in tobacco in the epidemiological investigation of cancer and tumour formation. In the present work, the estimation of alpha radioactivity in tobacco leaves taken from tobacco plants grown using different types of chemical fertilizers like diammonium phosphate (DAP), zinc sulphate, potash, super phosphate, urea etc. in varying amounts before the plantation of the seedlings has been made. For these measurements we used {alpha}-sensitive LR-115 type II plastic track detectors. The results indicate an increase in alpha radioactivity with the use of some fertilizers.

Failure of isolated rat tibial periosteal cells to 5 alpha reduce testosterone to 5 alpha-dihydrotestosterone

Energy Technology Data Exchange (ETDEWEB)

Turner, R.T.; Bleiberg, B.; Colvard, D.S.; Keeting, P.E.; Evans, G.; Spelsberg, T.C. (Mayo Clinic, Rochester, MN (USA))

1990-07-01

Periosteal cells were isolated from tibiae of adult male rats after collagenase treatment. Northern blot analysis of total cytoplasmic RNA extracted from the isolated periosteal cells was positive for expression of genes encoding the osteoblast marker proteins osteocalcin (BGP) and pre-pro-alpha 2(I) chain of type 1 precollagen. The isolated periosteal cells were incubated with 1 nM (3H)testosterone (({sup 3}H)T) for up to 240 minutes and the reaction products separated by high-performance liquid chromatography. ({sup 3}H)5 alpha-dihydrotestosterone (({sup 3}H)DHT) was not detected in extracts of periosteal cell incubations. In contrast, ({sup 3}H)DHT was produced in a time-dependent manner by cells from seminal vesicles. These results suggest that testosterone 5 alpha-reductase activity is not expressed by osteoblasts in rat tibial periosteum and that the anabolic effects of androgens in this tissue are not mediated by locally produced DHT.

Metabolic tumour burden assessed by 18F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection

International Nuclear Information System (INIS)

Xu, Hua-Xiang; Chen, Tao; Wang, Wen-Quan; Wu, Chun-Tao; Liu, Chen; Long, Jiang; Xu, Jin; Liu, Liang; Yu, Xian-Jun; Zhang, Ying-Jian; Chen, Run-Hao

2014-01-01

Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by 18 F-FDG PET/CT in patients with resectable PDAC. Included in the study were 122 PDAC patients who received preoperative 18 F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. (orig.)

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

Induction of cancers in the rat after inhalation of alpha-emitting radionuclides

International Nuclear Information System (INIS)

Morin, M.; Nenot, J.C.; Masse, R.; Nolibe, D.; Metivier, H.; Lafuma, J.

1976-01-01

Experiments have been conducted for several years on the toxic action of inhaled alpha-emitters on laboratory rats. The inhaled radionuclides were 239 Pu, 238 Pu and 241 Am in oxide and nitrate form. The initial alveolar activities varied to give total activities ranging from 1 to 200 thousand million alpha-particles per gram of lung. Variations, depending on the physico-chemical form of the nuclides, in the space and time distributions of the dose are observed. The influence of the two parameters on life span reduction, latency time and frequency of cancer occurrence, initial location of tumours and their histological types were studied. A theoretical model relating the cancerogenous effect to the dose is compared with experimental data. (author)

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.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

LENUS (Irish Health Repository)

Brennan, Donal J

2010-01-01

BACKGROUND: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. METHODS: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). RESULTS: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. CONCLUSION: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

LENUS (Irish Health Repository)

Brennan, Donal J

2010-04-01

Abstract Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

International Nuclear Information System (INIS)

Brennan, Donal J; Jirstrom, Karin; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm

2010-01-01

Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens

Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

Science.gov (United States)

Kulkarni, R P; Reynolds, K W; Newlands, E S; Dawson, P M; Makey, A R; Theodorou, N A; Bradley, J; Begent, R H; Rustin, G J; Bagshawe, K D

1991-02-01

Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

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)

Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

Energy Technology Data Exchange (ETDEWEB)

Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

2011-04-22

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

Alpha-synuclein levels in blood plasma decline with healthy aging.

Science.gov (United States)

Koehler, Niklas K U; Stransky, Elke; Meyer, Mirjam; Gaertner, Susanne; Shing, Mona; Schnaidt, Martina; Celej, Maria S; Jovin, Thomas M; Leyhe, Thomas; Laske, Christoph; Batra, Anil; Buchkremer, Gerhard; Fallgatter, Andreas J; Wernet, Dorothee; Richartz-Salzburger, Elke

2015-01-01

There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (phealthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.

MRI characteristics of midbrain tumours

International Nuclear Information System (INIS)

Sun, B.; Wang, C.C.; Wang, J.

1999-01-01

We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary midbrain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases. (orig.) (orig.)

Neurofibromatosis type 1: brain stem tumours

International Nuclear Information System (INIS)

Bilaniuk, L.T.; Molloy, P.T.; Zimmerman, R.A.; Phillips, P.C.; Vaughan, S.N.; Liu, G.T.; Sutton, L.N.; Needle, M.

1997-01-01

We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs

Surgical management of epithelial parotid tumours

International Nuclear Information System (INIS)

Obaid, M.A.; Yusuf, A.

2004-01-01

Objective: To describe the clinicopathological presentation and treatment options in epithelial parotid tumours with emphasis on surgery. Subjects and Methods: Epithelial parotid tumours diagnosed and operated by an ENT surgeon and a general surgeon in 10 years during their posting in different teaching hospitals were included in the study. Clinical presentation, preoperative investigations, operative procedure, histopathology report, postoperative complications and further management were recorded. The data was collected and reviewed from the records of all the patients maintained by the authors. Results: Fifty-two patients presented with parotid tumour. Average age was 38 years. Commonest presentation was painless lump over the parotid region (85%), pain (15%), facial palsy, and enlarged neck nodes. Majority of tumours were benign, only two were recurrent. Parotid pleomorphic Adenoma (PPA) was the commonest benign tumour, others being Warthin's tumour and monomorphic adenoma. Adenoid cystic carcinoma was the commonest malignant tumour 29% followed by mucoepidermoid carcinoma. Others were carcinoma in PPA squamous cell carcinoma, malignant mixed tumour, malignant Iymphoepithelioma and undifferentiated carcinoma. Superficial parotidectomy (SP) was the commonest operation performed in 69%. Other procedures were total conservative parotidectomy in 11%, total radical surgery in 9% and enucleation in only one patient earliest in the series. Neck node dissection was done in 2 patients. Except for one child, rest of the 13 patients received postoperative radiotherapy and one patient of Iymphoepithelioma received chemotherapy in addition. Commonest postoperative complication was temporary facial weakness in 35% (18/52). Permanent facial palsy occurred in 08 patients. Of these 07 had a malignant process and only one patient had excision biopsy. Conclusion: Benign and malignant epithelial parotid tumours can be diagnosed by there clinical presentation . supplemented with

Prostate specific antigen: a useful but limited marker for prostate ...

African Journals Online (AJOL)

the liver (cPSA and fPSA) and the kidney. (fPSA). The half-life of PSA in serum is ±2-3 days.7. Prostate cancer and PSA. PSA is widely used as a tumour marker in. Pca. Typically, PSA levels are elevated in. Pca mainly due to disruption of the normal glandular architecture, resulting in more. PSA being released into the ...

Functional features of gene expression profiles differentiating gastrointestinal stromal tumours according to KIT mutations and expression

International Nuclear Information System (INIS)

Ostrowski, Jerzy; Dobosz, Anna Jerzak Vel; Jarosz, Dorota; Ruka, Wlodzimierz; Wyrwicz, Lucjan S; Polkowski, Marcin; Paziewska, Agnieszka; Skrzypczak, Magdalena; Goryca, Krzysztof; Rubel, Tymon; Kokoszyñska, Katarzyna; Rutkowski, Piotr; Nowecki, Zbigniew I

2009-01-01

Gastrointestinal stromal tumours (GISTs) represent a heterogeneous group of tumours of mesenchymal origin characterized by gain-of-function mutations in KIT or PDGFRA of the type III receptor tyrosine kinase family. Although mutations in either receptor are thought to drive an early oncogenic event through similar pathways, two previous studies reported the mutation-specific gene expression profiles. However, their further conclusions were rather discordant. To clarify the molecular characteristics of differentially expressed genes according to GIST receptor mutations, we combined microarray-based analysis with detailed functional annotations. Total RNA was isolated from 29 frozen gastric GISTs and processed for hybridization on GENECHIP ® HG-U133 Plus 2.0 microarrays (Affymetrix). KIT and PDGFRA were analyzed by sequencing, while related mRNA levels were analyzed by quantitative RT-PCR. Fifteen and eleven tumours possessed mutations in KIT and PDGFRA, respectively; no mutation was found in three tumours. Gene expression analysis identified no discriminative profiles associated with clinical or pathological parameters, even though expression of hundreds of genes differentiated tumour receptor mutation and expression status. Functional features of genes differentially expressed between the two groups of GISTs suggested alterations in angiogenesis and G-protein-related and calcium signalling. Our study has identified novel molecular elements likely to be involved in receptor-dependent GIST development and allowed confirmation of previously published results. These elements may be potential therapeutic targets and novel markers of KIT mutation status

A forgotten facial nerve tumour: granular cell tumour of the parotid and its implications for treatment.

Science.gov (United States)

Lerut, B; Vosbeck, J; Linder, T E

2011-04-01

We present a rare case of a facial nerve granular cell tumour in the right parotid gland, in a 10-year-old boy. A parotid or neurogenic tumour was suspected, based on magnetic resonance imaging. Intra-operatively, strong adhesions to surrounding structures were found, and a midfacial nerve branch had to be sacrificed for complete tumour removal. Recent reports verify that granular cell tumours arise from Schwann cells of peripheral nerve branches. The rarity of this tumour within the parotid gland, its origin from peripheral nerves, its sometimes misleading imaging characteristics, and its rare presentation with facial weakness and pain all have considerable implications on the surgical strategy and pre-operative counselling. Fine needle aspiration cytology may confirm the neurogenic origin of this lesion. When resecting the tumour, the surgeon must anticipate strong adherence to the facial nerve and be prepared to graft, or sacrifice, certain branches of this nerve.

The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression

DEFF Research Database (Denmark)

Atlasi, Yaser; Noori, Rubina; Marolin, Ivana

2016-01-01

burden characteristic of the Apc1638N model. In agreement with these results, S100a4 appears to be co-expressed together with mesenchymal stem cell (MSC) markers in desmoid tumours from Apc1638N/+ mice, as well as from sporadic and hereditary human desmoids. Conclusion Our data provide the first report...

VIP secreting tumours in infancy

International Nuclear Information System (INIS)

Davies, R.P.; Slavotinek, J.P.; Dorney, S.F.A.

1990-01-01

Vasoactive intestinal polypeptide (VIP) secreting neural crest tumours are an uncommon but important treatable cause of intractable childhood diarrhoea. The radiological appearances of two cases are presented with a review of radiological findings in childhood VIP secreting neural crest tumours. Twenty eight cases of childhood VIP secreting neural crest tumours were reviewed. Nineteen (68%) were ganglioneuroblastomas and nine (32%) were ganglioneuromas. The majority of tumours (66%) were in a paravertebral location in the abdomen indicating that a search for such a tumour should be initiated at this site. Eighteen of the twenty eight cases reviewed discussed relevant radiological investigations. Calcification was detected in 50% of abdominal radiographs. Gut dilatation was often a prominent feature. A mass was detected in 5 of 5 cases where ultrasound findings were reported, and seven of seven cases with CT findings reported. Prior to the availability of CT and ultrasound the most useful investigation was IVU which demonstrated evidence of a mass in 5 of 9 cases. The presence of paravertebral calcification and gut dilatation on the plain radiograph of a child with intractable diarrhoea suggests the presence of a VIP secreting neural crest tumour. If an abdominal tumour is not found in the appropriate clinical setting and VIP levels are elevated, a widespread search of the paravertebral region is indicated. (orig.)

Targeting radiation to tumours

International Nuclear Information System (INIS)

Wheldon, T.E.; Greater Glasgow Health Board, Glasgow

1994-01-01

Biologically targeted radiotherapy entails the preferential delivery of radiation to solid tumours or individual tumour cells by means of tumour-seeking delivery vehicles to which radionuclides can be conjugated. Monoclonal antibodies have attracted attention for some years as potentially selective targeting agents, but advances in tumour and molecular biology are now providing a much wider choice of molecular species. General radiobiological principles may be derived which are applicable to most forms of targeted radiotherapy. These principles provide guidelines for the appropriate choice of radionuclide in specific treatment situations and its optimal combination with other treatment modalities. In future, the availability of gene targeting agents will focus attention on the use of Auger electron emitters whose high potency and short range selectivity makes them attractive choices for specific killing of cancer cells whose genetic peculiarities are known. (author)

[Gastric mesenchymal tumours (GIST)].

Science.gov (United States)

Spivach, Arrigo; Fezzi, Margherita; Sartori, Alberto; Belgrano, Manuel; Rimondini, Alessandra; Cuttin-Zernich, Roberto; Covab, Maria Assunta; Bonifacio, Daniela; Buri, Luigi; Pagani, Carlo; Zanconati, Fabrizio

2008-01-01

The incidence of gastrointestinal stromal tumours (GIST) has increased in recent years. A number of authors have attempted to define the actual nature of these tumours. Immunohistochemistry highlighting the positivity of tyrosine-kinase (CD117/c-Kit) has revealed the difference between gastrointestinal stromal tumours and other mesenchymal tumours and, therefore, the possibility of medical rather than surgical therapy. We retrospectively reviewed 19 patients affected by primary gastric GIST, who underwent surgery in recent years with subsequent follow-up. Gastroscopy and gastrointestinal tract radiography were used not only to obtain the diagnosis but also to establish the size, density, contours, ulceration, regional lymphadenopathy, mesenteric infiltration and the presence of metastases. The aim of this study was to evaluate the roles of endoscopy and radiology in this pathology and the advantages and limitations of each individual technique.

Neutrophil-induced transmigration of tumour cells treated with tumour-conditioned medium is facilitated by granulocyte-macrophage colony-stimulating factor.

LENUS (Irish Health Repository)

Wu, Q D

2012-02-03

OBJECTIVE: To investigate the effect of different cytokines that are present in tumour-conditioned medium on human neutrophil (PMN)-induced tumour cell transmigration. DESIGN: Laboratory study. SETTING: University hospital, Ireland. MATERIAL: Isolated human PMN and cultured human breast tumour cell line, MDA-MB-231. Interventions: Human PMN treated with either tumour-conditioned medium or different media neutralised with monoclonal antibodies (MoAb), and MDA-MB-231 cells were plated on macrovascular and microvascular endothelial monolayers in collagen-coated transwells to assess migration of tumour cells. MAIN OUTCOME MEASURES: Cytokines present in tumour-conditioned medium, PMN cytocidal function and receptor expression, and tumour cell transmigration. RESULTS: tumour-conditioned medium contained high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8), but not granulocyte colony-stimulating factor (G-CSF) and interleukin 3 (IL-3). Anti-GM-CSF MoAb significantly reduced PMN-induced transmigration of tumour cells treated with tumour-conditioned medium (p < 0.05), whereas anti-VEGF and anti-IL-8 MoAbs did not affect their migration. In addition, anti-GM-CSF MoAb, but not anti-VEGF or anti-IL-8 MoAb, reduced PMN CD11b and CD18 overexpression induced by tumour-conditioned medium (p < 0.05). CONCLUSION: These results indicate that the GM-CSF that is present in tumour-conditioned medium may be involved, at least in part, in alterations in PMN function mediated by the medium and subsequently PMN-induced transmigration of tumour cells.

Anti-tumour immune effect of oral administration of Lactobacillus plantarum to CT26 tumour-bearing mice.

Science.gov (United States)

Hu, Jingtao; Wang, Chunfeng; Ye, Liping; Yang, Wentao; Huang, Haibin; Meng, Fei; Shi, Shaohua; Ding, Zhuang

2015-06-01

Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN-gamma (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

Nuclear expression of Snail1 in borderline and malignant epithelial ovarian tumours is associated with tumour progression

International Nuclear Information System (INIS)

Tuhkanen, Hanna; Soini, Ylermi; Kosma, Veli-Matti; Anttila, Maarit; Sironen, Reijo; Hämäläinen, Kirsi; Kukkonen, Laura; Virtanen, Ismo; Mannermaa, Arto

2009-01-01

Transcription factor Snail1 has a central role in induction of epithelial-mesenchymal transition (EMT). The aim of the present study was to elucidate the expression of Snail1 protein during epithelial ovarian tumourigenesis and to study the association of Snail1 expression with clinicopathological factors and prognosis. Epithelial and stromal fibroblast-like fusiform cells of 14 normal ovarian samples, 21 benign, 24 borderline and 74 malignant epithelial ovarian tumours were studied for Snail1 protein using immunohistochemistry. Nuclei of surface peritoneal cells of normal ovaries (n = 14) were regarded as negative for Snail1. Nuclear expression of Snail1 protein in epithelial ovarian tumours was increased during tumour progression from precursor lesions into carcinomas both in epithelial (p = 0.006) and stromal cells (p = 0.007). Nuclei of benign tumours (n = 21) were negative for Snail1. In borderline tumours (n = 24) occasional positive epithelial cells were found in 2 (8%) samples and in 3 (13%) samples stromal cells were focally positive for Snail1. In carcinomas (n = 74) focal Snail1 staining in epithelial cells was present in 17 (23%) tumours, and in stromal cells in 18 (24%) tumours. Nuclear expression of Snail1 in epithelial or stromal cells was not associated with clinicopathological factors or prognosis. Nuclear Snail1 expression seems to be related to tumour progression, and expression in borderline tumours indicates a role for Snail1 in early epithelial ovarian tumour development. Snail1 also appears to function more generally in tissue remodelling as positive staining was demonstrated in stromal cells

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

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

Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Almstrup, K; Nielsen, J E

2005-01-01

AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG...... expression. In the present study we analysed the protein expression of NANOG during normal development of human testis and in a large series of neoplastic/dysgenetic specimens. METHODS AND RESULTS: We detected abundant expression of NANOG in CIS and in CIS-derived testicular tumours with marked differences...

Metabolic tumour burden assessed by {sup 18}F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection

Energy Technology Data Exchange (ETDEWEB)

Xu, Hua-Xiang; Chen, Tao; Wang, Wen-Quan; Wu, Chun-Tao; Liu, Chen; Long, Jiang; Xu, Jin; Liu, Liang; Yu, Xian-Jun [Fudan University, Shanghai Cancer Center, Pancreatic Cancer Institute and Department of Pancreatic and Hepatobiliary Surgery, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Zhang, Ying-Jian [Fudan University, Shanghai Cancer Center, Department of Nuclear Medicine, Shanghai (China); Fudan University, Department of Oncology, Shanghai Medical College, Shanghai (China); Chen, Run-Hao [Fudan University, Department of General Surgery, Jinshan Hospital, Shanghai (China)

2014-06-15

Tumour burden is one of the most important prognosticators for pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the predictive significance of metabolic tumour burden measured by {sup 18}F-FDG PET/CT in patients with resectable PDAC. Included in the study were 122 PDAC patients who received preoperative {sup 18}F-FDG PET/CT examination and radical pancreatectomy. Metabolic tumour burden in terms of metabolic tumour volume (MTV) and total lesion glycolysis (TLG), pathological tumour burden (tumour size), serum tumour burden (baseline serum CA19-9 level), and metabolic activity (maximum standard uptake value, SUVmax) were determined, and compared for their performance in predicting overall survival (OS) and recurrence-free survival (RFS). MTV and TLG were significantly associated with baseline serum CA19-9 level (P = 0.001 for MTV, P < 0.001 for TLG) and tumour size (P < 0.001 for MTV, P = 0.001 for TLG). Multivariate analysis showed that MTV, TLG and baseline serum CA19-9 level as either categorical or continuous variables, but not tumour size or SUVmax, were independent risk predictors for both OS and RFS. Time-dependent receiving operating characteristics analysis further indicated that better predictive performances for OS and RFS were achieved by MTV and TLG compared to baseline serum CA19-9 level, SUVmax and tumour size (P < 0.001 for all). MTV and TLG showed strong consistency with baseline serum CA19-9 level in better predicting OS and RFS, and might serve as surrogate markers for prediction of outcome in patients with resectable PDAC. (orig.)

Vasculogenic Mimicry of HT1080 Tumour Cells In Vivo: Critical Role of HIF-1α-Neuropilin-1 Axis

Science.gov (United States)

Misra, Roli M.; Bajaj, Manmohan S.; Kale, Vaijayanti P.

2012-01-01

HT1080 - a human fibrosarcoma-derived cell line – forms aggressive angiogenic tumours in immuno-compromised mice. In spite of its extensive use as a model of tumour angiogenesis, the molecular event(s) initiating the angiogenic program in these cells are not known. Since hypoxia stimulates tumour angiogenesis, we examined the hypoxia-induced events evoked in these cells. In contrast to cells grown under normoxic conditions, hypoxia-primed (1% O2) HT1080 cells formed robust tubules on growth factor-reduced matrigel and formed significantly larger tumours in xenograft models in a chetomin-sensitive manner, indicating the role of HIF-1α-mediated transcription in these processes. Immuno-histochemical analyses of tumours formed by GFP-expressing HT1080 cells clearly showed that the tumour cells themselves expressed various angiogenic markers including Neuropilin-1 (NRP-1) and formed functional vessels containing red blood cells, thereby unambiguously demonstrating the vasculogenic mimicry of HT1080 cells in vivo. Experiments performed with the HT1080 cells stably transfected with plasmid constructs expressing shNRP-1 or full-length NRP-1 clearly established that the HIF1α-mediated up-regulation of NRP-1 played a deterministic role in the process. Hypoxia-exposure resulted in an up-regulation of c-Myc and OCT3/4 and a down-regulation of KLF4 mRNAs, suggesting their involvement in the tumour formation and angiogenesis. However, silencing of NRP-1 alone, though not affecting proliferation in culture, was sufficient to abrogate the tumour formation completely; clearly establishing that the hypoxia-mediated HIF-1α-dependent up-regulation of NRP-1 is a critical molecular event involved in the vasculogenic mimicry and tumor formation by HT1080 cells in vivo. PMID:23185562

Thallium uptake and biological behaviour in childhood brain tumours

International Nuclear Information System (INIS)

Bernard, E.J.; Howman-Giles, R.; Kellie, S.; Uren, R.F.

1998-01-01

Full text: The histopathological grade and radiological appearance of the diverse cerebral neoplasms in childhood frequently poorly reflect their biological behaviour. We examined thallium accumulation prior to treatment (and in several cases, at intervals there after) in 13 children to determine its usefulness as a tumour marker. 23 SPECT studies were acquired 20 minutes after the injection of 1-3 mCi of 201 TI. Thallium index (TI), the ratio of counts in tumour/normal brain, was calculated. No uptake was seen in two patients (pts) with a Grade 1 cerebellar astrocytomas (disease free at 4/12 f/u). Three pts with medulloblastomas were studied. One pt showed intense uptake (Tl =12). His tumour (proliferative antigen stain Ki67 = 50%) recurred early after debulking surgery (Tl +ve prior to CT or MRI changes). The second pt was imaged at relapse Ki67 = 60%) and showed intense uptake, Tl = 17. The third pt showed lower level uptake (Tl = 2), Ki67 = 5%, and is disease-free at 5/12 (as per 201 TI and MRI). One pt with a Grade 1 brainstem glioma showed Tl = 5 and has progressed rapidly despite low grade histology. Four pts with chiasmatic-hypothalamic gliomas have been studied. Although these neoplasms are usually low grade histologically, their growth properties vary greatly. Two pts with Tl 3.5 and have required aggressive treatment for rapid disease progression. One pt with a large pilocytic astrocytoma of the optic chiasm showed Tl = 9.5. Active treatment was not undertaken. One pt with a pineal germ cell tumour showed avid 201 TI uptake (Tl not performed) and has had two normal studies, and is clinically well, since BMT. Avid 201 TI uptake also seen in one pt with cerebral neuroblastoma. (Died at 8/12 after Dx.) Thus, 201 TI accumulates in histologically diverse paediatric neoplasms. The Tl appears to reflect biological behaviour in the limited number of medulloblastoma and optic gliomas pts studied. Whilst promising, further patient studies and longer follow-up is

Field production and functional evaluation of chloroplast-derived interferon-alpha2b.

Science.gov (United States)

Arlen, Philip A; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M; Oishi, Karen K; Daniell, Henry

2007-07-01

Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-alpha2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-alpha2b for the treatment of hepatitis C infection is $26,000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-alpha2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-alpha2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-alpha2b had similar in vitro biological activity to commercially produced PEG-Introntrade mark when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-alpha2b were also seen in vivo. Chloroplast-derived IFN-alpha2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-alpha2b purified from chloroplast transgenic lines (cpIFN-alpha2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-alpha2b, transgene containment and biological activity akin to that of commercial preparations of IFN-alpha2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization.

131I-MIBG and neuroendocrine tumours

International Nuclear Information System (INIS)

Oliva Gonzalez, Juan Perfecto; Gonzalez Gonzalez, Joaquin Jorge; Calderon Marin, Carlos Fabian

2012-01-01

Neuroendocrine tumours are neoplasms that arise from various tissues closely linked to the neural crest by their common embryological origin. These tumours have the ability to synthesize neurotransmitter peptides and hormones, as well as to store catecholamines. Some of these tumours express somatostatin receptors at their membranes, what have allowed nuclear medicine to be involved in their diagnosis, treatment and monitoring. Since they arise from different and varied types of tissues, these tumours have a wide range of signs and symptoms different for every one of them. These signs and symptoms mainly depend on their biochemical characteristics, given by the substances they secrete, as well as by their location, and consequently, they also depend on the place where the tumour appears, its local infiltration, and potential long-distance metastasis resulting from the tumour). Neuroendocrine tumours are diagnosed by means of nuclear medicine images, which are obtained by using different techniques and radiopharmaceuticals such as 99 mTc dimercaptosuccinic acid (DMSA(V)), 99 mTc-methoxy-isobutyl-isonitrile (MIBI), metaiodobenzylguanidine (MIBG) labelled with 131 I or 123 I ( 131 I-MIBG or 123 I -MIBG), 111 In-labelled octreotide, positron emission tomography, using 68 Ga-labelled somatostatin analogues and carcinoembryonic antigen monoclonal antibodies. Nuclear medicine uses mainly somatostatin analogues labelled with 90 Y or 177 Lu for the treatment of these tumours. This paper is aimed at showing our experience in the use of 131 I-MIBG for the diagnosis and treatment of neuroendocrine tumours.(author)

Fifty years of discovery of alpha-fetoprotein as the first tumor marker

Directory of Open Access Journals (Sweden)

Nikulina Dina

2015-01-01

Full Text Available Alpha-fetoprotein represents the most prominent oncobiomarker, widely used in the diagnosis of hepatocellular carcinoma for monitoring of tumor progression, presence of metastasis, assessment of cancer prognosis and successful antitumor therapeutic measures. Yuri Semenovich Tatarinov is a Russian scientist who first published antigen specific for human hepatocellular carcinoma in 1963. To commemorate the 50th anniversary of the discovery of alpha-fetoprotein, 9th International Scientific- Practical Conference entitled “Achievements of fundamental science and translational medicine capabilities in solving actual problems of practical public health”, was held from May 6-8th, 2013 in Astrakhan, Russia. The conference was held in memory of historical scientific work of Yuri Semenovich Tatarinov. [Projekat Ministarstva nauke Republike Srbije, br. 175056

Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas

Energy Technology Data Exchange (ETDEWEB)

Hulshof, Maarten C.C.M. [Department of Radiation Oncology, University of Amsterdam (Netherlands)]. E-mail: m.c.hulshof@amc.uva.nl; Andel, George van [Department of Urology, Onze Lieve Vrouwe Gasthuis, Amsterdam (Netherlands); Bel, Arjen [Department of Radiation Oncology, University of Amsterdam (Netherlands); Gangel, Pieter [Department of Radiation Oncology, University of Amsterdam (Netherlands); Kamer, Jeroen B. van de [Department of Radiation Oncology, University of Amsterdam (Netherlands)

2007-07-15

A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas

International Nuclear Information System (INIS)

Hulshof, Maarten C.C.M.; Andel, George van; Bel, Arjen; Gangel, Pieter; Kamer, Jeroen B. van de

2007-01-01

A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer

Intravesical markers for delineation of target volume during external focal irradiation of bladder carcinomas.

Science.gov (United States)

Hulshof, Maarten C C M; van Andel, George; Bel, Arjen; Gangel, Pieter; van de Kamer, Jeroen B

2007-07-01

A clip forceps was developed which can insert markers at the border of a bladder tumour through a rigid cystoscope. This technique proved to be simple and safe and is of help for delineation of the target volume during CT simulation for focal boost irradiation of bladder cancer.

Tocopherol in irradiation of temporary hypoxic tumours

International Nuclear Information System (INIS)

Kaagerud, A.; Lund, N.; Peterson, H.I.

1981-01-01

The influence of tocopherol on the effect of local irradiation under induced ischaemia by temporary tourniquet of two rat tumours transplanted intramuscularly into one hindleg was evaluated. An impaired retardation of growth rate occurred in tumours irradiated under ischaemia. This effect was eliminated by pretreatment of animals with tocopherol. In separate experiments the method of inducing ischaemia was investigated by MDO-electrode measurements of tumour tissue oxygen pressure. A significant tumour hypoxia was found under tourniquet of the tumour-bearing leg of the animals. Pretreatment with tocopherol did not influence the tumour pO 2 . (Auth.)

Tumour and lymph node uptakes on dual-phased 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography correlate with prognostic parameters in breast cancer.

Science.gov (United States)

Chang, Chin-Chuan; Tu, Hung-Pin; Chen, Yu-Wen; Lin, Chia-Yang; Hou, Ming-Feng

2014-12-01

To examine correlations between the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) by primary tumours and axillary lymph nodes, and clinical and biological tumour prognostic parameters, in patients with newly diagnosed breast cancer. Newly diagnosed breast cancer patients who had received a dual-phased FDG positron emission tomography/computed tomography scan for pretreatment staging were enrolled retrospectively. Maximal standardized uptake values at 1 h (SUV1), 2 h (SUV2), and retention indices (RI) of the tumours and ipsilateral axillary lymph nodes were measured. SUV and RI were compared with clinical and biological prognostic parameters. A total of 32 patients participated in the study. Tumour FDG uptake correlated with histological grade and tumour size. FDG uptake in axillary lymph nodes correlated positively with lymph node status, metastasis status and clinical stage. RI values for the tumour and lymph nodes were significantly positively correlated with human epidermal growth factor receptor-2 positivity. FDG uptake in tumours and lymph nodes showed correlations with some clinical and biological parameters, and may serve as a predictive marker of tumour biological behaviour in breast cancer. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Detection of benign hilar bile duct stenoses - A retrospective analysis in 250 patients with suspicion of Klatskin tumour.

Science.gov (United States)

Scheuermann, Uwe; Widyaningsih, Rizky; Hoppe-Lotichius, Maria; Heise, Michael; Otto, Gerd

2016-06-01

The aim of this study was to identify clinical, laboratory and radiological parameters to distinguish benign from malignant stenoses of the proximal bile duct. Between 1997 and 2011, 250 patients were referred to our clinic with hilar bile duct stenoses suspicious for Klatskin tumour. Medical histories, clinical data, pre-interventional laboratory tests, imaging findings, as well as therapeutic approach and patient outcome were compared to final histological results. All data were retrieved from our prospectively maintained database and analysed retrospectively. We found benign bile duct lesions in 34 patients (13.6%). Among the entire study population, uni- and multivariate analyses of 18 clinicopathological parameters revealed that patient age, serum alkaline phosphatase, tumour marker CA19-9 and presence of tumour mass in computed tomography were independent predictors for malignant biliary stenoses (p hilar biliary stenoses of 74.6%, 80.0% and 83.5%, respectively. Surgical resection could be avoided by preoperative work-up and surgical exploration in 10 out of 34 patients with benign lesions. Rates of major liver resections performed were 66.7% in the benign lesion group and 90.7% in the Klatskin tumour group. Despite improvements of preoperative diagnostics, it remains difficult to differentiate between benign and malignant hilar bile duct stenosis. Even explorative laparotomy was not able to safely exclude Klatskin tumour in all cases and therefore major liver resection was inevitable.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

MRI of primary meningeal tumours in children

International Nuclear Information System (INIS)

Yoon, H.K.; Na, D.G.; Byun, H.S.; Han, B.K.; Kim, S.S.; Kim, I.O.; Shin, H.J.

1999-01-01

Childhood meningeal tumours are uncommon and mostly meningiomas. We reviewed the histological and radiological findings in meningeal tumours in six children aged 12 years or less (four benign meningiomas, one malignant meningioma and one haemangiopericytoma). Compared to the adult counterpart, childhood meningiomas showed atypical features: cysts, haemorrhage, aggressiveness and unusual location. MRI features varied according to the site of the tumour, histology, haemorrhage, and presence of intra- or peritumoral cysts. Diagnosis of the extra-axial tumour was relatively easy in two patients with meningiomas, one malignant meningioma and one haemangiopericytoma. MRI findings strongly suggested an intra-axial tumour in two patients with benign meningiomas, because of severe adjacent edema. Awareness of the variable findings of childhood meningiomas and similar tumours may help in differentiation from brain tumours. (orig.)

Acetyltransferases and tumour suppression

International Nuclear Information System (INIS)

Phillips, A C; Vousden, Karen H

2000-01-01

The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers

Musculoskeletal desmoid tumours: Diagnostic imaging appearances

International Nuclear Information System (INIS)

Liu, Daniel; Perera, Warren; Schlicht, Stephen; Choong, Peter; Slavin, John; Pianta, Marcus

2015-01-01

This study aimed to discuss the role medical imaging has on diagnosis of musculoskeletal desmoid tumours and to describe their radiological appearances on various imaging modalities. Imaging of histologically proven cases of desmoid tumours at St. Vincent's Hospital Melbourne were obtained via picture archiving communication system (PACS) and then assessed by two musculoskeletal radiologists. Suitable imagings were obtained from PACS. All imaging chosen was de-identified. Desmoid tumours can occur in many areas of the body. Imaging plays an important role in the diagnosis of these tumours and magnetic resonance imaging has been the gold standard for imaging and is the most accurate in terms of assessing tumour margins and involvement of surrounding structure.

Pitfalls in colour photography of choroidal tumours

Science.gov (United States)

Schalenbourg, A; Zografos, L

2013-01-01

Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

Pitfalls in colour photography of choroidal tumours.

Science.gov (United States)

Schalenbourg, A; Zografos, L

2013-02-01

Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

Imaging oxygenation of human tumours

International Nuclear Information System (INIS)

Padhani, Anwar R.; Krohn, Kenneth A.; Lewis, Jason S.; Alber, Markus

2007-01-01

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. 18 F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy. (orig.)

Granular cell tumour of the neurohypophysis: a rare sellar tumour with specific radiological and operative features.

LENUS (Irish Health Repository)

Aquilina, K

2012-02-03

Symptomatic granular cell tumours of the neurohypophysis are rare sellar lesions. Preoperative prediction of the diagnosis on the basis of radiological appearance is useful as these tumours carry specific surgical difficulties. This is possible when the tumour arises from the pituitary stalk, rostral to a normal pituitary gland. This has not been emphasized previously.

Anti-tumour action of 64Cu-bleomycin on Ehrlich ascites tumour cells in vivo

International Nuclear Information System (INIS)

Maki, Hirotoshi; Kawai, Kenichi; Akaboshi, Mitsuhiko

1979-01-01

The anti-tumor action of the complex of Bleomycin (BLM) with high specific-radioactivity 64 Cu on Ehrlich ascites tumour (EAT) was studied in vivo. The 64 Cu-BLM was administered into intraperitoneal cavity of mice from 1 to 4 days after inoculation of EAT cells. The effect of 64 Cu-BLM to suppress the tumour growth as demonstrated by prolonging life span was observed. The amounts of 64 Cu-BLM (800 μCi-8 mg/Kg) were administered at 4, 8 and 16 times separately. Then, the shorter the time interval and the less the amounts of drugs at a time, the higher the suppressing effect for the tumour growth was. It was confirmed that anti-tumour action of 64 Cu-BLM was in all the cases higher than that of BLM alone. (author)

Synchronous and Metachronous Malignant Tumours expect the un-expected

International Nuclear Information System (INIS)

Mehdi, I.; Shah, A.H.; Moona, M.S.; Verma, K.; Abussa, A.; Elramih, R.; El-Hashmi, H.

2010-01-01

Objective: To evaluate occurrence of synchronous and metachronous malignant tumours, to find tumour types, age group, and relationship to treatment received. Methods: Previously diagnosed first primary tumour cases experiencing a synchronous or metachronous tumour, seen at AOI from February 2003 to August 2009 (78 months) were included. The cases were analyzed for morphology/histology of first primary tumour, age and gender of patient, treatment received for first tumour, time interval between the first and second primary tumour, morphology/histology of second tumour, and the treatment conferred for second tumour. Results: The second synchronous and metachronous tumours were 46/4025 (1.14%), in 18 males and 28 females (M:F 1:1.6). The age range was 16-75 years (median 43 years). The follow up time was 24-150 months. The time to second primary tumour was 2-132 months. The first primary tumours were breast, ovary, GIT and urinary bladder. The patients received surgery, radiotherapy, chemotherapy, and hormonal therapy alone or as multi-modality treatment for the first tumours. The frequent second tumours were breast, ovary and Gastro Intestinal tumours. Conclusion: It is imperative that patients with a primary malignant tumour should be thoroughly, closely, and regularly followed. Genetic counseling, risk estimation, cancer screening and hemo prevention must be emphasized. Every subsequent occurring tumour should be biopsied. The effect of first tumour on the second or vice versa are still not fully understood and need exploration. The second primary tumour is usually more aggressive, treatment resistant, and metastasizes early requiring a more aggressive treatment strategy. (author)

MHC class II molecules and tumour immunotherapy

International Nuclear Information System (INIS)

Oven, I.

2005-01-01

Background. Tumour immunotherapy attempts to use the specificity and capability of the immune system to kill malignant cells with a minimum damage to normal tissue. Increasing knowledge of the identity of tumour antigens should help us design more effective therapeutic vaccines. Increasing evidence has demonstrated that MHC class II molecules and CD4+ T cells play important roles in generating and maintaining antitumour immune responses in animal models. These data suggest that it may be necessary to involve both CD4+ and CD8+ T cells for more effective antitumour therapy. Novel strategies have been developed for enhancing T cell responses against cancer by prolonging antigen presentation of dendritic cells to T cells, by the inclusion of MHC class II-restricted tumour antigens and by genetically modifying tumour cells to present antigen to T lymphocytes directly. Conclusions. Vaccines against cancers aim to induce tumour-specific effector T cells that can reduce tumour mass and induce development of tumour-specific T cell memory, that can control tumour relapse. (author)

Imaging of solid kidney tumours in children

International Nuclear Information System (INIS)

Hugosson, C.; Nyman, R.; Jacobsson, B.; Jorulf, H.; Sackey, K.; McDonald, P.

1995-01-01

Eighteen children aged 6 months to 12 years with 20 solid renal tumours; 13 Wilms' tumours (WT), 2 clear cell sarcomas of the kidney, 1 malignant rhabdoid tumour of the kidney and 2 cases of bilateral nephroblastomatosis with Wilms' tumour underwent evaluation with US, CT and MR imaging. Contrast-enhanced CT and non-enhanced MR were equally accurate in determining the size and origin of the tumour but were unreliable in separation of stages I, II and III. US could only accurately assess the size of the tumours. MR characteristics varied somewhat between WTs and non-WTs but contrast-enhanced MR imaging might be useful for separation of WTs from nephroblastomatosis. (orig.)

Treatment Of Brain Tumours In Childhood

International Nuclear Information System (INIS)

Stancokova, T.

2007-01-01

Children tumours are the second most common oncologic diseases in childhood (20 %) with highest incidence of mortality in children oncology. Brain tumours form a heterogenous group of tumours with their classification,diagnostic criteria and therapeutic modalities. General principles of treatment involve neurosurgery, which is a prognostic factor, its radicality depends on localization. Radiotherapy has limitations in children until 3 years for possible late effects. Chemotherapy is effective in tumours with high growing rate. These days challenge is to improve therapeutic outcomes and minimalize toxicity of therapy. (author)

Prognostic impact of HIF-1{alpha} expression in patients with definitive radiotherapy for cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Dellas, K.; Bache, M.; Kappler, M.; Haensgen, G. [Halle-Wittenberg Univ., Halle (Germany). Dept. of Radiotherapy; Pigorsch, S.U. [Technische Univ. Muenchen (Germany). Dept. of Radiotherapy and Radiation Oncology; Taubert, H.; Holzhausen, H.J. [Halle-Wittenberg Univ., Halle (Germany). Inst. of Pathology; Holzapfel, D.; Zorn, E. [Halle-Wittenberg Univ., Halle (Germany). Dept. of Radiotherapy; Halle-Wittenberg Univ., Halle (Germany). Inst. of Pathology

2008-03-15

Purpose: To investigate the relationship between the hypoxia-inducible factor-(HIF-)1{alpha} expression in tumor tissue, tumor oxygenation and hemoglobin levels in patients with advanced cervical cancers prior to radiotherapy and the effect on clinical outcome. Patients and Methods: The investigation included 44 patients who underwent definitive radiotherapy for advanced cervical cancers between May 1995 and March 1999. Tumor biopsies were taken prior to treatment, and HIF-1{alpha} expression was determined by immunohistochemistry. In the same tumor area, tumor tissue oxygenation (pO{sub 2}) was measured using the Eppendorf device. Results: The 5-year cancer-specific survival of all patients was 60%. Twelve of 44 tumor specimens were HIF-1{alpha}-negative with a significantly better 5-year survival (92 {+-} 8%) versus 32 patients who were HIF-1{alpha}-positive (45 {+-} 10%; p < 0.02). There was no correlation between HIF-1{alpha} expression and tumor oxygenation (p = 0.57 both for pO{sub 2} median and hypoxic fraction < 5 mmHg vs. HIF-1{alpha} expression). However, patients with hemoglobin levels < 11 g/dl showed elevated HIF-1{alpha} expression compared to patients with hemoglobin levels > 12.5 g/dl (p = 0.04). Furthermore, HIF-1{alpha} correlated with vascular endothelial growth factor expression (p = 0.002). In a multivariate Cox regression model, HIF-1{alpha} expression (relative risk [RR] = 7.5; p = 0.05) revealed an increased risk of tumor-related death. Conclusion: The study indicates, that endogenous tumor markers such as HIF-1{alpha} may serve as prognostic markers of clinical outcome concerning cervical cancer after primary radiotherapy. (orig.)

MRI appearances of borderline ovarian tumours

Energy Technology Data Exchange (ETDEWEB)

Bent, C.L. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)], E-mail: clare.bent@bartsandthelondon.nhs.uk; Sahdev, A.; Rockall, A.G. [Department of Diagnostic Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Singh, N. [Department of Pathology, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom); Sohaib, S.A. [Department of Radiology, Royal Marsden Hospital, London (United Kingdom); Reznek, R.H. [Cancer Imaging, St Bartholomew' s Hospital, West Smithfield, London (United Kingdom)

2009-04-15

This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm{sup 3}) and mucinous (6358.2 cm{sup 3}) subtypes (p = 0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.

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.

Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

International Nuclear Information System (INIS)

Yan, Bing; Stantic, Marina; Zobalova, Renata; Bezawork-Geleta, Ayenachew; Stapelberg, Michael; Stursa, Jan; Prokopova, Katerina; Dong, Lanfeng; Neuzil, Jiri

2015-01-01

Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2 high tumours derived from breast TICs by inducing apoptosis in tumour cells. These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells. The online version of this article (doi:10.1186/s12885-015-1394-7) contains supplementary material, which is available to authorized users

Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

International Nuclear Information System (INIS)

Christian, Nicolas; Bol, Anne; Bast, Marc de; Labar, Daniel; Lee, John; Mahy, Pierre; Gregoire, Vincent

2007-01-01

The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [ 18 F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [ 18 F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). C3H mice were injected i.v. with an average of 12.95 MBq of [ 18 F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Ornidazole decreased the urinary excretion and increased the liver uptake of [ 18 F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation. (orig.)

CNS embryonal tumours: WHO 2016 and beyond.

Science.gov (United States)

Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

2018-02-01

Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers.

LENUS (Irish Health Repository)

Jansen, Michael

2010-07-01

Over the past 10 years, there has been an increasing use of molecular markers in the assessment and management of adult malignant gliomas. Some molecular signatures are used diagnostically to help pathologists classify tumours, whereas others are used to estimate prognosis for patients. Most crucial, however, are those markers that are used to predict response to certain therapies, thereby directing clinicians to a particular treatment while avoiding other potentially deleterious therapies. Recently, large-scale genome-wide surveys have been used to identify new biomarkers that have been rapidly developed as diagnostic and prognostic tools. Given these developments, the pace of discovery of new molecular assays will quicken to facilitate personalised medicine in the setting of malignant glioma.

Primary bone tumours in infants

Energy Technology Data Exchange (ETDEWEB)

Kozlowski, K.; Beluffi, G.; Cohen, D.H.; Padovani, J.; Tamaela, L.; Azouz, M.; Bale, P.; Martin, H.C.; Nayanar, V.V.; Arico, M.

1985-09-01

Ten cases of primary bone tumours in infants (1 osteosarcoma, 3 Ewing's sarcoma, 1 chondroblastoma and 5 angiomastosis) are reported. All cases of angiomatosis showed characteristic radiographic findings. In all the other tumours the X-ray appearances were different from those usually seen in older children and adolescents. In the auhtors' opinion the precise diagnosis of malignant bone tumours in infancy is very difficult as no characteristic X-ray features are present in this age period.

Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

Energy Technology Data Exchange (ETDEWEB)

Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

2005-03-03

Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

In situ protein expression in tumour spheres: development of an immunostaining protocol for confocal microscopy

International Nuclear Information System (INIS)

Weiswald, Louis-Bastien; Guinebretière, Jean-Marc; Richon, Sophie; Bellet, Dominique; Saubaméa, Bruno; Dangles-Marie, Virginie

2010-01-01

Multicellular tumour sphere models have been shown to closely mimic phenotype characteristics of in vivo solid tumours, or to allow in vitro propagation of cancer stem cells (CSCs). CSCs are usually characterized by the expression of specific membrane markers using flow cytometry (FC) after enzymatic dissociation. Consequently, the spatial location of positive cells within spheres is not documented. Confocal microscopy is the best technique for the imaging of thick biological specimens after multi-labelling but suffers from poor antibody penetration. Thus, we describe here a new protocol for in situ confocal imaging of protein expression in intact spheroids. Protein expression in whole spheroids (150 μm in diameter) from two human colon cancer cell lines, HT29 and CT320X6, has been investigated with confocal immunostaining, then compared with profiles obtained through paraffin immunohistochemistry (pIHC) and FC. Target antigens, relevant for colon cancer and with different expression patterns, have been studied. We first demonstrate that our procedure overcomes the well-known problem of antibody penetration in compact structures by performing immunostaining of EpCAM, a membrane protein expressed by all cells within our spheroids. EpCAM expression is detected in all cells, even the deepest ones. Likewise, antibody access is confirmed with CK20 and CD44 immunostaining. Confocal imaging shows that 100% of cells express β-catenin, mainly present in the plasma membrane with also cytoplasmic and nuclear staining, in agreement with FC and pIHC data. pIHC and confocal imaging show similar CA 19-9 cytoplasmic and membranar expression profile in a cell subpopulation. CA 19-9 + cell count confirms confocal imaging as a highly sensitive method (75%, 62% and 51%, for FC, confocal imaging and pIHC, respectively). Finally, confocal imaging reveals that the weak expression of CD133, a putative colon CSC marker, is restricted to the luminal cell surface of colorectal cancer acini

Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

Science.gov (United States)

Dizdar, Omer; Barista, Ibrahim; Kalyoncu, Umut; Karadag, Omer; Hascelik, Gulsen; Cila, Aysenur; Pinar, Asli; Celik, Ismail; Kars, Ayse; Tekuzman, Gulten

2007-03-01

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated. Copyright (c) 2006 Wiley-Liss, Inc.

Preoperative estimation of the pathological breast tumour size by physical examination, mammography and ultrasound: a prospective study on 105 invasive tumours

International Nuclear Information System (INIS)

Bosch, Anne M.; Kessels, Alfons G.H.; Beets, Geerard L.; Rupa, Jan D.; Koster, Dick; Engelshoven, Jos M.A. van; Meyenfeldt, Maarten F. von

2003-01-01

Objective: The clinical breast tumour size can be assessed preoperatively by physical examination, mammography and ultrasound. At present it is not clear which modality correlates best with the histological invasive breast tumour size. This prospective study aims to determine the most accurate clinical method (physical examination, mammography or ultrasound) to predict the histological invasive tumour size preoperatively. Methods and patients: Between October 1999 and August 2000, 96 women with 105 invasive malignant breast tumours were included in this study. All patients underwent excision and the tumour size was measured on histology. Tumour size was measured by all three modalities in 73 cases. Results were evaluated by calculating correlation coefficients. The examination modalities presenting the best estimation of the pathological tumour size were used in a stepwise linear regression analysis to construct a formula predicting the pathological tumour size from the result of the various diagnostic modalities. Results: The correlation coefficient between ultrasound and pathological size (r=0.68) was significantly better than the correlations between physical examination and pathological size (r=0.42) and mammographic and pathological size (r=0.44). Physical examination overestimates and ultrasound underestimates breast tumour classification. The most accurate prediction formula was: Pathological tumour size (mm) equals sonographic tumour size (mm)+3 mm. Conclusion: When comparing physical examination, mammography and ultrasound for the prediction of the pathological size of a malignant breast tumour, ultrasound is the best predictor. The ensuing regression formula determines pathological size as tumour size by ultrasound+3 mm. However, with the wide 95% confidence interval of ±11 mm, it remains difficult to predict the exact pathological size for an individual invasive breast tumour. A small deviation in millimetres of the tumour size could lead to a change in

Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting

Directory of Open Access Journals (Sweden)

Sander A. A. Kooijmans

2016-03-01

Full Text Available Background: Extracellular vesicles (EVs are attractive candidate drug delivery systems due to their ability to functionally transport biological cargo to recipient cells. However, the apparent lack of target cell specificity of exogenously administered EVs limits their therapeutic applicability. In this study, we propose a novel method to equip EVs with targeting properties, in order to improve their interaction with tumour cells. Methods: EV producing cells were transfected with vectors encoding for anti-epidermal growth factor receptor (EGFR nanobodies, which served as targeting ligands for tumour cells, fused to glycosylphosphatidylinositol (GPI anchor signal peptides derived from decay-accelerating factor (DAF. EVs were isolated using ultrafiltration/size-exclusion liquid chromatography and characterized using western blotting, Nanoparticle Tracking Analysis, and electron microscopy. EV–tumour cell interactions were analyzed under static conditions using flow cytometry and under flow conditions using a live-cell fluorescence microscopy-coupled perfusion system. Results: V analysis showed that GPI-linked nanobodies were successfully displayed on EV surfaces and were highly enriched in EVs compared with parent cells. Display of GPI-linked nanobodies on EVs did not alter general EV characteristics (i.e. morphology, size distribution and protein marker expression, but greatly improved EV binding to tumour cells dependent on EGFR density under static conditions. Moreover, nanobody-displaying EVs showed a significantly improved cell association to EGFR-expressing tumour cells under flow conditions. Conclusions: We show that nanobodies can be anchored on the surface of EVs via GPI, which alters their cell targeting behaviour. Furthermore, this study highlights GPI-anchoring as a new tool in the EV toolbox, which may be applied for EV display of a variety of proteins, such as antibodies, reporter proteins and signaling molecules.

Proline-hydroxylated hypoxia-inducible factor 1α (HIF-1α upregulation in human tumours.

Directory of Open Access Journals (Sweden)

Cameron E Snell

Full Text Available The stabilisation of HIF-α is central to the transcriptional response of animals to hypoxia, regulating the expression of hundreds of genes including those involved in angiogenesis, metabolism and metastasis. HIF-α is degraded under normoxic conditions by proline hydroxylation, which allows for recognition and ubiquitination by the von-Hippel-Lindau (VHL E3 ligase complex. The aim of our study was to investigate the posttranslational modification of HIF-1α in tumours, to assess whether there are additional mechanisms besides reduced hydroxylation leading to stability. To this end we optimised antibodies against the proline-hydroxylated forms of HIF-1α for use in formalin fixed paraffin embedded (FFPE immunohistochemistry to assess effects in tumour cells in vivo. We found that HIF-1α proline-hydroxylated at both VHL binding sites (Pro402 and Pro564, was present in hypoxic regions of a wide range of tumours, tumour xenografts and in moderately hypoxic cells in vitro. Staining for hydroxylated HIF-1α can identify a subset of breast cancer patients with poorer prognosis and may be a better marker than total HIF-1α levels. The expression of unhydroxylated HIF-1α positively correlates with VHL in breast cancer suggesting that VHL may be rate-limiting for HIF degradation. Our conclusions are that the degradation of proline-hydroxylated HIF-1α may be rate-limited in tumours and therefore provides new insights into mechanisms of HIF upregulation. Persistence of proline-hydroxylated HIF-1α in perinecrotic areas suggests there is adequate oxygen to support prolyl hydroxylase domain (PHD activity and proline-hydroxylated HIF-1α may be the predominant form associated with the poorer prognosis that higher levels of HIF-1α confer.

Acute effect of oral, intraperitoneal, and intravenous 1 alpha-hydroxycholecalciferol on markers of bone metabolism

DEFF Research Database (Denmark)

Joffe, P; Ladefoged, S D; Cintin, C

1994-01-01

,25-(OH)2D3 was measured. DESIGN: Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3. MAIN RESULTS...

Alpha-synuclein levels in blood plasma decline with healthy aging.

Directory of Open Access Journals (Sweden)

Niklas K U Koehler

Full Text Available There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years compared to younger (avg. 27.6 years individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001, possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.

Apoptotic intrinsic pathway proteins predict survival in canine cutaneous mast cell tumours.

Science.gov (United States)

Barra, C N; Macedo, B M; Cadrobbi, K G; Pulz, L H; Huete, G C; Kleeb, S R; Xavier, J G; Catão-Dias, J L; Nishiya, A T; Fukumasu, H; Strefezzi, R F

2018-03-01

Mast cell tumours (MCTs) are the most frequent canine round cell neoplasms and show variable biological behaviours with high metastatic and recurrence rates. The disease is treated surgically and wide margins are recommended. Adjuvant chemotherapy and radiotherapy used in this disease cause DNA damage in neoplastic cells, which is aimed to induce apoptotic cell death. Resisting cell death is a hallmark of cancer, which contributes to the development and progression of tumours. The aim of this study was to investigate the expression of the proteins involved in the apoptotic intrinsic pathway and to evaluate their potential use as prognostic markers for canine cutaneous MCTs. Immunohistochemistry for BAX, BCL2, APAF1, Caspase-9, and Caspase-3 was performed in 50 canine cases of MCTs. High BAX expression was associated with higher mortality rate and shorter survival. BCL2 and APAF1 expressions offered additional prognostic information to the histopathological grading systems. The present results indicate that variations in the expression of apoptotic proteins are related to malignancy of cutaneous MCTs in dogs. © 2017 John Wiley & Sons Ltd.

Tumours of the fetal body: a review

Energy Technology Data Exchange (ETDEWEB)

Avni, Fred E.; Massez, Anne; Cassart, Marie [University Clinics of Brussels - Erasme Hospital, Department of Medical Imaging, Brussels (Belgium)

2009-11-15

Tumours of the fetal body are rare, but lesions have been reported in all spaces, especially in the mediastinum, the pericardial space, the adrenals, the kidney, and the liver. Lymphangioma and teratoma are the commonest histological types encountered, followed by cardiac rhabdomyoma. Adrenal neuroblastoma is the commonest malignant tumour. Imaging plays an essential role in the detection and work-up of these tumours. In addition to assisting clinicians it also helps in counselling parents. Most tumours are detected by antenatal US, but fetal MRI is increasingly used as it brings significant additional information in terms of tumour extent, composition and complications. (orig.)

Impact of F DOPA-PET on therapeutic decision in endocrine tumours: digestive tumours, medullary thyroid cancer or pheochromocytoma

International Nuclear Information System (INIS)

Montravers, F.; Grahek, D.; Kerrou, K.; Gutman, F.; Beco, V. de; Nataf, V.; Balard, M.; Talbot, J.N.

2006-01-01

FDOPA-PET has been proposed for a decade in oncology, in particular in endocrine tumours. To the best of our knowledge, only one impact rate has been reported: 31% in 17 patients with digestive carcinoid tumours. We did a questionnaire survey to evaluate this impact reported by the referring clinician in 87 patients who had FDOPA PET due to digestive carcinoid tumour or another type of digestive endocrine tumour or a medullary thyroid cancer or a pheochromocytoma. The response rate to the survey was 87%. The overall impact of FDOPA PET on patient's management was 36%. Its value was greater for digestive carcinoid tumour and for medullary thyroid cancer; the number of patients with pheochromocytoma is still limited. In the other digestive endocrine tumours, a change in patient management was less frequent and FDOPA PET should be performed when the other examinations are inconclusive. (author)

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