Inhibitory effect of magnolol on tumour metastasis in mice.

Science.gov (United States)

Ikeda, Koji; Sakai, Yoshimichi; Nagase, Hisamitsu

2003-09-01

It has previously been reported that magnolol, a phenolic compound isolated from Magnolia obovata, inhibited tumour cell invasion in vitro. The purpose of this study was to investigate the antimetastatic effect of magnolol on tumour metastasis in vivo with experimental and spontaneous metastasis models and to clarify the mechanism. The antimetastatic effects of magnolol were evaluated by an experimental liver and spleen metastasis model using L5178Y-ML25 lymphoma, or an experimental and spontaneous lung metastasis model using B16-BL6 melanoma. Intraperitoneal (i.p.) administration of 2 or 10 mg/kg of magnolol significantly suppressed liver and spleen metastasis or lung metastasis. As for the spontaneous lung metastasis model using B16-BL6 melanoma, multiple i.p. administrations of 10 mg/kg of magnolol after and before tumour inoculation significantly suppressed lung metastasis and primary tumour growth. In addition, magnolol significantly inhibited B16-BL6 cell invasion of the reconstituted basement membrane (Matrigel, MG) without affecting cell growth. These data from the in vivo experiments suggest that magnolol possesses strong antimetastatic ability and that it may be a lead compound for drug development. The antimetastatic action of magnolol is considered to be due to its ability to inhibit tumour cell invasion. Copyright 2003 John Wiley & Sons, Ltd.

The potential role of cyclooxygenase-2 inhibitors in the treatment of experimentally-induced mammary tumour: does celecoxib enhance the anti-tumour activity of doxorubicin?

Science.gov (United States)

Awara, Wageh M; El-Sisi, Alaa E; El-Sayad, Magda E; Goda, Ahmed E

2004-11-01

The potential anti-tumour activity of non-steroidal anti-inflammatory drugs (NSAIDS) has been previously discussed. This study was undertaken to assess the possible anti-tumour activity of the cyclooxygenase-2 (COX-2) inhibitor; celecoxib in an animal model of mammary carcinoma; the solid Ehrlich carcinoma (SEC). The possibility that celecoxib may modulate the anti-tumour activity of doxorubicin on the SEC was also studied. Some of the possible mechanisms underlying such modulation were investigated. The anti-tumour activity of celecoxib (25 mg kg(-1)), diclofenac (12.5 mg kg(-1)) and doxorubicin (2 mg kg(-1)) either alone or in combination were investigated on SEC in vivo through the assessment of tumour growth delay (TGD) and tumour volume (TV), changes in tumour DNA content and nitric oxide (NO) levels, immunohistochemical staining of the tumour suppressor gene product; p53 histopathological examination and determination of apoptotic index of SEC. In addition, the influence of these drugs on the DNA fragmentation pattern of Ehrlich carcinoma cells (ECC) was studied. It was found that both celecoxib and diclofenac lack the anti-tumour activity on SEC. In addition there was a significant increase in doxorubicin anti-tumour activity when administered in combination with celecoxib. Moreover, it was found that both celecoxib and diclofenac have the potential to inhibit the function of P-glycoprotein (P-gp) in ECC using rhodamine uptake and efflux assays. Therefore, the current study suggested the chemosensitizing potential of celecoxib in the SEC animal model of mammary tumour, which could be explained in part on the basis of inhibition of P-gp function, with possible enhancement of doxorubicin anti-tumour activity.

Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

Science.gov (United States)

Ali, Selman A; Ahmad, Murrium; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Choolun, Esther; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

2004-09-09

OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

Science.gov (United States)

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

2012-01-01

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

The inhibitory effect of Binens bipinnata L . extract on U14 tumour in ...

African Journals Online (AJOL)

Its inhibition rate was 70.44% at a concentration of 80ìg/L. Solid tumour inhibition rates in the high- and low-dose groups and cisplatin group were 49.13%, 2.26% and 75.72% respectively; life prolongation rates in each ascites tumour group were 63.63%, 34.86% and 87.34% respectively. The Bidens bipinnata L. extract ...

Inhibition of platelet-tumour cell interaction with ibrutinib reduces ...

African Journals Online (AJOL)

BTK) inhibitor, ibrutinib, in tumour cell-platelet crosstalk in lung cancer. Methods: Human lung cancer cells A549 were treated with ibrutinib or DMSO. mRNA expression was assessed using reverse transcription-quantitative polymerase chain ...

The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

Science.gov (United States)

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

2015-02-27

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

Tumour-derived GM-CSF promotes granulocyte immunosuppression in mesothelioma patients.

Science.gov (United States)

Khanna, Swati; Graef, Suzanne; Mussai, Francis; Thomas, Anish; Wali, Neha; Yenidunya, Bahar Guliz; Yuan, Constance M; Morrow, Betsy; Zhang, Jingli; Korangy, Firouzeh; Greten, Tim F; Steinberg, Seth M; Stetler-Stevenson, Maryalice; Middleton, Gary; De Santo, Carmela; Hassan, Raffit

2018-03-30

The cross talk between tumour cells, myeloid cells, and T cells play a critical role in tumour pathogenesis and response to immunotherapies. Although the aetiology of mesothelioma is well understood the impact of mesothelioma on the surrounding immune microenvironment is less well studied. In this study the effect of the mesothelioma microenvironment on circulating and infiltrating granulocytes and T cells is investigated. Tumour and peripheral blood from mesothelioma patients were evaluated for presence of granulocytes, which were then tested for their T cell suppression. Co-cultures of granulocytes, mesothelioma cells, T cells were used to identify the mechanism of T cell inhibition. Analysis of tumours showed that the mesothelioma microenvironment is enriched in infiltrating granulocytes, which inhibit T cell proliferation and activation. Characterisation of the blood at diagnosis identified similar, circulating, immunosuppressive CD11b+CD15+HLADR- granulocytes at increased frequency compared to healthy controls. Culture of healthy-donor granulocytes with human mesothelioma cells showed that GM-CSF upregulates NOX2 expression and the release of Reactive Oxygen Species (ROS) from granulocytes, resulting in T cell suppression. Immunohistochemistry and transcriptomic analysis revealed that a majority of mesothelioma tumours express GM-CSF and that higher GM-CSF expression correlated with clinical progression. Blockade of GM-CSF with neutralising antibody, or ROS inhibition, restored T cell proliferation suggesting that targeting of GM-CSF could be of therapeutic benefit in these patients. Our study presents the mechanism behind the cross-talk between mesothelioma and the immune micro-environment and indicates that targeting GM-CSF could be a novel treatment strategy to augment immunotherapy. Copyright ©2018, American Association for Cancer Research.

Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction

International Nuclear Information System (INIS)

Rouschop, Kasper M.A.; Dubois, Ludwig; Schaaf, Marco B.E.; Beucken, Twan van den; Lieuwes, Natasja; Keulers, Tom G.H.; Savelkouls, Kim G.M.; Bussink, Johan; Kogel, Albert J. van der; Koritzinsky, Marianne; Wouters, Bradly G.

2011-01-01

Background and purpose: Tumour hypoxia is an important limiting factor in the successful treatment of cancer. Adaptation to hypoxia includes inhibition of mTOR, causing scavenging of eukaryotic initiation factor 4E (eIF4E), the rate-limiting factor for cap-dependent translation. The aim of this study was to determine the effect of preventing mTOR-dependent translation inhibition on hypoxic cell survival and tumour sensitivity towards irradiation. Material and methods: The effect of eIF4E-overexpression on cell proliferation, hypoxia-tolerance, and radiation sensitivity was assessed using isogenic, inducible U373 and HCT116 cells. Results: We found that eIF4E-overexpression significantly enhanced proliferation of cells under normal conditions, but not during hypoxia, caused by increased cell death during hypoxia. Furthermore, eIF4E-overexpression stimulated overall rates of tumour growth, but resulted in selective loss of hypoxic cells in established tumours and increased levels of necrosis. This markedly increased overall tumour sensitivity to irradiation. Conclusions: Our results demonstrate that hypoxia induced inhibition of translational control through regulation of eIF4E is an important mediator of hypoxia tolerance and radioresistance of tumours. These data also demonstrate that deregulation of metabolic pathways such as mTOR can influence the proliferation and survival of tumour cells experiencing metabolic stress in opposite ways of nutrient replete cells.

Tetraspanin 7 (TSPAN7) expression is upregulated in multiple myeloma patients and inhibits myeloma tumour development in vivo

Energy Technology Data Exchange (ETDEWEB)

Cheong, Chee Man [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Chow, Annie W.S. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); Fitter, Stephen [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Hewett, Duncan R. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Martin, Sally K. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); School of Medicine, University of Adelaide, Adelaide 5005, SA (Australia); Williams, Sharon A. [Myeloma Research Laboratory, School of Medical Sciences, University of Adelaide, and South Australian Health and Medical Research Institute (SAHMRI), Adelaide 5000, SA (Australia); To, L. Bik [Department of Haematology, SA Pathology, Adelaide 5000, SA (Australia); and others

2015-03-01

Background: Increased expression of the tetraspanin TSPAN7 has been observed in a number of cancers; however, it is unclear how TSPAN7 plays a role in cancer progression. Methods: We investigated the expression of TSPAN7 in the haematological malignancy multiple myleoma (MM) and assessed the consequences of TSPAN7 expression in the adhesion, migration and growth of MM plasma cells (PC) in vitro and in bone marrow (BM) homing and tumour growth in vivo. Finally, we characterised the association of TSPAN7 with cell surface partner molecules in vitro. Results: TSPAN7 was found to be highly expressed at the RNA and protein level in CD138{sup +} MM PC from approximately 50% of MM patients. TSPAN7 overexpression in the murine myeloma cell line 5TGM1 significantly reduced tumour burden in 5TGM1/KaLwRij mice 4 weeks after intravenous adminstration of 5TGM1 cells. While TSPAN7 overexpression did not affect cell proliferation in vitro, TSPAN7 increased 5TGM1 cell adhesion to BM stromal cells and transendothelial migration. In addition, TSPAN7 was found to associate with the molecular chaperone calnexin on the cell surface. Conclusion: These results suggest that elevated TSPAN7 may be associated with better outcomes for up to 50% of MM patients. - Highlights: • TSPAN7 expression is upregulated in newly-diagnosed patients with active multiple myeloma. • Overexpression of TSPAN7 inhibits myeloma tumour development in vivo. • TSPAN7 interacts with calnexin at the plasma membrane in a myeloma cell line.

Triptonide inhibits the pathological functions of gastric cancer-associated fibroblasts.

Science.gov (United States)

Wang, Zhenfei; Ma, Daguang; Wang, Changshan; Zhu, Zhe; Yang, Yongyan; Zeng, Fenfang; Yuan, Jianlong; Liu, Xia; Gao, Yue; Chen, Yongxia; Jia, Yongfeng

2017-12-01

Direct attacks on tumour cells with chemotherapeutic drugs have the drawbacks of accelerating tumour metastasis and inducing tumour stem cell phenotypes. Inhibition of tumour-associated fibroblasts, which provide nourishment and support to tumour cells, is a novel and promising anti-tumour strategy. However, effective drugs against tumour-associated fibroblasts are currently lacking. In the present study, we explored the possibility of inhibiting the pathological functions of tumour-associated fibroblasts with triptonide. Paired gastric normal fibroblasts (GNFs) and gastric cancer-associated fibroblasts (GCAFs) were obtained from resected tissues. GCAFs showed higher capacities to induce colony formation, migration, and invasion of gastric cancer cells than GNFs. Triptonide treatment strongly inhibited the colony formation-, migration-, and invasion-promoting capacities of GCAFs. The expression of microRNA-301a was higher and that of microRNA-149 was lower in GCAFs than in GNFs. Triptonide treatment significantly down-regulated microRNA-301a expression and up-regulated microRNA-149 expression in GCAFs. Re-establishment of microRNA expression balance increased the production and secretion of tissue inhibitor of metalloproteinase 2, a tumour suppressive factor, and suppressed the production and secretion of IL-6, an oncogenic factor, in GCAFs. Moreover, triptonide treatment abolished the ability of GCAFs to induce epithelial-mesenchymal transition in gastric cancer cells. These results indicate that triptonide inhibits the malignancy-promoting capacity of GCAFs by correcting abnormalities in microRNA expression. Thus, triptonide is a promisingly therapeutic agent for gastric cancer treatment, and traditional herbs may be a valuable source for developing new drugs that can regulate the tumour microenvironment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prolactin, TNF alpha and nitric oxide expression in nitroso-N-methylurea-induced-mammary tumours

Directory of Open Access Journals (Sweden)

Vegh Irene

2007-11-01

Full Text Available Abstract Background The N-Nitrosomethylurea breast cancer model induced in rats is used for the study of carcinogenesis in mammary cancer, prostate, pancreas, etc. This model is very similar to human neoplastic disease. Methods The present experimental study was designed to assess whether metoclopramide administration has any effect on development of MNU-induced tumours, and evaluate the treatment of goserelin acetate on PRL, TNF alpha and NO expression. NMU was administered to female Wistar rats on 2 occasions (5 mg/100 g body w/rat. PRL and TNF alpha were performed by immune-assay. Nitric Oxide by semi automated-assay and ploidy analyses by flow cytometry. Results The administration of metoclopramide made the induction time shorter and increased the incidence and average of tumours per rat. Tumours development was inhibited by a goserelin chronic administration. The ploidy of adenocarcinoma was polyploid-aneuploid type (average S = 60%. It was higher basal PRL plasma levels in rats with NMU induced tumours than in basal controls without tumour (p Conclusion The increase of blood PRL levels in NMU-induced rats may be an indicator of a poor prognosis of mammary cancer evolution. The metoclopramide administration accelerates tumour growth. However goserelin administration achieves regression in tumour development associated to inhibition PRL, TNF alpha and NO expression.

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

Science.gov (United States)

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

2016-04-30

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

Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression

Energy Technology Data Exchange (ETDEWEB)

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

2014-01-27

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

Tumour eradication using synchronous thermal ablation and Hsp90 chemotherapy with protein engineered triblock biopolymer-geldanamycin conjugates.

Science.gov (United States)

Chen, Yizhe; Youn, Pilju; Pysher, Theodore J; Scaife, Courtney L; Furgeson, Darin Y

2014-12-01

Hepatocellular carcinoma (HCC) suffers high tumour recurrence rate after thermal ablation. Heat shock protein 90 (Hsp90) induced post-ablation is critical for tumour survival and progression. A combination therapy of thermal ablation and polymer conjugated Hsp90 chemotherapy was designed and evaluated for complete tumour eradication of HCC. A thermo-responsive, elastin-like polypeptide (ELP)-based tri-block biopolymer was developed and conjugated with a potent Hsp90 inhibitor, geldanamycin (GA). The anti-cancer efficacy of conjugates was evaluated in HCC cell cultures with and without hyperthermia (43 °C). The conjugates were also administered twice weekly in a murine HCC model as a single treatment or in combination with single electrocautery as the ablation method. ELP-GA conjugates displayed enhanced cytotoxicity in vitro and effective heat shock inhibition under hyperthermia. The conjugates alone significantly slowed the tumour growth without systemic toxicity. Four doses of thermo-responsive ELP-GA conjugates with concomitant simple electrocautery accomplished significant Hsp90 inhibition and sustained tumour suppression. Hsp90 inhibition plays a key role in preventing the recurrence of HCC, and the combination of ablation with targeted therapy holds great potential to improve prognosis and survival of HCC patients.

Modification of postradiation developments in Guerin's tumour by means of hypothermia

International Nuclear Information System (INIS)

Karakulov, R.K.; Balmukhanov, S.B.

1979-01-01

Albino noninbred mice weighing 100-110 g were used to study the growth rate of the entire mass of Guerin's tumour and changes is cytokinetic parameters during irradiation and under the conditions of hypothermia. The animals were cooled according to the Giaja method down to the rectal temperature of 20-21 deg C, the tumour was exposed to single irradiation, locally in a dose of 2500 R. It was shown that irradiation against the background of hypothermia enhanced inhibition of the tumour growth that points to a greater tumour damage. The radiomodifying effect of the low temperature manifests itself cytokinetically as a decrease in the proliferative pool and prolongation of intermitotic time, mainly at the expense of the DNA synthesis phase

Increasing the radiosensitivity of tumours in an hypoxic environment using inhibitors of the pentose phosphate pathway

International Nuclear Information System (INIS)

Sahasrabudhe, M.B.; Bhonsle, S.R.; Krishnamurti, K.; Tilak, B.D.

1977-01-01

Rapidly growing tumours contain few blood vessels in the tumour mass. Cells in such tumours obtain nutrients and oxygen from the periphery by diffusion, resulting in a diminishing oxygen and nutrient gradient from the periphery to centre of the tumour mass. In normal tissues, oxygen is utilized via a tricarboxylic acid (TCA) cycle; in tumour cells oxygen is utilized via a hexose monophosphate (HMP) pathway and through the TCA cycle at a 30% reduced level. Interference with the HMP pathway selectively inhibits the utilization of oxygen by tumour cells, thus increasing the availability of oxygen to hypoxic cells situated deeper in the tumour mass. This effect has been exploited for increasing the radiosensitivity of tumour cells situated in an hypoxic environment. The influence of sixteen potential antimetabolites on the HMP pathway has been studied. Of these, six compounds, namely, (1) 2-carboxy 5-hydroxymethyl thiophene, (2) the sodium salt of 2:5 dicarbethoxy 3:4 dihydroxy thiophene, (3) the dihydrazide of 2:5 dicarboxy thiophene, (4) the dihydrazide of 3:4 dimethoxy 2:5 dicarboxy thiophene, (5) trithiocyanuric acid, and (6) cyanuric trithioglycollic acid showed an inhibiting effect on the HMP pathway without any influence on the TCA cycle. Influence of administration of compounds (1), (2) and (4) prior to radiation on the growth of transplanted fibrosarcomas in mice has been studied and is reported here. These three compounds showed marked potentiation of radiosensitivity of tumours. (author)

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

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

Science.gov (United States)

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

2009-10-06

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

Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways

Directory of Open Access Journals (Sweden)

Ferrari Stefano

2009-12-01

Full Text Available Abstract Background Osteosarcoma (OS is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory. Results We investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006 in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice. Conclusion In conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both in vitro and in vivo, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.

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

Science.gov (United States)

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

2015-08-15

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

Anti-metastatic effects of viral and non-viral mediated Nk4 delivery to tumours.

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Buhles, Alexandra; Collins, Sara A; van Pijkeren, Jan P; Rajendran, Simon; Miles, Michelle; O'Sullivan, Gerald C; O'Hanlon, Deirdre M; Tangney, Mark

2009-03-09

The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metastasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate

The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

International Nuclear Information System (INIS)

Jiménez-Medina, Eva; Berruguilla, Enrique; Romero, Irene; Algarra, Ignacio; Collado, Antonia; Garrido, Federico; Garcia-Lora, Angel

2008-01-01

Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G 0 /G 1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells

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

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

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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.

Platelets Inhibit Migration of Canine Osteosarcoma Cells.

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Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

2017-01-01

The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis

Directory of Open Access Journals (Sweden)

Garrido Federico

2008-03-01

Full Text Available Abstract Background Protein-bound polysaccharide (PSK is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. Methods The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. Results PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. Conclusion These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

Photodynamic effect and mechanism study of selenium-enriched phycocyanin from Spirulina platensis against liver tumours.

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Liu, Zijian; Fu, Xiang; Huang, Wei; Li, Chunxia; Wang, Xinyan; Huang, Bei

2018-03-01

Selenium-containing phycocyanin (Se-PC) has been proved to have many biological effects, including anti-inflammatory and antioxidant. In this study, we investigated the photodynamic therapy (PDT) effects of Se-PC against liver tumour in vitro and in vivo experiment. Our results demonstrated that the half lethal dose of Se-PC PDT on HepG2 cells was 100μg/ml PC containing 20% selenium. Se-PC location migration from lysosomes to mitochondria was time dependent. In in vivo experiments, the tumour inhibition rate was 75.4% in the Se-PC PDT group, compared to 52.6% in PC PDT group. Histological observations revealed that the tumour cells outside the tissue showed cellular necrosis, and those inside the tissue exhibited apoptotic nuclei and digested vacuoles in the cytoplasm after Se-PC PDT treatment. Antioxidant enzyme analysis indicated that GSH-Px activity was linked to the selenium content of Se-PC, and SOD activity was affected by PC PDT. Therefore, Se-PC PDT could induce cell death through free radical production of PDT in tumours and enhance the activity of antioxidant enzymes with selenium in vivo. The mechanism of Se-PC PDT against liver tumour involves hematocyte damage and mitochondria-mediated apoptosis accompanied with autophagy inhibition during early stage of tumour development, which displayed new prospect and offered relatively safe way for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model.

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Tzong-Tyng Hung

Full Text Available BACKGROUND: The bisphosphonate, zoledronic acid (ZOL, can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM, to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. METHODS: The model involves intracardiac injection for arterial dissemination of the RM1(BM cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. FINDINGS: Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. CONCLUSIONS: ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a

Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway.

Science.gov (United States)

Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

2015-11-01

Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1(+) CD11b(+) monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1(+) CD11b(+) MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1(+) CD11b(+) MDSCs by pAbM treatment had less ability to convert the CD4(+) CD25(-) cells into CD4(+) CD25(+) phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1(+ ) CD11b(+) monocytes, nether CD8(+) T cells nor CD4(+) T cells. In addition to, pAbM did not inhibit tumour growth in TLR2(-/-) mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1(+) CD11b(+) MDSCs. © 2015 John Wiley & Sons Ltd.

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

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

2011-10-15

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

In vivo covalent cross-linking of photon-converted rare-earth nanostructures for tumour localization and theranostics

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Ai, Xiangzhao; Ho, Chris Jun Hui; Aw, Junxin; Attia, Amalina Binte Ebrahim; Mu, Jing; Wang, Yu; Wang, Xiaoyong; Wang, Yong; Liu, Xiaogang; Chen, Huabing; Gao, Mingyuan; Chen, Xiaoyuan; Yeow, Edwin K. L.; Liu, Gang; Olivo, Malini; Xing, Bengang

2016-01-01

The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

The Janus face of death receptor signalling during tumour immunoediting.

Directory of Open Access Journals (Sweden)

Eimear O' Reilly

2016-10-01

Full Text Available Cancer immune-surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognised by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumour cells by expressing death ligand cytokines of the tumour necrosis factor ligand family. However, some tumour cells can escape immune elimination and progress. Acquisition of resistance to the death-ligand induced apoptotic pathway can be obtained through cleavage of effector-cell expressed death-ligands into a poorly active form, mutations or silencing of the death receptors or overexpression of decoy receptors and pro-survival proteins. Although the immune system is highly effective in the elimination of malignantly transformed cells, abnormal/ dysfunctional death-ligand signalling curbs its cytotoxicity. Moreover, death receptors can also transmit pro-survival and pro-migratory signals. Consequently, dysfunctional death receptor-mediated apoptosis/necroptosis signalling does not only give a passive resistance against cell death, but actively drives tumour cell motility, invasion and contributes to consequent metastasis. This dual contribution of the death ligand-death receptor signalling in both the early, elimination phase and then in the late, escape phase of the tumour immunoediting process is discussed in this review. Death receptor agonists still hold potential for cancer therapy since they can execute the tumour-eliminating immune-effector function even in the absence of activation of the immune system against the tumour. The opportunities and challenges of developing death receptor agonists into effective cancer therapeutics are also discussed.

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

Targeted radionuclide therapy for neuroendocrine tumours: principles and application.

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Druce, Maralyn R; Lewington, Val; Grossman, Ashley B

2010-01-01

Neuroendocrine tumours comprise a group of neoplasms with variable clinical behaviour. Their growth and spread is often very slow and initially asymptomatic, and thus they are often metastatic at the time of diagnosis and incurable by surgery. An exciting therapeutic strategy for cytoreduction, both for stabilisation of tumour growth and inhibition of hormone production, is the use of targeted radionuclide therapy. Evidence from large-scale, randomised, placebo-controlled trials is very difficult to obtain in these rare diseases, but current data appear promising. It is timely to review the principles underlying the use of these therapies, together with the clinical outcomes to date and potential directions for future research. Copyright 2009 S. Karger AG, Basel.

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

Characterization of tumour virus proteins, 2

International Nuclear Information System (INIS)

Higuchi, T.

1977-01-01

The structural protein in murine tumour virus P30 has been measured by radioiummunoassay. The titer of each serum was determined by using as antigen the purified Rauscher viral protein labeled with 125 iodine. Standard competition curve was constructed in order to determine the equivalent of protein to inhibit the precipitation reaction under limited antibody concentration. Competition by purified Kirsten virus suspension normal rat kidney cells, transformed-productive and transformed non-productive cells were measured in homologous and heterologous systems [pt

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.

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.

Cancer and Exercise: Warburg Hypothesis, Tumour Metabolism and High-Intensity Anaerobic Exercise.

Science.gov (United States)

Hofmann, Peter

2018-01-31

There is ample evidence that regular moderate to vigorous aerobic physical activity is related to a reduced risk for various forms of cancer to suggest a causal relationship. Exercise is associated with positive changes in fitness, body composition, and physical functioning as well as in patient-reported outcomes such as fatigue, sleep quality, or health-related quality of life. Emerging evidence indicates that exercise may also be directly linked to the control of tumour biology through direct effects on tumour-intrinsic factors. Beside a multitude of effects of exercise on the human body, one underscored effect of exercise training is to target the specific metabolism of tumour cells, namely the Warburg-type highly glycolytic metabolism. Tumour metabolism as well as the tumour⁻host interaction may be selectively influenced by single bouts as well as regularly applied exercise, dependent on exercise intensity, duration, frequency and mode. High-intensity anaerobic exercise was shown to inhibit glycolysis and some studies in animals showed that effects on tumour growth might be stronger compared with moderate-intensity aerobic exercise. High-intensity exercise was shown to be safe in patients; however, it has to be applied carefully with an individualized prescription of exercise.

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.

Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

DEFF Research Database (Denmark)

Lasko, Loren M; Jakob, Clarissa G; Edalji, Rohinton P

2017-01-01

-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft...... to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have...... also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent...

Tumour-induced osteomalacia.

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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.

Adnexal Tumours Of Skin

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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%.

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

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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

Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model.

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Araceli Tobío

Full Text Available Yessotoxins (YTXs are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant. In addition, YTX exhibited strong cytotoxicity against the human B-chronic lymphocytic leukaemia cell line MEC1 and the murine melanoma cell line B16F10. To analyse the potential role of YTX as an anti-cancer drug in vivo we used the well-established B16F10 melanoma preclinical mouse model. Our results demonstrate that a few local application of YTX around established tumours dramatically diminished tumour growth in the absence of any significant toxicity as determined by the absence of weight loss and haematological alterations. Our data support that YTX may have a minor role as an anti-allergic drug, but reveals an important potential for its use as an anti-cancer drug.

The contribution of tumour-derived exosomes to the hallmarks of cancer.

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Meehan, Katie; Vella, Laura J

2016-01-01

Exosomes are small, biologically active extracellular vesicles and over the last decade, both stromal and tumour-derived exosomes (TDE) have been implicated in cancer onset, progression and metastases. Cancer is a complex disease that is underpinned by several "cancer hallmarks", originally described by Hanahan and Weinberg in 2000 and then revised in 2011. The hallmarks of cancer comprise six biological capabilities, along with two emerging hallmarks and two enabling characteristics that facilitate tumour growth and metastatic dissemination. Ample evidence supports a clear role for TDE in four of the original biological hallmarks (sustaining proliferative signalling, resisting cell death, inducing angiogenesis and activating invasion and metastases). A less-defined role exists for TDE in evading growth suppressors, and currently, there is no evidence to suggest a role for TDE in enabling replicative immortality. TDE are intimately involved in the newly defined hallmarks of cancer and enabling characteristics, most evidently in immune inhibition and tumour-promoting inflammation, which ultimately enable escape from immune destruction and tumour progression. Herein, we discuss the role of TDE in the context of the hallmarks and enabling characteristics of cancer as defined by Hanahan and Weinberg.

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

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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.

Nicotinamide and other benzamide analogs as agents for overcoming hypoxic cell radiation resistance in tumours

International Nuclear Information System (INIS)

Horsman, M.

1996-01-01

Oxygen deficient hypoxic cells, which are resistant to sparsely ionising radiation, have now been identified in most animal and some human solid tumours and will influence the response of those tumours to radiation treatment. This hypoxia can be either chronic, arising from an oxygen diffusion limitation, or acute, resulting from transient stoppages in microregional blood flow. Extensive experimental studies, especially in the last decade, have shown that nicotinamide and structurally related analogs can effectively sensitize murine tumours to both single and fractionated radiation treatments and that they do so in preference to the effects seen in mouse normal tissues. The earliest studies suggested that this enhancement of radiation damage was the result of an inhibition of the repair mechanisms. However, recent studies in mouse tumours have shown that these drugs prevent transient cessations in blood flow, thus inhibiting the development of acute hypoxia. This novel discovery led to the suggestion that the potential role of these agents as radiosensitizers would be when combined with treatments that overcame chronic hypoxia. The combined nicotinamide with hyperthermia proved that the enhancement of radiation damage by both agents together was greater than that seen with each agent alone. Similar results were later seen for nicotinamide combined with a perfluorochemical emulsion, carbogen breathing, and pentoxifylline, and in all these studies the effects in tumours were always greater than those seen in appropriate normal tissues. Of all the analogs, it is nicotinamide itself which has been the most extensively studied as a radiosensitizer in vivo and the one that shows the greatest effect in animal tumours. It is also an agent that has been well established clinically, with daily doses of up to 6 g, associated with a low incidence of side effects. This human dose is equivalent to 100-200 mg/kg in mice and such doses will maximally sensitize murine tumours to

Cannabidiol inhibits angiogenesis by multiple mechanisms.

Science.gov (United States)

Solinas, M; Massi, P; Cantelmo, A R; Cattaneo, M G; Cammarota, R; Bartolini, D; Cinquina, V; Valenti, M; Vicentini, L M; Noonan, D M; Albini, A; Parolaro, D

2012-11-01

Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis. Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice. CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down-modulation of several angiogenesis-related molecules. This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

The PDGF-BB-SOX7 axis-modulated IL-33 in pericytes and stromal cells promotes metastasis through tumour-associated macrophages

DEFF Research Database (Denmark)

Yang, Yunlong; Andersson, Patrik; Hosaka, Kayoko

2016-01-01

Signalling molecules and pathways that mediate crosstalk between various tumour cellular compartments in cancer metastasis remain largely unknown. We report a mechanism of the interaction between perivascular cells and tumour-associated macrophages (TAMs) in promoting metastasis through the IL-33......-ST2-dependent pathway in xenograft mouse models of cancer. IL-33 is the highest upregulated gene through activation of SOX7 transcription factor in PDGF-BB-stimulated pericytes. Gain- and loss-of-function experiments validate that IL-33 promotes metastasis through recruitment of TAMs. Pharmacological...... inhibition of the IL-33-ST2 signalling by a soluble ST2 significantly inhibits TAMs and metastasis. Genetic deletion of host IL-33 in mice also blocks PDGF-BB-induced TAM recruitment and metastasis. These findings shed light on the role of tumour stroma in promoting metastasis and have therapeutic...

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.)

Mutant p53 drives cancer by subverting multiple tumour suppression pathways

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Sue eHaupt

2016-01-01

Full Text Available The tumour suppressor p53 normally acts as a brake to halt damaged cells from perpetrating their genetic errors into future generations. If p53 is disrupted by mutation, it may not only lose these corrective powers, but counter-productively acquire new capacities that drive cancer. A newly emerging manner in which mutant p53 executes its cancer promoting functions is by harnessing key proteins (including many transcription factors, which normally partner with its wild type, tumour-inhibiting counterpart. In association with the subverted activities of these protein partners, mutant p53 is empowered to act across multiple fundamental cellular pathways (regulating cell division and metabolism and corrupt them to become cancer promoting.

The evaluation of in vitro effect of daunorubicin and tamoxifen in ehrlich ascites tumour (EAT) cells

International Nuclear Information System (INIS)

Topcul, M.; Topcul, F.; Oezalpan, A.

2001-01-01

In the most countries, breast cancer is still the most important cancer among women. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of Ehrlich Ascites Tumour (EAT) cells, initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is estrogen receptor positive was used. An anthracycline-derived antibiotic, Daunorubicin (DNR, Cerubidine) is one of the clinically used anticancer drugs. DNR has been used alone or in combination with other cytotoxic agents against a variety of animal and human tumours. In vitro cell culture studies show that DNR enters the cell nuclei, inhibits nucleic acid synthesis, and arrest cell division. Tamoxifen (TAM, Nolvadex) is a semi-synthetical estrogen antagonist, used in the management of pre and post menopausal breast cancer. This drug bind to intracellular estrogen receptors, and prevents endogenous estrogens from binding to their own receptors. It is known that Ehrlich Ascites Tumour is experimental breast cancer model in animal. The cells used in the study are hyper diploid line of EAT cells initially provided to us from Institute of Pathology, Koln University. In the present study, an hyper diploid line which is Estrogen Receptor (+) was used. Estrogen Receptor levels were studied by the methods of Lippman and Huff and Raynaud et al. with minor modifications. Estrogen Receptor activity as demonstrated by dextran-coated charcoal technique is closely correlated with the clinical ability of Tamoxifen to inhibit tumour growth

Notch3 signalling promotes tumour growth in colorectal cancer.

Science.gov (United States)

Serafin, Valentina; Persano, Luca; Moserle, Lidia; Esposito, Giovanni; Ghisi, Margherita; Curtarello, Matteo; Bonanno, Laura; Masiero, Massimo; Ribatti, Domenico; Stürzl, Michael; Naschberger, Elisabeth; Croner, Roland S; Jubb, Adrian M; Harris, Adrian L; Koeppen, Hartmut; Amadori, Alberto; Indraccolo, Stefano

2011-08-01

Increased Notch1 activity has been observed in intestinal tumours, partially accomplished by β-catenin-mediated up-regulation of the Notch ligand Jagged-1. Whether further mechanisms of Notch activation exist and other Notch receptors might be involved is unclear. Microarray data indicated that Notch3 transcript levels are significantly up-regulated in primary and metastatic CRC samples compared to normal mucosa. Moreover, Notch3 protein was expressed at strong/moderate levels by 19.7% of 158 CRC samples analysed, and at weak levels by 51.2% of the samples. Intrigued by these findings, we sought to investigate whether Notch3 modulates oncogenic features of CRC cells. By exploiting xenografts of CRC cells with different tumourigenic properties in mice, we found that the aggressive phenotype was associated with altered expression of components of the Notch pathway, including Notch3, Delta-like 4 (DLL4), and Jagged-1 ligands. Stimulation with immobilized recombinant DLL4 or transduction with DLL4-expressing vectors dramatically increased Notch3 expression in CRC cells, associated with accelerated tumour growth. Forced expression of an active form of Notch3 mirrored the effects of DLL4 stimulation and increased tumour formation. Conversely, attenuation of Notch3 levels by shRNA resulted in perturbation of the cell cycle followed by reduction in cell proliferation, clonogenic capacity, and inhibition of tumour growth. Altogether, these findings indicate that Notch3 can modulate the tumourigenic properties of CRC cells and contributes to sustained Notch activity in DLL4-expressing tumours. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Extracts of Crinum latifolium inhibit the cell viability of mouse lymphoma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro.

Science.gov (United States)

Nguyen, Hoang-Yen T; Vo, Bach-Hue T; Nguyen, Lac-Thuy H; Bernad, Jose; Alaeddine, Mohamad; Coste, Agnes; Reybier, Karine; Pipy, Bernard; Nepveu, Françoise

2013-08-26

Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear. To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages. The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages). The total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not

The Askin tumour. Neuroactodermic tumour of the thoracic wall

International Nuclear Information System (INIS)

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

Novel somatic and germline mutations in intracranial germ cell tumours.

Science.gov (United States)

Wang, Linghua; Yamaguchi, Shigeru; Burstein, Matthew D; Terashima, Keita; Chang, Kyle; Ng, Ho-Keung; Nakamura, Hideo; He, Zongxiao; Doddapaneni, Harshavardhan; Lewis, Lora; Wang, Mark; Suzuki, Tomonari; Nishikawa, Ryo; Natsume, Atsushi; Terasaka, Shunsuke; Dauser, Robert; Whitehead, William; Adekunle, Adesina; Sun, Jiayi; Qiao, Yi; Marth, Gábor; Muzny, Donna M; Gibbs, Richard A; Leal, Suzanne M; Wheeler, David A; Lau, Ching C

2014-07-10

Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway.

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

Science.gov (United States)

Annibali, Daniela; Whitfield, Jonathan R; Favuzzi, Emilia; Jauset, Toni; Serrano, Erika; Cuartas, Isabel; Redondo-Campos, Sara; Folch, Gerard; Gonzàlez-Juncà, Alba; Sodir, Nicole M; Massó-Vallés, Daniel; Beaulieu, Marie-Eve; Swigart, Lamorna B; Mc Gee, Margaret M; Somma, Maria Patrizia; Nasi, Sergio; Seoane, Joan; Evan, Gerard I; Soucek, Laura

2014-08-18

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.

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

Energy Technology Data Exchange (ETDEWEB)

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.)

Radiological diagnosis of liver tumours

International Nuclear Information System (INIS)

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.)

Significance of manipulating tumour hypoxia and radiation dose rate in terms of local tumour response and lung metastatic potential, referring to the response of quiescent cell populations

Science.gov (United States)

Masunaga, S; Matsumoto, Y; Kashino, G; Hirayama, R; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kinashi, Y; Maruhashi, A; Ono, K

2010-01-01

The purpose of this study was to evaluate the influence of manipulating intratumour oxygenation status and radiation dose rate on local tumour response and lung metastases following radiotherapy, referring to the response of quiescent cell populations within irradiated tumours. B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation at high dose rate (HDR) or reduced dose rate (RDR) following treatment with the acute hypoxia-releasing agent nicotinamide or local hyperthermia at mild temperatures (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the quiescent (Q) and total (proliferating + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Following HDR irradiation, nicotinamide and MTH enhanced the sensitivity of the total and Q-cell populations, respectively. The decrease in sensitivity at RDR irradiation compared with HDR irradiation was slightly inhibited by MTH, especially in Q cells. Without γ-ray irradiation, nicotinamide treatment tended to reduce the number of lung metastases. With γ-rays, in combination with nicotinamide or MTH, especially the former, HDR irradiation decreased the number of metastases more remarkably than RDR irradiation. Manipulating both tumour hypoxia and irradiation dose rate have the potential to influence lung metastasis. The combination with the acute hypoxia-releasing agent nicotinamide may be more promising in HDR than RDR irradiation in terms of reducing the number of lung metastases. PMID:20739345

Differential radioprotection of bone marrow and tumour cells by zinc aspartate

International Nuclear Information System (INIS)

Floersheim, G.L.; Chiodetti, N.; Bieri, A.

1988-01-01

The radioprotector zinc aspartate did not inhibit the radiotherapeutic effect of γ rays on human tumours grown as xenografts in immunosuppressed mice, while aminothiol radioprotectors afforded a slight inhibition. On the other hand, zinc aspartate significantly reduced the fall in the haematocrit and numbers of thrombocytes, erythrocytes and leucocytes caused by irradiation, indicating a sparing effect on bone marrow precursors of peripheral blood cells. This differential protection of neoplastic and normal cells may be of considerable benefit in clinical cancer radiotherapy, provided that zinc aspartate is better tolerated and has a more favourable therapeutic index in humans than aminothiol radioprotectors. (author)

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)

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

Growth of extrapulmonary tumours after inhalation of small doses of plutonium oxide by rats

International Nuclear Information System (INIS)

Nolibe, D.; Masse, R.; L'Hullier, I.; Metivier, H.; Lafuma, J.

1983-01-01

After inhalation of plutonium oxide ( 239 PuO 2 ) involving initial lung burdens ranging from 74 to 103 Bq, male rats of the Wistar strain are kept in conditions allowing maximum survival; tumour incidences for the target organ (lung) and for the rest of the organs are calculated separately after the death of the animals. In the outbred Wistar rat the incidence of lung tumours is 18.5% for an initial lung burden of 74 Bq. The mean survival time of animals having such tumours is 973 days after inhalation. For an initial burden of 103 Bq syngenetic Wistar AG rats show a lower frequency of lung tumours (6.1%), but also a much reduced mean survival time, namely 757 days. Compared with the frequencies observed in the corresponding control groups, the frequency of non-pulmonary tumours is twice as high (12%) in consanguineous rats and six times as high (25.9%) in conventional rats. A supralinear dose-effect relationship at very low doses seems improbable in view of the dose delivered ( -3 Gy in the most exposed organs, such as the liver) and, in particular, because there is no correlation between the dose delivered to the organs and the location of the tumours. The exposed animals show, on the one hand, no specificity of organs for the surplus extrapulmonary tumours observed, and on the other, an inhibition by about 45% in the natural cytotoxic activity (natural killers) measured one year after inhalation. These observations suggest the hypothesis that an anti-tumour control mechanism is affected, perhaps as a result of the irradiation experienced during the circulation of blood cells in the lung capillaries. The failure of this system would in that case allow the expression of neoplastic characters as ageing progresses. A non-specific BCG immunotherapy does not restore this anti-tumour control system. (author)

Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours

Czech Academy of Sciences Publication Activity Database

Reiniš, Milan; Šímová, Jana; Indrová, Marie; Bieblová, Jana; Přibylová, Hana; Moravcová, Simona; Jandlová, Táňa; Bubeník, Jan

2007-01-01

Roč. 30, č. 4 (2007), s. 1011-1017 ISSN 1019-6439 R&D Projects: GA MZd NR7807 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * MHC class I-deficient tumours * immunologic crossreaction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.295, year: 2007

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

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.

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,.

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)

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying-Nan P.; LaMarche, Matthew J.; Chan, Ho Man; Fekkes, Peter; Garcia-Fortanet, Jorge; Acker, Michael G.; Antonakos, Brandon; Chen, Christine Hiu-Tung; Chen, Zhouliang; Cooke, Vesselina G.; Dobson, Jason R.; Deng, Zhan; Fei, Feng; Firestone, Brant; Fodor, Michelle; Fridrich, Cary; Gao, Hui; Grunenfelder, Denise; Hao, Huai-Xiang; Jacob, Jaison; Ho, Samuel; Hsiao, Kathy; Kang, Zhao B.; Karki, Rajesh; Kato, Mitsunori; Larrow, Jay; La Bonte, Laura R.; Lenoir, Francois; Liu, Gang; Liu, Shumei; Majumdar, Dyuti; Meyer, Matthew J.; Palermo, Mark; Perez, Lawrence; Pu, Minying; Price, Edmund; Quinn, Christopher; Shakya, Subarna; Shultz, Michael D.; Slisz, Joanna; Venkatesan, Kavitha; Wang, Ping; Warmuth, Markus; Williams, Sarah; Yang, Guizhi; Yuan, Jing; Zhang, Ji-Hu; Zhu, Ping; Ramsey, Timothy; Keen, Nicholas J.; Sellers, William R.; Stams, Travis; Fortin , Pascal D. (Novartis)

2016-06-29

The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase1. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma1, 2, 3, 4, 5. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS–ERK signalling pathway2, 3. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways6, 7. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy8, 9. Here we report the discovery of a highly potent (IC50 = 0.071 μM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.

[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

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.

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

Directory of Open Access Journals (Sweden)

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.

Anti-Tumour Promoting Activity and Antioxidant Properties of Girinimbine Isolated from the Stem Bark of Murraya koenigii S.

Directory of Open Access Journals (Sweden)

Yih Yih Kok

2012-04-01

Full Text Available Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of Epstein-Barr virus (EA-EBV in Raji cells that was induced by the tumour promoter, phorbol 12-myristate 13-acetate. The concentration of this compound that gave an inhibition rate at fifty percent was 6.0 µg/mL and was not cytotoxic to the cells. Immunoblotting analysis of the expression of EA-EBV showed that girinimbine was able to suppress restricted early antigen (EA-R. However, diffused early antigen (EA-D was partially suppressed when used at 32.0 µg/mL. Girinimbine exhibited a very strong antioxidant activity as compared to a-tocopherol and was able to inhibit superoxide generation in the 12-O-tetradecanoylphorbol-13-acetate (TPA-induced differentiated premyelocytic HL-60 cells more than 95%, when treated with the compound at 5.3 and 26.3 µg/mL, respectively. However girinimbine failed to scavenge the stable diphenyl picryl hydrazyl (DPPH-free radical.

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

Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas.

Science.gov (United States)

Yoon, C; Lee, H-J; Park, D J; Lee, Y-J; Tap, W D; Eisinger-Mathason, T S K; Hart, C P; Choy, E; Simon, M C; Yoon, S S

2015-06-30

Human sarcomas with a poor response to vascular endothelial growth factor-A (VEGF-A) inhibition and radiation therapy (RT) have upregulation of hypoxia-inducible factor 1α (HIF-1α) and HIF-1α target genes. This study examines the addition of the hypoxia-activated chemotherapy TH-302 to VEGF-A inhibition and RT (a.k.a. trimodality therapy). Trimodality therapy was examined in two xenograft models and in vitro in tumour endothelial cells and sarcoma cell lines. In both mouse models, VEGF-A inhibition and radiation showed greater efficacy than either therapy alone in slowing sarcoma growth. When TH-302 was added, this trimodality therapy completely blocked tumour growth with tumours remaining dormant for over 3 months after cessation of therapy. Trimodality therapy caused 2.6- to 6.2-fold more endothelial cell-specific apoptosis than bimodality therapies, and microvessel density and HIF-1α activity were reduced to 11-13% and 13-20% of control, respectively. When trimodality therapy was examined in vitro, increases in DNA damage and apoptosis were much more pronounced in tumour endothelial cells compared with that in sarcoma cells, especially under hypoxia. The combination of TH-302, VEGF-A inhibition, and RT is highly effective in preclinical models of sarcoma and is associated with increased DNA damage and apoptosis in endothelial cells and decreased HIF-1α activity.

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.

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

Changes in auxin activity in tumourous and normal tobacco calluses treated with morphactin IT 3233

Directory of Open Access Journals (Sweden)

Z. Chirek

2015-01-01

Full Text Available The addition of morphactin IT 3233 in 1-40 mg/dm3 concentrations to the medium inhibited the growth in vitro of normal and tumourous tobacco calluses. The auxin activity (estimated by the Avena coleoptile straight growth test of the acid ether extracts from these tissues increased. The activity of zone I (Rf 0.2-0.4, 0.5, solvent system: butanol:water:ammonia 10:10:1 in normal tissues increased more intensively than that of zone II (Rf 0.6-0.8, 0.9. In tumourous tissues, however, these changes were smaller and they concerned merely zone I of auxin activity (Rf 0.0-0.5. It seems that the mechanism of morphactin activity in both kinds of tissue is different. It may be supposed that the excessive accumulation of auxins induces growth inhibition of tissues. A previously found increase in the activity of IAA-oxidase influenced by morphactin might be considered as an adaptation to a higher level of IAA.

Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

Science.gov (United States)

Wang, Hai-Jun; Liu, Yu; Zhou, Bao-Jun; Zhang, Zhan-Xue; Li, Ai-Ying; An, Ran; Yue, Bin; Fan, Li-Qiao; Li, Yong

2018-05-01

Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO 3 vehicle alone or CP dissolved in NaHCO 3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

Teratoid Wilms tumour with chemotherapy resistance

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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.

Potential role of TRIM3 as a novel tumour suppressor in colorectal cancer (CRC) development.

Science.gov (United States)

Piao, Mei-Yu; Cao, Hai-Long; He, Na-Na; Xu, Meng-Que; Dong, Wen-Xiao; Wang, Wei-Qiang; Wang, Bang-Mao; Zhou, Bing

2016-01-01

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the United States. Recent cancer genome-sequencing efforts and complementary functional studies have led to the identification of a collection of candidate 'driver' genes involved in CRC tumorigenesis. Tripartite motif (TRIM3) is recently identified as a tumour suppressor in glioblastoma but this tumour-suppressive function has not been investigated in CRC. In this study, we investigated the potential role of TRIM3 as a tumour suppressor in CRC development by manipulating the expression of TRIM3 in two authentic CRC cell lines, HCT116 and DLD1, followed by various functional assays, including cell proliferation, colony formation, scratch wound healing, soft agar, and invasion assays. Xenograft experiment was performed to examine in vivo tumour-suppressive properties of TRIM3. Small-interfering RNA (siRNA) mediated knockdown of TRIM3 conferred growth advantage in CRC cells. In contrast, overexpression of TRIM3 affected cell survival, cell migration, anchorage independent growth and invasive potential in CRC cells. In addition, TRIM3 was found to be down-regulated in human colon cancer tissues compared with matched normal colon tissues. Overexpression of TRIM3 significantly inhibited tumour growth in vivo using xenograft mouse models. Mechanistic investigation revealed that TRIM3 can regulate p53 protein level through its stabilisation. TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. Therefore, this protein may represent a novel therapeutic target for prevention or intervention of CRC.

Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

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Alex Henke

2016-08-01

Full Text Available Background: Prostate cancer-associated fibroblasts (CAF can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; Methods: We isolated CAF from prostate cancer patients of Gleason Score 6–10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90 inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; Results: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2 levels in CAF; Conclusions: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment.

A novel technique of serial biopsy in mouse brain tumour models.

Directory of Open Access Journals (Sweden)

Sasha Rogers

Full Text Available Biopsy is often used to investigate brain tumour-specific abnormalities so that treatments can be appropriately tailored. Dacomitinib (PF-00299804 is a tyrosine kinase inhibitor (TKI, which is predicted to only be effective in cancers where the targets of this drug (EGFR, ERBB2, ERBB4 are abnormally active. Here we describe a method by which serial biopsy can be used to validate response to dacomitinib treatment in vivo using a mouse glioblastoma model. In order to determine the feasibility of conducting serial brain biopsies in mouse models with minimal morbidity, and if successful, investigate whether this can facilitate evaluation of chemotherapeutic response, an orthotopic model of glioblastoma was used. Immunodeficient mice received cortical implants of the human glioblastoma cell line, U87MG, modified to express the constitutively-active EGFR mutant, EGFRvIII, GFP and luciferase. Tumour growth was monitored using bioluminescence imaging. Upon attainment of a moderate tumour size, free-hand biopsy was performed on a subgroup of animals. Animal monitoring using a neurological severity score (NSS showed that all mice survived the procedure with minimal perioperative morbidity and recovered to similar levels as controls over a period of five days. The technique was used to evaluate dacomitinib-mediated inhibition of EGFRvIII two hours after drug administration. We show that serial tissue samples can be obtained, that the samples retain histological features of the tumour, and are of sufficient quality to determine response to treatment. This approach represents a significant advance in murine brain surgery that may be applicable to other brain tumour models. Importantly, the methodology has the potential to accelerate the preclinical in vivo drug screening process.

The in vitro effect of gefitinib ('Iressa' alone and in combination with cytotoxic chemotherapy on human solid tumours

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Knight Louise A

2004-11-01

Full Text Available Abstract Background Activation of the epidermal growth factor receptor (EGFR triggers downstream signaling pathways that regulate many cellular processes involved in tumour survival and growth. Gefitinib ('Iressa' is an orally active tyrosine kinase inhibitor (TKI targeted to the ATP-binding domain of EGFR (HER1; erbB1. Methods In this study we have used a standardised ATP-based tumour chemosensitivity assay (ATP-TCA to measure the activity of gefitinib alone or in combination with different cytotoxic drugs (cisplatin, gemcitabine, oxaliplatin and treosulfan against a variety of solid tumours (n = 86, including breast, colorectal, oesophageal and ovarian cancer, carcinoma of unknown primary site, cutaneous and uveal melanoma, non-small cell lung cancer (NSCLC and sarcoma. The IC50 and IC90 were calculated for each single agent or combination. To allow comparison between samples the IndexSUM was calculated based on the percentage tumour growth inhibition (TGI at each test drug concentration (TDC. Gefitinib was tested at concentrations ranging from 0.0625–2 microM (TDC = 0.446 microg/ml. This study represents the first use of a TKI in the assay. Results There was heterogeneity in the degree of TGI observed when tumours were tested against single agent gefitinib. 7% (6/86 of tumours exhibited considerable inhibition, but most showed a more modest response resulting in a low TGI. The median IC50 value for single agent gefitinib in all tumours tested was 3.98 microM. Interestingly, gefitinib had both positive and negative effects when used in combination with different cytotoxics. In 59% (45/76 of tumours tested, the addition of gefitinib appeared to potentiate the effect of the cytotoxic agent or combination (of these, 11% (5/45 had a >50% decrease in their IndexSUM. In 38% of tumours (29/76, the TGI was decreased when the combination of gefitinib + cytotoxic was used in comparison to the cytotoxic alone. In the remaining 3% (2/76 there was no

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

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.

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 ...

Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells

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Nardou Katya

2008-06-01

Full Text Available Abstract Background Histone deacetylase inhibitors (HDACi are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities. Results We show here that the HDACi Sodium Butyrate (NaB, suberoylanilide hydroxamic acid (SAHA and Trichostatin A (TSA strongly reduce NB cells viability. The anti-tumour activity of these HDACi involved the induction of cell cycle arrest in the G2/M phase, followed by the activation of the intrinsic apoptotic pathway, via the activation of the caspases cascade. Moreover, HDACi mediated the activation of the pro-apoptotic proteins Bid and BimEL and the inactivation of the anti-apoptotic proteins XIAP, Bcl-xL, RIP and survivin, that further enhanced the apoptotic signal. Interestingly, the activity of these apoptosis regulators was modulated by several different mechanisms, either by caspases dependent proteolytic cleavage or by degradation via the proteasome pathway. In addition, HDACi strongly impaired the hypoxia-induced secretion of VEGF by NB cells. Conclusion HDACi are therefore interesting new anti-tumour agents for targeting highly malignant tumours such as NB, as these agents display a strong toxicity toward aggressive NB cells and they may possibly reduce angiogenesis by decreasing VEGF production by NB cells.

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.)

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)

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

Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction

NARCIS (Netherlands)

Rouschop, K.M.; Dubois, L.; Schaaf, M.B.; Beucken, T. van den; Lieuwes, N.; Keulers, T.G.; Savelkouls, K.G.; Bussink, J.; Kogel, A.J. van der; Koritzinsky, M.; Wouters, B.G.

2011-01-01

BACKGROUND AND PURPOSE: Tumour hypoxia is an important limiting factor in the successful treatment of cancer. Adaptation to hypoxia includes inhibition of mTOR, causing scavenging of eukaryotic initiation factor 4E (eIF4E), the rate-limiting factor for cap-dependent translation. The aim of this

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

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.

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.

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.

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

RNA and protein synthesis of irradiated Ehrlich ascites tumour cells. Pt. 2

International Nuclear Information System (INIS)

Skog, S.; Tribukait, B.; Nygard, O.; Wenner-Gren-Center foer Vetenskaplig Forskning, Stockholm

1985-01-01

Poly(A)-containing RNA (m-RNA) was studied in in vivo growing Ehrlich ascites tumour cells following a roentgen irradiation dose of 5 Gy. m-RNA increased significantly during the first 12 hours after irradiation. Thus, the observed decrease in protein synthesis rate during this time seems not to be due to radiation induced changes at the transcriptional level. The protein synthesis rate of in vivo irradiated cells incubated in vitro in culture medium was unchanged. On the other hand, the protein synthesis rate of non-irradiated cells incubated in vitro in ascites fluid from irradiated animals was decreased. We concluded that factor(s) inhibiting protein synthesis or the lack of factor(s) promoting protein synthesis in the ascites fluid is(are) of significance for the reduced protein synthesis of tumour cells found in irradiated in vivo growing cells. (orig.)

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)

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.)

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.

Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.

Science.gov (United States)

García-Rivera, Dagmar; Delgado, René; Bougarne, Nadia; Haegeman, Guy; Berghe, Wim Vanden

2011-06-01

Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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.)

Depletion of Treg cells inhibits minimal residual disease after surgery of HPV16-associated tumours

Czech Academy of Sciences Publication Activity Database

Šímová, Jana; Bubeník, Jan; Bieblová, Jana; Rosalia, Rodney Alexander; Frič, Jan; Reiniš, Milan

2006-01-01

Roč. 29, č. 6 (2006), s. 1567-1571 ISSN 1019-6439 R&D Projects: GA ČR(CZ) GA301/04/0492 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Liga proti rakovině(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * residual tumour disease * Treg cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.556, year: 2006

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.

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

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)

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.

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)

A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours

NARCIS (Netherlands)

Paridaens, R; Uges, DRA; Barbet, N; Choi, L; Seeghers, M; van der Graaf, WTA; Groen, HJM; Dumez, H; Van Buuren, [No Value; Muskiet, F; Capdeville, R; van Oosterom, AT; de Vries, EGE

Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme

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)

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.

MiR-1254 inhibits proliferation, migration and invasion of human ...

African Journals Online (AJOL)

MiR-1254 inhibits proliferation, migration and invasion of human brain tumour cell lines. ... The transcripts were analysed by real-time polymerase chain reaction (RT-PCR) ... Over-expression of miR- 1254 also led to significant decrease in cell ...

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.

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.

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.

Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo

International Nuclear Information System (INIS)

Colquhoun, AJ; Mchugh, LA; Tulchinsky, E.; Kriajevska, M.; Mellon, JK

2007-01-01

External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p=0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p=0.04). Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial. (author)

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

The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.

Science.gov (United States)

Abdul-Sada, Hussein; Müller, Marietta; Mehta, Rajni; Toth, Rachel; Arthur, J Simon C; Whitehouse, Adrian; Macdonald, Andrew

2017-04-11

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response. Here we demonstrate that regulation of NF-kB activation involves a previously undocumented interaction between tAg and regulatory sub-unit 1 of protein phosphatase 4 (PP4R1). Formation of a complex with PP4R1 and PP4c is required to bridge MCPyV tAg to the NEMO adaptor protein, allowing deactivation of the NF-kB pathway. Mutations in MCPyV tAg that fail to interact with components of this complex, or siRNA depletion of PP4R1, prevents tAg-mediated inhibition of NF-kB and pro-inflammatory cytokine production. Comparison of tAg binding partners from other human polyomavirus demonstrates that interactions with NEMO and PP4R1 are unique to MCPyV. Collectively, these data identify PP4R1 as a novel target for virus subversion of the host anti-viral response.

Anti-tumour potential of a gallic acid-containing phenolic fraction from Oenothera biennis.

Science.gov (United States)

Pellegrina, Chiara Dalla; Padovani, Giorgia; Mainente, Federica; Zoccatelli, Gianni; Bissoli, Gaetano; Mosconi, Silvia; Veneri, Gianluca; Peruffo, Angelo; Andrighetto, Giancarlo; Rizzi, Corrado; Chignola, Roberto

2005-08-08

A phenolic fraction purified form defatted seeds of Oenothera biennis promoted selective apoptosis of human and mouse bone marrow-derived cell lines following first-order kinetics through a caspase-dependent pathway. In non-leukemia tumour cell lines, such as human colon carcinoma CaCo(2) cells and mouse fibrosarcoma WEHI164 cells, this fraction inhibited (3)H-thymidine incorporation but not cell death or cell cycle arrest. Human peripheral blood mononuclear cells showed low sensitivity to treatment. Single bolus injection of the phenolic fraction could delay the growth of established myeloma tumours in syngeneic animals. HPLC and mass spectrometry analysis revealed that the fraction contains gallic acid. However, the biological activity of the fraction differs from the activity of this phenol and hence it should be attributed to other co-purified molecules which remain still unidentified.

Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

Science.gov (United States)

Pang, Lisa Y; Gatenby, Emma L; Kamida, Ayako; Whitelaw, Bruce A; Hupp, Ted R; Argyle, David J

2014-01-01

Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation.

Directory of Open Access Journals (Sweden)

Lisa Y Pang

Full Text Available Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs, which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05, and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation.

Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

International Nuclear Information System (INIS)

Knight, Louise A; Kurbacher, Christian M; Glaysher, Sharon; Fernando, Augusta; Reichelt, Ralf; Dexel, Susanne; Reinhold, Uwe; Cree, Ian A

2009-01-01

Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

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)

Prodrugs designed to discriminate pathological (tumour) and physiological (normal tissue) hypoxia

International Nuclear Information System (INIS)

Wilson, W.R.; Patterson, A.V.

2003-01-01

There is now abundant evidence that hypoxic contributes to treatment failure in radiation therapy. As a target for therapeutic intervention, hypoxia is especially attractive because it is a common feature of most human tumours and therefore a potential 'pan target' across many tumour types. However, attempts to exploit hypoxia face the problem that oxygen concentrations in some normal tissues are also heterogeneous and that O 2 distributions in tumours and normal tissues overlap. Simply adjusting the K value (O 2 concentration for 50% inhibition of activation) does not provide a satisfactory solution. Bioreductive drugs like tirapazamine with high K values are activated significantly in several normal tissues, while nitro compounds and quinones with low K values spare the hypoxic tumour cells at 'intermediate' O 2 tensions (1-10 mM O 2 ) which are considered to be major contributors to tumour radioresistance. A potential strategy for overcoming this dilemma is to design prodrugs that are activated only at very low K values, but give relatively stable cytotoxic metabolites capable of diffusing to cells at higher O 2 concentrations. This approach redefines the therapeutic target as cells adjacent to zones of pathological hypoxia ( 2 ), providing discrimination from physiological hypoxia in normal tissues. Detecting bioreductive prodrugs capable of providing bystander killing of this kind is not straightforward. We have adapted a multicellular layer (MCL) co-culture model for quantifying bystander effects in GDEPT (Wilson et al., Cancer Res., 62: 1425-1432, 2002), and have used this to measure bystander effects of hypoxia-activated prodrugs. This model uses differences in metabolic activation of bioreductive drugs between A459 cell lines with low and high cytochrome P450 reductase activity, rather than O 2 gradients, to effect localised prodrug activation. It shows that TPZ and the nitroimidazole RSU-1069 have little or no bystander effect, but that dinitrobenzamide

Metformin treatment modulates the tumour-induced wasting effects in muscle protein metabolism minimising the cachexia in tumour-bearing rats

International Nuclear Information System (INIS)

Oliveira, André G.; Gomes-Marcondes, Maria Cristina C.

2016-01-01

Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition. Wistar rats received or not tumour implant and metformin treatment and were distributed into four groups, as followed: control (C), Walker 256 tumour-bearing (W), metformin-treated (M) and tumour-bearing treated with metformin (WM). Animals were weighed three times a week, and after cachexia state has been detected, the rats were euthanised and muscle and tumour excised and analysed by biochemical and molecular assays. Tumour growth promoted some deleterious effects on chemical body composition, increasing water and decreasing fat percentage, and reducing lean body mass. In muscle tissue, tumour led to a decreased protein synthesis and an increased proteolysis, showing the higher activity of the ubiquitin-proteasome pathway. On the other hand, the metformin treatment likely minimised the tumour-induced wasting state; in this way, this treatment ameliorated chemical body composition, reduced the higher activities of proteolytic enzymes and decreased the protein waste. Metformin treatment not only decreases the tumour growth but also improves the protein metabolism in gastrocnemius muscle in tumour-bearing rats

Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting

International Nuclear Information System (INIS)

Reubi, Jean Claude; Waser, Beatrice

2003-01-01

Peptide receptors have been found to represent excellent targets for in vivo cancer diagnosis and therapy. Recent in vitro studies have shown that many cancers can overexpress not only one but several peptide receptors concomitantly. One of the challenges for nuclear medicine in this field in the coming decade will be to take advantage of the co-expression of peptide receptors for multireceptor tumour targeting. In vitro receptor studies can reveal which peptide receptor is overexpressed in which tumour and which receptors are co-expressed in an individual tumour; such knowledge is a prerequisite for successful in vivo development. One group of tumours of particular interest in this respect is the neuroendocrine tumours, which have previously been shown often to express peptide receptors. This review summarises our investigations of the concomitant expression of 13 different peptide receptors, in more than 100 neuroendocrine tumours of the human intestine, pancreas and lung, using in vitro receptor autoradiography with subtype-selective ligands. The incidence and density of the somatostatin receptors sst 1 -sst 5 , the VIP receptors VPAC 1 and VPAC 2 , the CCK 1 and CCK 2 receptors, the three bombesin receptor subtypes BB 1 (NMB receptor), BB 2 (GRP receptor) and BB 3 , and GLP-1 receptors were evaluated. While the presence of VPAC 1 and sst 2 was detected in the majority of these neuroendocrine tumours, the other receptors, more differentially expressed, revealed a characteristic receptor pattern in several tumour types. Ileal carcinoids expressed sst 2 and VPAC 1 receptors in virtually all cases and had CCK 1 , CCK 2 , sst 1 or sst 5 in approximately half of the cases; they were the only tumours of this series to express NMB receptors. Insulinomas were characterised by a very high incidence of GLP-1, CCK 2 and VPAC 1 receptors, with the GLP-1 receptors expressed in a particularly high density; they expressed sst 2 in two-thirds and sst 1 in approximately half of

Role of diamine oxidase during the treatment of tumour-bearing mice with combinations of polyamine anti-metabolites.

Science.gov (United States)

Kallio, A; Jänne, J

1983-01-01

Treatment of mice bearing L1210 leukaemia with 2-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase (EC 4.1.1.17), produced a profound depletion of putrescine and spermidine in the tumour cells. Sequential combination of methylglyoxal bis(guanylhydrazone), an inhibitor of adenosylmethionine decarboxylase (EC 4.1.1.50), with difluoromethylornithine largely reversed the polyamine depletion and led to a marked accumulation of cadaverine in the tumour cells. Experiments carried out with the combination of difluoromethylornithine and aminoguanidine, a potent inhibitor of diamine oxidase (EC 1.4.3.6), indicated that the methylglyoxal bis(guanylhydrazone)-induced reversal of polyamine depletion was mediated by the known inhibition of diamine oxidase by the diguanidine. In spite of the normalization of the tumour cell polyamine pattern upon administration of methylglyoxal bis(guanylhydrazone) to difluoromethylornithine-treated animals, the combination of these two drugs produced a growth-inhibitory effect not achievable with either of the compounds alone. PMID:6411077

Diagnostic value of quantitative scintiscanning in tumours and tumour-like lesions of the skeleton

International Nuclear Information System (INIS)

Schmitt-Orlewicz, C.

1986-01-01

Following administration of 99mTc phosphate compounds quantitative scintiscanning and, in particular, the 'region of interest' technique were used in 277 patients investigated for tumours and tumour-like lesions of the extremities. The following results were obtained: 1) In primary malignant bone tumours of the extremities tracer accumulation is increased by a factor of more than 2.5 as compared to that observed in normal bone tissue (the only exception here being plasmacytoma and histiocytoma). 2) In metastatic and benign bone tumours this tendency towards increased tracer accumulation generally is less pronounced so that the values calculated here remained below a factor of 2.5. 3) The accumulation behaviour of tumour-like bone changes of the extremities did not follow a uniform pattern. 4) As a general rule, the values measured in the region of the vertebral column were increased by a factor of less than 2.5. Quantitative scintiscanning, even though being a step towards a more sophisticated radiopharmaceutical method of examination, may occasionally not provide all the information required to establish a firm diagnosis or to evaluate the severity of a disease. One important domaine of this technique is the medical surveillance of patients, both before and after treatment. (TRV) [de

Childhood Adrenocortical Tumours: a Review

Directory of Open Access Journals (Sweden)

Marques-Pereira Rosana

2006-05-01

Full Text Available Abstract Childhood adrenocortical tumour (ACT is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6% or mixed with Cushing's syndrome (42.0% was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.

Elevated tumour marker: an indication for imaging?

LENUS (Irish Health Repository)

McMahon, Colm J

2012-02-01

INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

Surgical approach to pineal tumours.

Science.gov (United States)

Pluchino, F; Broggi, G; Fornari, M; Franzini, A; Solero, C L; Allegranza, A

1989-01-01

During a period of 10 years (1977-1986) 40 cases of tumour of the pineal region have been treated at the Istituto Neurologico "C. Besta"-of Milan. Out of these 40 cases, 27 (67.5%) were in the paediatric (10-15 years) or juvenile (15-20 years) age at the time of operation. Since 1983 a specific diagnostic and therapeutic protocol has been adopted and thereafter direct surgical removal of the tumour was performed only when the neuroradiological investigations were highly suggestive of a benign extrinsic lesion. Sixteen cases in this series underwent direct surgical removal; in the remaining 24 cases stereotactic biopsy of the tumour was performed in the first instance. On the basis of the histological diagnosis obtained by this procedure surgical excision of the tumour (9 cases) or radiotherapy (15 cases) was then performed. 25 cases underwent surgical removal of the lesion. In all the cases the infratentorial supracerebellar approach as introduced by Krause and then modified by Stein was adopted. On analysis of the data of this series it was observed that in 25% of the cases completely benign resectable tumours were found; in 25% of the cases astrocytoma (grade I-II) which could be treated at least by partial removal were present; in 30% of the cases radiosensitive lesions were encountered. In the remaining 20% of the cases highly malignant tumours were found which should be treated only by radiotherapy and/or chemotherapy.

Malignant tumours of the kidney: imaging strategy

International Nuclear Information System (INIS)

Smets, Anne M.; Kraker, Jan de

2010-01-01

Primitive malignant renal tumours comprise 6% of all childhood cancers. Wilms tumour (WT) or nephroblastoma is the most frequent type accounting for more than 90%. Imaging alone cannot differentiate between these tumours with certainty but it plays an important role in screening, diagnostic workup, assessment of therapy response, preoperative evaluation and follow-up. The outcome of WT after therapy is excellent with an overall survival around 90%. In tumours such as those where the outcome is extremely good, focus can be shifted to a risk-based stratification to maintain excellent outcome in children with low risk tumours while improving quality of life and decreasing toxicity and costs. This review will discuss the imaging issues for WT from the European perspective and briefly discuss the characteristics of other malignant renal tumours occurring in children and new imaging techniques with potential in this matter. (orig.)

Cystic tumours of the pancreas

Energy Technology Data Exchange (ETDEWEB)

Itai, Y. [Dept. of Radiology, Inst. of Clinical Medicine, Tsukuba Univ. (Japan); Ohtomo, K. [Univ. of Tokyo Hospital, Tokyo (Japan)

1996-12-01

In this pictorial essay we present the typical appearances of cystic pancreatic tumours, the wide spectrum of their features, and differential features among cystic pancreatic masses with an emphasis on CT. Pseudocysts are the most common cystic lesion in the pancreas and can be induced by pancreatitis, trauma or surgery. Pseudocysts appear as a round cystic mass with a definite wall. However, they can mimic cystic tumours associated with internal septation and/or necrotic mass of various shapes. Conversely, cystic tumours can appear as a simple cyst lacking any thickening of wall, septation or mural nodule. Pancreatic carcinoma not infrequently induces secondary cysts upstream of the obstructed pancreatic duct. The cysts are pseudocysts or retention cysts in nature. When cysts are formed in the pancreatic parenchyma or adjacent to pancreatic carcinoma they may mimic cystic tumour. (orig./VHE)

Cystic tumours of the pancreas

International Nuclear Information System (INIS)

Itai, Y.; Ohtomo, K.

1996-01-01

In this pictorial essay we present the typical appearances of cystic pancreatic tumours, the wide spectrum of their features, and differential features among cystic pancreatic masses with an emphasis on CT. Pseudocysts are the most common cystic lesion in the pancreas and can be induced by pancreatitis, trauma or surgery. Pseudocysts appear as a round cystic mass with a definite wall. However, they can mimic cystic tumours associated with internal septation and/or necrotic mass of various shapes. Conversely, cystic tumours can appear as a simple cyst lacking any thickening of wall, septation or mural nodule. Pancreatic carcinoma not infrequently induces secondary cysts upstream of the obstructed pancreatic duct. The cysts are pseudocysts or retention cysts in nature. When cysts are formed in the pancreatic parenchyma or adjacent to pancreatic carcinoma they may mimic cystic tumour. (orig./VHE)

Primary vertebral tumours in children

Energy Technology Data Exchange (ETDEWEB)

Kozlowski, K.; Beluffi, G.; Masel, J.; Diard, F.; Ferrari-Ciboldi, F.; Le Dosseur, P.; Labatut, J.

1984-03-01

20 cases of primary benign and malignant bone tumours in children were reported. The most common tumours were Ewing's sarcoma, aneurismal bone cyst, benign osteoblastoma and osteoid osteoma. Some rare primary bone tumours in children (osteochondroma, chondroblastoma 6F, primary lymphoma of bone and neurofibromatosis with unusual cervical spinal changes) were also reported. The authors believe that radiographic findings together with clinical history and clinical examination may yield a high percentage of accurate diagnoses. Although microscopy is essential in the final diagnosis, the microscopic report should be also accepted with caution.

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.

Mohs micrographic surgery of rare cutaneous tumours

NARCIS (Netherlands)

Flohil, S.C.; Lee, C.B. van; Beisenherz, J.; Mureau, M.A.M.; Overbeek, L.I.H.; Nijsten, T.; Bos, R.R.

2017-01-01

BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined. OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre. METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated

Cooperative tumour cell membrane targeted phototherapy

Science.gov (United States)

Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

2017-06-01

The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

Perinatal tumours: the contribution of radiology to management

Energy Technology Data Exchange (ETDEWEB)

Donoghue, Veronica; Ryan, Stephanie; Twomey, Eilish [Children' s University Hospital, Radiology Department, Dublin (Ireland)

2008-06-15

A formal classification does not exist and they are probably best classified by their location. Overall the most common neoplasms are - Extracranial teratoma - Neuroblastoma - Soft-tissue tumours - Brain tumours - Leukaemia - Renal tumours - Liver tumours - Retinoblastoma. The prognosis is generally poor, although there are some exceptions such as congenital neuroblastoma and hepatoblastoma. These tumours have a tendency to regress and have a benign clinical course despite a clear malignant histological picture. Other tumours, though histologically benign, may be fatal because of their size and location. Large benign masses may cause airway or cardiovascular compromise and death. Others may cause significant mass effect preventing normal organ development. As normal embryonic cells have a high mitotic rate it is not surprising that perinatal tumours may have a rapid growth rate and become enormous in size. (orig.)

Neonatal testicular tumour presenting as an acute scrotum ...

African Journals Online (AJOL)

Juvenile granulosa cell tumour (JGCT) is a rare benign stromal cell tumour of the testis accounting for approximately 1% of all paediatric testicular tumours. Presenting primarily as a painless testicular mass, the tumour may be associated with undescended testis, hydrocele or testicular torsion. Abnormal karyotype has also ...

Neonatal testicular tumour presenting as an acute scrotum

African Journals Online (AJOL)

Neonatal testicular tumour presenting as an acute scrotum. Joyce M. Muhlschlegel, Alice L. Mears and Rowena J. Hitchcock. Juvenile granulosa cell tumour (JGCT) is a rare benign stromal cell tumour of the testis accounting for approximately 1% of all paediatric testicular tumours. Presenting primarily as a painless ...

A study of technetium-labelled sulphide colloid uptake by regional lymph nodes draining a tumour-bearing area

International Nuclear Information System (INIS)

Boak, J.L.; Agwunobi, T.C.

1978-01-01

With appropriate controls, experimental groups of inbred C 3 H mice bearing a syngeneic mammary carcinoma challenge in their right rear footpads were injected in both rear footpads with 99 Tcsup(m)ASC. Mice were sacrificed 15 and 90 min after the labelled colloid injection. Popliteal and sacral lymph nodes were weighed and counted in a well scintillation counter. A marked inhibition of labelled colloid uptake was demonstrated in regional lymph nodes draining a tumour-bearing area. Rabbits bearing VX 2 carcinoma in a forelimb received 99 Tc sup(m)ASC into each front footpad. Depression of labelled colloid uptake by regional lymph nodes draining tumour was evident on gamma-camera scanning. (author)

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.

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

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Christian, Nicolas; Bol, Anne; Bast, Marc de; Labar, Daniel; Lee, John; Mahy, Pierre; Gregoire, Vincent [Universite Catholique de Louvain, Center for Molecular Imaging and Experimental Radiotherapy, Brussels (Belgium)

2007-09-15

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 [{sup 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 [{sup 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 [{sup 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 [{sup 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.)

Tumour regrowth after irradiation. An experimental approach

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Yamaura, H; Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

1979-03-01

Structural changes in irradiated tumours and their regrowth were studied in a rat hepatoma, AH109A, using histological and transparent-chamber techniques. The development of the tumour was examined by means of vascular morphometry as observed in the chamber. Schematically, the tumour tissue was divided into four isocentric layers according to vascular morphology and measurements of vessel volume, surface area, and length per mm/sup 3/ of tissue. The vascularity was greatest in the outermost region, decreased towards the inner parts and reached an absence of vascularity at the central necrosis. The tumours were gamma- or X-irradiated with various doses. The inside hypoxic region was destroyed completely after 300 rad, and regrowths started exclusively from the outermost area of the tumour where enhancement of the effect of radiation by oxygen was thought to be greatest. Possible mechanisms of tumour regrowth are discussed.

Tumour-induced osteomalacia: An emergent paraneoplastic syndrome.

Science.gov (United States)

Alonso, Guillermo; Varsavsky, Mariela

2016-04-01

Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Transfer of intestine-derived diamines into tumour cells during treatment of Ehrlich-ascites--carcinoma-bearing mice with polyamine anti-metabolites.

Science.gov (United States)

Kallio, A; Nikula, P; Jänne, J

1984-01-01

Treatment of Ehrlich-ascites-carcinoma-bearing mice with methylglyoxal bis(guanylhydrazone) alone or in combination with 2-difluoromethylornithine greatly enhanced the transfer of intragastrically administered radioactive putrescine and cadaverine into the carcinoma cells. Difluoromethylornithine alone did not have any effect on the accumulation of intestine-derived diamines in the tumour cells. The frequently reported restoration of difluoromethylornithine-induced polyamine depletion on administration of methylglyoxal bis(guanylhydrazone) is in all likelihood attributable to a profound inhibition of intestinal diamine oxidase (EC 1.4.3.6), resulting in an enhanced entry of intestinal (bacterial) diamines into general circulation and finally into tumour cells. PMID:6424664

Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting

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Reubi, Jean Claude; Waser, Beatrice [Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, 3010, Berne (Switzerland)

2003-05-01

Peptide receptors have been found to represent excellent targets for in vivo cancer diagnosis and therapy. Recent in vitro studies have shown that many cancers can overexpress not only one but several peptide receptors concomitantly. One of the challenges for nuclear medicine in this field in the coming decade will be to take advantage of the co-expression of peptide receptors for multireceptor tumour targeting. In vitro receptor studies can reveal which peptide receptor is overexpressed in which tumour and which receptors are co-expressed in an individual tumour; such knowledge is a prerequisite for successful in vivo development. One group of tumours of particular interest in this respect is the neuroendocrine tumours, which have previously been shown often to express peptide receptors. This review summarises our investigations of the concomitant expression of 13 different peptide receptors, in more than 100 neuroendocrine tumours of the human intestine, pancreas and lung, using in vitro receptor autoradiography with subtype-selective ligands. The incidence and density of the somatostatin receptors sst{sub 1}-sst{sub 5}, the VIP receptors VPAC{sub 1} and VPAC{sub 2}, the CCK{sub 1} and CCK{sub 2} receptors, the three bombesin receptor subtypes BB{sub 1} (NMB receptor), BB{sub 2} (GRP receptor) and BB{sub 3}, and GLP-1 receptors were evaluated. While the presence of VPAC{sub 1} and sst{sub 2} was detected in the majority of these neuroendocrine tumours, the other receptors, more differentially expressed, revealed a characteristic receptor pattern in several tumour types. Ileal carcinoids expressed sst{sub 2} and VPAC{sub 1} receptors in virtually all cases and had CCK{sub 1}, CCK{sub 2}, sst{sub 1} or sst{sub 5} in approximately half of the cases; they were the only tumours of this series to express NMB receptors. Insulinomas were characterised by a very high incidence of GLP-1, CCK{sub 2} and VPAC{sub 1} receptors, with the GLP-1 receptors expressed in a

Tumour screening by means of tomography methods

International Nuclear Information System (INIS)

Diederich, S.

2005-01-01

Tomography methods such as computer tomography (CT), magnetic resonance tomography (MRT), and sonography/ultrasound examinations make it possible to detect small asymptomatic tumours, thus potentially preventing their manifestation at an advanced stage and improving survival prospects for the patients concerned. There are data available on various common tumours which show that modern tomography methods are capable of detecting not only small asymptomatic tumours but also their benign precursors (e.g. polyps of the large intestine). This has been demonstrated for lung cancer, colon cancer and breast cancer. However, it has not been possible to date to show for any tomography method or any type of tumour that the systematic use of such diagnostic procedures does anything to lower the mortality rate for that tumour. For other types of tumour (pancreatic cancer, kidney cancer, ovary cancer) the above named methods are either not sufficiently sensitive or the body of data that has accumulated on their respective use is too small to judge the benefit of tomography screenings. Current technical developments make it appear probable that for many types of cancer the reliability with which small tumours can be detected will improve in future. Studies aimed at clarifying the potential of screenings for reducing mortality rates are already underway for lung cancer and would be worthwhile performing for other tumour types

Phase congruency map driven brain tumour segmentation

Science.gov (United States)

Szilágyi, Tünde; Brady, Michael; Berényi, Ervin

2015-03-01

Computer Aided Diagnostic (CAD) systems are already of proven value in healthcare, especially for surgical planning, nevertheless much remains to be done. Gliomas are the most common brain tumours (70%) in adults, with a survival time of just 2-3 months if detected at WHO grades III or higher. Such tumours are extremely variable, necessitating multi-modal Magnetic Resonance Images (MRI). The use of Gadolinium-based contrast agents is only relevant at later stages of the disease where it highlights the enhancing rim of the tumour. Currently, there is no single accepted method that can be used as a reference. There are three main challenges with such images: to decide whether there is tumour present and is so localize it; to construct a mask that separates healthy and diseased tissue; and to differentiate between the tumour core and the surrounding oedema. This paper presents two contributions. First, we develop tumour seed selection based on multiscale multi-modal texture feature vectors. Second, we develop a method based on a local phase congruency based feature map to drive level-set segmentation. The segmentations achieved with our method are more accurate than previously presented methods, particularly for challenging low grade tumours.

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.

Breast tumours of adolescents in an African population

Directory of Open Access Journals (Sweden)

Umanah Ivy

2010-01-01

Full Text Available Background: Tumours of the breast are uncommon in childhood and adolescence. Patients in this age group often require a different approach to diagnosis and treatment. The purpose of this study is to highlight the clinicopathologic features of breast tumours in adolescents in a Nigerian city. Materials and Methods: Eighty-four breast tumour materials from patients aged 10-19 years were analyzed over a 10-year period at the Department of Pathology, University of Benin Teaching Hospital (UBTH, Benin City, Edo State, Benin City, Nigeria. Results: A majority of the breast tumours were benign. Fibroadenoma was the most common tumour with 46 cases (54.8%, followed by fibrocystic changes with 15 cases (17%. Malignancy was extremely rare in this group, with only one case (1.2% of an invasive ductal carcinoma. Histologically, most tumours were indistinguishable from the adult types. Conclusion: Fibroadenoma is the most common breast tumour in adolescents in Benin City, Nigeria. Breast cancer and male breast tumours are rare in this age group. Routine complete physical examination of children and adolescents should include breast examination.

Imaging in unilateral Wilms tumour

International Nuclear Information System (INIS)

Brisse, Herve J.; Smets, Anne M.; Kaste, Sue C.; Owens, Catherine M.

2008-01-01

Wilms tumour is one of the most common malignancies in children, with an excellent prognosis after therapy. There is a very diverse approach to treatment according to geographical location. This variation in therapeutic attitude toward Wilms tumour, particularly between the United States and Europe, has consequences for the choice of imaging modality at diagnosis. In Europe, the International Society of Paediatric Oncology (SIOP) treatment protocol is based on chemotherapy followed by surgery. Imaging (US, CT and MRI), clinical history and examination will help predict whether the findings are consistent with Wilms tumour. Furthermore, in the UK preoperative image-guided biopsy is advised to help identify the small group of patients who, despite typical imaging features of Wilms tumour, have other types of neoplasia that require alternative management. In the United States, the National Wilms Tumor Study (NWTS) advises surgery prior to chemo- and radiotherapy. Hence imaging must provide detailed anatomical information for surgical planning. This article discusses the role of imaging at diagnosis and the relative strengths and weaknesses of the available radiological techniques. We also focus on imaging the lung for metastatic disease and the consequences (to the patient's ultimate outcome) of CT-diagnosed small pulmonary nodules and discuss the radiological diagnosis and consequences of tumour rupture present at diagnosis. (orig.)

Paeoniflorin inhibits the growth of bladder carcinoma via deactivation of STAT3

Directory of Open Access Journals (Sweden)

Yang Jianhui

2018-06-01

Full Text Available Bladder cancer (BCa is one of the most common urinary cancers. The present study aims to investigate whether Paeoniflorin (Pae can exert inhibitory effects on BCa. The results showed that Pae inhibited proliferation of human BCa cell lines in a concentration- and time-dependent manner. Pae and cisplatin (Cis synergistically inhibited the growth of tumours in RT4-bearing mice. Pae treatment neutralized the body loss induced by Cis. Moreover, Pae induced apoptosis in RT4 cells and increased the activities of caspase3, caspase8 and caspase9. Western blotting and immunohistochemical analysis revealed that the phosphorylated signal transducer and activator of transcription-3 (p-STAT3 level were decreased in Pae-treated RT4 cells and Pae-treated tumour-bearing mice. Furthermore, STAT3 transcriptional target B-cell lymphoma-2 was decreased in Pae-treated RT4 cells. Interestingly, Pae prevented translocation of STAT3 to the nucleus in RT4 cells. Collectively, Pae inhibits the growth of BCa, at least in part, via a STAT3 pathway.

Modelling of tumour repopulation after chemotherapy

International Nuclear Information System (INIS)

Marcu, Loredana; Bezak, Eva

2010-01-01

Full text: While repopulation is a clinically observed phe nomenon after radiotherapy, repopulation of tumour cells between cycles of chemotherapy is usually a neglected factor in cancer treatment. As the effect of both radiotherapy and chemotherapy on tumour cells is the same (attack on cancer cells), the response of the tumour to injury and cell loss from the two treatment methods should be similar, including repopulation. Cell recruitment is known to be a possible mechanism responsible for tumour regrowth after radio therapy. The literature data regarding mechanisms of repopulation after chemotherapy is very limited. The current paper employs a Monte Carlo modelling approach to implement the pharmacokinetics of a widely used drug (cisplatin) into a previously developed vit1ual head and neck tumour and to study the effect of cisplatin on tumour regres sion and regrowth during treatment. The mechanism of cell recruitment was modelled by releasing various percentages (5-50%) of quiescent cells into the mitotic cycle after each chemotherapy cell kill. The onset of repopulation was also simulated, with both immediate onset and late onset of cell recruitment. Repopulation during chemotherapy, if occu ring, is a highly potent phenomenon, similar to drug resis tance, therefore it should not be neglected during treatment.

EVALUATION OF BRAIN TUMOURS USING COMPUTED TOMOGRAPHY

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B. Vinod Kumar

2016-07-01

Full Text Available BACKGROUND The brain is basically formed by the neurons and the supporting cells. Tumours arising of neurons are almost impossible because the neurons never divide. Tumours arising from the supporting cells are almost frequently seen. The tumour characteristics depend upon the cell of origin. The brain is covered by meninges and the vascular tissue supplies the essential nutrients to all these components of the brain. Unfortunately, the brain is placed in a rigid box called as neurocranium. According to Monro–Kellie principle, if any of the one component increases in a rigid box, the other components will be compensated. So in a limited space if any of the catastrophes occur i.e. space occupying lesions, then the other components will be compensated and as a result the effects will be seen in a very small amount of time. A sincere effort has been put in this study to understand and evaluate the Brain Tumours using a CT scan. This study is intended to be useful to the diagnosing radiologists, internal medicine practitioners and general practitioners and surgeons. METHODS The aim of the study is to evaluate the brain tumours using CT and to confirm the diagnosis by sending to the Histopathology Department. The study is a cross-sectional study and is done in the Department of Radiology, Fathima Medical College, Kadapa, Andhra Pradesh. The study was done from December 2014 to May 2016. The study was done using thirty cases who were believed to have brain tumour and were studied in the Department of Radiology after initial clinical evaluation. First, the plain CT was done and was checked for the location, size, characteristics of the lesion and the surrounding characteristics were observed. RESULT In the present study, the most common of all tumours were those of the neuroepithelial groups. Next in frequency were the tumours of meninges of all intracranial tumours. This was followed by tumours of cranial nerves, metastatic tumour, one lymphoma case

Molecular pathology of bone tumours: diagnostic implications.

Science.gov (United States)

Puls, Florian; Niblett, Angela J; Mangham, D Chas

2014-03-01

Alongside histomorphology and immunohistochemistry, molecular pathology is now established as one of the cornerstones in the tissue diagnosis of bone tumours. We describe the principal molecular pathological techniques employed, and each of the bone tumour entities where their identified characteristic molecular pathological changes can be detected to support and confirm the suspected histological diagnosis. Tumours discussed include fibrous dysplasia, classical and subtype osteosarcomas, central and surface cartilaginous tumours, Ewing's sarcoma, vascular tumours, aneurysmal bone cyst, chordoma, myoepithelioma, and angiomatoid fibrous histiocytoma. This is a rapidly evolving field with discoveries occurring every few months, and some of the newer entities (the Ewing's-like sarcomas), which are principally identified by their molecular pathology characteristics, are discussed. © 2013 John Wiley & Sons Ltd.

Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

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Lasko, Loren M.; Jakob, Clarissa G.; Edalji, Rohinton P.; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L.; Hansen, T. Matt; Risi, Roberto M.; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T.; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G.; Martin, Ruth L.; Torrent, Maricel; Chiang, Gary G.; Karukurichi, Kannan; Langston, J. William; Weinert, Brian T.; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H.; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A.; Rosenberg, Saul H.; Michaelides, Michael R.; Lai, Albert; Bromberg, Kenneth D. (AbbVie); (UCopenhagen); (Petra Pharma); (UPENN); (JHU); (Van Drie); (Faraday)

2017-09-27

The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription1 and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind2. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer3). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products4, bi-substrate analogues5 and the widely used small molecule C6466,7, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

Fatty degeneration in a Wilms' tumour after chemotherapy

International Nuclear Information System (INIS)

Jeanes, A.C.; Beese, R.C.; McHugh, K.; Ramsay, A.D.

2002-01-01

We report a case of extensive fatty change in a Wilms' tumour after chemotherapy demonstrated on CT associated with an increase in tumour volume, in a 10-month-old girl with Beckwith-Wiedemann syndrome. Changes in tumour characteristics after chemotherapy on imaging usually reflect necrosis, haemorrhage and calcification. Assessment of response to therapy is dependent on a documented reduction in tumour volume. In this case, CT showed an increase in tumour size with development of an extensive fatty component following treatment. Subsequent histological examination on the nephrectomy specimen confirmed an extensive fatty component with no evidence of residual blastema. The development of such an extensive fatty component is very unusual. In this case such fatty change was an indicator of tumour sensitivity and response to treatment. (orig.)

Carcinoid Tumour of the Ovary

African Journals Online (AJOL)

Abstract. A case of bilateral carcinoid tumour of the ovary, with benign cystic teratoma in one ovary, in a 38 year old woman is presented. She had total abdominal hysterectomy, bilateral salpingoophorectomy, infracolic omentectomy and appendectomy. There was no macroscopic tumour in the vermiform appendix and the ...

Computed tomography in malignant primary bone tumours

International Nuclear Information System (INIS)

Kersjes, W.; Harder, T.; Haeffner, P.

1990-01-01

The importance of computed tomography is examined in malignant primary bone tumours using a strongly defined examination group of 13 Patients (six Ewing's-sarcomas, five osteosarcomas, one chondrosarcoma and one spindle-shaped cell sarcoma). Computed tomography is judged superior compared to plain radiographs in recognition of bone marrow infiltration and presentation of parosteal tumour parts as well as in analysis of tissue components of tumours, CT is especially suitable for therapy planning and evaluating response to therapy. CT does not provide sufficient diagnostic information to determine dignity and exact diagnosis of bone tumours. (orig.) [de

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)

Analysis of clonogenic human brain tumour cells: preliminary results of tumour sensitivity testing with BCNU

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Rosenblum, M L; Dougherty, D A; Deen, D F; Hoshino, T; Wilson, C B [California Univ., San Francisco (USA). Dept. of Neurology

1980-04-01

Biopsies from 6 patients with glioblastoma multiforme were disaggregated and single cells were treated in vitro with various concentrations of 1,3-bis(2-chloroethyl)-1-nitroso urea (BCNU) and plated for cell survival. One patient's cells were sensitive to BCNU in vitro; after a single dose of BCNU her brain scan reverted to normal and she was clinically well. Five tumours demonstrated resistance in vitro. Three of these tumours progressed during the first course of chemotherapy with a nitrosourea and the patients died at 21/2, 4 and 81/2 months after operation. Two patients who showed dramatic responses to radiation therapy were considered unchanged after the first course of nitrosourea therapy (although one demonstrated tumour enlargement on brain scan). The correlation of in vitro testing of tumour cell sensitivity with actual patient response is encouraging enough to warrant further work to determine whether such tests should weigh in decisions on patient therapy.

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

Parotid gland tumours: a six years experience

International Nuclear Information System (INIS)

Malik, K.A.

2006-01-01

To find out the different types of Parotid tumours in out setup and their prevalence in different age groups. All patients admitted with Parotid swellings, irrespective of age and sex. The detailed data of the patients was collected and analyzed. A total of 27 patients, 15 males and 12 females, with ages ranging from 15 to 65 years were included in the study. Most of the patients were in the 31-50 years of age group. Pleomorphic adenoma was the commonest benign tumour with an incidence of 66.6%, while Mucoepidermoid Carcinoma with an incidence of 11.11% was the most common malignant tumour. Parotid gland is the principal site of salivary gland tumours. Males are affected more and Pleomorphic adenoma is the most common benign and Mucoepidermoid carcinoma the most common malignant tumour. (author)

Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

Science.gov (United States)

Di Caro, Giuseppe; Cortese, Nina; Castino, Giovanni Francesco; Grizzi, Fabio; Gavazzi, Francesca; Ridolfi, Cristina; Capretti, Giovanni; Mineri, Rossana; Todoric, Jelena; Zerbi, Alessandro; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

2016-10-01

Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer. In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX). In vitro, we dissected the synergism of CTX and TAMs. In human PDAC, TAMs predominantly exhibited an immunoregulatory profile, characterised by expression of scavenger receptors (CD206, CD163) and production of interleukin 10 (IL-10). Surprisingly, while the density of TAMs associated to worse prognosis and distant metastasis, CTX restrained their protumour prognostic significance. High density of TAMs at the tumour-stroma interface positively dictated prognostic responsiveness to CTX independently of T-cell density. Accordingly, in vitro, gemcitabine-treated macrophages became tumoricidal, activating a cytotoxic gene expression programme, inhibiting their protumoural effect and switching to an antitumour phenotype. In patients with human PDAC, neoadjuvant CTX was associated to a decreased density of CD206(+) and IL-10(+) TAMs at the tumour-stroma interface. Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Interobserver delineation variation in lung tumour stereotacticbody radiotherapy

DEFF Research Database (Denmark)

Persson, G. F.; Nygaard, D. E.; Hollensen, Christian

2012-01-01

the interobserver delineation variation for stereotactic body radiotherapy (SBRT) of peripheral lung tumours using a cross-sectional study design. Methods 22 consecutive patients with 26 tumours were included. Positron emission tomography/CT scans were acquired for planning of SBRT. Three oncologists and three......-sectional analysis of delineation variation for peripheral lung tumours referred for SBRT, establishing the evidence that interobserver variation is very small for these tumours....

[Occurrence of associated tumours in chronic lymphocytic leukemia].

Science.gov (United States)

Szerafin, László; Jakó, János; Varju, Lóránt

2016-10-01

Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

Aqp 9 and Brain Tumour Stem Cells

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Guri Fossdal

2012-01-01

Full Text Available Several studies have implicated the aquaporins (aqp 1, 4, and 9 in the pathogenesis of malignant brain tumours, suggesting that they contribute to motility, invasiveness, and oedema formation and facilitate metabolism in tumour cells under hypoxic conditions. We have studied the expression of aqp1, 4, and 9 in biopsies from glioblastomas, isolated tumour stem cells grown in a tumoursphere assay and analyzed the progenitor and differentiated cells from these cultures. We have compared these to the situation in normal rat brain, its stem cells, and differentiated cells derived thereof. In short, qPCR in tumour tissue showed presence of aqp1, 4, and 9. In the tumour progenitor population, aqp9 was markedly more highly expressed, whilst in tumour-derived differentiated cells, aqp4 was downregulated. However, immunostaining did not reveal increased protein expression of aqp9 in the tumourspheres containing progenitor cells; in contrast, its expression (both mRNA and protein was high in differentiated cultures. We, therefore, propose that aquaporin 9 may have a central role in the tumorigenesis of glioblastoma.

Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion

Energy Technology Data Exchange (ETDEWEB)

Elmpt, Wouter van; Zegers, Catharina M.L.; Reymen, Bart; Even, Aniek J.G.; Oellers, Michel; Troost, Esther G.C.; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Dingemans, Anne-Marie C. [Maastricht University Medical Centre, Department of Pulmonology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Wildberger, Joachim E.; Das, Marco [Maastricht University Medical Centre, Department of Radiology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Mottaghy, Felix M. [Maastricht University Medical Centre, Department of Nuclear Medicine, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); University Hospital RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany)

2016-02-15

Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p = 0.014), hypoxic fraction (-0.60, p = 0.025) and TBR (-0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia. (orig.)

Supratentorial tumours. Part II: tumors of neurolglial cells

International Nuclear Information System (INIS)

Sage, M.R.

1991-01-01

Tumors arising from neuroglial cells are the most common primary brain tumours, representing approximately 45% of all tumours. A simplified classification of these tumours is given, based on the degree of anaplasia. Both computed tomography and magnetic resonance imaging appearance of such lesions is presented and the relevance of these techniques in the detection and differential diagnosis of neuroglial cells tumours is discussed. 39 refs., 1 tab., 11 figs

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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)

Primitive neuroectodermal tumour (PNET) of the kidney: a rare renal tumour in adolescents with seemingly characteristic radiological features

International Nuclear Information System (INIS)

Chu, Winnie C.; Reznikov, Boris; Lee, Edward Y.; Grant, Ronald M.; Cheng, Frankie W.T.; Babyn, Paul

2008-01-01

Primitive neuroectodermal tumours (PNETs) constitute a family of neoplasms of presumed neuroectodermal origin that predominantly present as bone or soft-tissue masses in adolescents and young adults. PNET arising in the kidney is rare. To describe the radiological features in three patients with primary renal PNET. The radiological features of primary renal PNET in three adolescent patients (age 10, 14 and 16 years) are described. Tumour thrombus extending into the renal vein and inferior vena cava was noted in all three patients. In addition, further tumour extension into the atrium was seen in two patients with extension into a pulmonary artery in one patient. Neural foraminal and intraspinal extension close to the origin of the tumour was identified in two patients. Liver, bone and lung metastases were identified. While rare, one should consider the diagnosis of PNET when encountering a renal mass with aggressive features such as inferior vena cava tumour thrombus, direct intraspinal invasion and distant metastasis. (orig.)

Response and recovery kinetics of a solid tumour after irradiation

International Nuclear Information System (INIS)

Rowley, R.; Hopkins, H.A.; Ritenour, E.R.; Looney, W.B.

1980-01-01

The effects of local tumour radiation over the dose range 7.5-30 Gy on the growth and cell kinetics of rat hepatoma H-4-II-E have been investigated. A plot of growth delays against log surviving fraction was linear below a fraction of 0.03, but failed to extrapolate to the origin. Following a single dose of 15 Gy to the tumour, DNA-precursor incorporation, labelling and mitotic indices were depressed for 7 days. Tumour cellularity, measured as DNA/g tumour was reduced and the rate of increase of total clonogenic cells slower than after complete tumour recovery. From Day 7 to Day 9 all indices of proliferation recovered to about control levels, clonogenic cell numbers increased more rapidly and tumour cellularity was restored. Repopulation of the tumour therefore appeared to take place mainly after Day 7. Incorporation of [ 3 H]-TdR into tumour DNA reached twice the control values on Day 9. The rate of tumour growth accelerated after the initial decrease, and maximum tumour growth rate was also twice the control values on Day 13. Accelerated growth rates in irradiated tumours, above those of control tumours, occurred 10-16 days after treatment. The effectiveness of sequential therapy may therefore be improved if given during this period of accelerated tumour growth. (author)

Presentation of a salivary tumour si mil primitive lung with metastases of carcinoid tumour of the colon

International Nuclear Information System (INIS)

Cataldi, S.; Ximenez; Carzoglio, J.

2010-01-01

Introduction: Colon carcinoid tumors are primary tumors in the colon, a rare histology. The lung tumour Si mil - Amyloid is within primary lung tumours, infrequent histology and often behaves like a benign tumour. In this paper we present the case of a patient with a history of having undergone colon surgery for a malignant carcinoid. Two years after developing a lung salivary tumour simile initially presented as metastasis Colonic carcinoid lung tumour. Clinical case: It is about a female patient of 64 years, who in September 2008 he makes a right hemicolectomy extended by an occlusive syndrome sub. Anatomic Pathology (A P) accounted for Carcinoid Tumor Malignant one that committed the entire wall and 50 lymph nodes are resected, all free metastasis. The patient does not receive complementary treatments and an imaging over in December 2009 is evident in a tomographic study a bulky upper lobe pulmonary parenchymal process right. The fiberoptic bronchoscopy (Fob) showed complete obstruction of the right upper lobe bronchus by a vegetating process whose biopsy reported a malignant lung tumor commitment carcinoid support primitive colonic confirmed by immunohistochemistry (IHC). The March 23, 2010 takes place the right upper lobectomy with lymphadenectomy. The A P and IHC study confirmed adenosquamous carcinoma with stroma simile amiloide low degree of malignancy. This injury can be approved to a salivary tumour early lung simile. Bronchial compromised by tumor margin and 22 negative lymph nodes. The patient is referred for additional radiation treatment. Discussion: Tumours of salivary gland type of primitive lung is a very rare condition and diagnosis is a r arity . Usually they originate in the bronchial epithelium submucosal gland. Endo luminal lesions usually occur as infrequently and develop in outlying areas. The development of lung tumours unrelated bronchial structure has been explained by a possible origin from a primitive stem cell that can differentiate a

Tumours associated with medical X-ray therapy exposure in childhood

International Nuclear Information System (INIS)

Colman, M.; Kirsch, M.; Creditor, M.

1978-01-01

A total of 5166 persons who were exposed to limited field (80-100 cm 2 ) X-ray irradiation to the head, neck and upper chest region during childhood and adolescence have provided an outstanding opportunity for the study of tumour incidence following medical X-ray therapy. More than 3254 subjects have been traced, 3108 have completed questionnaires eliciting information on tumour incidence, and 1539 of these were subjected to a thorough clinical screening procedure that included a thyroid scintigram. The prevalence of thyroid tumours in the 1539 clinically screened subjects and the prevalence of all other tumours in the 3254 subjects traced can therefore be assumed to reflect the risks in the group of irradiated subjects as a whole. Median age at irradiation was 3.5 years, and median radiation dose 790 rads (7.9 Gy). Thyroid tumour was diagnosed in 413 subjects. Of those undergoing surgery (273) 30.3% were found to have thyroid cancer. A total of 366 surgical pathology specimens of the thyroid, including 93 from subjects who were diagnosed at other hospitals, were examined revealing 73 papillary carcinomas, 12 follicular carcinomas and 26 microscopic papillary carcinomas. One hundred and eighty-seven other (non-thyroid) neoplasmas identified included 27 benign and 10 malignant salivary gland tumours, 16 benign and seven malignant tumours of neural origin (brain, spinal cord, cranial and peripheral nerves), 37 skin tumours, 9 lymphomas, 8 gonadal tumours, 45 breast tumours and 28 tumours of miscellaneous sites. The incidence of thyroid tumours, salivary gland tumours and primary brain tumours was considerably in excess of the expected incidence (p values<0.0001), and a radiation dose-effect correlation was observed for thyroid and brain tumours. Gonadal tumours and lymphomas did not occur in excess of the expected incidence

[10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple negative breast cancer in vivo.

Science.gov (United States)

Martin, Ana Carolina B M; Fuzer, Angelina M; Becceneri, Amanda B; da Silva, James Almada; Tomasin, Rebeka; Denoyer, Delphine; Kim, Soo-Hyun; McIntyre, Katherine A; Pearson, Helen B; Yeo, Belinda; Nagpal, Aadya; Ling, Xiawei; Selistre-de-Araújo, Heloisa S; Vieira, Paulo Cézar; Cominetti, Marcia R; Pouliot, Normand

2017-09-22

There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin ( Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo . We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro . In addition, [10]-gingerol is well tolerated in vivo , induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.

Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer.

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Laxmidhar Das

Full Text Available Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.

Measurement of tumour size with mammography, sonography and magnetic resonance imaging as compared to histological tumour size in primary breast cancer

International Nuclear Information System (INIS)

Gruber, Ines V; Rueckert, Miriam; Kagan, Karl O; Staebler, Annette; Siegmann, Katja C; Hartkopf, Andreas; Wallwiener, Diethelm; Hahn, Markus

2013-01-01

Tumour size in breast cancer influences therapeutic decisions. The purpose of this study was to evaluate sizing of primary breast cancer using mammography, sonography and magnetic resonance imaging (MRI) and thereby establish which imaging method most accurately corresponds with the size of the histological result. Data from 121 patients with primary breast cancer were analysed in a retrospective study. The results were divided into the groups “ductal carcinoma in situ (DCIS)”, invasive ductal carcinoma (IDC) + ductal carcinoma in situ (DCIS)”, “invasive ductal carcinoma (IDC)”, “invasive lobular carcinoma (ILC)” and “other tumours” (tubular, medullary, mucinous and papillary breast cancer). The largest tumour diameter was chosen as the sizing reference in each case. Bland-Altman analysis was used to determine to what extent the imaging tumour size correlated with the histopathological tumour sizes. Tumour size was found to be significantly underestimated with sonography, especially for the tumour groups IDC + DCIS, IDC and ILC. The greatest difference between sonographic sizing and actual histological tumour size was found with invasive lobular breast cancer. There was no significant difference between mammographic and histological sizing. MRI overestimated non-significantly the tumour size and is superior to the other imaging techniques in sizing of IDC + DCIS and ILC. The histological subtype should be included in imaging interpretation for planning surgery in order to estimate the histological tumour size as accurately as possible

Evaluating the agreement between tumour volumetry and the estimated volumes of tumour lesions using an algorithm

Energy Technology Data Exchange (ETDEWEB)

Laubender, Ruediger P. [German Cancer Consortium (DKTK), Heidelberg (Germany); University Hospital Munich - Campus Grosshadern, Institute of Medical Informatics, Biometry, and Epidemiology (IBE), Munich (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Lynghjem, Julia; D' Anastasi, Melvin; Graser, Anno [University Hospital Munich - Campus Grosshadern, Institute for Clinical Radiology, Munich (Germany); Heinemann, Volker; Modest, Dominik P. [University Hospital Munich - Campus Grosshadern, Department of Medical Oncology, Munich (Germany); Mansmann, Ulrich R. [University Hospital Munich - Campus Grosshadern, Institute of Medical Informatics, Biometry, and Epidemiology (IBE), Munich (Germany); Sartorius, Ute; Schlichting, Michael [Merck KGaA, Darmstadt (Germany)

2014-07-15

To evaluate the agreement between tumour volume derived from semiautomated volumetry (SaV) and tumor volume defined by spherical volume using longest lesion diameter (LD) according to Response Evaluation Criteria In Solid Tumors (RECIST) or ellipsoid volume using LD and longest orthogonal diameter (LOD) according to World Health Organization (WHO) criteria. Twenty patients with metastatic colorectal cancer from the CIOX trial were included. A total of 151 target lesions were defined by baseline computed tomography and followed until disease progression. All assessments were performed by a single reader. A variance component model was used to compare the three volume versions. There was a significant difference between the SaV and RECIST-based tumour volumes. The same model showed no significant difference between the SaV and WHO-based volumes. Scatter plots showed that the RECIST-based volumes overestimate lesion volume. The agreement between the SaV and WHO-based relative changes in tumour volume, evaluated by intraclass correlation, showed nearly perfect agreement. Estimating the volume of metastatic lesions using both the LD and LOD (WHO) is more accurate than those based on LD only (RECIST), which overestimates lesion volume. The good agreement between the SaV and WHO-based relative changes in tumour volume enables a reasonable approximation of three-dimensional tumour burden. (orig.)

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.

Tumours of the pineal region in childhood

International Nuclear Information System (INIS)

Herrmann, H.D.; Schulte, F.J.; Winkler, D.; Mueller, D.

1988-01-01

36 patients with tumours in the pineal region were treated between 1980 and 1986, 19 of whom were under 20 years of age. Diagnosis was based on cranial CT, supplemented to by MRI as from 1986. Preoperative angiography was peformed on all patients to demonstrate tumour vascularization and type of vascular supply. Stereotactic biopsies were complemented by intraoperative ventriculography. Stereotactic biopsy only was performed in 13 patients out of the total group to verify tumour histology. 23 patients were directly operated on primarily. 3 of these died postoperative. In cases of germ-cell tumours and pineal blastomas the total brain and the vertebral canal were irradiated. (orig./MG) [de

Peptide receptor radionuclide therapy of neuroendocrine tumours

International Nuclear Information System (INIS)

Bodei, L.; Giammarile, F.

2009-01-01

Neuroendocrine tumours are considered relatively rare tumours that have the characteristic property of secreting bioactive substances, such as amines and hormones. They constitute a heterogeneous group, characterized by good prognosis, but important disparities of the evolutionary potential. In the aggressive forms, the therapeutic strategies are limited. The metabolic or internal radiotherapy, using radiolabelled peptides, which can act at the same time on the primary tumour and its metastases, constitutes a tempting therapeutic alternative, currently in evolution. The prospects are related to the development of new radiopharmaceuticals, with the use of other peptide analogues whose applications will overflow the framework of the neuro-endocrine tumours. (authors)

Malignant Peripheral Nerve Sheath Tumour of the Maxilla

Directory of Open Access Journals (Sweden)

Puja Sahai

2014-01-01

Full Text Available A 38-year-old man was diagnosed with malignant peripheral nerve sheath tumour of the maxilla. He was treated with total maxillectomy. Histopathological examination of the resected specimen revealed a close resection margin. The tumour was of high grade with an MIB-1 labelling index of almost 60%. At six weeks following the surgery, he developed local tumour relapse. The patient succumbed to the disease at five months from the time of diagnosis. The present report underlines the locally aggressive nature of malignant peripheral nerve sheath tumour of the maxilla which necessitates an early therapeutic intervention. A complete resection with clear margins is the most important prognostic factor for malignant peripheral nerve sheath tumour in the head and neck region. Adjuvant radiotherapy may be considered to improve the local control. Future research may demarcate the role of targeted therapy for patients with malignant peripheral nerve sheath tumour.

An unusual presentation of a glomus tumour.

LENUS (Irish Health Repository)

Nugent, N

2011-02-01

Glomus tumours are benign, soft tissue tumours, usually of fingertips. Classically they present with severe pain, temperature sensitivity and localised tenderness. The diagnosis is often delayed due to sometimes non-specific symptoms and rarity of the disorder. While usually a clinical diagnosis, imaging may be necessary for diagnosis and localisation. We present a case of glomus tumour of the fingertip with an unusual history.

Patient Survival Periods and Death Causes Following Surgical Treatment of Mammary Gland Tumours Depending on Histological Type of Tumour: Retrospective Study of 221 Cases

Directory of Open Access Journals (Sweden)

Jana Lorenzová

2010-01-01

Full Text Available This retrospective study evaluated a canine patient group operated on for mammary neoplasms (221 females. After surgical treatment, the animals were divided based on histological findings into groups and subgroups according to the WHO system. In the individual groups and subgroups the length of their survival following a mammary tumour surgery and death causes were followed. Of their total number, 164 tumours were malignant, 39 were benign and 18 were mammary hyperplasias. With regard to malignant tumours, invasive tubular carcinoma (20.81% was identified most frequently; fibroadenoma reached the highest occurrence (10.41% as regards benign tumours. The length of survival in females with malignant tumours ranged from 12 to 37.4 months, depending on histological subtypes. In females with benign mammary neoplasms the length of survival ranged from 39.1 to 59.3 months and in animals with hyperplasia it was 50.2 months. As a result of mammary tumour, 41 females (25% died in the malignant tumour group, none died in the benign tumour group and 2 females (11.1% died in the hyperplasia group. The survival periods in surgically treated patients with mammary tumours were shorter for solid and complex carcinomas, compared to patients affected with the remainder of the histological subtypes. The longest survival period following operation was recorded in the group suffering from adenoma. The least favourable illness prognosis for patients with mammary tumours in respect to linking the death cause to the mammary tumour was for those having invasive papillary carcinoma. The most favourable illness prognosis was for patients with benign tumours and non-invasive tubular carcinoma. A frequent death cause in females with mammary tumours was another illness unrelated to mammary tumours.

Primary malignant bone tumour in a tropical African University ...

African Journals Online (AJOL)

Bone tumours are relatively rare tumours as compared with all other tumours. The relative frequency has not been well documented in this environment. The aim of the study was to define the frequency of primary malignant bone tumours in an African University teaching hospital in Ibadan. The medical records of 114 ...

[Gender differences in the use of tumour markers].

Science.gov (United States)

Moreno-Campoy, E E; Mérida-De la Torre, F J; Martos-Crespo, F; Plebani, M

2015-01-01

Gender is one of the factors that can influence the use of health resources. The use of tumour markers is widespread, due to the importance of these in monitoring cancer development. The aim of this study is to analyse the influence of gender on the use of tumour markers, and to investigate whether there are differences in their use. A longitudinal, retrospective and descriptive study, with a 2-year follow-up, was conducted in the catchment area of the University Hospital of Padua. An analysis was performed on 23,059 analytical requests for tumour markers. A descriptive and frequency analysis was performed on all variables. The statistical analysis was performed using Chi squared, Student t and Mann-Whitney U to test for significance. The number of requests for women (1.5) was lower than men (1.6). In patients with tumour pathology, the number of requests was higher than in patients without tumour disease. In the analysis by disease and gender, the difference remained significant. As regards the number of tumour markers per request, the difference between genders was also significant: 2.13 in males versus 2.85 in women. Similar results were obtained when requests for tumour markers linked to gender-related diseases were eliminated. There are differences in the use of tumour markers by gender with the number of requests for male patients being higher than for females. However, the number of tumour markers per request is greater in women than in men. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

Recent advances and opportunities in proteomic analyses of tumour heterogeneity.

Science.gov (United States)

Bateman, Nicholas W; Conrads, Thomas P

2018-04-01

Solid tumour malignancies comprise a highly variable admixture of tumour and non-tumour cellular populations, forming a complex cellular ecosystem and tumour microenvironment. This tumour heterogeneity is not incidental, and is known to correlate with poor patient prognosis for many cancer types. Indeed, non-malignant cell populations, such as vascular endothelial and immune cells, are known to play key roles supporting and, in some cases, driving aggressive tumour biology, and represent targets of emerging therapeutics, such as antiangiogenesis and immune checkpoint inhibitors. The biochemical interplay between these cellular populations and how they contribute to molecular tumour heterogeneity remains enigmatic, particularly from the perspective of the tumour proteome. This review focuses on recent advances in proteomic methods, namely imaging mass spectrometry, single-cell proteomic techniques, and preanalytical sample processing, that are uniquely positioned to enable detailed analysis of discrete cellular populations within tumours to improve our understanding of tumour proteomic heterogeneity. This review further emphasizes the opportunity afforded by the application of these techniques to the analysis of tumour heterogeneity in formalin-fixed paraffin-embedded archival tumour tissues, as these represent an invaluable resource for retrospective analyses that is now routinely accessible, owing to recent technological and methodological advances in tumour tissue proteomics. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Nuclear medicine procedures to diagnose endocrine pancreatic tumours

International Nuclear Information System (INIS)

Bares, R.; Besenfelder, H.; Eschmann, S.M.; Pfannenberg, C.

2003-01-01

The typical clinical features of endocrine pancreatic tumours are either symptoms caused by excessive hormone production or progressive tumour growth. In several prospective studies it has been shown that somatostatin receptor scintigraphy is the most accurate imaging technique currently available to detect endocrine pancreatic tumours. Therefore it should be used whenever curative surgical treatment appears to be feasible. Furthermore it should be applied if a radionuclide treatment of inoperable tumours is considered. In this situation scintigraphy with 123 I-mIBG might be useful, too. Future developments include the use of PET with labelled somatostatin analogues or DOPA derivatives as well as image fusion techniques to optimize preoperative tumour localization. (orig.) [de

Primary Malignant Bone Tumours at the University Teaching ...

African Journals Online (AJOL)

Introduction: Primary malignant bone tumours include malignancies arising primarily from bone tissue. This is opposed to secondary bone tumours in which case the neoplastic elements arise primarily from other sites within the body and secondarily spread to bone. Primary malignant bone tumours are generally ...

Malignant insulinoma: The problems of tumour localization and ...

African Journals Online (AJOL)

Malignant insulinomas of the pancreas are rare tumours, accounting for 10% of ... Histological examination showed a R-cell malignant tumour of the pancreas with ... Associated vaso-. SA MEDICAL JOURNAL VOLUME 63 23 APRIL 1983 ... 52 cases of pancreatic endocrine malignant tumours, which have similar behaviour.

Narrative skills of children treated for brain tumours: The impact of tumour and treatment related variables on microstructure and macrostructure.

Science.gov (United States)

Docking, Kimberley; Munro, Natalie; Marshall, Tara; Togher, Leanne

2016-01-01

The narrative skills of children with brain tumours were examined. Influence of tumour location, radiotherapy, time post-treatment and presence of hydrocephalus was also investigated, as well as associations between narrative and language abilities. Seventeen children (aged 5;6-14;11) treated for brain tumour and their matched controls completed a narrative assessment and comprehensive language testing. Audio recorded narratives were analysed for microstructure and macrostructure elements. Between-group comparisons were conducted. Narrative elements were explored in association with tumour and treatment-related variables. Correlation analysis examined relationships between narrative scores and language test performance. While significant differences were not found between two groups of children across narrative elements, sub-group comparisons revealed marginal differences in macrostructure related to tumour location and hydrocephalus. Children treated with methods other than radiotherapy showed a significant increase in number of mazes in their narratives compared to children who received radiotherapy. Strong positive correlations also existed between narrative elements and language performance. Preliminary findings highlight the importance of investigating narrative abilities as part of a comprehensive language assessment. Macrostructure should be routinely examined where children are diagnosed with either posterior fossa tumour or hydrocephalus or have undergone surgery and/or chemotherapy for brain tumour.

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

Science.gov (United States)

Moch, Holger; Cubilla, Antonio L; Humphrey, Peter A; Reuter, Victor E; Ulbright, Thomas M

2016-07-01

The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "blue book"), published in 2016, contains significant revisions. These revisions were performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions. This review summarizes the most significant differences between the newly published classification and the prior version for renal, penile, and testicular tumours. Newly recognized epithelial renal tumours are hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome-associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, acquired cystic disease-associated RCC, and clear cell papillary RCC. The WHO/International Society of Urological Pathology renal tumour grading system was recommended, and the definition of renal papillary adenoma was modified. The new WHO classification of penile squamous cell carcinomas is based on the presence of human papillomavirus and defines histologic subtypes accordingly. Germ cell neoplasia in situ (GCNIS) of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours, and testicular germ cell tumours are now separated into two fundamentally different groups: those derived from GCNIS and those unrelated to GCNIS. Spermatocytic seminoma has been designated as a spermatocytic tumour and placed within the group of non-GCNIS-related tumours in the 2016 WHO classification. The 2016 World Health Organization (WHO) classification contains new renal tumour entities. The classification of penile squamous cell carcinomas is based on the presence of human papillomavirus. Germ cell neoplasia in situ of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All

Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

DEFF Research Database (Denmark)

Sørensen, M D; Dahlrot, R H; Boldt, H B

2018-01-01

AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...... automated quantitative double immunofluorescence. METHODS: Samples from 240 patients with primary glioma were stained with antibodies against ionized calcium-binding adaptor molecule-1 (IBA-1) and cluster of differentiation 204 (CD204) to detect TAMs and M2-like TAMs. The expression levels were quantified...... by software-based classifiers. The associations between TAMs, gemistocytic cells and glioblastoma subtype were examined with immuno- and haematoxylin-eosin stainings. Three tissue arrays containing glioblastoma specimens were included to study IBA-1/CD204 levels in central tumour and tumour periphery...

Haematogenous tumour growth in the inferior vena cava in a patient with a nonseminomatous testicular tumour

NARCIS (Netherlands)

Ham, S J; Koops, H Schraffordt; Sleijfer, D T; Freling, N M; Molenaar, W M

1991-01-01

The case history is reported of a patient with an invasion of the inferior vena cava by metastases of a non-seminomatous testicular tumour. He was treated with combination chemotherapy, followed by laparotomy and resection of residual tumour tissue. Fourteen months after this operation he is in good

Primary Central Nervous System Tumours in Children and ...

African Journals Online (AJOL)

Primary CNS tumours are the commonest childhood solid tumours in most developed countries, accounting for 25-30% of cases. In our environment they occur less frequently. These tumours are nonetheless the cause of significant morbidity and mortality in the paediatric age group worldwide. However paediatric CNS ...

Primitive neuroectodermal tumour of the kidney: radiologic-pathological correlations.

Science.gov (United States)

Chea, Y W; Agrawal, Rashi; Poh, Angeline C C

2008-06-01

A primitive neuroectodermal tumour of the kidney is a rare malignancy. We report the computed tomographic features and the histopathological correlation of such a tumour occurring in a middle-aged man. Although the radiological appearance has significant overlap with other renal tumours, this tumour should be included in the differential diagnosis of a large renal mass in younger patients.

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.

Positron emission tomography (PET) and pancreatic tumours

International Nuclear Information System (INIS)

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

2005-01-01

Neoplasms of the pancreas may originate front both exocrine and endocrine cells but in 90% of the cases, they correspond to ductal adenocarcinomas. For adenocarcinomas, the major indication of FDG-PET corresponds to the pre-operative staging because unexpected distant metastases can be detected by FDG-PET in about 20 to 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. For the characterisation of the pancreatic tumour, the performance of FDG-PET is sometimes limited due to poor cellularity, hyperglycemia or inflammatory processes. especially for large tumours and is indicated only in cases of doubtful results of CT or MRI. For endocrine pancreatic tumours, FDG-PET is useful only in case of poorly-differentiated and aggressive tumours. F-DOPA PET can he useful, complementary to pentetreotide scintigraphy, in well-differentiated endocrine tumours. (authors)

Pathology of Neuroendocrine Tumours of the Female Genital Tract.

Science.gov (United States)

Howitt, Brooke E; Kelly, Paul; McCluggage, W Glenn

2017-09-01

Neuroendocrine tumours are uncommon or rare at all sites in the female genital tract. The 2014 World Health Organisation (WHO) Classification of neuroendocrine tumours of the endometrium, cervix, vagina and vulva has been updated with adoption of the terms low-grade neuroendocrine tumour and high-grade neuroendocrine carcinoma. In the endometrium and cervix, high-grade neoplasms are much more prevalent than low-grade and are more common in the cervix than the corpus. In the ovary, low-grade tumours are more common than high-grade carcinomas and the term carcinoid tumour is still used in WHO 2014. The term ovarian small-cell carcinoma of pulmonary type is included in WHO 2014 for a tumour which in other organs is termed high small-cell neuroendocrine carcinoma. Neuroendocrine tumours at various sites within the female genital tract often occur in association with other neoplasms and more uncommonly in pure form.

Relevance of high-dose chemotherapy in solid tumours

NARCIS (Netherlands)

Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with

Irradiation-induced tumours of the head and neck

Energy Technology Data Exchange (ETDEWEB)

Aanesen, J P; Olofsson, J [Linkoepings Hoegskola (Sweden)

1979-09-01

Though irradiation-induced tumours are uncommon, they represent a well defined entity. At this Hospital, 14 irradiation-induced head and neck tumours were encountered in 11 patients over a 10-year period. The irradiation had been given for tuberculous lymphadenitis in 6 of the patients, for lupus vulgaris in one, and thyrotoxicosis in another; the other 3 patients had received radiotherapy for malignant tumours. The interval between the treatment and the diagnosis of the tumour disease ranged from 9 to 48 years (mean 32). Three of the patients had multiple tumours. In view of the risk of cancer-albeit a small one-associated with radiological diagnosis and radiotherapy, these should be performed only on strict indications, expecially in young patients.

Skull base tumours

Energy Technology Data Exchange (ETDEWEB)

Borges, Alexandra [Instituto Portugues de Oncologia Francisco Gentil, Servico de Radiologia, Rua Professor Lima Basto, 1093 Lisboa Codex (Portugal)], E-mail: borgesalexandra@clix.pt

2008-06-15

With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base.

Skull base tumours

International Nuclear Information System (INIS)

Borges, Alexandra

2008-01-01

With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base

Carcinoid tumour of the middle ear

LENUS (Irish Health Repository)

Baig, Salman

2012-09-01

A case of middle ear mass in a young female from Ireland is described, who presented with left ear hearing loss and intermittent bloody discharge from the same ear. Examination under microscope revealed occlusive polyp in the left ear and a biopsy had been taken under general anaesthesia. Histopathology report described an adenoma \\/ carcinoid tumour of the middle ear confirmed by positive immunohistochemical staining. CT temporal bones revealed the extension of the disease. The patient underwent left tympanotomy and excision of the tumour. In general, these tumours are regarded as benign but may be mistaken for adenocarcinomas because of their histological heterogenecity.

Discrimination of paediatric brain tumours using apparent diffusion coefficient histograms

International Nuclear Information System (INIS)

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

2012-01-01

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

Augmented reality in bone tumour resection

Science.gov (United States)

Park, Y. K.; Gupta, S.; Yoon, C.; Han, I.; Kim, H-S.; Choi, H.; Hong, J.

2017-01-01

Objectives We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143. PMID:28258117

Histopathological review of breast tumours in children and ...

African Journals Online (AJOL)

... of all tumours followed by tubular adenoma (n = 11; 8.2%) and adenosis (n = 10; 7.4%). No case of malignancy was recorded in this study. Conclusion: Fibroadenoma is the most common breast tumour in children and adolescents in our environment. Key words: Adolescents, breast tumours, childhood, fi broadenoma ...

Paediatric laryngeal granular cell tumour

Directory of Open Access Journals (Sweden)

Dauda Ayuba

2009-01-01

Full Text Available Granular cell tumour (GCT affecting the larynx is not common, especially in children. Most cases are apt to be confused with respiratory papilloma and may even be mistaken for a malignant neoplasia. We present a case of laryngeal GCT in a 12-year-old child to emphasize that the tumour should be regarded in the differential of growths affecting the larynx in children.

Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumour growth and sensitises to irinotecan in vivo.

Science.gov (United States)

Murray, Jayne; Valli, Emanuele; Yu, Denise M T; Truong, Alan M; Gifford, Andrew J; Eden, Georgina L; Gamble, Laura D; Hanssen, Kimberley M; Flemming, Claudia L; Tan, Alvin; Tivnan, Amanda; Allan, Sophie; Saletta, Federica; Cheung, Leanna; Ruhle, Michelle; Schuetz, John D; Henderson, Michelle J; Byrne, Jennifer A; Norris, Murray D; Haber, Michelle; Fletcher, Jamie I

2017-09-01

The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

International Nuclear Information System (INIS)

Bacman, David; Merkel, Susanne; Croner, Roland; Papadopoulos, Thomas; Brueckl, Wolfgang; Dimmler, Arno

2007-01-01

Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2

Life history, immunity, Peto's paradox and tumours in birds.

Science.gov (United States)

Møller, A P; Erritzøe, J; Soler, J J

2017-05-01

Cancer and tumours may evolve in response to life-history trade-offs between growth and duration of development on one hand, and between growth and maintenance of immune function on the other. Here, we tested whether (i) bird species with slow developmental rates for their body size experience low incidence of tumours because slow development allows for detection of rapid proliferation of cell lineages. We also test whether (ii) species with stronger immune response during development are more efficient at detecting tumour cells and hence suffer lower incidence of tumours. Finally, we tested Peto's paradox, that there is a positive relationship between tumour incidence and body mass. We used information on developmental rates and body mass from the literature and of tumour incidence (8468 birds) and size of the bursa of Fabricius for 7659 birds brought to a taxidermist in Denmark. We found evidence of the expected negative relationship between incidence of tumours and developmental rates and immunity after controlling for the positive association between tumour incidence and body size. These results suggest that evolution has modified the incidence of tumours in response to life history and that Peto's paradox may be explained by covariation between body mass, developmental rates and immunity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Tumour cell expansion in bladder epithelium

NARCIS (Netherlands)

J.M.J. Rebel (Annemarie)

1995-01-01

textabstractBladder cancer is common in western society. The major problem of patients with superficial bladder cancer is the high recurrence rate and multifocality of these tumours. In 70 % of the patients superficial bladder cancer recurs after local resection of the tumour within 15 years. The

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.

The mechanism of 67Ga uptake in animal and human tumours

International Nuclear Information System (INIS)

Hammersley, P.A.G.; Cronshaw, S.; Taylor, D.M.; Kernforschungszentrum Karlsruhe G.m.b.H.

1980-01-01

The subcellular distribution of 67 Ga has been studied by differential centrifugation in 3 transplantable mouse tumours, 3 transplantable rat tumours, 1 dog tumour, 3 human tumour xenografts and 2 human tumours in situ at various times after injection of the citrate complex. From 24 h post injection the nuclide was located predominantly in lysosomal structures in all the tumours studied. Studies in two murine tumours showed marked differences in the rate of lysosomal accumulation of 67 Ga. In the ADJ/PC6 plasmacytoma lysosomal uptake of 67 Ga had reached a plateau within 15 min while in the S180 tumour lysosomal accumulation of the nuclide occurred over the first 24 h. Normal mouse liver showed a similar pattern to this latter tumour. It is postulated that these variations in the rate of lysosomal accumulation of 67 Ga reflect differences in the permeability of the lysosomal membrane. While large amounts of 67 Ga were found in the crude nuclear fraction of some tumours this was attributed to unbroken cells as studies with purified nuclei from 7 different tumours indicated that between 2 and 14% of the total tumour 67 Ga was associated with the nuclei. (orig.)

Role of tumour necrosis factor in pathogenesis of radicular cyst

International Nuclear Information System (INIS)

Qureshi, W.U.R.; Idris, M.; Khan, S.A.

2011-01-01

Background: The radicular cyst is very common odontogenic cyst of the jaws, which is usually associated with a tooth with necrotic pulp. The cyst formation requires proliferation of the epithelial rest cells of Malassez present in the periodontal ligament. Proliferation of epithelial rest cells of Malassez is an essential event in the Pathogenesis of radicular cyst. The wall of the cyst contains epithelial cells, macrophages, fibroblasts and other cells. TNF is one of inflammatory mediators, which is produced by macrophages and monocytes. This study was carried out to investigate the role of tumour necrosis factor in the pathogenesis of radicular cyst, which is by far the commonest cystic lesion of the jaws. Methods: Explants from 20 radicular cysts were cultured in vitro to grow the epithelial cells. However, the cultures were rapidly contaminated with fibroblasts and it was impossible to grow the epithelial cells separately. Therefore, the proliferative effect of Tumour Necrosis Factor (TNF) was studied on mammalian epithelial cells. Results: TNF at low concentration had a proliferative effect on the epithelial cells, which may play some role in pathogenesis of radicular cyst. Conclusion: TNF stimulated the epithelial cell proliferation in low concentration and inhibit the proliferation in higher concentrations. These two effects may have some implications in the pathogenesis of radicular cyst. (author)

Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

DEFF Research Database (Denmark)

Sørensen, M D; Dahlrot, R H; Boldt, H B

2018-01-01

(+) TAMs co-expressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia-inducible factor-1α. CONCLUSIONS: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold......AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...

The hypoxic tumour cell in radiation therapy

International Nuclear Information System (INIS)

Trott, K.R.; Gesellschaft fuer Strahlen- und Umweltforschung m.b.H., Neuherberg/Muenchen

1976-01-01

In most tumours there is a disproportion between the tumour cells and vascular connective tissue. A lack of oxygen depending on extent and duration, leads to changes of the metabolism and of the proliferative properties of the cells, to an increase of radiation resistance and to a reduction of the ability to recover from radiation injuries. Finally with longer duration, hypoxy leads to cell killing. As a result of irradiation, a reoxygenation of a part of the previous hypoxic tumour cell occurs more or less quickly. The time and topographic changes of these factors are involved in a complex manner in the radiotherapy of malignant tumours and essentially share the responsibility regarding the curative success of radiotherapy. (orig./LH) [de

New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours.

Science.gov (United States)

Speight, Paul M; Takata, Takashi

2018-03-01

The latest (4th) edition of the World Health Organization Classification of Head and Neck tumours has recently been published with a number of significant changes across all tumour sites. In particular, there has been a major attempt to simplify classifications and to use defining criteria which can be used globally in all situations, avoiding wherever possible the use of complex molecular techniques which may not be affordable or widely available. This review summarises the changes in Chapter 8: Odontogenic and maxillofacial bone lesions. The most significant change is the re-introduction of the classification of the odontogenic cysts, restoring this books status as the only text which classifies and defines the full range of lesions of the odontogenic tissues. The consensus group considered carefully the terminology of lesions and were concerned to ensure that the names used properly reflected the best evidence regarding the true nature of specific entities. For this reason, this new edition restores the odontogenic keratocyst and calcifying odontogenic cyst to the classification of odontogenic cysts and rejects the previous terminology (keratocystic odontogenic tumour and calcifying cystic odontogenic tumour) which were intended to suggest that they are true neoplasms. New entities which have been introduced include the sclerosing odontogenic carcinoma and primordial odontogenic tumour. In addition, some previously poorly defined lesions have been removed, including the ameloblastic fibrodentinoma, ameloblastic fibro-odontoma, which are probably developing odontomas, and the odontoameloblastoma, which is not regarded as an entity. Finally, the terminology "cemento" has been restored to cemento-ossifying fibroma and cemento-osseous dysplasias, to properly reflect that they are of odontogenic origin and are found in the tooth-bearing areas of the jaws.

Primitive neuroectodermal tumour of the kidney with vena caval and atrial tumour thrombus: a case report

Directory of Open Access Journals (Sweden)

Ong Poh

2008-08-01

Full Text Available Abstract Introduction Renal primitive neuroectodermal tumour is an extremely rare malignancy. Case presentation A 21-year-old woman presented with microscopic haematuria, a palpable right loin mass, dyspnoea, dizziness and fatigue. Initial ultrasound scan of the kidneys revealed an 11 cm right renal mass with venous extension into the inferior vena cava. Computed tomography of the thorax and abdomen revealed an extension of the large renal mass into the right renal vein, inferior vena cava and up to the right atrium. A small paracaval lymph node was noted and three small metastatic nodules were identified within the lung parenchyma. The patient underwent a radical nephrectomy and inferior vena caval tumour (level IV thrombectomy with cardiopulmonary bypass and deep hypothermic circulatory arrest. Immunohistochemical staining of the specimen showed a highly specific cluster of differentiation (CD 99, thus confirming the diagnosis of a primitive neuroectodermal tumour. Conclusion It is important that a renal primitive neuroectodermal tumour be considered, particularly in young patients with a renal mass and extensive thrombus.

Prognostic impact of nomogram based on whole tumour size, tumour disappearance ratio on CT and SUVmax on PET in lung adenocarcinoma

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Song, So Hee; Lee, Ho Yun; Kim, Eun Young; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Gangnam-Gu, Seoul (Korea, Republic of); Ahn, Joong Hyun [Samsung Biomedical Research Institute, Biostatistics Team, Seoul (Korea, Republic of); Lee, Geewon [Pusan National University Hospital, Pusan National University School of Medicine, Department of Radiology and Medical Research Institute, Busan (Korea, Republic of); Choi, Joon Young [Sungkyunkwan University School of Medicine, Departments of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Kang, Jun [Catholic University of Korea, Department of Pathology, Inchun St. Mary' s Hospital, College of Medicine, Inchun (Korea, Republic of); Han, Joungho [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of); Kwon, O.J. [Sungkyunkwan University School of Medicine, Division of Respiratory and Critical Medicine of the Department of Internal Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Shim, Young Mog [Sungkyunkwan University School of Medicine, Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Seoul (Korea, Republic of)

2016-06-15

Lung adenocarcinoma frequently manifests as subsolid nodules, and the solid portion and ground-glass-opacity (GGO) portion on CT have different prognostic significance. Therefore, current T descriptor, defined as the whole tumour diameter without discrimination between solid and GGO, is insufficient. We aimed to determine the prognostic significance of solid tumour size and attempt to include prognostic factors such as tumour disappearance rate (TDR) on CT and SUVmax on PET/CT. Five hundred and ninety-five patients with completely resected lung adenocarcinoma were analyzed. We developed a nomogram using whole tumour size, TDR, and SUVmax. External validation was performed in another 102 patients. In patients with tumours measuring ≤2 cm and >2 to 3 cm, disease free survival (DFS) was significantly associated with solid tumour size (P < 0.001), but not with whole tumour size (P = 0.052). Developed nomogram was significantly superior to the conventional T stage (area under the curve of survival ROC; P = 0.013 by net reclassification improvement) in stratification of patient survival. In the external validation group, significant difference was noted in DFS according to proposed T stage (P = 0.009). Nomogram-based T descriptors provide better prediction of survival and assessment of individual risks than conventional T descriptors. (orig.)

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

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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.

The epidemiology of neonatal tumours. Report of an international working group.

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Moore, S W; Satgé, D; Sasco, A J; Zimmermann, A; Plaschkes, J

2003-09-01

Neonatal tumours occur every 12,500-27,500 live births and comprise 2% of childhood malignancies, but there is little clarity as to their real prevalence, sites of origin and pathological nature as reported series vary. As an entity, neonatal tumours provide a unique window of opportunity to study tumours in which minimal environmental interference has occurred. The majority of tumours present with a mass at birth (e.g., teratomas, neuroblastomas, mesoblastic nephroma, fibromatosis), which are not infrequently identified on antenatal ultrasound. Histologically, teratoma and neuroblastoma remain the two main tumour types encountered with soft tissue sarcoma, renal tumours, CNS tumours and leukaemia being the next most common tumour types identified. Malignant tumours are uncommon in the neonatal period per se and benign tumours may have malignant potential. A particular problem exists in clinical classification, as histological features of malignancy do not always correlate with clinical behaviour. Benign tumours may also be life threatening because of their size and location. Other tumours may demonstrate local invasiveness, but no metastatic potential, and tumours that are clearly malignant may demonstrate unpredictable or uncertain behaviour. Screening programmes have brought more tumours to light, but do not appear to affect the overall prognosis. They may provide clues to the stage at which tumours develop in foetu. The aetiology of cancer in children is multifactorial and includes both genetic and environmental factors. The association between congenital abnormalities and tumours is well established (15% of neonatal tumours). Genetic defects are highly likely in neonatal tumours and include those with a high risk of malignancy (e.g., retinoblastoma), but also genetically determined syndromes with an increased risk of malignancy and complex genetic rearrangements. Tumours are mostly genetically related at a cellular level and factors influencing cellular

Non-invasive vascular imaging: assessing tumour vascularity

International Nuclear Information System (INIS)

Delorme, S.; Knopp, M.V.

1998-01-01

Non-invasive assessment of vascularity is a new diagnostic approach to characterise tumours. Vascular assessment is based on the pathophysiology of tumour angiogenesis and its diagnostic implications for tumour biology, prognosis and therapy response. Two current techniques investigating vascular features in addition to morphology are Doppler ultrasonography and contrast-enhanced MRI. Diagnostic differentiation has been shown to be possible with Doppler, and a high degree of observed vascularity could be linked to an aggressive course of the disease. Dynamic MRI using gadolinium chelates is already used clinically to detect and differentiate tumours. The histological correlation shows that capillary permeability is increased in malignant tumours and is the best criterion for differentiation from benign processes. Permeability and perfusion factors seem to be more diagnostic than overall vessel density. New clinical applications are currently being established for therapy monitoring. Further instrumental developments will bring harmonic imaging in Doppler, and faster imaging techniques, higher spatial resolution and novel pharmacokinetic concepts in MRI. Upcoming contrast agents for both Doppler and MRI will further improve estimation of intratumoural blood volume and vascular permeability. (orig.)

A database survey of equine tumours in the United Kingdom.

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Knowles, E J; Tremaine, W H; Pearson, G R; Mair, T S

2016-05-01

Survey data on equine tumours are sparse compared with other species and may have changed over time. To describe the most frequently diagnosed equine tumours recorded by a diagnostic pathology laboratory over 29 years, to identify background factors associated with tumour type, and to identify any changes in the tumours diagnosed or the background of cases submitted during the study period. Observational; cross-sectional analysis of records of a diagnostic pathology laboratory. The records of all neoplastic equine histology submissions to the University of Bristol (January 1982-December 2010) were accessed from a database, and a list of diagnoses compiled. The 6 most commonly diagnosed tumour types were analysed using logistic regression to identify background factors associated with tumour type. The overall population of equine tumour submissions and the relative frequency of diagnosis of the most common tumour types were compared between decades. There were 964 cases included. The most frequently diagnosed tumours were: sarcoid (24% cases), squamous cell carcinoma (SCC) (19%), lymphoma (14%), melanoma (6%), gonadal stromal tumour (6%) and mast cell tumour (MCT) (4%). With sarcoid, Thoroughbred/Thoroughbred cross and gelding as reference categories: increasing age was significantly associated with the odds of each of the other tumour types, mares were at reduced risk of SCC, Arab/Arab cross had a higher risk of MCT, Cob/Cob cross had an increased risk of SCC and MCT, and ponies had an increased risk of melanoma. The mean age of submissions increased in each successive decade and the breed composition became broader. Sarcoids and lymphoma formed a smaller proportion of diagnoses in later decades. The types of tumours submitted to this laboratory have changed over the last 3 decades. Current data inform clinicians and researchers and further studies are warranted to follow trends. © 2015 EVJ Ltd.

Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis.

Science.gov (United States)

Cui, Qi; Yang, Su; Ye, Peng; Tian, E; Sun, Guoqiang; Zhou, Jiehua; Sun, Guihua; Liu, Xiaoxuan; Chen, Chao; Murai, Kiyohito; Zhao, Chunnian; Azizian, Krist T; Yang, Lu; Warden, Charles; Wu, Xiwei; D'Apuzzo, Massimo; Brown, Christine; Badie, Behnam; Peng, Ling; Riggs, Arthur D; Rossi, John J; Shi, Yanhong

2016-02-03

Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma.

An experimental study of tumour size and radiosensitivity

International Nuclear Information System (INIS)

Hill, S.A.; Denekamp, J.

1989-01-01

When designing experimental studies of tumours, it is considered important to control all variables that might alter the radiosensitivity and hence influence the variability of the data. One such variable is tumour size. We have studied the regrowth delay of a mammary carcinoma treated at 2-10 mm mean diameter (a 125-fold change of volume) with X-rays alone or X-rays plus misonidazole (MISO). The data were analysed to give dose-response curves, using four endpoints. Regrowth to a fixed size (4.5 mm larger than treatment size), or by a fixed increment (4 times the original volume) was expressed either as absolute delay, or as specific growth delay to allow for the changes in volume doubling time as the tumour grows. The method of analysis made no difference to the measured sensitizer enhancement ratio (SER) for MISO. The SER was dose-dependent, being higher doses, but was not different in tumours of 2 or 10 mm diameter. However, when comparing response to X-rays alone, the method of analysis made a very big difference to the conclusions. Regrowth to R + 4.5 mm showed no change in radiosensitivity with tumour size, but regrowth to 4 times the original volume (the most logical endpoint) indicated that large tumours were more sensitive than small. We conclude that regrowth delay may be an inappropriate method for comparing absolute sensitivities of tumours of different sizes. However, for studying the effectiveness of a radiomodifier the constraints of tumour size at irradiation seem to be less severe than previously believed. (author). 8 refs.; 8 figs

STUDY OF PAEDIATRIC SOLID TUMOURS FOR A PERIOD OF 5 YEARS

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Basumitra Das

2017-12-01

Full Text Available BACKGROUND Paediatric Solid Neoplasms (PSN are a global problem. There is significant variation of incidence of paediatric solid neoplasms in various regions of the world. Benign tumours are more common than cancer. In an effort to better understand the prevalence of paediatric solid tumours in our region, a retrospective review of the tumours diagnosed histopathologically was carried out. MATERIALS AND METHODS This is a retrospective study undertaken in a tertiary care hospital for a period of five years. All the benign and malignant paediatric solid tumours of children below 14 years from January 2012 to December 2016 were retrieved and analysed according to age, sex and histopathological diagnosis. Leukaemias were excluded from our study. All tumours were diagnosed on conventional haematoxylin and eosin-stained sections. RESULTS A total of 109 cases of solid paediatric tumours were received during this period. Of these, maximum of 30 tumours were of soft tissue tumours followed by Central Nervous System (CNS and bone tumours with 24 and 23 cases, respectively. 7 cases of blastomas were also observed. CONCLUSION This study showed benign and malignant tumours to be of near-equal prevalence. Soft tissue tumours were the most common. Ratio of benign tumours to malignant were almost equal below 4 years. Malignant tumours were higher in 5-9 years group.

Childhood vascular Tumours in Benin City, Nigeria | Igbe | Annals of ...

African Journals Online (AJOL)

Background: Vasoformative tumours are one of the commonest tumours in childhood. The patterns of these tumours in Benin City, however, are not known. Objective: To determine the incidence and morphological patterns of childhood vascular tumours as seen in the Department of Pathology University of Benin Teaching ...

In vitro effects of substance P analogue [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P on human tumour and normal cell growth.

OpenAIRE

Everard, M. J.; Macaulay, V. M.; Miller, J. L.; Smith, I. E.

1992-01-01

Analogues of the neurotransmitter substance P (SP) can interact with neuropeptide receptors, and are reported to inhibit growth of small cell lung cancer cell lines (SCLC CLs). We found [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P (D-Phe5SP) significantly inhibited DNA synthesis by 10/10 human tumour CLs; six SCLC, one N-SCLC (squamous), two ovarian and one squamous cervical carcinoma, with inhibition to 50% control levels (IC50) of 20-50 microM. There was dose dependent inhibition of colony...

Haemorrhagic pituitary tumours

International Nuclear Information System (INIS)

Lazaro, C.M.; Philippine General Hospital, Manila; Guo, W.Y.; Sami, M.; Hindmarsch, T.; Ericson, K.; Hulting, A.L.; Wersaell, J.

1994-01-01

In a group of 69 patients with pituitary tumours, 12 were found to have evidence of intratumoral haemorrhage on MRI, characterized by high signal intensity on short TR/TE sequences. This was verified in all but 1 patient. The majority of the bleedings occurred in macroadenomas. Five (42%) were prolactinomas and 4 (33%) were non-functioning adenomas. There were 2 GH- and 1 ACTH-secreting tumours. All 5 patients with prolactinomas were on bromocriptine medication. Two of the patients had a clinical picture of pituitary apoplexy. The haemorrhage was not large enough to prompt surgery in any of the patients. However, surgical verification of the diagnosis was obtained in 5 cases, while 6 patients were examined with follow-up MRI. (orig.)

Automatic tumour volume delineation in respiratory-gated PET images

International Nuclear Information System (INIS)

Gubbi, Jayavardhana; Palaniswami, Marimuthu; Kanakatte, Aparna; Mani, Nallasamy; Kron, Tomas; Binns, David; Srinivasan, Bala

2011-01-01

Positron emission tomography (PET) is a state-of-the-art functional imaging technique used in the accurate detection of cancer. The main problem with the tumours present in the lungs is that they are non-stationary during each respiratory cycle. Tumours in the lungs can get displaced up to 2.5 cm during respiration. Accurate detection of the tumour enables avoiding the addition of extra margin around the tumour that is usually used during radiotherapy treatment planning. This paper presents a novel method to detect and track tumour in respiratory-gated PET images. The approach followed to achieve this task is to automatically delineate the tumour from the first frame using support vector machines. The resulting volume and position information from the first frame is used in tracking its motion in the subsequent frames with the help of level set (LS) deformable model. An excellent accuracy of 97% is obtained using wavelets and support vector machines. The volume calculated as a result of the machine learning (ML) stage is used as a constraint for deformable models and the tumour is tracked in the remaining seven phases of the respiratory cycle. As a result, the complete information about tumour movement during each respiratory cycle is available in relatively short time. The combination of the LS and ML approach accurately delineated the tumour volume from all frames, thereby providing a scope of using PET images towards planning an accurate and effective radiotherapy treatment for lung cancer.

Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours.

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Ujvari, Beata; Pearse, Anne-Maree; Swift, Kate; Hodson, Pamela; Hua, Bobby; Pyecroft, Stephen; Taylor, Robyn; Hamede, Rodrigo; Jones, Menna; Belov, Katherine; Madsen, Thomas

2014-02-01

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial.

Tumour therapy with radionuclides: assessment of progress and problems

International Nuclear Information System (INIS)

Carlsson, Joergen; Forssell Aronsson, Eva; Hietala, Sven-Ola; Stigbrand, Torgny; Tennvall, Jan

2003-01-01

Radionuclide therapy is a promising modality for treatment of tumours of haematopoietic origin while the success for treatment of solid tumours so far has been limited. The authors consider radionuclide therapy mainly as a method to eradicate disseminated tumour cells and small metastases while bulky tumours and large metastases have to be treated surgically or by external radiation therapy. The promising therapeutic results for haematological tumours give hope that radionuclide therapy will have a breakthrough also for treatment of disseminated cells from solid tumours. New knowledge related to this is continuously emerging since new molecular target structures are being characterised and the knowledge on pharmacokinetics and cellular processing of different types of targeting agents increases. There is also improved understanding of the factors of importance for the choice of appropriate radionuclides with respect to their decay properties and the therapeutic applications. Furthermore, new methods to modify the uptake of radionuclides in tumour cells and normal tissues are emerging. However, we still need improvements regarding dosimetry and treatment planning as well as an increased knowledge about the tolerance doses for normal tissues and the radiobiological effects on tumour cells. This is especially important in targeted radionuclide therapy where the dose rates often are lower than 1 Gy/h

Anti-tumour activity in RAS-driven tumours by blocking AKT and MEK

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Tolcher, Anthony W.; Khan, Khurum; Ong, Michael; Banerji, Udai; Papadimitrakopoulou, Vassiliki; Gandara, David R.; Patnaik, Amita; Baird, Richard D.; Olmos, David; Garrett, Christopher R.; Skolnik, Jeffrey M.; Rubin, Eric H.; Smith, Paul D.; Huang, Pearl; Learoyd, Maria; Shannon, Keith A.; Morosky, Anne; Tetteh, Ernestina; Jou, Ying-Ming; Papadopoulos, Kyriakos P.; Moreno, Victor; Kaiser, Brianne; Yap, Timothy A.; Yan, Li; de Bono, Johann S.

2014-01-01

Purpose KRAS is the most commonly mutated oncogene in human tumours. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. Experimental Design We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumours. Recommended dosing schedules were defined as MK-2206 135 mg weekly and selumetinib 100 mg once-daily. Results Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhoea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug-drug interactions. Clinical anti-tumour activity included RECIST 1.0-confirmed partial responses in non-small cell lung cancer and low-grade ovarian carcinoma. Conclusion Responses in KRAS-mutant cancers were generally durable. Clinical co-targeting of MEK and AKT signalling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748). PMID:25516890

Low-energy electron emitters for targeted radiotherapy of small tumours

International Nuclear Information System (INIS)

Bernhardt, Peter; Forssell-Aronsson, Eva; Jacobsson, Lars; Skarnemark, Gunnar

2001-01-01

The possibility of using electron emitters to cure a cancer with metastatic spread depends on the energy of the emitted electrons. Electrons with high energy will give a high, absorbed dose to large tumours, but the absorbed dose to small tumours or single tumour cells will be low, because the range of the electrons is too long. The fraction of energy absorbed within the tumour decreases with increasing electron energy and decreasing tumour size. For tumours smaller than 1 g, the tumour-to-normal-tissue mean absorbed dose-rate ratio, TND, will be low, e.g. for 131 I and 90 Y, because of the high energy of the emitted electrons. For radiotherapy of small tumours, radionuclides emitting charged particles with short ranges (a few m u m ) are required. A mathematical model was constructed to evaluate the relation between TND and electron energy, photon-to-electron energy ratio, p/e, and tumour size. Criteria for the selection of suitable radionuclides for the treatment of small tumours were defined based on the results of the TND model. In addition, the possibility of producing such radionuclides and their physical and chemical properties were evaluated. Based on the mathematical model, the energy of the emitted electrons should be = 40 keV for small tumours ( 58m Co, 103m Rh, 119 Sb, 161 Ho, and 189m Os. All of these nuclides by internal transition or electron capture, which yields conversion and Auger electrons, and it should be possible to produce most of them in therapeutic amounts. The five low-energy electron-emitting radionuclides identified may be relevant in the radiation treatment of small tumours, especially if bound to internalizing radiopharmaceuticals

Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats

International Nuclear Information System (INIS)

Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Jong, Johan R. de; Vries, Erik F. de; Dierckx, Rudi A.; Waarde, Aren van; Ishiwata, Kiichi

2009-01-01

Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist 11 C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. 11 C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of 11 C-SA4503 to C6 cells was increased (∝50%) upon removal and decreased (∝60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC 50 progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of 11 C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of 11 C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: model for the hyperparathyroidism-jaw tumour syndrome.

Science.gov (United States)

Walls, G V; Stevenson, M; Lines, K E; Newey, P J; Reed, A A C; Bowl, M R; Jeyabalan, J; Harding, B; Bradley, K J; Manek, S; Chen, J; Wang, P; Williams, B O; Teh, B T; Thakker, R V

2017-07-13

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73 +/- ) and conditional parathyroid-specific (Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73 +/+ and Cdc73 +/+ /PTH-Cre) littermates. Survival of Cdc73 +/- mice, when compared to Cdc73 +/+ mice was reduced (Cdc73 +/- =80%; Cdc73 +/+ =90% at 18 months of age, Pfourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73 +/- , Cdc73 +/L /PTH-Cre and Cdc73 L/L /PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73 +/- mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73 +/- mice did not develop bone or renal tumours but female Cdc73 +/- mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73 +/- mice had increased proliferation rates that were 2-fold higher than in Cdc73 +/+ mice (P<0.05). Thus, our studies, which have established mouse models for parathyroid tumours and uterine neoplasms that develop in the HPT-JT syndrome, provide in vivo models for future studies of these tumours.

TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

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Papadopoulos Thomas

2007-08-01

Full Text Available Abstract Background Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Methods Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4 in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2 vs. high-grade (i.e. grade 3 and 4, lymph node metastasis, distant metastasis, 5 year cancer related survival using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. Results High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and

Endogenous biotin expression in renal and testicular tumours and literature review.

Science.gov (United States)

Fahmy, Nader; Woo, Mark; Alameldin, Mona; Lee, Joe King; MacDonald, Kyle; Goneau, Lee W; Cadieux, Peter; Burton, Jeremy; Pautler, Stephen

2014-07-01

The aim of this study was to examine endogenous biotin levels in tumour specimens collected from patients with renal and testicular tumours and compare them to the surrounding non-neoplastic surgical margin. Frozen samples were obtained from the Ontario Tumour Bank. Renal and testicular tumour tissue were included in this study. Normal tissue from the negative surgical margins of each tumour served as a control. Biotin detection in tissue specimens was determined using immunohistochemistry (IHC). Specimens collected from 56 patients (36 men and 20 women) were included in this study. Histopathology of the 52 renal tumours included 31 (60%) conventional type RCC, 5 (10%) chromophobe RCC, 5 (10%) papillary RCC, 1 (2%) oncocytoma and 10 (19%) upper tract urothelial carcinoma (UC). The 4 testicular tumours included 1 seminomatous (25%) germ cell tumour and 3 (75%) non seminomatous germ cell tumours. No biotin signal was perceived in all tested tumour samples. Endogenous biotin expression was detected in the matching non-neoplastic surgical margin of tested renal tissues. This lack of staining may prove to be a valuable tool in future studies.

The TrkAIII oncoprotein inhibits mitochondrial free radical ROS-induced death of SH-SY5Y neuroblastoma cells by augmenting SOD2 expression and activity at the mitochondria, within the context of a tumour stem cell-like phenotype.

Directory of Open Access Journals (Sweden)

Pierdomenico Ruggeri

Full Text Available The developmental and stress-regulated alternative TrkAIII splice variant of the NGF receptor TrkA is expressed by advanced stage human neuroblastomas (NBs, correlates with worse outcome in high TrkA expressing unfavourable tumours and exhibits oncogenic activity in NB models. In the present study, we report that constitutive TrkAIII expression in human SH-SY5Y NB cells inhibits Rotenone, Paraquat and LY83583-induced mitochondrial free radical reactive oxygen species (ROS-mediated death by stimulating SOD2 expression, increasing mitochondrial SOD2 activity and attenuating mitochondrial free radical ROS production, in association with increased mitochondrial capacity to produce H2O2, within the context of a more tumour stem cell-like phenotype. This effect can be reversed by the specific TrkA tyrosine kinase inhibitor GW441756, by the multi-kinase TrkA inhibitors K252a, CEP-701 and Gö6976, which inhibit SOD2 expression, and by siRNA knockdown of SOD2 expression, which restores the sensitivity of TrkAIII expressing SH-SY5Y cells to Rotenone, Paraquat and LY83583-induced mitochondrial free radical ROS production and ROS-mediated death. The data implicate the novel TrkAIII/SOD2 axis in promoting NB resistance to mitochondrial free radical-mediated death and staminality, and suggest that the combined use of TrkAIII and/or SOD2 inhibitors together with agents that induce mitochondrial free radical ROS-mediated death could provide a therapeutic advantage that may also target the stem cell niche in high TrkA expressing unfavourable NB.

Somatostatin receptor subtype expression in human thyroid tumours.

Science.gov (United States)

Klagge, A; Krause, K; Schierle, K; Steinert, F; Dralle, H; Fuhrer, D

2010-04-01

Somatostatin receptors (SSTR) are expressed in various endocrine tumours. The expression of SSTR at the tumour cell surface confers the possibility for diagnostic imaging and therapy of tumours using radiolabeled somatostatin analogues. The majority of currently available somatostatin analogues show a higher binding affinity for the SSTR2 subtype. To date, the precise expression pattern of the SSTR subtypes 1-5 in thyroid epithelial tumours remains to be determined. We investigated the mRNA expression of SSTR1-5 in benign and malignant epithelial thyroid tumours [20 cold thyroid nodules (CTNs), 20 toxic thyroid nodules (TTNs), 20 papillary, 20 follicular, and 5 anaplastic carcinomas (PTCs, FTCs, ATCs, respectively)] and compared them to normal surrounding thyroid tissues. Four out of five SSTR subtypes were detected in malignant thyroid tumours, benign neoplasia, and normal surrounding tissue with a predominant expression of SSTR2 and SSTR5, and a weak expression of SSTR1 and SSTR3. Weak SSTR4 mRNA expression was detected in some PTCs. Compared to normal thyroid tissue, SSTR2 was significantly upregulated in PTC and ATC. In addition significant upregulation of SSTR3 was found in PTC. SSTR5 mRNA expression was increased in PTC and FTC and significantly decreased in CTN and TTN compared to normal thyroid tissue. SSTR2 is the predominant subtype in thyroid epithelial tumours with a high expression pattern, in particular, in PTC . Perspectively, the expression of distinct SSTR in thyroid epithelial tumours might represent a promising avenue for diagnostics and therapy of advanced thyroid cancer with somatostatin analogues. Georg Thieme Verlag KG Stuttgart New York.

The protein histidine phosphatase LHPP is a tumour suppressor.

Science.gov (United States)

Hindupur, Sravanth K; Colombi, Marco; Fuhs, Stephen R; Matter, Matthias S; Guri, Yakir; Adam, Kevin; Cornu, Marion; Piscuoglio, Salvatore; Ng, Charlotte K Y; Betz, Charles; Liko, Dritan; Quagliata, Luca; Moes, Suzette; Jenoe, Paul; Terracciano, Luigi M; Heim, Markus H; Hunter, Tony; Hall, Michael N

2018-03-29

Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase. Consistent with these observations, global histidine phosphorylation was significantly upregulated in the liver tumours. Sustained, hepatic expression of LHPP in the hepatocellular carcinoma mouse model reduced tumour burden and prevented the loss of liver function. Finally, in patients with hepatocellular carcinoma, low expression of LHPP correlated with increased tumour severity and reduced overall survival. Thus, LHPP is a protein histidine phosphatase and tumour suppressor, suggesting that deregulated histidine phosphorylation is oncogenic.

Tumour-specific radiosensitizers for radiation therapy

International Nuclear Information System (INIS)

Denekamp, J.

1977-01-01

Recently Adams and coworkers at the Gray Laboratory have developed a new class of radiosensitizers which act specifically on hypoxic cells by abolishing the protection afforded by low oxygen concentrations. Since most experimental tumours contain a high proportion of oxygen-deprived cells, and most normal tissues are well oxygenated, these drugs are tumour specific radiosensitizers. Based on the hypothesis that sensitization increases with increasing electron affinity, the two nitroimidazoles, metronidazole (Flagyl) and Ro-07/0582 were identified as potent radiosensitizers with low toxicity. These drugs are effective only in the absence of oxygen, and only if the drug is present at the time of irradiation. The degree of sensitization increases with drug concentration rapidly over the range 0.1 to 1.0mg/g body weight for Ro-07-0582, and more gradually for Flagyl. Tumour studies have been performed on at least 12 different experimental tumours, using a variety of end points. Significant sensitization has been observed in every tumour studied, often corresponding to a dose reduction factor of 2.0 for high but non-toxic drug doses. Fractionated studies have also been performed on a few tumour lines. In most cases a useful therapeutic advantage was observed, although the sensitization was smaller. Ro-07-0582 used with X-rays gives a therapeutic gain comparable with that from cyclotron-produced fast neutrons. Neutrons used together with Ro-07-0582 are even more effective. In addition to the radiosensitization there is a specific cytotoxicity to hypoxic cells after prolonged exposure to Ro-07-0582. This cytotoxicity can be greatly enhanced in vitro by moderate hyperthermia. Flagyl and Ro-07-0582 have been used clinically as radiosensitizers, with promising early results. The clinical application is limited to certain dose fractionation patterns because of neurotoxicity. (author)

Second primary tumours in oral cancer

NARCIS (Netherlands)

van der Waal, I.; de Bree, R.

2010-01-01

Second primary tumours in patients treated for oral cancer occur at a rate of 3% to 7% per year. The majority of these tumours show up at least six months after the detection of the primary and are often located in the upper aerodigestive tract. Cessation of smoking habits may reduce the risk of the

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)

Radiation-induced malignant tumours: a specific cytogenetic profile?

International Nuclear Information System (INIS)

Chauveinc, L.; Gaboriaux, G.; Dutrillaux, A. M.; Dutrillaux, B.; Chauveinc, L.; Ricoul, M.; Sabatier, L.; Dutrillaux, B.

1997-01-01

To date, there is no criterion enabling to determine the spontaneous or radio-induced origin of malignant tumour occurring in a previously irradiated patient. Biological studies are rare. The cytogenetic data which could be found in the literature for eleven radio-induced tumours suggest that aneuploidies and polyclonality are frequent events. We studied, by R-Banding cytogenetic technique, five patients with short-term cultures (3 cases), short and long-term cultures (1 case) and xeno-grafting on nude pattern a high rate of balanced translocations, numerous random break points and a polyclonal evolution (10 clones). All other tumours, including the xeno-grafting sarcoma, had a monoclonal profile with complex karyotypes, hypo-diploid formulas and many deletions. These results show that the mechanism of radiation-induced tumours frequently involves chromosomes losses and deletions. The most likely explanation is that these alterations unmask radiation induced recessive mutations of tumour suppressor genes. (authors)

Endoscopic modified medial maxillectomy for odontogenic cysts and tumours.

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Nakayama, Tsugihama; Otori, Nobuyoshi; Asaka, Daiya; Okushi, Tetsushi; Haruna, Shin-ichi

2014-12-01

Odontogenic maxillary cysts and tumours originate from the tooth root and have traditionally been treated through an intraoral approach. Here, we report the efficacy and utility of endoscopic modified medial maxillectomy (EMMM) for the treatment of odontogenic maxillary cysts and a tumour. We undertook EMMM under general anaesthesia in six patients: four had radicular cysts, one had a dentigerous cyst, and one had a keratocystic odontogenic tumour. The cysts and tumours were completely excised and the inferior turbinate and nasolacrimal duct were preserved in all patients. There were no peri- or postoperative complications, and no incidences of recurrence. Endoscopic modified medial maxillectomy appears to be an effective and safe technique for treating odontogenic cysts and tumours.

Imaging of gastrointestinal stromal tumour (GIST)

International Nuclear Information System (INIS)

Lau, S.; Tam, K.F.; Kam, C.K.; Lui, C.Y.; Siu, C.W.; Lam, H.S.; Mak, K.L.

2004-01-01

Gastrointestinal stromal tumour (GIST) represents the most common kind of mesenchymal tumour that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumour containing spindle cells (or less commonly epithelioid cells or rarely both) and showing CD117 (c-kit protein) positivity. Targeted molecular therapy of non-resectable GIST using imatinib, a specific tyrosine kinase receptor inhibitor, represents a real milestone in the management of solid malignancy. Imaging studies, both anatomical and functional, are playing an increasingly important role in management of patients with GIST. This review illustrates the radiological appearance of GISTs and the site-specific roles of each imaging tool. Clinical features and radiological differential diagnosis of GIST are also discussed

Tumour resistance to cisplatin: a modelling approach

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Marcu, L [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Bezak, E [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Olver, I [Faculty of Medicine, University of Adelaide, North Terrace, SA 5000 (Australia); Doorn, T van [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia)

2005-01-07

Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

Tumour resistance to cisplatin: a modelling approach

International Nuclear Information System (INIS)

Marcu, L; Bezak, E; Olver, I; Doorn, T van

2005-01-01

Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

Regional tumour glutamine supply affects chromatin and cell identity

DEFF Research Database (Denmark)

Højfeldt, Jonas W; Helin, Kristian

2016-01-01

Limited perfusion of solid tumours produces a nutrient-deprived tumour core microenvironment. Low glutamine levels in the tumour core are now shown to lead to reduced levels of α-ketoglutarate and decreased histone demethylase activity, thereby promoting a less differentiated and more therapy-res...

Fas Ligand Expression in Lynch Syndrome-Associated Colorectal Tumours

NARCIS (Netherlands)

Koornstra, Jan J.; de Jong, Steven; Boersma-van Eck, Wietske; Zwart, Nynke; Hollema, Harry; de Vries, Elisabeth G. E.; Kleibeuker, Jan H.

Fas Ligand (FasL) expression by cancer cells may contribute to tumour immune escape via the Fas counterattack against tumour-infiltrating lymphocytes (TILs). Whether this plays a role in colorectal carcinogenesis in Lynch syndrome was examined studying FasL expression, tumour cell apoptosis and

Bilateral ovarian tumour in a young girl | Govindarajan | African ...

African Journals Online (AJOL)

Bilateral ovarian tumour in a girl presents the dilemma of conservative versus aggressive approach towards these tumours. When faced with suspicious tumour and complete replacement of the ovaries bilaterally, bilateral oophorectomy is a viable option, though the certain possibility of infertility and lifelong hormonal ...

Insulin resistance in vascular endothelial cells promotes intestinal tumour formation

DEFF Research Database (Denmark)

Wang, X; Häring, M-F; Rathjen, Thomas

2017-01-01

in vascular endothelial cells. Strikingly, these mice had 42% more intestinal tumours than controls, no change in tumour angiogenesis, but increased expression of vascular cell adhesion molecule-1 (VCAM-1) in primary culture of tumour endothelial cells. Insulin decreased VCAM-1 expression and leukocyte...... adhesion in quiescent tumour endothelial cells with intact insulin receptors and partly prevented increases in VCAM-1 and leukocyte adhesion after treatment with tumour necrosis factor-α. Knockout of insulin receptors in endothelial cells also increased leukocyte adhesion in mesenteric venules...

The Askin tumour. Neuroactodermic tumour of the thoracic wall; Tumor de Askin: tumor neuroectodermico de la pared toracica

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Velazquez, P.; Nicolas, A. I.; Vivas, I.; Damaso Aquerreta, J.; Martinez-Cuesta, A. [Clinica Universitaria de Navarra. Pamplona (Spain)

1999-07-01

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.

Pancreatic pseudopapillary tumour: A rare misdiagnosed entity.

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Affirul, C A; Qisti, F N; Zamri, Z; Azlanuddin, A; Hairol, A O; Razman, J

2014-01-01

Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. We discuss the presentations, diagnosis and pathology findings of this rare pathology. The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

MRI of intraspinal nerve sheath tumours presenting with sciatica

International Nuclear Information System (INIS)

Loke, T.K.L.; Chan, C.S.; Ma, H.T.G.; Ward, S.C.; Metreweli, C.

1995-01-01

The magnetic resonance imaging (MRI) characteristics of 14 intraspinal nerve sheath tumours (NST) presenting with sciatica were reviewed. The group comprised seven schwannomas, six neurofibromas and one perineuroma. The tumours were either iso- or hypointense with respect to spinal cord on T1-weighted (T1W) images; almost all tumours were hyperintense compared with spinal cord on T2-weighted (T2W) images. The tumours were all detectable on unenhanced T1 W images. Nine NST were scanned following Gadolinium-Diethylenetriamine penta acetic acid (DTPA) injection and all showed intense enhancement. This aids differentiation from sequestrated disc fragments. Tumours were more likely to show homogeneous enhancement unless they were recurrent tumours. Rim enhancement occurs more commonly in schwannomas and this can be used to differentiate these from neurofibromas. It is estimated that on unenhanced images, schwannomas cannot be distinguished from neurofibromas. Four tumours occurred at T1 1-T12. There was poor correlation of the site of the lesion with the clinical findings. It is recommended that the MRI studies in patients with sciatica should include the lower thoracic region especially if no protruded disc was found in the lumbar region. 15 refs., 4 figs

MRI of intraspinal nerve sheath tumours presenting with sciatica

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Loke, T.K.L.; Chan, C.S. [United Christian Hospital (Hong Kong). Dept. of Diagnostic Radiology; Ma, H.T.G. [St Teresa`s Hospital, Kowloon (Hong Kong). MRI and CT scanning Dept.; Ward, S.C.; Metreweli, C. [Prince of wales Hospital, New Territories (Hong Kong). Dept. of Diagnostic Radiology

1995-08-01

The magnetic resonance imaging (MRI) characteristics of 14 intraspinal nerve sheath tumours (NST) presenting with sciatica were reviewed. The group comprised seven schwannomas, six neurofibromas and one perineuroma. The tumours were either iso- or hypointense with respect to spinal cord on T1-weighted (T1W) images; almost all tumours were hyperintense compared with spinal cord on T2-weighted (T2W) images. The tumours were all detectable on unenhanced T1 W images. Nine NST were scanned following Gadolinium-Diethylenetriamine penta acetic acid (DTPA) injection and all showed intense enhancement. This aids differentiation from sequestrated disc fragments. Tumours were more likely to show homogeneous enhancement unless they were recurrent tumours. Rim enhancement occurs more commonly in schwannomas and this can be used to differentiate these from neurofibromas. It is estimated that on unenhanced images, schwannomas cannot be distinguished from neurofibromas. Four tumours occurred at T1 1-T12. There was poor correlation of the site of the lesion with the clinical findings. It is recommended that the MRI studies in patients with sciatica should include the lower thoracic region especially if no protruded disc was found in the lumbar region. 15 refs., 4 figs.

Review article: Pathogenesis and management of gastric carcinoid tumours.

Science.gov (United States)

Burkitt, M D; Pritchard, D M

2006-11-01

Gastric carcinoid tumours are rare, but are increasing in incidence. To discuss tumour pathogenesis and outline current approaches to patient management. Review of published articles following a Pubmed search. Although interest in gastric carcinoids has increased since it was recognized that they are associated with achlorhydria, to date there is no definite evidence that humans taking long-term acid suppressing medication are at increased risk. Type I tumours are associated with autoimmune atrophic gastritis and hypergastrinaemia, type II are associated with Zollinger-Ellison syndrome, multiple endocrine neoplasia-1 and hypergastrinaemia and sporadic type III carcinoids are gastrin-independent and carry the worst prognosis. Careful investigation of these patients is required, particularly to identify the tumour type, the source of hypergastrinaemia and the presence of metastases. Treatment can be directed at the source of hypergastrinaemia if type I or II tumours are still gastrin responsive and not growing autonomously. Type III tumours should be treated surgically. Advances in our understanding of the pathogenesis of gastric carcinoids have led to recent improvements in investigation and management. Challenges remain in identifying the genetic and environmental factors, in addition to hypergastrinaemia, that are responsible for tumour development in susceptible patients.

Results of irradiating brain tumours (1959-1969)

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Zu Eulenburg, G

1973-01-01

The results of the radiation treatment of brain tumours were evaluated for 78 patients. The calculated average survival times, as well as the shape of survival curves show, as compared to numerous other authors, that there is no great deviation for any tumour group. The interpretation of the ratio of an amnesis to survival time shows that with fast growing brain tumours as with glioblastoma, the success of radiotherapy is very small. Radiotherapy was well successful in almost all cases of patients with a longer than average anamnesis.

Advanced soft computing diagnosis method for tumour grading.

Science.gov (United States)

Papageorgiou, E I; Spyridonos, P P; Stylios, C D; Ravazoula, P; Groumpos, P P; Nikiforidis, G N

2006-01-01

To develop an advanced diagnostic method for urinary bladder tumour grading. A novel soft computing modelling methodology based on the augmentation of fuzzy cognitive maps (FCMs) with the unsupervised active Hebbian learning (AHL) algorithm is applied. One hundred and twenty-eight cases of urinary bladder cancer were retrieved from the archives of the Department of Histopathology, University Hospital of Patras, Greece. All tumours had been characterized according to the classical World Health Organization (WHO) grading system. To design the FCM model for tumour grading, three experts histopathologists defined the main histopathological features (concepts) and their impact on grade characterization. The resulted FCM model consisted of nine concepts. Eight concepts represented the main histopathological features for tumour grading. The ninth concept represented the tumour grade. To increase the classification ability of the FCM model, the AHL algorithm was applied to adjust the weights of the FCM. The proposed FCM grading model achieved a classification accuracy of 72.5%, 74.42% and 95.55% for tumours of grades I, II and III, respectively. An advanced computerized method to support tumour grade diagnosis decision was proposed and developed. The novelty of the method is based on employing the soft computing method of FCMs to represent specialized knowledge on histopathology and on augmenting FCMs ability using an unsupervised learning algorithm, the AHL. The proposed method performs with reasonably high accuracy compared to other existing methods and at the same time meets the physicians' requirements for transparency and explicability.

Tumours and cancers in Graeco-Roman times | Retief | South ...

African Journals Online (AJOL)

In Hippocratic literature tumours were mainly classified as karkin6mata, phumata, and oidemata. Phumata included a large variety of tumours, inflammatory and neoplastic in origin, and mostly benign (in modern terms), while oidemata were soft, painless tumours and even included generalised oedema (dropsy). Although ...

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Science.gov (United States)

Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

2016-01-01

The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma. PMID:27009516

Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour

Science.gov (United States)

Scott, R H; Stiller, C A; Walker, L; Rahman, N

2006-01-01

Wilms tumour has been reported in association with over 50 different clinical conditions and several abnormal constitutional karyotypes. Conclusive evidence of an increased risk of Wilms tumour exists for only a minority of these conditions, including WT1 associated syndromes, familial Wilms tumour, and certain overgrowth conditions such as Beckwith‐Wiedemann syndrome. In many reported conditions the rare co‐occurrence of Wilms tumour is probably due to chance. However, for several conditions the available evidence cannot either confirm or exclude an increased risk, usually because of the rarity of the syndrome. In addition, emerging evidence suggests that an increased risk of Wilms tumour occurs only in a subset of individuals for some syndromes. The complex clinical and molecular heterogeneity of disorders associated with Wilms tumour, together with the apparent absence of functional links between most of the known predisposition genes, suggests that abrogation of a variety of pathways can promote Wilms tumorigenesis. PMID:16690728

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

Cancer of rat ovaries: Sertoli cell or granulosa-theca cell tumours

International Nuclear Information System (INIS)

Knowles, J.F.

1983-01-01

The effects of X-radiation (0-1.25 Gy) given 24 hours after neonatal injections of the carcinogen ethyl nitrosourea (ENU) (0-10 mg/kg) in female rats were studied. Twelve out of 118 rats bore single ovarian tumours. A substantial excess of ovarian tumours occurred in the rats given 4 mg/kg ENU and 1.25 GY X-rays but not in others given ENU alone, radiation alone or 10 mg/kg ENU and 1.25 Gy. The tumours were all found in old rats (657-1085 days). In all of the tumours the presence of tubular formations suggested a diagnosis of ovarian Sertoli cell tumour. In two tumours, only a few tubular structures were seen and fibrous stromal tissue predominated, suggesting a diagnosis of granulosa-theca cell tumour. All other tumours were a mixture of both elements. (U.K.)

Radiological diagnosis of malignant tumours in patients with renal transplants

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Raaijmakers, P A.M.; Rosenbusch, G; Hoitsma, A J; Boetes, C; Strijk, S P; Koene, R A.P.

1984-12-01

17 of 400 patients with a total of 537 renal transplantations developed a malignant tumour (4,2%). 3 patients had a tumour of the skin or lips, 5 a solid lymphoma, 2 a hepatocellular carcinoma and 7 each another tumour. The radiologic findings of the patients are described. The problems around the diagnostics of malignant tumours in patients with renal transplantations are discussed.

Preoperative embolization of hypervascular head and neck tumours

International Nuclear Information System (INIS)

Gupta, A. K.; Purkayastha, S.; Bodhey, N. K.; Kapilamoorthy, T. R.; Kesavadas, C.

2007-01-01

Full text: The embolization of vascular tumours of the head and neck has become an important adjunct to the surgical treatment of these tumours. A vascular tumour in the head and neck region in a surgically treatable patient may be a candidate for embolization. Palliative embolization may be the sole treatment for high risk patients. Reducing intraoperative bleeding may shorten surgery time thus decreasing morbidity and mortality. The purpose of this study is to assess the efficacy of embolization as an adjunct to surgery or as a curative measure in the management of hypervascular head and neck tumours. We retrospectively reviewed the records of 46 consecutive patients 27 men and 16 women; mean age, 37.8 years) with 48 hypervascular head and neck tumours that had undergone preoperative transarterial, direct puncture or combined mode of embolization. Diagnosis of tumours was made on the basis of findings of imaging studies. The 46 patients underwent embolization either through transarterial route, by direct puncture technique or both direct puncture and arterial route. The devascularization reached 90-95% with the use of NBCA. The amount of devascularization reached by transarterial particle embolization is a little lesser. One patient (carotid body tumour) developed mild unilateral seventh, ninth and 10th cranial nerve palsy after transarterial embolization, transient hemiparesis was seen in another patient (nasopharyngeal angiofibroma). Both patients improved completely with steroids and had no deficit on follow up. One patient developed delayed glue migration into the middle cerebral artery territory 6 h after the procedure with no reported increase in size of the lesion in the following 5 years. Preoperative embolization of hypervascular tumour of head and neck region appears to be safe and improves the chance of complete removal during surgery with minimal blood loss

Tumours and cancers in Graeco-Roman times | Retief | Acta ...

African Journals Online (AJOL)

In Hippocratic literature tumours were mainly classified as karkinômata, phumata and oidêmata. Phumata included a large variety of tumours, inflammatory and neoplastic in origin, and mostly benign (in modern terms), whilst oidêmata were soft, painless tumours and even included generalised oedema (dropsy). Although ...

Hepatic Metastases of Granulosa Cell Tumour of the Ovary

Directory of Open Access Journals (Sweden)

José I. Rodríguez García

1996-01-01

Full Text Available A case of metastatic granulosa cell tumour of the ovary is reported. Investigations revealed a secondary tumour in segment VI and VII of the liver. Right hepatic resection was performed. Microscopic findings revealed a tumour with histological features identical to that removed eleven years before.

Malignant Renal Tumours in Adults in Nnamdi Azikiwe University ...

African Journals Online (AJOL)

It is however the urological tumour with the highest mortality/ incidence ratio. OBJECTIVE: To review the frequency, mode of presentation and histological pattern of patients with malignant renal tumours in Nnamdi Azikiwe University Teaching Hospital. METHOD: A 7 year retrospective review of all our renal tumour folders in ...

Juvenile Granulosa Cell Tumour: Anaplastic Variant with Omental Deposits

Science.gov (United States)

Rao, Anuradha C.K.; Monappa, Vidya

2016-01-01

Juvenile Granulosa Cell Tumour (JGCT) of ovary represents a small fraction of all primary ovarian malignancies. It is a subtype of granulosa cell tumour that is almost always found during the first three decades of life. Histologically, it differs from the typical adult type of granulosa cell tumour. It accounts for 5-15% of all granulosa cell tumours, majority being unilateral. Herein, we describe an unusual histopathological variant of JGCT with numerous large cystic spaces, anaplasia and focal syncytiotrophoblast like giant cells. PMID:27042471

Tirapazamine causes vascular dysfunction in HCT-116 tumour xenografts

International Nuclear Information System (INIS)

Huxham, Lynsey A.; Kyle, Alastair H.; Baker, Jennifer H.E.; McNicol, Krista L.; Minchinton, Andrew I.

2006-01-01

Background and purpose: Tirapazamine is a hypoxic cytotoxin currently undergoing Phase II/III clinical evaluation in combination with radiation and chemotherapeutics for the treatment of non-hematological cancers. Tissue penetration studies using multicellular models have suggested that tirapazamine exposure may be limited to cells close to blood vessels. However, animal studies show tirapazamine enhances the anti-tumour activity of radiation and chemotherapy and clinical studies with tirapazamine, so far, are promising. To investigate this apparent paradox we examined the microregional effects of tirapazamine in vivo by mapping drug effects with respect to the position of blood vessels in tumour cryosections. Patients and methods: Tirapazamine was administered i.p. to mice bearing HCT-116 tumours, which were excised at various times after treatment. Images of multiple-stained cryosections were overlaid to provide microregional information on the relative position of proliferating cells, hypoxia, perfusion and vasculature. Results: We observed extensive and permanent vascular dysfunction in a large proportion of tumours from mice treated with tirapazamine. In the affected tumours, blood flow ceased in the centrally located tumour vessels, leaving a rim of functional vessels around the periphery of the tumour. This vascular dysfunction commenced within 24 h after tirapazamine administration and the areas affected appeared to be replaced by necrosis over the following 24-48 h. Conclusions: Because the majority of hypoxic cells are located in the center of tumours we propose that the activity of tirapazamine in vivo may be related to its effects on tumour vasculature and that its activity against hypoxic cells located distal to functional blood vessels may not be as important as previously believed

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

International Nuclear Information System (INIS)

Salehi, N.; Lichtenstein, M.

1998-01-01

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

[Adrenal tumours in childhood].

Science.gov (United States)

Martos-Moreno, G A; Pozo-Román, J; Argente, J

2013-09-01

This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Early death, late death and repair factor in three human tumour cell lines

International Nuclear Information System (INIS)

Courdi, A.; Gioanni, J.; Mari, D.; Chauvel, P.

1997-01-01

The in vivo colony method used to generate survival curves following exposure to ionizing irradiation allows to score large clones, representing surviving cells, and small colonies, representing late reproductive death. By subtraction, early-dying cells can be estimated. In the three human tumour cell lines examined, we have observed that early cell death is a major mode of action of irradiation. The contribution of early cell death to total mortality increases as the dose increases. Moreover, repair due to dose-splitting and delayed plating in densely-inhibited cells is not observed in early-dying cells. (authors)

Renal angiomyoadenomatous tumour: Imaging features

Science.gov (United States)

Sahni, V. Anik; Hirsch, Michelle S.; Silverman, Stuart G.

2012-01-01

Renal angiomyoadenomatous tumour is a rare, recently described neoplasm with a distinctive histological appearance. Although reported in the pathology literature, to our knowledge, no prior reports have described its imaging appearance. We describe the computed tomography and magnetic resonance imaging features of an incidentally detected renal angiomyoadenomatous tumour that appeared as a well-marginated, solid T2-hypointense enhancing mass, in a 50-year-old woman. It is indistinguishable from a variety of benign and malignant renal neoplasms. PMID:23093565

Clinicopathological features of liver tumours: a ten-year study

International Nuclear Information System (INIS)

Zahir, S.T.; Aalipour, E.

2015-01-01

Various diseases affect the liver, among them, malignant and benign tumours with hepatic nodules are the most important. We aimed to evaluate the clinicopathological findings related to hepatic tumours and nodules. Methods: This retrospective study was carried out during November 2014 to August 2015 by reviewing the hospital medical records of 164 registered patients with liver biopsies referred to Shahid Sadoughi educational General Hospital, Yazd, Iran, between 2004 and 2014. The samples were selected through the census method. Age, gender, clinical symptoms, initial clinical diagnosis, pathology reports and ultrasound results were considered as variables. Data were analysed by using SPSS-17. Results: There were 87 (53%) men and 77 (47%) women. The mean ages of presentation for malignant and benign tumours were 57.9 ±17.2 and 44.9±19.4 years, respectively. Seventy benign tumours and 147 malignant tumours were recorded. The most frequent chief complaint was abdominal pain (54.9%) in both malignant (56.50%) and benign tumours (41.20%). Hepatocellular carcinoma (HCC) and hemangioma were the most prevalent malignant and benign hepatic tumours, respectively. In our study, correlation between pathology reports and primary diagnoses was 40.9%, and a significant relationship was found between sonography and pathological findings (p=0.038). Conclusions: We found that only when primary clinical diagnosis and sonography were in favour of malignancy, they were correlated with pathology results. Clinicopathological assessments can help physicians in their diagnosis in order to facilitate the management of hepatic tumours. (author)

Salivary gland tumours in a Mexican sample. A retrospective study.

Science.gov (United States)

Ledesma-Montes, C; Garces-Ortiz, M

2002-01-01

Salivary gland tumours are an important part of the Oral and Maxillofacial Pathology, unfortunately, only few studies on these tumours have been done in Latin-American population. The aim of this study was to compare demographic data on salivary gland tumours in a Mexican sample with those previously published from Latin American and non-Latin American countries. All cases of salivary gland tumours or lesions diagnosed in our service were reviewed. Of the reviewed cases,67 were confirmed as salivary gland tumours. Out of these 64.2% were benign neoplasms, 35.8% were malignant and a slight female predominance (56.7%) was found. The most common location was palate followed by lips and floor of the mouth. Mean age for benign tumours was 40.6 years with female predominance (60.5%). Mean age for malignant tumours was 41 years and female predominance was found again. Palate followed by retromolar area were the usual locations. Pleomorphic adenoma (58.2%), mucoepidermoid carcinoma (17.9%) and adenoid cystic carcinoma (11.9%) were the more frequent neoplasms. All retromolar cases were malignant and all submandibular gland tumours were benign. We found a high proportion of salivary gland neoplasms in children. Our results showed that differences of the studied tumours among our sample and previously reported series exist. These differences can be related to race and geographical location.

Nuclear hBD-1 accumulation in malignant salivary gland tumours

International Nuclear Information System (INIS)

Wenghoefer, M; Merkelbach-Bruse, S; Fischer, HP; Novak, N; Winter, J; Pantelis, A; Dommisch, H; Götz, W; Reich, R; Bergé, S; Martini, M; Allam, JP; Jepsen, S

2008-01-01

Whereas the antimicrobial peptides hBD-2 and -3 are related to inflammation, the constitutively expressed hBD-1 might function as 8p tumour suppressor gene and thus play a key role in control of transcription and induction of apoptosis in malignant epithelial tumours. Therefore this study was conducted to characterise proteins involved in cell cycle control and host defence in different benign and malignant salivary gland tumours in comparison with healthy salivary gland tissue. 21 paraffin-embedded tissue samples of benign (n = 7), and malignant (n = 7) salivary gland tumours as well as healthy (n = 7) salivary glands were examined immunohistochemically for the expression of p53, bcl-2, and hBD-1, -2, -3. HBD-1 was distributed in the cytoplasm of healthy salivary glands and benign salivary gland tumours but seems to migrate into the nucleus of malignant salivary gland tumours. Pleomorphic adenomas showed cytoplasmic as well as weak nuclear hBD-1 staining. HBD-1, 2 and 3 are traceable in healthy salivary gland tissue as well as in benign and malignant salivary gland tumours. As hBD-1 is shifted from the cytoplasm to the nucleus in malignant salivary gland tumours, we hypothesize that it might play a role in the oncogenesis of these tumours. In pleomorphic adenomas hBD-1 might be connected to their biologic behaviour of recurrence and malignant transformation

Increased risk of post-operative complications in patients with Crohn's disease treated with anti-tumour necrosis factor α agents - a systematic review

DEFF Research Database (Denmark)

El-Hussuna, Alaa; Theede, Klaus; Olaison, Gunnar

2014-01-01

INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

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

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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

Synchronized moving aperture radiation therapy (SMART): average tumour trajectory for lung patients

International Nuclear Information System (INIS)

Neicu, Toni; Shirato, Hiroki; Seppenwoolde, Yvette; Jiang, Steve B

2003-01-01

Synchronized moving aperture radiation therapy (SMART) is a new technique for treating mobile tumours under development at Massachusetts General Hospital (MGH). The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumour motion induced by respiration. SMART is based on the concept of the average tumour trajectory (ATT) exhibited by a tumour during respiration. During the treatment simulation stage, tumour motion is measured and the ATT is derived. Then, the original IMRT MLC leaf sequence is modified using the ATT to compensate for tumour motion. During treatment, the tumour motion is monitored. The treatment starts when leaf motion and tumour motion are synchronized at a specific breathing phase. The treatment will halt when the tumour drifts away from the ATT and will resume when the synchronization between tumour motion and radiation beam is re-established. In this paper, we present a method to derive the ATT from measured tumour trajectory data. We also investigate the validity of the ATT concept for lung tumours during normal breathing. The lung tumour trajectory data were acquired during actual radiotherapy sessions using a real-time tumour-tracking system. SMART treatment is simulated by assuming that the radiation beam follows the derived ATT and the tumour follows the measured trajectory. In simulation, the treatment starts at exhale phase. The duty cycle of SMART delivery was calculated for various treatment times and gating thresholds, as well as for various exhale phases where the treatment begins. The simulation results show that in the case of free breathing, for 4 out of 11 lung datasets with tumour motion greater than 1 cm from peak to peak, the error in tumour tracking can be controlled to within a couple of millimetres while maintaining a reasonable delivery efficiency. That is to say, without any breath coaching/control, the ATT is a valid concept for some lung

A reproducible brain tumour model established from human glioblastoma biopsies

International Nuclear Information System (INIS)

Wang, Jian; Chekenya, Martha; Bjerkvig, Rolf; Enger, Per Ø; Miletic, Hrvoje; Sakariassen, Per Ø; Huszthy, Peter C; Jacobsen, Hege; Brekkå, Narve; Li, Xingang; Zhao, Peng; Mørk, Sverre

2009-01-01

Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression

A reproducible brain tumour model established from human glioblastoma biopsies

Directory of Open Access Journals (Sweden)

Li Xingang

2009-12-01

Full Text Available Abstract Background Establishing clinically relevant animal models of glioblastoma multiforme (GBM remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.

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.

Malignant Giant Cell Tumour of Bone with Axillary Metastasis

African Journals Online (AJOL)

2002-06-06

Jun 6, 2002 ... SUMMARY. Giant Cell Tumour of bone is a typically benign and solitary tumour. However, multiple lesions have been described and 5-10% of lesions may be malignant. We present a case of a malignant giant cell tumour of the distal radius with metastasis to the ipsilateral axilla (an uncommon location).

Scintigraphic assessment of vascularity and blood-tissue barrier of human brain tumours

International Nuclear Information System (INIS)

Front, D.

1978-01-01

Assessment of vascularity and blood-tissue barrier was performed by sequential scintigraphy in 43 patients with brain tumours. The blood-tumour barrier was evaluated by use of sup(99m)Tc-pertechnetate, and vascularity using sup(99m)Tc-labelled red blood cells. Three groups of tumours were found: tumours with low vascularity and permeable barrier, tumours with high vascularity and permeable barrier, and tumours with low vascularity and relatively impermeable barrier. The first group indicates that when vessels are permeable, there may be a rapid penetration of large amounts of pertechnetate into the tumour even when vascularity is not increased. In the other two groups penetration of pertechnetate into the tumour is affected by vascularity, as it determines the total area where passage of the radiopharmaceutical takes place. It is suggested that the permeability of the blood-tumour barrier and the amount of vascularity may have an effect on the success of chemotherapy in brain tumours. (author)

Radiopharmaceuticals as probes to characterize tumour tissue

International Nuclear Information System (INIS)

Alam, Israt S.; Arshad, Mubarik A.; Nguyen, Quang-De; Aboagye, Eric O.

2015-01-01

Tumour cells exhibit several properties that allow them to grow and divide. A number of these properties are detectable by nuclear imaging methods. We discuss crucial tumour properties that can be described by current radioprobe technologies, further discuss areas of emerging radioprobe development, and finally articulate need areas that our field should aspire to develop. The review focuses largely on positron emission tomography and draws upon the seminal 'Hallmarks of Cancer' review article by Hanahan and Weinberg in 2011 placing into context the present and future roles of radiotracer imaging in characterizing tumours. (orig.)

Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study

Science.gov (United States)

Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

2012-01-01

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2. Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most

Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study.

Science.gov (United States)

Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

2012-03-27

Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1-7.2. Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1-7.2 is most promising.

The CT diagnose of pleural metastasis tumour

International Nuclear Information System (INIS)

Chen Liqun; Han Kaibin; Pan Heng; Huang Xiaoru; Zhou Bingcao; Huang Yuehua

2007-01-01

Objective: To discuss the CT characteristic of pleural metastasis tumour,enhance the diagnostic level of pleural metastasis tumour. Methods: Review 30 cases which have been performed CT scan in our hospital during March 2002 to June 2003, which have been approved to pleural metastasis tumour by pathology and clinic. Make use of GE Hispeed.zx/i spiral CT,10mm thickness,10mm increment, l.5 pitch, some of them use 10mm or high resolution mode. All cases have been performed normal scan, 25 cases with contrast scan. Results: The CT representation of pleural metastasis tumour are encapsulated pleural effusion with irregular pleural thickening(56.6%), nodular pleural thickening(46.6%), pleural masses (13.3%), pneumothorax (3.3%), etc. Encapsulated pleural effusion and nodular pleural thickening are 76.6%, use contrast mode to scan pleural pathological changes enhance upon middle level, CT value increment > 20HU, there are 66.6% cases with other chest metastasis symptom, 73.3% primary lesion are pulmonary cancer, and 20% no primary lesion are found. Conclusion: Combine primary lesion history and other chest metastasis symptom, Spiral CT examination can differentiate most of pleural metastasis tumour, but it is difficult to differentiate the cases between with a little pleural effusion or light band pleural thickening and reactive alteration. (authors)

Renal space-occupying solid growth of uncertain tumour status in metastasising tumour of the testicles

International Nuclear Information System (INIS)

Engelhard, K.; Sarmiento-Garcia, G.; Worlicek, H.; Krankenhaus Martha-Maria, Nuernberg

1988-01-01

On the basis of a particular case of 'atypical' hypernephroma the main differential diagnosis of solid renal masses are described with reference to the basis disease: testicle tumour causing metastasis. The problems of determining the dignity of the disease by methods of sonography, pyelogram and CT are pointed out as well as the differences between those characteristics of the said tumour revealed by X-ray diagnosis and the known characteristics of substantial kidney deformations as described in medical literature. (orig.) [de

Reproductive tract tumours: the scourge of woman reproduction ails Indian rhinoceroses.

Directory of Open Access Journals (Sweden)

Robert Hermes

Full Text Available In Indian rhinoceros, extensive leiomyoma, a benign smooth muscle tumour, was sporadically diagnosed post mortem and commonly thought of as contributing factor for reduced fecundity of this species in captivity. However, to date, the prevalence of reproductive tract tumours and their relevance for fecundity are unknown. Our analysis of the international studbook now reveals that females cease reproducing at the age of 18.1±1.2 years; equivalent to a reproductive lifespan of just 9.5±1.3 years. This short reproductive life is in sharp contrast to their longevity in captivity of over 40 years. Here we show, after examining 42% of the captive female population, that age-related genital tract tumours are highly prevalent in this endangered species. Growth and development of these tumours was found to be age-related, starting from the age of 10 years. All females older than 12 years had developed genital tumours, just 7-9 years past maturity. Tumour sizes ranged from 1.5-10 cm. With age, tumours became more numerous, sometimes merging into one large diffuse tumour mass. These tumours, primarily vaginal and cervical, presumably cause widespread young-age infertility by the age of 18 years. In few cases, tumour necrosis suggested possible malignancy of tumours. Possible consequences of such genital tract tumour infestation are hindered intromission, pain during mating, hampered sperm passage, risk of ascending infection during pregnancy, dystocia, or chronic vaginal bleeding. In humans, leiomyoma affect up to 80% of pre-menopause women. While a leading cause for infertility, pregnancy is known to reduce the risk of tumour development. However, different from human, surgical intervention is not a viable treatment option in rhinoceroses. Thus, in analogy to humans, we suggest early onset and seamless consecutive pregnancies to help reduce prevalence of this disease, better maintain a self-sustained captive population and improve animal welfare.

Approaches to the management of antenatally diagnosed congenital tumours

International Nuclear Information System (INIS)

Mahony, Rhona; McParland, Peter

2009-01-01

Congenital fetal tumours are rare, but current imaging modalities including US and MRI facilitate antenatal diagnosis and investigation, allowing a presumptive diagnosis and management strategy. Although the prevalence of fetal tumours is difficult to ascertain, an incidence of 7.2 per 100,000 live births has previously been reported, with the incidence of neonatal malignancy estimated at 36.5 per million births. Teratomas and neuroblastomas are the most common solid tumours described. Tumours may be very large or associated with severe hydrops leading to significant dystocia with the potential for difficult vaginal or caesarean delivery. Once the diagnosis of a fetal tumour is made, optimal management incorporates a multidisciplinary approach including obstetrician, neonatologist, paediatric surgeon and paediatric oncologist so that counselling is appropriate and a clear management plan is in place for parents. (orig.)

Approaches to the management of antenatally diagnosed congenital tumours

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Mahony, Rhona; McParland, Peter [National Maternity Hospital, Department of Fetal and Maternal Medicine, Dublin (Ireland)

2009-11-15

Congenital fetal tumours are rare, but current imaging modalities including US and MRI facilitate antenatal diagnosis and investigation, allowing a presumptive diagnosis and management strategy. Although the prevalence of fetal tumours is difficult to ascertain, an incidence of 7.2 per 100,000 live births has previously been reported, with the incidence of neonatal malignancy estimated at 36.5 per million births. Teratomas and neuroblastomas are the most common solid tumours described. Tumours may be very large or associated with severe hydrops leading to significant dystocia with the potential for difficult vaginal or caesarean delivery. Once the diagnosis of a fetal tumour is made, optimal management incorporates a multidisciplinary approach including obstetrician, neonatologist, paediatric surgeon and paediatric oncologist so that counselling is appropriate and a clear management plan is in place for parents. (orig.)

The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer.

Science.gov (United States)

Patel, Meera; McSorley, Stephen T; Park, James H; Roxburgh, Campbell S D; Edwards, Joann; Horgan, Paul G; McMillan, Donald C

2018-03-06

There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer. Clinicopathological characteristics were extracted from a prospective database. MMR and BRAF status was determined using immunohistochemistry. The tumour microenvironment was assessed using routine H&E pathological sections. SIR was assessed using modified Glasgow Prognostic Score (mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and lymphocyte:monocyte ratio (LMR). Overall, 972 patients were included. The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right-sided tumour location was associated with older age (P=0.001), deficient MMR (P=0.005), higher T stage (Plocation was consistently associated with a high SIR, mGPS (Plocation, adjuvant chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275 patients who received adjuvant chemotherapy, right-sided location was not associated with the MMR status (P=0.509) but was associated with higher T stage (P=0.001), venous invasion (P=0.036), CD3 + at the invasive margin (P=0.033) and CD3 + within cancer nests (P=0.012). There was no relationship between tumour location, SIR or CSS in the adjuvant group. Right-sided tumour location was associated with an elevated tumour lymphocytic infiltrate and an elevated SIR. There was no association between tumour location and

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

Facial Nerve Morbidity Following Surgery for Benign Parotid Tumours

International Nuclear Information System (INIS)

Musani, M. A.; Suhail, Z.; Zafar, A.; Malik, S.; Mirza, D.

2014-01-01

Objective: To determine the frequency and severity of facial nerve dysfunction following surgery for benign parotid gland tumours. Study Design: A case series. Place and Duration of Study: ENT Department, Karachi Medical and Dental College and Abbasi Shaheed Hospital and Ziauddin University Hospital, from 1990 to 2010. Methodology: Data was collected of all patients who were surgically managed for benign parotid tumours from 1990 to 2010. Data was reviewed for presentation of tumour, age and gender of the patient, site of tumour, nature and morphology of the tumour, primary or recurrent, surgical procedure adopted and the complications of the surgery especially the facial nerve dysfunction, its severity, complete or partial paresis and transient or permanent and time of recovery. Results were described as frequency percentages. Results: Out of 235 patients, 159 (67.65%) were female and 76 (32.35%) were male. Age ranged from 18 to 70 years. Pleomorphic adenoma was the most common tumour (n=194, 82.6%), followed by Warthin's tumour. Superficial parotidectomy was done in 188 cases and extended parotidectomy in 47 cases. In the immediate postoperative period facial nerve function was normal in 169 (72%) patients and nerve dysfunction was observed in 66 (28%) patients. Complete paresis involving all the branches of facial nerve was seen in 25 (10.6%) patients and 41 (17.4%) patients were having incomplete dysfunction. Of these, 62 (26.3%) recovered and 04 (1.7%) had permanent facial nerve dysfunction. Marginal mandibular branch of facial nerve was involved in 57 (86.3%) cases. Conclusion: The frequency of temporary and permanent facial nerve dysfunction was 26.3% and 1.7% respectively in 235 consecutive parotidectomies for benign parotid gland tumours. Higher frequency of facial nerve dysfunction was found in recurrent and deep lobe tumours. (author)

Gene expression of circulating tumour cells and its correlation with tumour stage in breast cancer patients

Directory of Open Access Journals (Sweden)

Bölke E

2009-09-01

Full Text Available Abstract Background Breast cancer (BC represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting. Materials and methods Circulating tumour cells (CTC of 63 BC patients were isolated from peripheral blood (PB through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes ga733.2, muc-1, c-erbB2, mgb-1, spdef and c-erbB2 were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls. Results Significant correlations with tumour stages were found in single gene analyses of ga733.2, muc-1 and in multi-gene analyses of ga733.2/muc-1/mgb1/spdef. Furthermore, a significant correlation of Ca 15-3 and all studied genes was also observed. Conclusion Herein, we demonstrated a positive correlation of a gene signature consisting of ga733.2, muc-1, mgb1 and spdef and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with Ca 15-3 positive cases.

A STUDY OF TUMOURS OF THE CRANIAL NERVE AND PARASPINAL NERVE

Directory of Open Access Journals (Sweden)

Sudesh Shetty

2016-03-01

Full Text Available INTRODUCTION One of the frequent sites of tumour formation is the cranial nerves and paraspinal nerves. The cranial nerves perform a plethora of functions and so the signs and symptoms caused may be different. They are mainly classified into four different types. The aim of the study is: 1. To study the tumours arising from the cranial nerves in an epidemiological point of view. 2. To study the tumours histopathologically. 3. To classify the tumours according to WHO classification. Thirty-eight brain tumor cases were studied in the Department of Medicine, A. J. Shetty Institute of Medical Sciences, Mangalore. Cranial nerve tumours accounts for 4(10% among the intracranial tumours. Schwannomas makes up 3(7.39% among the Intracranial tumours. and constituted 3(75% among cranial nerve tumours. All the 3 schwannomas were located in CP angle. The geographic distribution of cases was found to be 28 cases from Mangalore and 10 cases from Kerala.

Cytological Criteria to Distinguish Phyllodes Tumour of the Breast from Fibroadenoma.

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Maritz, Robert M; Michelow, Pamela M

2017-01-01

To determine whether there are significant differences between fibroadenomas and phyllodes tumours with regard to selected cytomorphological features. A 10-year retrospective review was performed of patients who underwent excision of a fibroadenoma or phyllodes tumour and in whom a preoperative fine-needle aspiration was performed. The following cytological criteria were assessed: number of stromal and epithelial fragments, stromal-to-epithelial ratio, stromal cellularity, stromal borders, stromal atypia, and proportion of background wavy spindled cells. Patient age, tumour laterality, and tumour size were recorded. Fifty fibroadenomas and 17 phyllodes tumours were included. Compared to phyllodes tumours, fibroadenomas had a larger number of epithelial fragments, a smaller number of stromal fragments, and a lower stromal-to-epithelial ratio. The stroma tended to be less cellular and less atypical compared to phyllodes tumours and the background cellular population contained fewer spindled cells. Fibroadenomas and phyllodes tumours differ with regard to various cytological features, aiding in their distinction on fine-needle aspiration biopsy. © 2017 S. Karger AG, Basel.

Quantifying heterogeneity in human tumours using MRI and PET.

Science.gov (United States)

Asselin, Marie-Claude; O'Connor, James P B; Boellaard, Ronald; Thacker, Neil A; Jackson, Alan

2012-03-01

Most tumours, even those of the same histological type and grade, demonstrate considerable biological heterogeneity. Variations in genomic subtype, growth factor expression and local microenvironmental factors can result in regional variations within individual tumours. For example, localised variations in tumour cell proliferation, cell death, metabolic activity and vascular structure will be accompanied by variations in oxygenation status, pH and drug delivery that may directly affect therapeutic response. Documenting and quantifying regional heterogeneity within the tumour requires histological or imaging techniques. There is increasing evidence that quantitative imaging biomarkers can be used in vivo to provide important, reproducible and repeatable estimates of tumoural heterogeneity. In this article we review the imaging methods available to provide appropriate biomarkers of tumour structure and function. We also discuss the significant technical issues involved in the quantitative estimation of heterogeneity and the range of descriptive metrics that can be derived. Finally, we have reviewed the existing clinical evidence that heterogeneity metrics provide additional useful information in drug discovery and development and in clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tumour size measurement in a mouse model using high resolution MRI

International Nuclear Information System (INIS)

Montelius, Mikael; Ljungberg, Maria; Horn, Michael; Forssell-Aronsson, Eva

2012-01-01

Animal models are frequently used to assess new treatment methods in cancer research. MRI offers a non-invasive in vivo monitoring of tumour tissue and thus allows longitudinal measurements of treatment effects, without the need for large cohorts of animals. Tumour size is an important biomarker of the disease development, but to our knowledge, MRI based size measurements have not yet been verified for small tumours (10 −2 –10 −1 g). The aim of this study was to assess the accuracy of MRI based tumour size measurements of small tumours on mice. 2D and 3D T2-weighted RARE images of tumour bearing mice were acquired in vivo using a 7 T dedicated animal MR system. For the 3D images the acquired image resolution was varied. The images were exported to a PC workstation where the tumour mass was determined assuming a density of 1 g/cm 3 , using an in-house developed tool for segmentation and delineation. The resulting data were compared to the weight of the resected tumours after sacrifice of the animal using regression analysis. Strong correlations were demonstrated between MRI- and necropsy determined masses. In general, 3D acquisition was not a prerequisite for high accuracy. However, it was slightly more accurate than 2D when small (<0.2 g) tumours were assessed for inter- and intraobserver variation. In 3D images, the voxel sizes could be increased from 160 3 μm 3 to 240 3 μm 3 without affecting the results significantly, thus reducing acquisition time substantially. 2D MRI was sufficient for accurate tumour size measurement, except for small tumours (<0.2 g) where 3D acquisition was necessary to reduce interobserver variation. Acquisition times between 15 and 50 minutes, depending on tumour size, were sufficient for accurate tumour volume measurement. Hence, it is possible to include further MR investigations of the tumour, such as tissue perfusion, diffusion or metabolic composition in the same MR session

AAV2-mediated in vivo immune gene therapy of solid tumours

LENUS (Irish Health Repository)

Collins, Sara A

2010-12-20

Abstract Background Many strategies have been adopted to unleash the potential of gene therapy for cancer, involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study, the feasibility of AAV2 mediated immunotherapy of growing tumours was examined, in isolation and combined with anti-angiogenic therapy. Methods Immune-competent Balb\\/C or C57 mice bearing subcutaneous JBS fibrosarcoma or Lewis Lung Carcinoma (LLC) tumour xenografts respectively were treated by intra-tumoural administration of AAV2 vector encoding the immune up-regulating cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) and the co-stimulatory molecule B7-1 to subcutaneous tumours, either alone or in combination with intra-muscular (IM) delivery of AAV2 vector encoding Nk4 14 days prior to tumour induction. Tumour growth and survival was monitored for all animals. Cured animals were re-challenged with tumourigenic doses of the original tumour type. In vivo cytotoxicity assays were used to investigate establishment of cell-mediated responses in treated animals. Results AAV2-mediated GM-CSF, B7-1 treatment resulted in a significant reduction in tumour growth and an increase in survival in both tumour models. Cured animals were resistant to re-challenge, and induction of T cell mediated anti-tumour responses were demonstrated. Adoptive transfer of splenocytes to naïve animals prevented tumour establishment. Systemic production of Nk4 induced by intra-muscular (IM) delivery of Nk4 significantly reduced subcutaneous tumour growth. However, combination of Nk4 treatment with GM-CSF, B7-1 therapy reduced the efficacy of the immune therapy. Conclusions Overall, this study demonstrates the potential for in vivo AAV2 mediated immune gene therapy, and provides data on the inter-relationship between tumour

Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

International Nuclear Information System (INIS)

Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

2008-01-01

High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically

Non-pituitary origin sellar tumours mimicking pituitary macroadenomas

Energy Technology Data Exchange (ETDEWEB)

Abele, T.A., E-mail: travaus@gmail.com [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States); Yetkin, Z.F.; Raisanen, J.M.; Mickey, B.E.; Mendelsohn, D.B. [University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States)

2012-08-15

Although the large majority of sellar tumours are pituitary adenomas, several other pituitary and non-pituitary origin tumours arise in the sellar and parasellar regions. Given their location, non-adenomatous lesions frequently mimic pituitary macroadenomas and can pose a diagnostic challenge for the radiologist. Distinguishing rare sellar lesions from the common macroadenoma helps to direct the correct surgical approach and reduce the risk of incomplete resection and/or complications such as cerebrospinal fluid leak with the potential for meningitis. The purpose of this article is to review the imaging features of non-pituitary-origin sellar tumours, focusing on characteristics that may distinguish them from pituitary macroadenomas. Lesions include meningioma, metastatic disease, epidermoid cyst, germinoma, chondrosarcoma, giant cell tumour, and giant aneurysm.

Quantification of antiangiogenic treatment effects on tissue heterogeneity in glioma tumour xenograft model using a combination of DCE-MRI and 3D-ultramicroscopy

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Dominietto, Marco [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); University of Basel, Biomaterials Science Center, Allschwil (Switzerland); Dobosz, Michael; Renner, Anja; Scheuer, Werner [Roche Innovation Center Penzberg, Discovery Oncology, Pharmaceutical Research and Early Development (pRED), Penzberg (Germany); Buergi, Sandra; Rudin, Markus [University and ETH Zurich, Institute for Biomedical Engineering, Zurich (Switzerland); Zahlmann, Gudrun [pRED, Oncology DTA, Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel (Switzerland)

2017-07-15

This study aimed at assessing the effects of an anti-angiogenic treatment, which neutralises vascular endothelial growth factor (VEGF), on tumour heterogeneity. Murine glioma cells have been inoculated into the right brain frontal lobe of 16 mice. Anti-VEGF antibody was administered to a first group (n = 8), while a second group (n = 8) received a placebo. Magnetic resonance acquisitions, performed at days 10, 12, 15 and 23 following the implantation, allowed the derivation of a three-dimensional features dataset characterising tumour heterogeneity. Three-dimensional ultramicroscopy and standard histochemistry analysis have been performed to verify in vivo results. Placebo-treated mice displayed a highly-vascularised area at the tumour periphery, a monolithic necrotic core and a chaotic dense vasculature across the entire tumour. In contrast, the B20-treated group did not show any highly vascularised regions and presents a fragmented necrotic core. A significant reduction of the number of vessel segments smaller than 17 μm has been observed. There was no difference in overall tumour volume and growth rate between the two groups. Region-specific analysis revealed that VEGF inhibition affects only: (1) highly angiogenic compartments expressing high levels of VEGF and characterised by small capillaries, and also (2) the formation and structure of necrotic regions. These effects appear to be transient and limited in time. (orig.)

Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.

Science.gov (United States)

Teoh, Seong Lin; Das, Srijit

2016-11-01

Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

Characterisation of musculoskeletal tumours by multivoxel proton MR spectroscopy

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Patni, Ruchi S.; Gogoi, Nripen [Assam Medical College, Department of Radio-diagnosis, Dibrugarh, Assam (India); Boruah, Deb K. [Assam Medical College, Department of Radio-diagnosis, Dibrugarh, Assam (India); M-Lane, RCC-4, Assam Medical College Campus, Dibrugarh, Assam (India); Sanyal, Shantiranjan [Airedale General Hospital, Consultant Radiologist, West Yorkshire (United Kingdom); Gogoi, Bidyut B. [NEIGHRMS, Department of Pathology, Shillong, Meghalaya (India); Patni, Maninder [Geetanjali Medical College, Department of Anesthesiology, Udaipur, Rajasthan (India); Khandelia, Rosy [Assam Medical College, Department of Pathology, Dibrugarh, Assam (India)

2017-04-15

The purpose of this study is to evaluate the role of multi-voxel proton MR spectroscopy in differentiating benign and malignant musculoskeletal tumours in a more objective way and to correlate the MRS data parameters with histopathology. A hospital-based prospective study was carried out comprising 42 patients who underwent MRI examinations from 1 July 2013 to 30 June 2014. After routine sequences, single-slice multi-voxel proton MR spectroscopy was included at TE-135 using the PRESS sequence. The voxel with the maximum choline/Cr ratio was used for analysis of data in 32 patients. The strength of association between the MR spectroscopy findings and the nature of tumour and histopathological grading were assessed. Of the 42 patients, the MR spectra were not of diagnostic quality in 10. In the remaining 32 patients, 12 (37.5%) had benign and 20 (62.5%) malignant tumours. The mean choline/Cr ratio was 6.97 ± 5.95 (SD) for benign tumours and 25.39 ± 17.72 (SD) for malignant tumours. In our study statistical significance was noted between the choline/Cr ratio and the histological nature of musculoskeletal tumours (p = 0.002) assessed by unpaired t-test. The choline/Cr ratio and histological grading were also found to be significant (p = 0.001) when assessed by one-way ANOVA test. Multi-voxel MR spectroscopy showed a higher choline/Cr ratio in malignant musculoskeletal tumours than in benign ones (p = 0.002). The choline/Cr ratio and histological grading of musculoskeletal tumours also showed statistical significance (p = 0.001). (orig.)

Immunoexpression of tumour necrosis factor-α, interleukin-1α and interleukin-10 on odontogenic cysts and tumours.

Science.gov (United States)

Sá, M C; de Matos, F R; Conceição, T S; Leitão, A C G H; Freitas, R A

2017-05-01

To analyse the immunoreactivity of IL-1α, TNF-α and IL-10 in odontogenic cysts and tumours and to investigate possible associations with established biological behaviours of these different lesions. Immunohistochemical expression of anti-IL-1α, anti-TNF-α and anti-IL-10 antibodies was assessed on epithelium and mesenchyme of 20 radicular cysts (RCs), 20 residual cysts (RECs), 20 dentigerous cysts (DCs), 18 solid ameloblastomas (SAs), 20 keratocystic odontogenic tumours (KCOTs) and 15 dental follicles (DFs). Comparative analysis of data was performed using the nonparametric Wilcoxon signed-rank test and Kruskal-Wallis's test. Significantly greater expression of IL-1α in the epithelium was noted in RC, KCOT and SA (P = 0.01), whilst IL-10 and TNF-α was in the epithelium of RC, DC and KCOT (P  IL-10 (P  IL10 ratio (P < 0.01). These results suggest involvement of the proteins in the pathogenesis of odontogenic cysts and tumours, with emphasis on the highest immunoreactivity of osteolysis stimulating factors in tumours with aggressive biological behaviour, such as SA and KCOT. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Quantitative MR imaging and spectroscopy of brain tumours: a step forward?

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Wagnerova, Dita; Herynek, Vit; Dezortova, Monika; Jiru, Filip; Skoch, Antonin; Hajek, Milan [Institute for Clinical and Experimental Medicine, Department of Diagnostic and Interventional Radiology, Prague (Czech Republic); Malucelli, Alberto; Bartos, Robert; Sames, Martin [JE Purkyne University and Masaryk Hospital, Department of Neurosurgery, Usti nad Labem (Czech Republic); Vymazal, Josef [Na Homolce Hospital, Department of Radiology, Prague (Czech Republic); Urgosik, Dusan [Na Homolce Hospital, Stereotactic and Radiation Neurosurgery, Prague (Czech Republic); Syrucek, Martin [Na Homolce Hospital, Department of Pathology, Prague (Czech Republic)

2012-11-15

A prospective quantitative MR study of brain tumours was performed to show the potential of combining different MR techniques to distinguish various disease processes in routine clinical practice. Twenty-three patients with various intracranial tumours before treatment (diagnosis confirmed by a biopsy) and 59 healthy subjects were examined on a 3-T system by conventional MR imaging, 1H spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Metabolic concentrations and their ratios, T2 relaxation times and mean diffusivities were calculated and correlated on a pixel-by-pixel basis and compared to control data. Different tumour types and different localisations revealed specific patterns of correlations between metabolic concentrations and mean diffusivity or T2 relaxation times. The patterns distinguish given tissue states in the examined area: healthy tissue, tissue infiltrated by tumour, active tumour, oedema infiltrated by tumour, oedema, etc. This method is able to describe the complexity of a highly heterogeneous tissue in the tumour and its vicinity, and determines crucial parameters for tissue differentiation. A combination of different MR parameters on a pixel-by-pixel basis in individual patients enables better identification of the tumour type, direction of proliferation and assessment of the tumour extension. (orig.)

Residential Radon and Brain Tumour Incidence in a Danish Cohort

DEFF Research Database (Denmark)

Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus Erik

2013-01-01

Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect of expo...... significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies.......Background: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective: To investigate the long-term effect...... of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods: During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced...

Three-dimensional reconstruction of prostate cancer architecture with serial immunohistochemical sections: hallmarks of tumour growth, tumour compartmentalisation, and implications for grading and heterogeneity.

Science.gov (United States)

Tolkach, Yuri; Thomann, Stefan; Kristiansen, Glen

2018-05-01

Conventional morphology of prostate cancer considers only the two-dimensional (2D) architecture of the tumour. Our aim was to examine the feasibility of three-dimensional (3D) reconstruction of tumour morphology based on multiple consecutive histological sections and to decipher relevant features of prostate cancer architecture. Seventy-five consecutive histological sections (5 μm) of a typical prostate adenocarcinoma (Gleason score of 3 + 4 = 7) were immunostained (pan-cytokeratin) and scanned for further 3D reconstructions with fiji/imagej software. The main findings related to the prostate cancer architecture in this case were: (i) continuity of all glands, with the tumour being an integrated system, even in Gleason pattern 4 with poorly formed glands-no short-range migration of cells by Gleason pattern 4 (poorly formed glands); (ii) no repeated interconnections between the glands, with a tumour building a tree-like branched structure with very 'plastic' branches (maximal depth of investigation 375 μm); (iii) very stark compartmentalisation of the tumour related to extensive branching, the coexistence of independent terminal units of such branches in one 2D slice explaining intratumoral heterogeneity; (iv) evidence of a craniocaudal growth direction in interglandular regions of the prostate and for a lateromedial growth direction in subcapsular posterolateral regions; and (v) a 3D architecture-based description of Gleason pattern 4 with poorly formed glands, and its continuum with Gleason pattern 3. Consecutive histological sections provide high-quality material for 3D reconstructions of the tumour architecture, with excellent resolution. The reconstruction of multiple regions in this typical case of a Gleason score 3 + 4 = 7 tumour provides insights into relevant aspects of tumour growth, the continuity of Gleason patterns 3 and 4, and tumour heterogeneity. © 2018 John Wiley & Sons Ltd.

Imaging and compartmental classification of solid pelvic tumours in children

International Nuclear Information System (INIS)

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

1996-01-01

Thirty-five children aged from 1 day to 16 years (median 5 years) with solid pelvic tumours were investigated with US, CT and MR. All three methods gave similar estimates of tumour size. For defining location of the tumours, the pelvis was divided into three midline compartments (anterior, middle and posterior) and a right and left lateral compartment. CT and MR were accurate and equally reliable in determining the tumour location, US was less accurate. Evaluation of confinement to organ of origin was uncertain, regardless of imaging modality. Tissue characteristics with CT and MR did not contribute to the differentiation of the various tumour types, and contrast medium enhancement did not improve the discrimination. Compartmental localization was equally well assessed by CT and MR and, together with sex, was found to correlate with the tumour type. (orig.). With 7 figs., 5 tabs

Steroid hormones affect binding of the sigma ligand {sup 11}C-SA4503 in tumour cells and tumour-bearing rats

Energy Technology Data Exchange (ETDEWEB)

Rybczynska, Anna A.; Elsinga, Philip H.; Sijbesma, Jurgen W.; Jong, Johan R. de; Vries, Erik F. de; Dierckx, Rudi A.; Waarde, Aren van [University of Groningen, Nuclear Medicine and Molecular Imaging, University of Groningen Medical Center, Groningen (Netherlands); Ishiwata, Kiichi [Tokyo Metropolitan Institute of Gerontology, Positron Medical Center, Tokyo (Japan)

2009-07-15

Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist {sup 11}C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. {sup 11}C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. Binding of {sup 11}C-SA4503 to C6 cells was increased ({proportional_to}50%) upon removal and decreased ({proportional_to}60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC{sub 50} progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of {sup 11}C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. The binding of {sup 11}C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids. (orig.)

REPORT OF SEVEN CASES OF METASTATIC TUMOURS

African Journals Online (AJOL)

Major Adebayo

Metastatic lesions may mimic odontogenic infections and other disease conditions in the oral cavity in presentation leading to late diagnosis by the unwary clinician. In Nigeria, reports on jaw tumours from metastasis elsewhere are quite scarce. This report presents a series of histologically verified metastatic tumours to the ...

Metastatic behaviour of primary human tumours in a zebrafish xenotransplantation model

International Nuclear Information System (INIS)

Marques, Ines J; Bagowski, Christoph P; Weiss, Frank Ulrich; Vlecken, Danielle H; Nitsche, Claudia; Bakkers, Jeroen; Lagendijk, Anne K; Partecke, Lars Ivo; Heidecke, Claus-Dieter; Lerch, Markus M

2009-01-01

Aberrant regulation of cell migration drives progression of many diseases, including cancer cell invasion and metastasis formation. Analysis of tumour invasion and metastasis in living organisms to date is cumbersome and involves difficult and time consuming investigative techniques. For primary human tumours we establish here a simple, fast, sensitive and cost-effective in vivo model to analyse tumour invasion and metastatic behaviour. We fluorescently labelled small explants from gastrointestinal human tumours and investigated their metastatic behaviour after transplantation into zebrafish embryos and larvae. The transparency of the zebrafish embryos allows to follow invasion, migration and micrometastasis formation in real-time. High resolution imaging was achieved through laser scanning confocal microscopy of live zebrafish. In the transparent zebrafish embryos invasion, circulation of tumour cells in blood vessels, migration and micrometastasis formation can be followed in real-time. Xenografts of primary human tumours showed invasiveness and micrometastasis formation within 24 hours after transplantation, which was absent when non-tumour tissue was implanted. Furthermore, primary human tumour cells, when organotopically implanted in the zebrafish liver, demonstrated invasiveness and metastatic behaviour, whereas primary control cells remained in the liver. Pancreatic tumour cells showed no metastatic behaviour when injected into cloche mutant embryos, which lack a functional vasculature. Our results show that the zebrafish is a useful in vivo animal model for rapid analysis of invasion and metastatic behaviour of primary human tumour specimen

Immunisation of colorectal cancer patients with autologous tumour cells

DEFF Research Database (Denmark)

Diederichsen, Alice; Stenholm, Anna Catharina Olsen; Kronborg, O

1998-01-01

Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression...... of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled...... the criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80...

Malignant salivary gland tumours

International Nuclear Information System (INIS)

Thompson, S.H.

1982-01-01

The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy

Malignant salivary gland tumours

Energy Technology Data Exchange (ETDEWEB)

Thompson, S.H. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Oral Pathology)

1982-08-01

The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy.

Central nervous system tumours in children in Ibadan, Nigeria: a ...

African Journals Online (AJOL)

CNS) tumours are uncommon in black children, these neoplasms are the fourth most common paediatric tumours in Ibadan. Our centre is the major referral centre for CNS tumours in Nigeria. The last major study of paediatric CNS neoplasms from ...

Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade.

Directory of Open Access Journals (Sweden)

Sylwia Libard

Full Text Available Human cytomegalovirus (HCMV has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.

Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

International Nuclear Information System (INIS)

Hu, Zhiwei; Rao, Benqiang; Chen, Shimin; Duanmu, Jinzhong

2010-01-01

The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia. Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model. We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT. We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers

Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility

Directory of Open Access Journals (Sweden)

Cara J. Valvona

2018-03-01

Full Text Available Medulloblastoma is the most common malignant paediatric brain tumour and current therapies often leave patients with severe neurological disabilities. Four major molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and Group 4, which include additional, recently defined subgroups with different prognosis and genetic characteristics. Lactate dehydrogenase A (LDHA is a key enzyme in the aerobic glycolysis pathway, an abnormal metabolic pathway commonly observed in cancers, associated with tumour progression and metastasis. Studies indicate MBs have a glycolytic phenotype; however, LDHA has not yet been explored as a therapeutic target for medulloblastoma. LDHA expression was examined in medulloblastoma subgroups and cell lines. The effects of LDHA inhibition by oxamate or LDHA siRNA on medulloblastoma cell line metabolism, migration and proliferation were examined. LDHA was significantly overexpressed in Group 3 and Wnt MBs compared to non-neoplastic cerebellum. Furthermore, we found that oxamate significantly attenuated glycolysis, proliferation and motility in medulloblastoma cell lines, but LDHA siRNA did not. We established that aerobic glycolysis is a potential therapeutic target for medulloblastoma, but broader LDH inhibition (LDHA, B, and C may be more appropriate than LDHA inhibition alone.

Increased risk of post-operative complications in patients with Crohn’s disease treated with anti-tumour necrosis factor α agents - a systematic review

DEFF Research Database (Denmark)

El-Hussuna, Alaa; Theede, Klaus; Olaison, Per Olov Gunnar

2014-01-01

INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents are increasi......INTRODUCTION: Tumour necrosis factor α (TNF-α) plays a role in the immune defence, angiogenesis and collagen synthesis. Inhibition of these pathways may increase the risk of infections and impair wound healing in patients after surgery. Biologic treatments including anti-TNF-α agents...... are increasingly used in the treatment of inflammatory bowel disease. Taking into consideration the biologics' mechanism of action, fears have been expressed that they might increase the rate of post-operative complications. Results from 18 retrospective studies were conflicting, and meta-analyses based...... an increased risk of overall post-operative complications and an increased rate of infectious or anastomosis-related complications in patients receiving anti-TNF-α. CONCLUSION: The use of anti-TNF-α agents in Crohn's disease patients is associated with an increased risk of post-operative complications after...

Lymphatic vessels assessment in feline mammary tumours

International Nuclear Information System (INIS)

Sarli, Giuseppe; Sassi, Francesco; Brunetti, Barbara; Rizzo, Antonio; Diracca, Laura; Benazzi, Cinzia

2007-01-01

The lymphatic vessels play a crucial role in a variety of human cancers since tumour cell lymphatic invasion significantly influences prognosis. It is not known if pre-existing lymphatics are enough for tumour dissemination or de novo development is necessary. VEGFR-3 is an angiogenetic mediator for both lymphatic and blood vessels during embryonic development, and only for lymphatics after birth. VEGF is a mediator of both vasculogenesis and angiogenesis, regulates the growth of lymphatics in various experimental models, and is produced in many solid tumours. CD44 mediates hyaluronic acid (HA)-dependent cell adhesion: besides promoting invasion, this interaction also supports neoangiogenesis that indirectly stimulates tumour cell proliferation. The expression of VEGF-C (Vascular Endothelial Growth Factor – C), its receptor VEGFR-3 and CD44, were studied on feline mammary samples to assess the importance of lymphangiogenesis and lymphangiotrophism in neoplasia. Samples were taken from six normal mammary glands (NMG), ten benign (BT) and 32 malignant (MT) tumours. Immunohistochemical laminin/VEGFR-3 double stain, VEGF-C and CD44 stains were applied to 4 μm-thick sections, and their expression evaluated in intratumoral/extratumoral and intramammary/extramammary fields. All groups revealed a higher number of lymphatics in the extratumoral/extramammary areas. VEGF-C expression in the epithelium paralleled the number of positive vessels in the NMG, BT and MT, whereas VEGF-C higher expression was noted in the intratumoral fields only in infiltrating MT. CD44 score was lower in extratumoral than intratumoral fields in tumours and showed a significant increase in extramammary/extratumoral fields from NMG to MT. Pearson test showed a significant and inversely proportional correlation between CD44 expression and the number of lymphatic vessels with VEGFR-3 in malignant infiltrating tumours. The number of both VEGFR-3 positive and negative lymphatics in the extratumoral

Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts

NARCIS (Netherlands)

García, S.; Bodaño, A.; Pablos, J. L.; Gómez-Reino, J. J.; Conde, C.

2008-01-01

To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Cultured FLS from patients with RA were

Angiographic appearances of rare renal tumours

International Nuclear Information System (INIS)

Schmidt, M.; Taenzer, V.

1980-01-01

Oncocytomas, called oxyphil proximal tubular adenomas in the Anglo Saxon literature, and benign hypernephromas are non-malignant, usually symptomless, rare tumours belonging to the renal adenomas. Oncocytomas have angiographic appearances sufficiently uniform to permit a tentative diagnosis. Histologically benign hypernephromas do not possess characteristic angiographic appearances and, in the presence of tumour in the renal vein or necrotic avascular areas, must be regarded as potentially malignant. (orig.) [de

[Biotherapy of neuroendocrine tumours of the gastrointestinal tract and pancreas

DEFF Research Database (Denmark)

Hansen, C.P.; Knigge, U.

2008-01-01

Biotherapy of hormonal symptoms and tumour growth is a mainstay in the therapy of metastatic neuroendocrine tumours of the gastrointestinal tract and pancreas. Symptomatic relief can be achieved by somatostatin analogues and interferon, either alone or in combination. The effect on tumour growth...

Abrogation of Wip1 expression by RITA-activated p53 potentiates apoptosis induction via activation of ATM and inhibition of HdmX

Science.gov (United States)

Spinnler, C; Hedström, E; Li, H; de Lange, J; Nikulenkov, F; Teunisse, A F A S; Verlaan-de Vries, M; Grinkevich, V; Jochemsen, A G; Selivanova, G

2011-01-01

Inactivation of the p53 tumour suppressor, either by mutation or by overexpression of its inhibitors Hdm2 and HdmX is the most frequent event in cancer. Reactivation of p53 by targeting Hdm2 and HdmX is therefore a promising strategy for therapy. However, Hdm2 inhibitors do not prevent inhibition of p53 by HdmX, which impedes p53-mediated apoptosis. Here, we show that p53 reactivation by the small molecule RITA leads to efficient HdmX degradation in tumour cell lines of different origin and in xenograft tumours in vivo. Notably, HdmX degradation occurs selectively in cancer cells, but not in non-transformed cells. We identified the inhibition of the wild-type p53-induced phosphatase 1 (Wip1) as the major mechanism important for full engagement of p53 activity accomplished by restoration of the ataxia telangiectasia mutated (ATM) kinase-signalling cascade, which leads to HdmX degradation. In contrast to previously reported transactivation of Wip1 by p53, we observed p53-dependent repression of Wip1 expression, which disrupts the negative feedback loop conferred by Wip1. Our study reveals that the depletion of both HdmX and Wip1 potentiates cell death due to sustained activation of p53. Thus, RITA is an example of a p53-reactivating drug that not only blocks Hdm2, but also inhibits two important negative regulators of p53 – HdmX and Wip1, leading to efficient elimination of tumour cells. PMID:21546907

Abrogation of Wip1 expression by RITA-activated p53 potentiates apoptosis induction via activation of ATM and inhibition of HdmX.

Science.gov (United States)

Spinnler, C; Hedström, E; Li, H; de Lange, J; Nikulenkov, F; Teunisse, A F A S; Verlaan-de Vries, M; Grinkevich, V; Jochemsen, A G; Selivanova, G

2011-11-01

Inactivation of the p53 tumour suppressor, either by mutation or by overexpression of its inhibitors Hdm2 and HdmX is the most frequent event in cancer. Reactivation of p53 by targeting Hdm2 and HdmX is therefore a promising strategy for therapy. However, Hdm2 inhibitors do not prevent inhibition of p53 by HdmX, which impedes p53-mediated apoptosis. Here, we show that p53 reactivation by the small molecule RITA leads to efficient HdmX degradation in tumour cell lines of different origin and in xenograft tumours in vivo. Notably, HdmX degradation occurs selectively in cancer cells, but not in non-transformed cells. We identified the inhibition of the wild-type p53-induced phosphatase 1 (Wip1) as the major mechanism important for full engagement of p53 activity accomplished by restoration of the ataxia telangiectasia mutated (ATM) kinase-signalling cascade, which leads to HdmX degradation. In contrast to previously reported transactivation of Wip1 by p53, we observed p53-dependent repression of Wip1 expression, which disrupts the negative feedback loop conferred by Wip1. Our study reveals that the depletion of both HdmX and Wip1 potentiates cell death due to sustained activation of p53. Thus, RITA is an example of a p53-reactivating drug that not only blocks Hdm2, but also inhibits two important negative regulators of p53 - HdmX and Wip1, leading to efficient elimination of tumour cells.

Dual role of delay effects in a tumour-immune system.

Science.gov (United States)

Yu, Min; Dong, Yueping; Takeuchi, Yasuhiro

2017-08-01

In this paper, a previous tumour-immune interaction model is simplified by neglecting a relatively weak direct immune activation by the tumour cells, which can still keep the essential dynamics properties of the original model. As the immune activation process is not instantaneous, we now incorporate one delay for the activation of the effector cells (ECs) by helper T cells (HTCs) into the model. Furthermore, we investigate the stability and instability regions of the tumour-presence equilibrium state of the delay-induced system with respect to two parameters, the activation rate of ECs by HTCs and the HTCs stimulation rate by the presence of identified tumour antigens. We show the dual role of this delay that can induce stability switches exhibiting destabilization as well as stabilization of the tumour-presence equilibrium. Besides, our results reveal that an appropriate immune activation time delay plays a significant role in control of tumour growth.

New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

Directory of Open Access Journals (Sweden)

Branka Zorc

2012-01-01

Full Text Available Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1, 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethylphenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1. Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.

Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12)

DEFF Research Database (Denmark)

du Bois, Andreas; Kristensen, Gunnar; Ray-Coquard, Isabelle

2016-01-01

BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the com...

Emerging treatments and combinations in the management of NSCLC

DEFF Research Database (Denmark)

Reck, Martin; Mellemgaard, Anders

2015-01-01

There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast...

Urothelial Tumours of the Urinary Bladder: A Histopathological Study of Cystoscopic Biopsies

Directory of Open Access Journals (Sweden)

Sujan Vaidya

2013-09-01

Full Text Available ABSTRACT Introduction: Bladder tumours constitute one of the most common urological conditions. Urothelial (transitional cell carcinoma accounts for 90% of all primary tumours of the bladder. These tumours are an important cause of morbidity and mortality. The objective of this study was to present the histopathological patterns of urothelial tumours and to determine the grade and stage of these tumours. Methods: This is a 3 year retrospective study of urothelial tumours carried out in the Department of Pathology, Patan Academy of Health Sciences (PAHS, Lalitpur, Nepal. Data of all cystoscopic biopsies collected during this period were analyzed. Results: Urothelial (transitional cell tumours accounted for 97.59% (81 cases of all bladder tumours. Transitional cell carcinoma (TCC was the most common tumour which was present in 67 cases (80.72%. Of these, 32 (47.76% were low grade TCC while 35 (52.24% were high grade TCC. Maximum number of tumours (70.37% were superficial (pTa and pT1 while (29.63% were muscle invasive (pT2. Sixteen percent of low grade and 76.92% of high grade tumours showed muscle invasion. Detrusor muscle was absent in 23.88% cases (16/67. Conclusion: Transitional cell carcinoma was the most common bladder cancer. Most of these tumours were high grade. A large percentage of high grade carcinomas presented with muscle invasion. Pathological grade and muscle invasion are the most valuable prognostic predictors of survival. The importance of including smooth muscle in the biopsy specimens needs to be emphasized Key words: cancer, high grade, low grade, transitional, tumour, urinary bladder.

Genetic and molecular analysis of radon-induced rat lung tumours

International Nuclear Information System (INIS)

Guilly, M.N.; Joubert, Ch.; Levalois, C.; Dano, L.; Chevillard, S.

2002-01-01

We have a model of radon-induced rat lung tumours, which allow us to analyse the cytogenetic and molecular alterations of the tumours. The aim is to better understand the mechanisms of radio-induced carcinogenesis and to define if it exists a specificity of radio-induced genetic alterations as compared to the genetic alterations found in the sporadic tumours. We have started our analysis by developing global cytogenetic and molecular approaches. We have shown that some alterations are recurrent. The genes that are potentially involved are the oncogene MET and the tumour suppressor Bene p16, which are also frequently altered in human lung tumours. Simultaneously, we have focussed our analysis by targeting the search of mutation in the tumour suppressor gene TP3. We have found that 8 of 39 tumours were mutated by deletion in the coding sequence of TP53. This high frequency of deletion, which is not observed in the human p53 mutation database could constitute a signature of radio-induced alterations. On this assumption, this type of alteration should not be only found on TP53 Bene but also in other suppressor genes which are inactivated by a mutation such as p16 for example. The work we are carrying out on radio-induced tumours among humans and animals is directed to this end. (author)

Monoclonal antibodies for radioimmunodetection of tumours and for targeting

International Nuclear Information System (INIS)

Baldwin, R.W.; Embleton, M.J.; Pimm, M.V.

1983-01-01

A monoclonal antibody 791T/36 prepared against human osteogenic sarcoma has been used to detect primary and metastatic colorectal carcinomas by external imaging of patients following injection of 131 I-labelled antibody. In 10 of 11 patients radiolabelled 791T/36 antibody localized in tumours, the tumour/non tumour ratio of radioactivity ranging from 1.5:1 to 8.1. 791T/36 antibody was also evaluated for its potential for targeting anti-tumour agents including cytotoxic drugs (Vindesine) and immunomodulating agents (interferon). Vindesine-791T/36 conjugates were preferentially cytotoxic in vitro for target cells expressing the 791T/36 anti-body defined antigen. Also interferon conjugated to 791T/36 antibody, like free interferon activated peripheral blood natural killer cell activity. These in vitro tests together with related studies on antibody localization in vivo indicate the potential of monoclonal antibody targeting of anti-tumour agents

CASE REPORT Paraspinal primitive neuroectodermal tumour (PNET)

African Journals Online (AJOL)

could be confirmed on the lateral lumbar spine X-ray. The T11 inter- pedicular distance was ... Department of Diagnostic Radiology, University of Limpopo, Medunsa Campus. CASE REPORT. 18. SA JOURNAL OF ... tumours from neural crest origin.1-4,6 PNET and ES are classified together into the Ewing family of tumours ...

Uncommon presentation of a rare tumour - incidental finding in an asymptomatic patient: case report and comprehensive review of the literature on intrapericardial solitary fibrous tumours

OpenAIRE

Czimbalmos, Csilla; Csecs, Ibolya; Polos, Miklos; Bartha, Elektra; Szucs, Nikolette; Toth, Attila; Maurovich-Horvat, Pal; Becker, David; Sapi, Zoltan; Szabolcs, Zoltan; Merkely, Bela; Vago, Hajnalka

2017-01-01

Background A solitary fibrous tumour is a rare, mainly benign spindle cell mesenchymal tumour most commonly originating from the pleura. An intrapericardial location of a solitary fibrous tumour is extremely unusual. We present a case of an asymptomatic patient with a slow-growing massive benign cardiac solitary fibrous tumour. Case presentation A 37-year-old asymptomatic female patient was referred to our hospital with an enlarged cardiac silhouette found on her screening chest X-ray. The ec...

Imaging biomarkers in primary brain tumours

Energy Technology Data Exchange (ETDEWEB)

Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

2015-04-01

We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents

Science.gov (United States)

Patil, Abhijit A.; Sayal, Parag; Depondt, Marie-Lise; Beveridge, Ryan D.; Roylance, Anthony; Kriplani, Deepti H.; Myers, Katie N.; Cox, Angela; Jellinek, David; Fernando, Malee; Carroll, Thomas A.; Collis, Spencer J.

2014-01-01

Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge. GBM survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome. PMID:25071006

CT-stereotactic interstitial Curie-therapy using iodine-125 seeds in inoperable brain tumours

International Nuclear Information System (INIS)

Mundinger, F.

1985-01-01

Iodine-125 seeds are a new radio-drug featuring favourable physical, biological and radiation protection characteristics and available for interstitial (local) irradiation (Curie-therapy) of non-resectable brain tumours as such (cerebral tumours) or of tumours of the interior of the neuro-cranium (extracerebral tumours). Emitters are inserted right into the tumour or tumour recurrence by means of computerized-tomography stereotaxy either permanently or temporarily with dose release being largely restricted to the tumour and the surrounding brain tissue being spared. (orig.) [de

3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

KAUST Repository

Perfahl, H.; Byrne, H. M.; Chen, T.; Estrella, V.; Alarcó n, T.; Lapin, A.; Gatenby, R. A.; Gillies, R. J.; Lloyd, M. C.; Maini, P. K.; Reuss, M.; Owen, M. R.

2012-01-01

We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

3D Multiscale Modelling of Angiogenesis and Vascular Tumour Growth

KAUST Repository

Perfahl, H.

2012-11-01

We present a three-dimensional, multiscale model of vascular tumour growth, which couples nutrient/growth factor transport, blood flow, angiogenesis, vascular remodelling, movement of and interactions between normal and tumour cells, and nutrient-dependent cell cycle dynamics within each cell. We present computational simulations which show how a vascular network may evolve and interact with tumour and healthy cells. We also demonstrate how our model may be combined with experimental data, to predict the spatio-temporal evolution of a vascular tumour.

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast

OpenAIRE

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-01-01

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast.

Science.gov (United States)

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-06-21

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

The influence of the oestrous cycle on the radiation response of solid tumours

Science.gov (United States)

Swann, Patricia R.

Oestrogen increases the transcription of nitric oxide synthase, thus increasing nitric oxide production, which can result in vasodilation of blood vessels. Fluctuating levels of oestrogen throughout the menstrual cycle has the potential to affect tumour blood flow. Variations of blood supply to a solid tumour can influence tumour oxygenation and subsequently the percentage of hypoxic cells. As hypoxic cells are more resistant to radiation than well-oxygenated cells, this could potentially affect the radiation response of the tumour. This project evaluated the impact of the oestrous stage on the radiation response of BCHT, RIF-1 and SCCvii tumours in syngeneic C3H mice. The oestrous cycle consists of the following stages, pro-oestrus, oestrus, metoestrus and dioestrus and each stage can be determined by the cellular composition of vaginal smears. The peak of oestrogen occurs in the ovulatory phase and a second smaller peak occurs in dioestrus. Subcutaneous tumour were treated at a volume of 200 - 250 mm3 with local irradiation of 10 Gy ionising radiation at different stages of the oestrous cycle. Tumours were excised either immediately or 24 hours after irradiation and disaggregated into a single cell suspension. Tumour cell survival was assessed by clonogenic assay of the excised tumour relative to untreated tumours excised at the corresponding oestrous stage. Tumours irradiated in oestrus consistently produced the lowest surviving fraction after immediate and delayed excision. Tumours irradiated in pro-oestrus and excised immediately after irradiation, showed a two-fold increase in surviving fraction compared to tumours irradiated in oestrus. The surviving fractions of tumours excised 24 hours after irradiation were less than for tumours excised immediately after irradiation. Surviving fractions of irradiated, clamped KHT tumours were independent of oestrous stage. To confirm that these oestrous stage dependent changes were due to changes in tumour perfusion, the

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

Germ cell tumours in neonates and infants: a distinct subgroup?

NARCIS (Netherlands)

Veltman, I.M.; Schepens, M.T.M.; Looijenga, L.H.J.; Strong, L.C.; Geurts van Kessel, A.H.M.

2003-01-01

Human germ cell tumours (GCTs) constitute a heterogeneous group of tumours that can be classified into four major subgroups. One of these subgroups encompasses (immature) teratomas and yolk sac tumours of patients under the age of 5 years. In this paper we review the various clinical, histological

Folate-targeted amphiphilic cyclodextrin nanoparticles incorporating a fusogenic peptide deliver therapeutic siRNA and inhibit the invasive capacity of 3D prostate cancer tumours.

Science.gov (United States)

Evans, James C; Malhotra, Meenakshi; Sweeney, Katrina; Darcy, Raphael; Nelson, Colleen C; Hollier, Brett G; O'Driscoll, Caitriona M

2017-10-30

The main barrier to the development of an effective RNA interference (RNAi) therapy is the lack of a suitable delivery vector. Modified cyclodextrins have emerged in recent years for the delivery of siRNA. In the present study, a folate-targeted amphiphilic cyclodextrin was formulated using DSPE-PEG 5000 -folate to target prostate cancer cells. The fusogenic peptide GALA was included in the formulation to aid in the endosomal release of siRNA. Targeted nanoparticles were less than 200nm in size with a neutral surface charge. The complexes were able to bind siRNA and protect it from serum nucleases. Incubation with excess free folate resulted in a significant decrease in the uptake of targeted nanoparticles in LNCaP and PC3 cells, both of which have been reported to have differing pathways of folate uptake. There was a significant reduction in the therapeutic targets, ZEB1 and NRP1 at mRNA and protein level following treatment with targeted complexes. In preliminary functional assays using 3D spheroids, treatment of PC3 tumours with targeted complexes with ZEB1 and NRP1 siRNA resulted in more compact colonies relative to the untargeted controls and inhibited infiltration into the Matrigel™ layer. Copyright © 2017 Elsevier B.V. All rights reserved.

Swiss Canine Cancer Registry 1955-2008: Occurrence of the Most Common Tumour Diagnoses and Influence of Age, Breed, Body Size, Sex and Neutering Status on Tumour Development.

Science.gov (United States)

Grüntzig, K; Graf, R; Boo, G; Guscetti, F; Hässig, M; Axhausen, K W; Fabrikant, S; Welle, M; Meier, D; Folkers, G; Pospischil, A

2016-01-01

This study is based on the Swiss Canine Cancer Registry, comprising 121,963 diagnostic records of dogs compiled between 1955 and 2008, in which 63,214 (51.83%) animals were diagnosed with tumour lesions through microscopical investigation. Adenoma/adenocarcinoma (n = 12,293, 18.09%) was the most frequent tumour diagnosis. Other common tumour diagnoses were: mast cell tumour (n = 4,415, 6.50%), lymphoma (n = 2,955, 4.35%), melanocytic tumours (n = 2,466, 3.63%), fibroma/fibrosarcoma (n = 2,309, 3.40%), haemangioma/haemangiosarcoma (n = 1,904, 2.80%), squamous cell carcinoma (n = 1,324, 1.95%) and osteoma/osteosarcoma (n = 842, 1.24%). The relative occurrence over time and the most common body locations of those tumour diagnoses are presented. Analyses of the influence of age, breed, body size, sex and neutering status on tumour development were carried out using multiple logistic regression. In certain breeds/breed categories the odds ratios (ORs) for particular tumours were outstandingly high: the boxer had higher ORs for mast cell tumour and haemangioma/haemangiosarcoma, as did the shepherd group for haemangioma/haemangiosarcoma, the schnauzer for squamous cell carcinoma and the rottweiler for osteoma/osteosarcoma. In small dogs, the risk of developing mammary tumours was three times higher than in large dogs. However, small dogs were less likely to be affected by many other tumour types (e.g. tumours of the skeletal system). Examination of the influence of sex and neutering status on tumour prevalence showed that the results depend on the examination method. In all sampling groups the risk for female dogs of developing adenoma/adenocarcinoma was higher than for male dogs. Females had a lower risk of developing haemangioma/haemangiosarcoma and squamous cell carcinoma than males. Neutered animals were at higher risk of developing specific tumours outside the genital organs than intact animals. The sample size allows detailed insight into the

Spatio-temporal cell dynamics in tumour spheroid irradiation

International Nuclear Information System (INIS)

Kempf, H.; Bleicher, M.; Meyer-Hermann, M.; Kempf, H.; Bleicher, M.; Kempf, H.; Meyer-Hermann, M.

2010-01-01

Multicellular tumour spheroids are realistic in vitro systems in radiation research that integrate cell-cell interaction and cell cycle control by factors in the medium. The dynamic reaction inside a tumour spheroid triggered by radiation is not well understood. Of special interest is the amount of cell cycle synchronization which could be triggered by irradiation, since this would allow follow-up irradiations to exploit the increased sensitivity of certain cell cycle phases. In order to investigate these questions we need to support irradiation experiments with mathematical models. In this article a new model is introduced combining the dynamics of tumour growth and irradiation treatments. The tumour spheroid growth is modelled using an agent-based Delaunay/Voronoi hybrid model in which the cells are represented by weighted dynamic vertices. Cell properties like full cell cycle dynamics are included. In order to be able to distinguish between different cell reactions in response to irradiation quality we introduce a probabilistic model for damage dynamics. The overall cell survival from this model is in agreement with predictions from the linear-quadratic model. Our model can describe the growth of avascular tumour spheroids in agreement to experimental results. Using the probabilistic model for irradiation damage dynamics the classic 'four Rs' of radiotherapy can be studied in silico. We found a pronounced reactivation of the tumour spheroid in response to irradiation. A majority of the surviving cells is synchronized in their cell cycle progression after irradiation. The cell synchronization could be actively triggered and should be exploited in an advanced fractionation scheme. Thus it has been demonstrated that our model could be used to understand the dynamics of tumour growth after irradiation and to propose optimized fractionation schemes in cooperation with experimental investigations. (authors)

Emotional and personality changes following brain tumour resection.

Science.gov (United States)

Jenkins, Lisanne M; Drummond, Katharine J; Andrewes, David G

2016-07-01

Psychological distress has a high prevalence in brain tumour patients, and understanding the emotional and personality changes that may follow neurosurgery is important for clinical management of these patients. We aimed to characterise these emotional and personality changes using subjective, observer-rated and clinical measures. We examined subjective changes in emotional experience and observer-rated changes to personality disturbances following neurosurgery for brain tumours (n=44), compared to a control group that had undergone spinal surgery (n=26). Participants completed the Hospital Anxiety and Depression Scale and a Subjective Emotional Change Questionnaire. Observers who knew the patients well also completed the Iowa Rating Scale of Personality Change. Compared to controls, patients with tumours reported significantly more changes to their subjective experience of emotions following neurosurgery, particularly anger, disgust and sadness. For the observer-ratings, tumour patients were described as having significant changes in the personality disturbances of irritability, impulsivity, moodiness, inflexibility, and being easily overwhelmed. Anxiety and depression were not significantly different between groups. Neurosurgical resection of a brain tumour is a major life event that changes patients' subjective experiences of different emotions, and leads to observer-rated changes in personality. In this study, these changes were not accompanied by increases in anxiety or depression. We conclude with a discussion of biological and psychosocial mechanisms that can impact emotional functioning and personality in patients with brain tumours. Copyright © 2015 Elsevier Ltd. All rights reserved.

A STUDY OF TUMOURS OF THE SELLER REGION

Directory of Open Access Journals (Sweden)

Rame

2016-03-01

Full Text Available BACKGROUND The tumours of the sellar region that are encountered according to literature are Craniopharyngioma [WHO grade I], Granular cell tumour of the neurohypophysis [WHO grade I], Pituicytoma [WHO grade I], Spindle cells oncocytoma of the adenohypophysis [WHO grade I]. The aim of the study is to study the tumours that are encountered in the Sellar Region. The incidence of the sellar region is very less in this region of Karnataka. METHOD The sample size included 100 cases of intra-cranial neoplasms that turned in the Department of Medicine in KVJ Medical College, Sullia and different local private hospitals of Sullia and Mangalore. RESULTS Only one case of craniopharyngioma was encountered in this study. It accounts for 1(1% of all intracranial tumours studied in this series. Tumour was located in the suprasellar region. This case was reported in a 52-year-old female patient. Presenting complaint was bilateral visual loss and loss of memory. Microscopically-Stratified squamous epithelium was seen lining a cyst and solid ameloblastomatous tissue, calcification ossification and inflammatory reaction were common features. CONCLUSION The incidence of the sellar region is very less in this region of Karnataka.

Expression of RNA interference triggers from an oncolytic herpes simplex virus results in specific silencing in tumour cells in vitro and tumours in vivo

International Nuclear Information System (INIS)

Anesti, Anna-Maria; Simpson, Guy R; Price, Toby; Pandha, Hardev S; Coffin, Robert S

2010-01-01

Delivery of small interfering RNA (siRNA) to tumours remains a major obstacle for the development of RNA interference (RNAi)-based therapeutics. Following the promising pre-clinical and clinical results with the oncolytic herpes simplex virus (HSV) OncoVEX GM-CSF , we aimed to express RNAi triggers from oncolytic HSV, which although has the potential to improve treatment by silencing tumour-related genes, was not considered possible due to the highly oncolytic properties of HSV. To evaluate RNAi-mediated silencing from an oncolytic HSV backbone, we developed novel replicating HSV vectors expressing short-hairpin RNA (shRNA) or artificial microRNA (miRNA) against the reporter genes green fluorescent protein (eGFP) and β-galactosidase (lacZ). These vectors were tested in non-tumour cell lines in vitro and tumour cells that are moderately susceptible to HSV infection both in vitro and in mice xenografts in vivo. Silencing was assessed at the protein level by fluorescent microscopy, x-gal staining, enzyme activity assay, and western blotting. Our results demonstrate that it is possible to express shRNA and artificial miRNA from an oncolytic HSV backbone, which had not been previously investigated. Furthermore, oncolytic HSV-mediated delivery of RNAi triggers resulted in effective and specific silencing of targeted genes in tumour cells in vitro and tumours in vivo, with the viruses expressing artificial miRNA being comprehensibly more effective. This preliminary data provide the first demonstration of oncolytic HSV-mediated expression of shRNA or artificial miRNA and silencing of targeted genes in tumour cells in vitro and in vivo. The vectors developed in this study are being adapted to silence tumour-related genes in an ongoing study that aims to improve the effectiveness of oncolytic HSV treatment in tumours that are moderately susceptible to HSV infection and thus, potentially improve response rates seen in human clinical trials

Association between vascular supply, stage and tumour size of juvenile nasopharyngeal angiofibroma.

Science.gov (United States)

Mehan, Raghav; Rupa, V; Lukka, Vijay Kumar; Ahmed, Munawar; Moses, Vinu; Shyam Kumar, N K

2016-12-01

Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular tumour seen in adolescent males. To study the vascular pattern of these tumours, we retrospectively reviewed the records of patients with JNA who underwent preoperative angiography. Most (82.2 %) of the 45 patients assessed were Radkowski stage III with a mean size of 5.29 cm. There was a significant association between tumour stage and size (p = 0.029). Ten different vessels were seen to supply these tumours. All tumours had primary supply from the distal third of the ipsilateral internal maxillary artery (IMA). Accessory vessel supply was chiefly from the Vidian branch of internal carotid artery (ICA) (55.6 %). Stage III tumours were supplied by a greater number of feeding vessels than earlier stage tumours (p < 0.01). Larger tumours were more likely to have ICA supply (p = 0.04). Bilateral supply was seen in 48.7 %. However, there was no predominance of bilateral over ipsilateral IMA supply even in advanced stage tumours. One patient in our series was found to have a caroticocavernous fistula. Residual or recurrent tumours were characterized by new vasculature (100 %) and greater accessory supply from the ipsilateral ICA (85.7 %). Our study highlights the fact that surgical planning cannot be dependent on staging alone and should include preoperative assessment of tumour vasculature by angiography.

Bioactive albumin-based carriers for tumour chemotherapy.

Science.gov (United States)

Shahzad, Yasser; Khan, Ikram Ullah; Hussain, Talib; Alamgeer; Serra, Christophe A; Rizvi, Syed A A; Gerber, Minja; du Plessis, Jeanetta

2014-01-01

Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them, have been regarded safe for drug delivery purposes by the United States Food and Drug Administration (FDA). Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, especially for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages over synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.

Radiation-induced bone tumours in the guinea-pig

International Nuclear Information System (INIS)

Knowles, J.F.

1981-01-01

A remarkably high proportion of guinea-pigs given localized irradiations of 20 Gy x-rays developed bone tumours, 46% of all irradiated with 20 Gy and 86% of those that survived at least a year. Untreated controls were not included in the present experiment, but the authors refer to an earlier experiment using guinea-pigs from the same colony where no bone tumour occurred in 69 unirradiated animals followed for their natural life span i.e. up to 87 months. It is concluded that the author's strain of guinea-pig (details given in a previous paper, Int. J. Radiol. Biol., 40, 265) is particularly prone to radiation-induced bone tumours. Their possible value for investigating processes associated with radiation induction of bone tumours is further enhanced by their relatively large size and long life span (up to 7 years). (U.K.)

Spatio-temporal tumour model for analysis and mechanism of action ...

Indian Academy of Sciences (India)

We have developed a one-dimensional tumour simulator to describe the biodistribution of chemotherapeutic drugs to a tumoral lesion and the tumour cell's response to therapy. A three-compartment model is used for drug dynamics within the tumour. The first compartment represents the extracellular space in which cells ...

N-hydroxyurea, mitomycin C and actinomycin D activity in the process of tumour formation on the primary leaves of the 'Pinto' bean

Directory of Open Access Journals (Sweden)

Aldona Rennert

2014-01-01

Full Text Available Mitomycin C (MC, N-hydroxyurea (HU and actinomycin D (AD inhibit tumour formation on the primary leaves of Pinto beans. Agrobacterium tumefaciens was inoculated into bean leaves with application of the above named inhibitors at various times. It was found that MC action is strongest during inoculation and immediately after it, the maximal effect of HU take place within 12 h after inoculation, whereas the antitumour action of AD starts as late as 12 h after leaf inoculation. In view of the different degree of susceptibility of bacteria and plant cells to the inhibitors applied, the above described results allowed to distinguish three critical periods in the process of tumour formation in the tested host-pathogen system.

Tumour response and morphological changes of acoustic neurinomas after radiosurgery

International Nuclear Information System (INIS)

Valentino, V.; Raimondi, A.J.

1995-01-01

Twenty-seven of the 1560 patients treated by radiosurgery during the period 1984-1993 had acoustic neurinomas. Four cases were excluded from this study because they had a follow-up of less than 2 years. There were 24 neurinomas treated in 23 patients as one patient had a bilateral tumour. Seven patients underwent radiosurgery for a recurrent tumour (already operated on once or twice), while it was the first treatment for 16 patients. The tumour volume ranged from 1.99 cm 3 to 18.30 cm 3 , and the patient follow-up was from 2 to 8 years. To determine the target on CT/NMR for linear accelerator stereotactic irradiation, the Greitz-Bergstroem non-invasive head fixation device was used. It was again adopted for subsequent serial imaging, and for repeat radiosurgery when necessary. The total peripheral tumour dose ranged from 12 to 45 Gy. In 9 patients there was a reduction in tumour volume varying from 39 to 100% , while 14 of the neurinomas appeared stable after an average follow-up of 3 years. In one patient there was an increase in size of the tumour. Variable morphological changes were present in 66% of the neurinomas treated. Radiosurgery is indicated as an alternative to microsurgery for inoperab1e patients and for those who refuse surgery, for recurrent tumours, and as a post-operative complementary treatment for partially removed tumours. A gradual approach to radiosurgery, depending on tumour response, allows a greater efficacy with minimal risk. In the present series no complications were observed. Hearing was preserved at almost the same level as that prior to radiosurgery in all patients. (author)

Tumour-induced osteomalacia: a literature review and a case report.

Science.gov (United States)

Dadoniene, Jolanta; Miglinas, Marius; Miltiniene, Dalia; Vajauskas, Donatas; Seinin, Dmitrij; Butenas, Petras; Kacergius, Tomas

2016-01-08

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. The epidemiology likewise aetiology is not known. The clinical presentation of TIO includes bone fractures, bone and muscular pains, and sometimes height and weight loss. TIO may be associated with mesenchymal tumours which may be benign or malignant in rare cases. Mesenchymal tumour itself may be related to fibroblast growth factor 23 (FGF23), which is responsible for hypophosphataemia and phosphaturia occurring in this paraneoplastic syndrome. Hypophosphataemia, phosphaturia and elevated alkaline phosphatase are the main laboratory readings that may lead to more precise investigations and better diagnosis. Finding the tumour can be a major diagnostic challenge and may involve total body magnetic resonance imaging, computed tomography and scintigraphy using radiolabelled somatostatin analogue. The treatment of choice for TIO is resection of a tumour with a wide margin to insure complete tumour removal, as recurrences of these tumours have been reported. We provide here an overview on the current available TIO case reports and review the best practices that may lead to earlier recognition of TIO and the subsequent treatment thereof, even though biochemical background and the long-term prognosis of the disease are not well understood. This review also includes a 4-year-long history of a patient that featured muscular pains, weakness and multiple stress fractures localised in the hips and vertebra with subsequent recovery after tumour resection. Because the occurrence of such a condition is rare, it may take years to correctly diagnose the disease, as is reported in this case report.

Multiple adenomatoid tumours in the Epididymis and Tunica vaginalis: Case report

Directory of Open Access Journals (Sweden)

Ahmed Abroaf

2014-03-01

Full Text Available We describe the case of a 65 year-old male presenting with a tender right testicular mass, confirmed to be a tumour on ultrasound. The patient underwent a radical inguinal orchidectomy and histology revealed multiple adenomatoid tumours in epididymis and tunica vaginalis. This is an infrequent benign tumour of mesothelial origin that has rarely been reported as multiple lesions in the literature. Immunohistochemistry demonstrates that adenomatoid tumour and mesotheliomas share the expression of podoplanin (D2-40 which is helpful to differentiate them from carcinomas. On the other hand adenomatoid tumour is differentiated from mesothelioma on morphological grounds since the former does not exhibit cellular atypia, mitotic activity or bland focal tumour necrosis. Although testis preserving surgery can be an option for benign adenomatoid tumours, most patients (as in our case proceed to orchidectomy as diagnosing them confidently can be difficult.---------------------------Cite this article as: Abroaf A, Veeratterapillay R, Vasdev N, Majo J, Sherif AE, Paez E. Multiple adenomatoid tumours in the Epididymis and Tunica vaginalis : Case Report. Int J Cancer Ther Oncol 2014; 2(1:02021.DOI: http://dx.doi.org/10.14319/ijcto.0202.1

DNA methylation-based classification of central nervous system tumours.

Science.gov (United States)

Capper, David; Jones, David T W; Sill, Martin; Hovestadt, Volker; Schrimpf, Daniel; Sturm, Dominik; Koelsche, Christian; Sahm, Felix; Chavez, Lukas; Reuss, David E; Kratz, Annekathrin; Wefers, Annika K; Huang, Kristin; Pajtler, Kristian W; Schweizer, Leonille; Stichel, Damian; Olar, Adriana; Engel, Nils W; Lindenberg, Kerstin; Harter, Patrick N; Braczynski, Anne K; Plate, Karl H; Dohmen, Hildegard; Garvalov, Boyan K; Coras, Roland; Hölsken, Annett; Hewer, Ekkehard; Bewerunge-Hudler, Melanie; Schick, Matthias; Fischer, Roger; Beschorner, Rudi; Schittenhelm, Jens; Staszewski, Ori; Wani, Khalida; Varlet, Pascale; Pages, Melanie; Temming, Petra; Lohmann, Dietmar; Selt, Florian; Witt, Hendrik; Milde, Till; Witt, Olaf; Aronica, Eleonora; Giangaspero, Felice; Rushing, Elisabeth; Scheurlen, Wolfram; Geisenberger, Christoph; Rodriguez, Fausto J; Becker, Albert; Preusser, Matthias; Haberler, Christine; Bjerkvig, Rolf; Cryan, Jane; Farrell, Michael; Deckert, Martina; Hench, Jürgen; Frank, Stephan; Serrano, Jonathan; Kannan, Kasthuri; Tsirigos, Aristotelis; Brück, Wolfgang; Hofer, Silvia; Brehmer, Stefanie; Seiz-Rosenhagen, Marcel; Hänggi, Daniel; Hans, Volkmar; Rozsnoki, Stephanie; Hansford, Jordan R; Kohlhof, Patricia; Kristensen, Bjarne W; Lechner, Matt; Lopes, Beatriz; Mawrin, Christian; Ketter, Ralf; Kulozik, Andreas; Khatib, Ziad; Heppner, Frank; Koch, Arend; Jouvet, Anne; Keohane, Catherine; Mühleisen, Helmut; Mueller, Wolf; Pohl, Ute; Prinz, Marco; Benner, Axel; Zapatka, Marc; Gottardo, Nicholas G; Driever, Pablo Hernáiz; Kramm, Christof M; Müller, Hermann L; Rutkowski, Stefan; von Hoff, Katja; Frühwald, Michael C; Gnekow, Astrid; Fleischhack, Gudrun; Tippelt, Stephan; Calaminus, Gabriele; Monoranu, Camelia-Maria; Perry, Arie; Jones, Chris; Jacques, Thomas S; Radlwimmer, Bernhard; Gessi, Marco; Pietsch, Torsten; Schramm, Johannes; Schackert, Gabriele; Westphal, Manfred; Reifenberger, Guido; Wesseling, Pieter; Weller, Michael; Collins, Vincent Peter; Blümcke, Ingmar; Bendszus, Martin; Debus, Jürgen; Huang, Annie; Jabado, Nada; Northcott, Paul A; Paulus, Werner; Gajjar, Amar; Robinson, Giles W; Taylor, Michael D; Jaunmuktane, Zane; Ryzhova, Marina; Platten, Michael; Unterberg, Andreas; Wick, Wolfgang; Karajannis, Matthias A; Mittelbronn, Michel; Acker, Till; Hartmann, Christian; Aldape, Kenneth; Schüller, Ulrich; Buslei, Rolf; Lichter, Peter; Kool, Marcel; Herold-Mende, Christel; Ellison, David W; Hasselblatt, Martin; Snuderl, Matija; Brandner, Sebastian; Korshunov, Andrey; von Deimling, Andreas; Pfister, Stefan M

2018-03-22

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

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.