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Sample records for breast tumour cells

  1. Galectin-3 coats the membrane of breast cells and makes a signature of tumours

    KAUST Repository

    Simone, Giuseppina; Malara, Natalia Maria; Trunzo, Valentina; Renne, Maria; Perozziello, Gerardo; Di Fabrizio, Enzo M.; Manz, Andreas

    2014-01-01

    Galectin-3, β-galactoside-binding lectin, coats the membrane of most cancer cells and is involved in metastasis and endothelium recognition as well as in evading immune surveillance through killing of activated T cells. To flag galectin as a biomarker of tumours and metastasis, it is pivotal to understand the role of this protein in different tumours and at different stages. Breast tumours have an anomalous behaviour of the galectin-3 compared to other tumour cells. Herein, FACS sorting and galactoside based assays were used to investigate the role of galectin-3 in metastasis and metastatisation of breast cancer cells. Breast galectin fingerprint at the FACS displayed a higher amount in healthy cells, compared to metastatic cells. The microfluidic assay was able to isolate tumour and metastatic cells more than healthy breast cells. Investigation was performed on samples from patients with breast tumours at stage I and stage III whilst MCF7 and EPH-4 cells were used to perform preliminary investigations. The readout of the conditioned medium (from culturing of stage I cells) fingerprint by FACS evidenced high expression of free galectin. Analysis of the results established that the galectin coating the membrane, by galactoside recognition of the breast cells, and engaged by the cells to form protein-carbohydrate complexes inside the microfluidic assay, resembled the tumour signature of tumours in breast cells whilst the galectin free is independent of those mechanisms. © 2014 The Royal Society of Chemistry.

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

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-04-26

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

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

    Directory of Open Access Journals (Sweden)

    Herbst Hermann

    2005-07-01

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

  4. 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.

  5. 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

  6. Recurrence and mortality according to Estrogen Receptor status for breast cancer patients undergoing conservative surgery. Ipsilateral breast tumour recurrence dynamics provides clues for tumour biology within the residual breast

    International Nuclear Information System (INIS)

    Demicheli, Romano; Ardoino, Ilaria; Boracchi, Patrizia; Coradini, Danila; Agresti, Roberto; Ferraris, Cristina; Gennaro, Massimiliano; Hrushesky, William JM; Biganzoli, Elia

    2010-01-01

    the study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection. Time span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative surgery with or without breast radiotherapy. The hazard rates for ipsilateral breast tumour recurrence (IBTR), distant metastasis (DM) and mortality throughout 10 years of follow-up were assessed. DM dynamics displays the same bimodal pattern (first early peak at about 24 months, second late peak at the sixth-seventh year) for both estrogen receptor (ER) positive (P) and negative (N) tumours and for all local treatments and metastatic sites. The hazard rates for IBTR maintain the bimodal pattern for ERP and ERN tumours; however, each IBTR recurrence peak for ERP tumours is delayed in comparison to the corresponding timing of recurrence peaks for ERN tumours. Mortality dynamics is markedly different for ERP and ERN tumours with more early deaths among patients with ERN than among patients with ERP primary tumours. DM dynamics is not influenced by the extent of conservative primary tumour resection and is similar for both ER phenotypes across different metastatic sites, suggesting similar mechanisms for tumour development at distant sites despite apparently different microenvironments. The IBTR risk peak delay observed in ERP tumours is an exception to the common recurrence risk rhythm. This suggests that the microenvironment within the residual breast tissue may enforce more stringent constraints upon ERP breast tumour cell growth than other tissues, prolonging the latency of IBTR. This local environment is, however, apparently less constraining to ERN cells, as IBTR dynamics is similar to the corresponding recurrence dynamics among other distant tissues

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

    LENUS (Irish Health Repository)

    Donatello, Simona

    2011-01-01

    Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

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

    Directory of Open Access Journals (Sweden)

    Shishido-Hara Yukiko

    2010-08-01

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

  9. The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours.

    Science.gov (United States)

    Varley, J M; Armour, J; Swallow, J E; Jeffreys, A J; Ponder, B A; T'Ang, A; Fung, Y K; Brammar, W J; Walker, R A

    1989-06-01

    We have analysed the organisation of the retinoblastoma (RB1) gene in 77 primary breast carcinomas, in metastatic tissue derived from 16 of those primary tumours, and in a variety of benign breast lesions. Expression of RB1 was also assessed in most samples by immunohistochemical detection of the RB1 protein in tissue sections. Structural abnormalities to RB1 were detected in DNA from 15/77 (19%) of primary breast carcinomas examined. Where DNA was available from metastatic tissue derived from such primary tumours, the same aberration could be detected. No alterations were seen in benign breast lesions. 16/56 (29%) of tumours examined for expression by immunohistochemical methods showed a proportion of tumour cells to be completely negative for the RB1 protein. All tumours in which a structural alteration to RB1 was detected had a proportion of negative cells, except for one case where all cells were positive. Several primary tumour samples were identified where there was no detectable structural change to the gene, but there was loss of expression in some tumour cells. The data presented here demonstrate that changes to the RB1 gene leading to loss of expression of both alleles are frequent in primary human breast tumours.

  10. 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.

  11. 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.

  12. Mast cells and eosinophils in invasive breast carcinoma

    International Nuclear Information System (INIS)

    Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

    2007-01-01

    Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

  13. Gene expression of circulating tumour cells in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Bölke E

    2009-09-01

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

  14. Breast spindle cell tumours: about eight cases

    Directory of Open Access Journals (Sweden)

    Abd El All Howayda S

    2006-07-01

    Full Text Available Abstract Background Breast spindle cell tumours (BSCTs, although rare, represent a heterogeneous group with different treatment modalities. This work was undertaken to evaluate the utility of fine needle aspiration cytology (FNAC, histopathology and immunohistochemistry (IHC in differentiating BSCTs. Methods FNAC of eight breast masses diagnosed cytologically as BSCTs was followed by wide excision biopsy. IHC using a panel of antibodies against vimentin, pan-cytokeratin, s100, desmin, smooth muscle actin, CD34, and CD10 was evaluated to define their nature. Results FNAC defined the tumors as benign (n = 4, suspicious (n = 2 and malignant (n = 3, based on the cytopathological criteria of malignancy. Following wide excision biopsy, the tumors were reclassified into benign (n = 5 and malignant (n = 3. In the benign group, the diagnosis was raised histologically and confirmed by IHC for 3 cases (one spindle cell lipoma, one myofibroblastoma and one leiomyoma. For the remaining two cases, the diagnosis was set up after IHC (one fibromatosis and one spindle cell variant of adenomyoepithelioma. In the malignant group, a leiomyosarcoma was diagnosed histologically, while IHC was crucial to set up the diagnosis of one case of spindle cell carcinoma and one malignant myoepithelioma. Conclusion FNAC in BSCTs is an insufficient tool and should be followed by wide excision biopsy. The latter technique differentiate benign from malignant BSCTs and is able in 50% of the cases to set up the definite diagnosis. IHC is of value to define the nature of different benign lesions and is mandatory in the malignant ones for optimal treatment. Awareness of the different types of BSCTs prevents unnecessary extensive therapeutic regimes.

  15. Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Alexopoulou, Annika N; Ho-Yen, Colan M; Papalazarou, Vassilis; Elia, George; Jones, J Louise; Hodivala-Dilke, Kairbaan

    2014-01-01

    Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

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

    Science.gov (United States)

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

    2015-01-01

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

  17. 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

  18. Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

    Science.gov (United States)

    Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

    2015-01-01

    The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

  19. Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

    Directory of Open Access Journals (Sweden)

    Christopher R S Banerji

    2015-03-01

    Full Text Available The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers.

  20. Tumour bed boost radiotherapy for women after breast-conserving surgery.

    Science.gov (United States)

    Kindts, Isabelle; Laenen, Annouschka; Depuydt, Tom; Weltens, Caroline

    2017-11-06

    Breast-conserving therapy, involving breast-conserving surgery followed by whole-breast irradiation and optionally a boost to the tumour bed, is a standard therapeutic option for women with early-stage breast cancer. A boost to the tumour bed means that an extra dose of radiation is applied that covers the initial tumour site. The rationale for a boost of radiotherapy to the tumour bed is that (i) local recurrence occurs mostly at the site of the primary tumour because remaining microscopic tumour cells are most likely situated there; and (ii) radiation can eliminate these causative microscopic tumour cells. The boost continues to be used in women at high risk of local recurrence, but is less widely accepted for women at lower risk. Reasons for questioning the boost are twofold. Firstly, the boost brings higher treatment costs. Secondly, the potential adverse events are not negligible. In this Cochrane Review, we investigated the effect of the tumour bed boost on local control and side effects. To assess the effects of tumour bed boost radiotherapy after breast-conserving surgery and whole-breast irradiation for the treatment of breast cancer. We searched the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to 1 March 2017), Embase (1980 to 1 March 2017), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on 1 March 2017. We also searched the European Society of Radiotherapy and Oncology Annual Meeting, the St Gallen Oncology Conferences, and the American Society for Radiation Oncology Annual Meeting for abstracts. Randomised controlled trials comparing the addition and the omission of breast cancer tumour bed boost radiotherapy. Two review authors (IK and CW) performed data extraction and assessed risk of bias using Cochrane's 'Risk of bias' tool, resolving any disagreements through discussion. We entered data into Review Manager 5 for

  1. 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.

  2. 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.

  3. 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 ...

  4. Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin

    DEFF Research Database (Denmark)

    Welinder, Charlotte; Baldetorp, Bo; Blixt, Klas Ola

    2013-01-01

    seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence....... The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1), which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin......-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4) did to some extent overlap with the presence of IgA1 in the tumours, but differences were...

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

    Science.gov (United States)

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

    2014-04-03

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

  6. Role of nuclear receptors in breast cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Alessio; Papi; Marina; Orlandi

    2016-01-01

    The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells,capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells(CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs(BCSCs) are likely to sustain the growth of the primary tumour mass, as wellas to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and proinflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the antiinflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse.

  7. 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

  8. Targeting Chromosomal Instability and Tumour Heterogeneity in HER2-Positive Breast Cancer

    DEFF Research Database (Denmark)

    Burrell, Rebecca A.; Birkbak, Nicolai Juul; Johnston, Stephen R.

    2010-01-01

    Chromosomal instability (CIN) is a common cause of tumour heterogeneity and poor prognosis in solid tumours and describes cell-cell variation in chromosome structure or number across a tumour population. In this article we consider evidence suggesting that CIN may be targeted and may influence...... response to distinct chemotherapy regimens, using HER2-positive breast cancer as an example. Pre-clinical models have indicated a role for HER2 signalling in initiating CIN and defective cell-cycle control, and evidence suggests that HER2-targeting may attenuate this process. Anthracyclines and platinum...... agents may target tumours with distinct patterns of karyotypic complexity, whereas taxanes may have preferential activity in tumours with relative chromosomal stability. A greater understanding of karyotypic complexity and identification of methods to directly examine and target CIN may support novel...

  9. Epigenetic reprogramming of breast cancer cells with oocyte extracts

    Directory of Open Access Journals (Sweden)

    Kumari Rajendra

    2011-01-01

    Full Text Available Abstract Background Breast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis. Results We show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts. Conclusions This study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.

  10. 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

  11. Strain histograms are equal to strain ratios in predicting malignancy in breast tumours

    DEFF Research Database (Denmark)

    Carlsen, Jonathan Frederik; Ewertsen, Caroline; Sletting, Susanne

    2017-01-01

    Objectives: To assess whether strain histograms are equal to strain ratios in predicting breast tumour malignancy and to see if either could be used to upgrade Breast Imaging Reporting and Data System (BI-RADS) 3 tumours for immediate biopsy. Methods: Ninety-nine breast tumours were examined using...

  12. Surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Clare; Boachie, Charles; Fraser, Cynthia; MacLennan, Graeme; Mowatt, Graham; Thomas, Ruth E. [University of Aberdeen, Health Services Research Unit, Aberdeen (United Kingdom); Ragupathy, Senthil Kumar Arcot [NHS Grampian, Radiology Department, Aberdeen Royal Infirmary, Aberdeen (United Kingdom); Heys, Steve D. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Division of Applied Medicine, School of Medicine and Dentistry, Aberdeen (United Kingdom); Gilbert, Fiona J. [University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom)

    2011-12-15

    To determine the diagnostic accuracy of surveillance mammography for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. A systematic review of surveillance mammography compared with ultrasound, magnetic resonance imaging (MRI), specialist-led clinical examination or unstructured primary care follow-up, using histopathological assessment for test positives and follow-up for test negatives as the reference standard. Nine studies met our inclusion criteria. Variations in study comparisons precluded meta-analysis. For routine ipsilateral breast tumour detection, surveillance mammography sensitivity ranged from 64-67% and specificity ranged from 85-97%. For MRI, sensitivity ranged from 86-100% and specificity was 93%. For non-routine ipsilateral breast tumour detection, sensitivity and specificity for surveillance mammography ranged from 50-83% and 57-75% and for MRI 93-100% and 88-96%. For routine metachronous contralateral breast cancer detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI. Although mammography is associated with high sensitivity and specificity, MRI is the most accurate test for detecting ipsilateral breast tumour recurrence and metachronous contralateral breast cancer in women previously treated for primary breast cancer. Results should be interpreted with caution because of the limited evidence base. (orig.)

  13. Breast cancer cell lines: friend or foe?

    International Nuclear Information System (INIS)

    Burdall, Sarah E; Hanby, Andrew M; Lansdown, Mark RJ; Speirs, Valerie

    2003-01-01

    The majority of breast cancer research is conducted using established breast cancer cell lines as in vitro models. An alternative is to use cultures established from primary breast tumours. Here, we discuss the pros and cons of using both of these models in translational breast cancer research

  14. Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation.

    Science.gov (United States)

    Arjunan, Ravi; Kumar, Durgesh; Kumar, K V Veerendra; Premlatha, C S

    2016-10-01

    Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC.

  15. Glycosyltransferases as marker genes for the quantitative polymerase chain reaction-based detection of circulating tumour cells from blood samples of patients with breast cancer undergoing adjuvant therapy.

    Science.gov (United States)

    Kölbl, Alexandra C; Hiller, Roman A; Ilmer, Mathias; Liesche, Friederike; Heublein, Sabine; Schröder, Lennard; Hutter, Stefan; Friese, Klaus; Jeschke, Udo; Andergassen, Ulrich

    2015-08-01

    Altered glycosylation is a predominant feature of tumour cells; it serves for cell adhesion and detachment, respectively, and facilitates the immune escape of these cells. Therefore changes in the expression of glycosyltransferase genes could help to identify circulating tumour cells (CTCs) in the blood samples of cancer patients using a quantitative polymerase chain reaction (PCR) approach. Blood samples of healthy donors were inoculated with certain numbers of established breast cancer cell line cells, thus creating a model system. These samples were analysed by quantitative PCR for the expression of six different glycosyltransferase genes. The three genes with the best results in the model system were consecutively applied to samples from adjuvant breast cancer patients and of healthy donors. FUT3 and GALNT6 showed the highest increase in relative expression, while GALNT6 and ST3GAL3 were the first to reach statistically significant different ∆CT-values comparing the sample with and without addition of tumour cells. These three genes were applied to patient samples, but did not show any significant results that may suggest the presence of CTCs in the blood. Although the relative expression of some of the glycosyltransferase genes exhibited reasonable results in the model system, their application to breast cancer patient samples will have to be further improved, e.g. by co-analysis of patient blood samples by gold-standard methods.

  16. 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.

  17. Irradiation specifically sensitises solid tumour cell lines to TRAIL mediated apoptosis

    International Nuclear Information System (INIS)

    Marini, Patrizia; Schmid, Angelika; Jendrossek, Verena; Faltin, Heidrun; Daniel, Peter T; Budach, Wilfried; Belka, Claus

    2005-01-01

    TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. Tumour cell systems derived from breast- (MDA MB231), lung- (NCI H460) colorectal- (Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor

  18. EPHB6 augments both development and drug sensitivity of triple-negative breast cancer tumours.

    Science.gov (United States)

    Toosi, Behzad M; El Zawily, Amr; Truitt, Luke; Shannon, Matthew; Allonby, Odette; Babu, Mohan; DeCoteau, John; Mousseau, Darrell; Ali, Mohsin; Freywald, Tanya; Gall, Amanda; Vizeacoumar, Frederick S; Kirzinger, Morgan W; Geyer, C Ronald; Anderson, Deborah H; Kim, TaeHyung; Welm, Alana L; Siegel, Peter; Vizeacoumar, Franco J; Kusalik, Anthony; Freywald, Andrew

    2018-04-27

    Triple-negative breast cancer (TNBC) tumours that lack expression of oestrogen, and progesterone receptors, and do not overexpress the HER2 receptor represent the most aggressive breast cancer subtype, which is characterised by the resistance to therapy in frequently relapsing tumours and a high rate of patient mortality. This is likely due to the resistance of slowly proliferating tumour-initiating cells (TICs), and understanding molecular mechanisms that control TICs behaviour is crucial for the development of effective therapeutic approaches. Here, we present our novel findings, indicating that an intrinsically catalytically inactive member of the Eph group of receptor tyrosine kinases, EPHB6, partially suppresses the epithelial-mesenchymal transition in TNBC cells, while also promoting expansion of TICs. Our work reveals that EPHB6 interacts with the GRB2 adapter protein and that its effect on enhancing cell proliferation is mediated by the activation of the RAS-ERK pathway, which allows it to elevate the expression of the TIC-related transcription factor, OCT4. Consistent with this, suppression of either ERK or OCT4 activities blocks EPHB6-induced pro-proliferative responses. In line with its ability to trigger propagation of TICs, EPHB6 accelerates tumour growth, potentiates tumour initiation and increases TIC populations in xenograft models of TNBC. Remarkably, EPHB6 also suppresses tumour drug resistance to DNA-damaging therapy, probably by forcing TICs into a more proliferative, drug-sensitive state. In agreement, patients with higher EPHB6 expression in their tumours have a better chance for recurrence-free survival. These observations describe an entirely new mechanism that governs TNBC and suggest that it may be beneficial to enhance EPHB6 action concurrent with applying a conventional DNA-damaging treatment, as it would decrease drug resistance and improve tumour elimination.

  19. 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

  20. Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer.

    Science.gov (United States)

    Murase, Ryuichi; Kawamura, Rumi; Singer, Eric; Pakdel, Arash; Sarma, Pranamee; Judkins, Jonathon; Elwakeel, Eiman; Dayal, Sonali; Martinez-Martinez, Esther; Amere, Mukkanti; Gujjar, Ramesh; Mahadevan, Anu; Desprez, Pierre-Yves; McAllister, Sean D

    2014-10-01

    The psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabinoid cannabidiol (CBD) can both reduce cancer progression, each through distinct anti-tumour pathways. Our goal was to discover a compound that could efficiently target both cannabinoid anti-tumour pathways. To measure breast cancer cell proliferation/viability and invasion, MTT and Boyden chamber assays were used. Modulation of reactive oxygen species (ROS) and apoptosis was measured using dichlorodihydrofluorescein and annexin/propidium iodide, respectively, in combination with cell flow cytometry. Changes in protein levels were evaluated using Western analysis. Orthotopic and i.v. mouse models of breast cancer metastasis were used to test the activity of cannabinoids in vivo. CBD reduced breast cancer metastasis in advanced stages of the disease as the direct result of down-regulating the transcriptional regulator Id1. However, this was associated with moderate increases in survival. We therefore screened for analogues that could co-target cannabinoid anti-tumour pathways (CBD- and THC-associated) and discovered the compound O-1663. This analogue inhibited Id1, produced a marked stimulation of ROS, up-regulated autophagy and induced apoptosis. Of all the compounds tested, it was the most potent at inhibiting breast cancer cell proliferation and invasion in culture and metastasis in vivo. O-1663 prolonged survival in advanced stages of breast cancer metastasis. Developing compounds that can simultaneously target multiple cannabinoid anti-tumour pathways efficiently may provide a novel approach for the treatment of patients with metastatic breast cancer. © 2014 The British Pharmacological Society.

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

    Science.gov (United States)

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

    2016-01-01

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

  2. Hypoxic enhancement of exosome release by breast cancer cells

    International Nuclear Information System (INIS)

    King, Hamish W; Michael, Michael Z; Gleadle, Jonathan M

    2012-01-01

    Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O 2 ) or severe (0.1% O 2 ) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O 2 ) and severe (0.1% O 2 ) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release

  3. 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

  4. Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer

    DEFF Research Database (Denmark)

    Willemoe, Gro L.; Hertel, Pernille Bræmer; Bartels, Annette

    2009-01-01

    PURPOSE: A number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell...

  5. Targeting of breast metastases using a viral gene vector with tumour-selective transcription.

    LENUS (Irish Health Repository)

    Rajendran, Simon

    2012-01-31

    BACKGROUND: Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. MATERIALS AND METHODS: We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis. RESULTS: Higher transgene expression levels were observed in subcutaneous MCF-7 tumours relative to normal tissue (muscle) using the CXCR4 promoter, unlike a ubiquitously expressing Cytomegalovirus promoter construct, with preferential AAVCXCR4 expression in epithelial tumour and CXCR4-positive cells. Transgene expression following intravenously administered AAVCXCR4 in a model of liver metastasis was detected specifically in livers of tumour bearing mice. Ex vivo analysis using patient samples also demonstrated higher AAVCXCR4 expression in tumour compared with normal liver tissue. CONCLUSION: This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.

  6. Histopathology of tumour associated sarcoid-like stromal reaction in breast cancer. An analysis of 5 cases with immunohistochemical investigations.

    Science.gov (United States)

    Bässler, R; Birke, F

    1988-01-01

    In 5 cases of invasive ductal and lobular carcinoma of the breast multiple epithelioid and giant cell containing granulomas were detected, localized mainly in circumferential regions, but also in the center of the carcinomas. These granulomas were interpreted as sarcoid-like stromal reactions, occurring as sarcoid-like lesions in uni- and bilateral primaries, in a recurrent tumour, and also in axillary lymph nodes. Histopathologically, these granulomas were not quite uniform, some of them corresponding to typical sarcoidosis, others showing marked proliferations of epithelioid or giant cells or containing fibrinoid exudate or necroses. The granulomas were surrounded by dense infiltrates of mononuclear cells. Tuberculosis and mycosis was excluded. There were no hints of generalized sarcoidosis. Pathogenetically, these are reactions in the tumour stroma of varying intensity, and are not caused by necroses of the tumour tissue nor by microbial infections. Such tumour-associated sarcoid-like stroma reactions are interpreted as a T-cell mediated immune response to an antigen expression of the carcinoma acting as the local trigger; in 2 cases they were connected with sarcoid-like lesions of the axillary lymph nodes. Their occurrence in bilateral carcinoma of the breast points to an immunological disposition for this special kind of host-versus-tumour response. The intensity of these changes in a recurrent tumour reflects an immunological hypersensitivity reaction. The pathogenetic and differential diagnostic aspects of epithelioid granulomas of the female breast in chronic granulomatous mastitis, panniculitis, foreign body reaction, rare infections, and in therapeutically induced sarcoidosis are described and discussed.

  7. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer

    International Nuclear Information System (INIS)

    Kang, Hua; Watkins, Gareth; Parr, Christian; Douglas-Jones, Anthony; Mansel, Robert E; Jiang, Wen G

    2005-01-01

    Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer. Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120). SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1 +/+ ) or with control plasmid pcDNA4/GFP (MDA-MB-231 +/- ). MDA-MB-231SDF1 +/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231 +/- ; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and

  8. Histopathological review of breast tumours in children and adolescents in Delta State Nigeria

    Directory of Open Access Journals (Sweden)

    Francis Nwachokor

    2013-01-01

    Full Text Available Background: Breast swellings in children and adolescents may be overlooked on assumption that they are physiological enlargement. Pathologic swellings including cancers have however been encountered in this age group. This study highlighted the spectrum of tumours in childhood and adolescents. Materials and Methods: This was a 7 year retrospective analysis of all histologically diagnosed breast tumours in people aged 0 - 19 years. Results: There were 134 breast tumour diagnoses occurring in 133 females and 1 male (gynaecomastia. One hundred and nineteen cases (88.8% were recorded in the 10 - 14 year age group and 15 cases (11.2% in the 15 - 19 year age group. No case was found in children aged less than 10 years. The most common tumour was fibroadenoma accounting for 75.4% (n = 101 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.

  9. Myofibroblastoma: An Unusual Rapidly Growing Benign Tumour in a Male Breast

    International Nuclear Information System (INIS)

    Rafique, A.; Arshad, A.

    2013-01-01

    Myofibroblastoma is an unusual benign tumour of the breast predominantly seen in men in their sixth to seventh decade. The gross appearance is that of a well circumscribed nodule, characteristically small, seldom exceeding 3 cm. We present a case of an unusually large myofibroblastoma, which mimicked a malignant breast tumour. A 40 years old male, known case of tetralogy of Fallot, was operated in infancy in abroad, presented with a rapid enlargement of right breast over 5 - 6 weeks. Examination revealed a firm 10 cm hemispherical lump occupying the whole of the right breast with normal overlying skin. Since core biopsy was inconclusive, a subcutaneous mastectomy was performed to remove the tumour, which weighed 500 gms. Histopathology and immunocytochemistry revealed a mixed classical and collagenised type of myofibroblastoma. The patient is well with no evidence of recurrence. (author)

  10. The relationship between vascular and metabolic characteristics of primary breast tumours

    International Nuclear Information System (INIS)

    Semple, Scott I.K.; Gilbert, Fiona J.; Redpath, Thomas W.; Staff, Roger T.; Ahearn, Trevor S.; Welch, Andrew E.; Heys, Steven D.; Hutcheon, Andrew W.; Smyth, Elizabeth H.; Chaturvedi, Shailesh

    2004-01-01

    The objective of this study was to investigate the relationship between vascular and metabolic characteristics of breast tumours in vivo, using contrast-enhanced dynamic MRI and 2-[ 18 F] fluoro-2-deoxy-d-glucose (FDG) PET imaging. Twenty patients with large or locally advanced primary breast cancers were imaged prior to therapy. MRI data were acquired using a dynamic gradient echo sequence and analysed using two pharmacokinetic models. Static PET data were acquired in 2D mode. A significant association (P<0.05) was observed between the calculated exchange rate constants of both pharmacokinetic models and calculated PET FDG dose uptake ratios (DUR). Statistical analysis showed that the exchange rate constants can explain between 27 and 44% of the variance observed in the PET FDG uptake ratios. A relationship was demonstrated between the vascular and metabolic characteristics of primary breast tumours showing that any assessment of tumour metabolic activity using PET may be controlled at least in part by delivery of uptake agent due to the vascular characteristics of the tumour. MRI and PET provide methods of assessing breast tumour vascularity and metabolism in vivo using the exchange rate constants of dynamic MRI, and DUR of PET, respectively, these measures being related but not equivalent. (orig.)

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  12. The relationship between tumour size, nodal status and distant metastases: on the origins of breast cancer.

    Science.gov (United States)

    Sopik, Victoria; Narod, Steven A

    2018-04-24

    In patients with breast cancer, increasing tumour size at diagnosis is associated with an increased likelihood of axillary lymph node involvement and increased breast cancer-specific mortality. However, this relation is based on studies which combine all tumours smaller than 1.0 cm in a single category and all tumours larger than 5.0 cm in another category. This coarse classification may obscure a nuanced description of the effects of tumour size across the full range of possible sizes. We examined the relationship between primary tumour size, lymph node status and distant metastases in a cohort of 819,647 women diagnosed with first primary invasive breast cancer from 1990 to 2014 in the Surveillance, Epidemiology and End Results (SEER) registries database. All patients in the cohort had a known primary tumour size between 1 and 150 mm in greatest dimension. Primary tumour size was examined as a continuous (1-150 mm) and categorical variable (15 size groups; 10-mm intervals). For each 1- or 10-mm size group, we determined the proportion of patients with positive lymph nodes at diagnosis, the proportion of patients with distant metastases at diagnosis and the actuarial cumulative risk of breast cancer-specific mortality at 15 years from diagnosis. Among 819,647 patients with invasive breast tumours between 1 and 150 mm in size, there was a non-linear correlation between increasing tumour size and the prevalence of lymph node metastases at diagnosis (% node-positive), the prevalence of distant metastases at diagnosis (% stage IV) and the 15-year rate of breast cancer-specific mortality across the entire size spectrum. For very small tumours (under 10 mm) and for very large tumours (larger than 60-90 mm) there was little correlation between tumour size and metastasis risk. The relationship between tumour size, lymph node status and distant metastases in patients with invasive breast cancer is not linear. This calls into question the conventional model that the

  13. A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas

    Science.gov (United States)

    Farace, F; Massard, C; Vimond, N; Drusch, F; Jacques, N; Billiot, F; Laplanche, A; Chauchereau, A; Lacroix, L; Planchard, D; Le Moulec, S; André, F; Fizazi, K; Soria, J C; Vielh, P

    2011-01-01

    Background: Circulating tumour cells (CTCs) can provide information on patient prognosis and treatment efficacy. However, there is no universal method to detect CTC currently available. Here, we compared the performance of two CTC detection systems based on the expression of the EpCAM antigen (CellSearch assay) or on cell size (ISET assay). Methods: Circulating tumour cells were enumerated in 60 patients with metastatic carcinomas of breast, prostate and lung origins using CellSearch according to the manufacturer's protocol and ISET by studying cytomorphology and immunolabelling with anti-cytokeratin or lineage-specific antibodies. Results: Concordant results were obtained in 55% (11 out of 20) of the patients with breast cancer, in 60% (12 out of 20) of the patients with prostate cancer and in only 20% (4 out of 20) of lung cancer patients. Conclusion: Our results highlight important discrepancies between the numbers of CTC enumerated by both techniques. These differences depend mostly on the tumour type. These results suggest that technologies limiting CTC capture to EpCAM-positive cells, may present important limitations, especially in patients with metastatic lung carcinoma. PMID:21829190

  14. Modelling breast cancer tumour growth for a stable disease population.

    Science.gov (United States)

    Isheden, Gabriel; Humphreys, Keith

    2017-01-01

    Statistical models of breast cancer tumour progression have been used to further our knowledge of the natural history of breast cancer, to evaluate mammography screening in terms of mortality, to estimate overdiagnosis, and to estimate the impact of lead-time bias when comparing survival times between screen detected cancers and cancers found outside of screening programs. Multi-state Markov models have been widely used, but several research groups have proposed other modelling frameworks based on specifying an underlying biological continuous tumour growth process. These continuous models offer some advantages over multi-state models and have been used, for example, to quantify screening sensitivity in terms of mammographic density, and to quantify the effect of body size covariates on tumour growth and time to symptomatic detection. As of yet, however, the continuous tumour growth models are not sufficiently developed and require extensive computing to obtain parameter estimates. In this article, we provide a detailed description of the underlying assumptions of the continuous tumour growth model, derive new theoretical results for the model, and show how these results may help the development of this modelling framework. In illustrating the approach, we develop a model for mammography screening sensitivity, using a sample of 1901 post-menopausal women diagnosed with invasive breast cancer.

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  16. Risk for new tumours after treatment of breast cancer of women

    International Nuclear Information System (INIS)

    Boice, J.D.

    1988-01-01

    In this article the chance for a new tumour after a succesful treatment of breast cancer is worked out. The chance of a second tumour for treated women turns out to be three times as large as the change which an arbitrary group of contemporaries has of cancer. These (second) tumours mostly occur in the other breast. It is not quite clear in how far treatment with ionizing radiation can influence the origin of new tumours. The chance for re-occurring of breast cancer appears to be somewhat higher for women who underwent radiotherapy than for woman who were treated otherwise. Also leukemia occurred more often in women treated with than without ionnizing radiation; however, absolutely seen it does concern very small numbers. The importance of a good registration of cancer and the way of treatment of cancer are illustrated. Epidemiologic research as described may contribute in finding the most effective treatment with the least side effects. (H.W.). 15 refs.; 3 figs.; 3 tabs

  17. Breast carcinoma with osteoclast-like giant cells

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Lauridsen, M C; Sørensen, Flemming Brandt

    2001-01-01

    Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the female breast. The clinical course, histological, immunohistochemical and ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast-like multinucleated giant cells (OMGCs) are reviewed and a new...... in the literature have shown that 86% of patients with these tumours are still alive after 5 years. Histologically, these tumours are invasive ductal carcinomas with OMGCs next to the neoplastic glands and within their lumen. Signs of recent and past haemorrhage are ubiquitously present in the highly vascularized...

  18. Identification of novel LRH-1 target genes in breast cancer cells

    OpenAIRE

    Zhao, Zhe

    2017-01-01

    The orphan nuclear receptor liver receptor homolog-1 (LRH-1) plays important roles in embryonic development, lipid homeostasis and steroidogenesis, and has been implicated in driving several cancers. In breast cancer, LRH-1 is expressed in tumour epithelial cells of invasive ductal carcinomas. We hypothesized that LRH-1 regulates epithelial cell proliferation and invasiveness to drive breast tumour progression. The overall goal of this study was to identify molecular mechanisms regulated by L...

  19. Alterations of monocarboxylate transporter densities during hypoxia in brain and breast tumour cells

    DEFF Research Database (Denmark)

    Cheng, Chang; Edin, Nina F Jeppesen; Lauritzen, Knut H

    2012-01-01

    Tumour cells are characterized by aerobic glycolysis, which provides biomass for tumour proliferation and leads to extracellular acidification through efflux of lactate via monocarboxylate transporters (MCTs). Deficient and spasm-prone tumour vasculature causes variable hypoxia, which favours...

  20. 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

  1. Classification of breast tumour using electrical impedance and machine learning techniques.

    Science.gov (United States)

    Al Amin, Abdullah; Parvin, Shahnaj; Kadir, M A; Tahmid, Tasmia; Alam, S Kaisar; Siddique-e Rabbani, K

    2014-06-01

    When a breast lump is detected through palpation, mammography or ultrasonography, the final test for characterization of the tumour, whether it is malignant or benign, is biopsy. This is invasive and carries hazards associated with any surgical procedures. The present work was undertaken to study the feasibility for such characterization using non-invasive electrical impedance measurements and machine learning techniques. Because of changes in cell morphology of malignant and benign tumours, changes are expected in impedance at a fixed frequency, and versus frequency of measurement. Tetrapolar impedance measurement (TPIM) using four electrodes at the corners of a square region of sides 4 cm was used for zone localization. Data of impedance in two orthogonal directions, measured at 5 and 200 kHz from 19 subjects, and their respective slopes with frequency were subjected to machine learning procedures through the use of feature plots. These patients had single or multiple tumours of various types in one or both breasts, and four of them had malignant tumours, as diagnosed by core biopsy. Although size and depth of the tumours are expected to affect the measurements, this preliminary work ignored these effects. Selecting 12 features from the above measurements, feature plots were drawn for the 19 patients, which displayed considerable overlap between malignant and benign cases. However, based on observed qualitative trend of the measured values, when all the feature values were divided by respective ages, the two types of tumours separated out reasonably well. Using K-NN classification method the results obtained are, positive prediction value: 60%, negative prediction value: 93%, sensitivity: 75%, specificity: 87% and efficacy: 84%, which are very good for such a test on a small sample size. Study on a larger sample is expected to give confidence in this technique, and further improvement of the technique may have the ability to replace biopsy.

  2. Classification of breast tumour using electrical impedance and machine learning techniques

    International Nuclear Information System (INIS)

    Amin, Abdullah Al; Parvin, Shahnaj; Kadir, M A; Tahmid, Tasmia; Alam, S Kaisar; Siddique-e Rabbani, K

    2014-01-01

    When a breast lump is detected through palpation, mammography or ultrasonography, the final test for characterization of the tumour, whether it is malignant or benign, is biopsy. This is invasive and carries hazards associated with any surgical procedures. The present work was undertaken to study the feasibility for such characterization using non-invasive electrical impedance measurements and machine learning techniques. Because of changes in cell morphology of malignant and benign tumours, changes are expected in impedance at a fixed frequency, and versus frequency of measurement. Tetrapolar impedance measurement (TPIM) using four electrodes at the corners of a square region of sides 4 cm was used for zone localization. Data of impedance in two orthogonal directions, measured at 5 and 200 kHz from 19 subjects, and their respective slopes with frequency were subjected to machine learning procedures through the use of feature plots. These patients had single or multiple tumours of various types in one or both breasts, and four of them had malignant tumours, as diagnosed by core biopsy. Although size and depth of the tumours are expected to affect the measurements, this preliminary work ignored these effects. Selecting 12 features from the above measurements, feature plots were drawn for the 19 patients, which displayed considerable overlap between malignant and benign cases. However, based on observed qualitative trend of the measured values, when all the feature values were divided by respective ages, the two types of tumours separated out reasonably well. Using K-NN classification method the results obtained are, positive prediction value: 60%, negative prediction value: 93%, sensitivity: 75%, specificity: 87% and efficacy: 84%, which are very good for such a test on a small sample size. Study on a larger sample is expected to give confidence in this technique, and further improvement of the technique may have the ability to replace biopsy. (paper)

  3. Contrast kinetics of the malignant breast tumour - border versus centre enhancement on dynamic midfield MRI

    DEFF Research Database (Denmark)

    Marklund, M.; Torp-Pedersen, S.; Bentzon, N.

    2008-01-01

    receptor negative tumours. CONCLUSION: The border/centre enhancement difference in malignant breast tumours is easily visualized on midfield dynamic magnetic resonance mammography. The dynamic behaviour is significantly correlated to histological features and receptor status of the tumours Udgivelsesdato......PURPOSE: To quantify the border versus centre enhancement of malignant breast tumours on dynamic magnetic resonance mammography. MATERIALS AND METHODS: Fifty-two women diagnosed with primary breast cancer underwent dynamic magnetic resonance mammography (Omniscan 0.2 mmol/kg bodyweight......) on a midfield scanner (0.6 T), prior to surgery. The following five variables were recorded from the border and centre regions of the tumours: Early Enhancement, Time to Peak, Wash-in rate, Wash-out rate and Area under Curve. Information on histology type, oestrogen and progesterone receptor status...

  4. Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

    KAUST Repository

    Fan, Ming; He, Ting; Zhang, Peng; Cheng, Hu; Zhang, Juan; Gao, Xin; Li, Lihua

    2017-01-01

    Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

  5. Diffusion-weighted imaging features of breast tumours and the surrounding stroma reflect intrinsic heterogeneous characteristics of molecular subtypes in breast cancer

    KAUST Repository

    Fan, Ming

    2017-12-16

    Breast cancer heterogeneity is the main obstacle preventing the identification of patients with breast cancer with poor prognoses and treatment responses; however, such heterogeneity has not been well characterized. The purpose of this retrospective study was to reveal heterogeneous patterns in the apparent diffusion coefficient (ADC) signals in tumours and the surrounding stroma to predict molecular subtypes of breast cancer. A dataset of 126 patients with breast cancer, who underwent preoperative diffusion-weighted imaging (DWI) on a 3.0-T image system, was collected. Breast images were segmented into regions comprising the tumour and surrounding stromal shells in which features that reflect heterogeneous ADC signal distribution were extracted. For each region, imaging features were computed, including the mean, minimum, variance, interquartile range (IQR), range, skewness, kurtosis and entropy of ADC values. Univariate and stepwise multivariate logistic regression modelling was performed to identify the magnetic resonance imaging features that optimally discriminate luminal A, luminal B, human epidermal growth factor 2 (HER2)-enriched and basal-like molecular subtypes. The performance of the predictive models was evaluated using the area under the receiver operating characteristic curve (AUC). Univariate logistic regression analysis showed that the skewness in the tumour boundary achieved an AUC of 0.718 for discrimination between luminal A and non-luminal A tumours, whereas the IQR of the ADC value in the tumour boundary had an AUC of 0.703 for classification of the HER2-enriched subtype. Imaging features in the tumour boundary and the proximal peritumoral stroma corresponded to a higher overall prediction performance than those in other regions. A multivariate logistic regression model combining features in all the regions achieved an overall AUC of 0.800 for the classification of the four tumour subtypes. These findings suggest that features in the tumour

  6. AN UNUSUAL PRESENTATION OF A HUGE BREAST TUMOUR IN AN ELDERLY FEMALE: A CASE REPORT

    OpenAIRE

    Prasenjit; Sudipta; Subir Kumar; Himadri Sekhar; Amalesh

    2014-01-01

    Pleomorphic breast carcinoma is a rare variety of breast carcinoma, with a highly aggresive behaviour and poor prognosis, which usually presents after 50 years of age. Our case presented in a very similar way as phyllodes’ tumour of breast (even the FNAC report also suggested it as a case of phyllodes’ tumour). But postoperative histopathological report clearly revealed it as a case of this rare entity of pleomorphic carcinoma of breast

  7. Morphology and genomic hallmarks of breast tumours developed by ATM deleterious variant carriers.

    Science.gov (United States)

    Renault, Anne-Laure; Mebirouk, Noura; Fuhrmann, Laetitia; Bataillon, Guillaume; Cavaciuti, Eve; Le Gal, Dorothée; Girard, Elodie; Popova, Tatiana; La Rosa, Philippe; Beauvallet, Juana; Eon-Marchais, Séverine; Dondon, Marie-Gabrielle; d'Enghien, Catherine Dubois; Laugé, Anthony; Chemlali, Walid; Raynal, Virginie; Labbé, Martine; Bièche, Ivan; Baulande, Sylvain; Bay, Jacques-Olivier; Berthet, Pascaline; Caron, Olivier; Buecher, Bruno; Faivre, Laurence; Fresnay, Marc; Gauthier-Villars, Marion; Gesta, Paul; Janin, Nicolas; Lejeune, Sophie; Maugard, Christine; Moutton, Sébastien; Venat-Bouvet, Laurence; Zattara, Hélène; Fricker, Jean-Pierre; Gladieff, Laurence; Coupier, Isabelle; Chenevix-Trench, Georgia; Hall, Janet; Vincent-Salomon, Anne; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Lesueur, Fabienne

    2018-04-17

    The ataxia telangiectasia mutated (ATM) gene is a moderate-risk breast cancer susceptibility gene; germline loss-of-function variants are found in up to 3% of hereditary breast and ovarian cancer (HBOC) families who undergo genetic testing. So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management. To characterise hallmarks of ATM-associated tumours, we performed systematic pathology review of tumours from 21 participants from ataxia-telangiectasia families and 18 participants from HBOC families, as well as copy number profiling on a subset of 23 tumours. Morphology of ATM-associated tumours was compared with that of 599 patients with no BRCA1 and BRCA2 mutations from a hospital-based series, as well as with data from The Cancer Genome Atlas. Absolute copy number and loss of heterozygosity (LOH) profiles were obtained from the OncoScan SNP array. In addition, we performed whole-genome sequencing on four tumours from ATM loss-of-function variant carriers with available frozen material. We found that ATM-associated tumours belong mostly to the luminal B subtype, are tetraploid and show LOH at the ATM locus at 11q22-23. Unlike tumours in which BRCA1 or BRCA2 is inactivated, tumours arising in ATM deleterious variant carriers are not associated with increased large-scale genomic instability as measured by the large-scale state transitions signature. Losses at 13q14.11-q14.3, 17p13.2-p12, 21p11.2-p11.1 and 22q11.23 were observed. Somatic alterations at these loci may therefore represent biomarkers for ATM testing and harbour driver mutations in potentially 'druggable' genes that would allow patients to be directed towards tailored therapeutic strategies. Although ATM is involved in the DNA damage response, ATM-associated tumours are distinct from BRCA1-associated tumours in terms of morphological

  8. The influence of elevated levels of platelet-derived endothelial cell growth factor/thymidine phosphorylase on tumourigenicity, tumour growth, and oxygenation

    International Nuclear Information System (INIS)

    Griffiths, L.; Stratford, I.J.

    1998-01-01

    Purpose: Investigation of the effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) on various aspects of tumour growth in a xenograft model, including growth rate, tumourigenicity and oxygenation levels. Methods and Materials: MDA 231 breast cancer cells overexpressing PD-ECGF/TP protein were made by retroviral transduction. These cells were grown in vitro and in vivo as xenografts. Direct measurement of tumours was used to record growth parameters, while the comet assay with the bioreductive drug RSU 1069 was used to assess tumour cell oxygenation. Results: We report that MDA 231 breast tumour cell lines expressing an increased range of levels of PD-ECGF/TP have increased tumourigenicity positively related to the level of PD-ECGF/TP when implanted in nude mice. As previously reported, tumours grown from these overexpressing cell lines grew faster than the parental line. These tumours expressed higher levels of TP activity and showed increased immunocytochemical staining for PD-ECGF. In addition, the rate of growth was found to be positively related to the level of PD-ECGF/TP expressed by the tumour cells. When the comet assay was used to compare the oxygenation status of cells between the parental and PD-ECGF/TP overexpressing tumours, the latter were found to have a larger proportion of well oxygenated cells. This is consistent with these tumours having an increased and functionally competent vascular supply in response to the expression of PD-ECGF/TP. Conclusion: PD-ECGF/TP appears to be capable of influencing tumourigenicity, angiogenesis and tumour growth in a proportional manner and can directly influence tumour oxygenation levels via its role in formation of functional vasculature

  9. Effects of biosurfactants on the viability and proliferation of human breast cancer cells.

    Science.gov (United States)

    Duarte, Cristina; Gudiña, Eduardo J; Lima, Cristovao F; Rodrigues, Ligia R

    2014-01-01

    Biosurfactants are molecules with surface activity produced by microorganisms that can be used in many biomedical applications. The anti-tumour potential of these molecules is being studied, although results are still scarce and few data are available regarding the mechanisms underlying such activity. In this work, the anti-tumour activity of a surfactin produced by Bacillus subtilis 573 and a glycoprotein (BioEG) produced by Lactobacillus paracasei subsp. paracasei A20 was evaluated. Both biosurfactants were tested against two breast cancer cell lines, T47D and MDA-MB-231, and a non-tumour fibroblast cell line (MC-3 T3-E1), specifically regarding cell viability and proliferation. Surfactin was found to decrease viability of both breast cancer cell lines studied. A 24 h exposure to 0.05 g l(-1) surfactin led to inhibition of cell proliferation as shown by cell cycle arrest at G1 phase. Similarly, exposure of cells to 0.15 g l(-1) BioEG for 48 h decreased cancer cells' viability, without affecting normal fibroblasts. Moreover, BioEG induced the cell cycle arrest at G1 for both breast cancer cell lines. The biosurfactant BioEG was shown to be more active than surfactin against the studied breast cancer cells. The results gathered in this work are very promising regarding the biosurfactants potential for breast cancer treatment and encourage further work with the BioEG glycoprotein.

  10. BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction pathways in triple negative breast cancer.

    Science.gov (United States)

    Shields, Sarah; Conroy, Emer; O'Grady, Tony; McGoldrick, Alo; Connor, Kate; Ward, Mark P; Useckaite, Zivile; Dempsey, Eugene; Reilly, Rebecca; Fan, Yue; Chubb, Anthony; Matallanas, David Gomez; Kay, Elaine W; O'Connor, Darran; McCann, Amanda; Gallagher, William M; Coppinger, Judith A

    2018-03-20

    Triple-negative breast cancer (TNBC), is a heterogeneous disease characterised by absence of expression of the estrogen receptor (ER), progesterone receptor (PR) and lack of amplification of human epidermal growth factor receptor 2 (HER2). TNBC patients can exhibit poor prognosis and high recurrence stages despite early response to chemotherapy treatment. In this study, we identified a pro-survival signalling protein BCL2- associated athanogene 3 (BAG3) to be highly expressed in a subset of TNBC cell lines and tumour tissues. High mRNA expression of BAG3 in TNBC patient cohorts significantly associated with a lower recurrence free survival. The epidermal growth factor receptor (EGFR) is amplified in TNBC and EGFR signalling dynamics impinge on cancer cell survival and disease recurrence. We found a correlation between BAG3 and EGFR expression in TNBC cell lines and determined that BAG3 can regulate tumour cell proliferation, migration and invasion in EGFR expressing TNBC cells lines. We identified an interaction between BAG3 and components of the EGFR signalling networks using mass spectrometry. Furthermore, BAG3 contributed to regulation of proliferation in TNBC cell lines by reducing the activation of components of the PI3K/AKT and FAK/Src signalling subnetworks. Finally, we found that combined targeting of BAG3 and EGFR was more effective than inhibition of EGFR with Cetuximab alone in TNBC cell lines. This study demonstrates a role for BAG3 in regulation of distinct EGFR modules and highlights the potential of BAG3 as a therapeutic target in TNBC.

  11. The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma

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    Kerry J. Davies

    2014-01-01

    Full Text Available Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.

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

    Science.gov (United States)

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

    2016-04-01

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

  13. Background parenchymal enhancement on breast MRI and mammographic breast density: correlation with tumour characteristics

    International Nuclear Information System (INIS)

    Kim, M.Y.; Choi, N.; Yang, J.-H.; Yoo, Y.B.; Park, K.S.

    2015-01-01

    Aim: To investigate the relationship between mammographic breast density (MGD) and background parenchymal enhancement (BPE) at breast MRI and histopathological features of invasive breast cancers. Materials and methods: A total of 178 women with unilateral invasive breast cancer who preoperatively underwent mammography and breast MRI were included in the study. Two radiologists rated MGD and BPE according to BI-RADS criteria in consensus. The relationship between MGD and BPE was investigated, and compared with histopathological features of invasive breast cancers according to the level of MGD and BPE. Results: At MRI, there is no significant difference in the distribution of MGD and BPE of the contralateral breast in women with invasive breast cancer according to menopausal status (p=0.226, 0.384). Women with high MGD (>50% glandular) were more likely to have oestrogen-receptor (ER)-positive breast cancer (p=0.045) and progesterone receptor (PR)-positive breast cancer (p=0.020). With regard to BPE, PR positivity correlated with moderate or marked BPE with borderline significance (p=0.054). Multivariate logistic regression analyses revealed that women with high MGD were less likely to have triple-negative (i.e., a cancer that is ER negative, PR negative, and human epidermal growth factor receptor type 2 [HER2] negative) breast cancer compared with ER (+)/HER2 (−) cancer (OR=0.231, 95% CI: 0.070, 0.760; p=0.016). No association between the histological tumour characteristics and BPE was observed. Conclusion: In women with invasive breast cancer, high MGD is associated with ER positivity of the invasive breast cancer. However, at MRI, BPE of the contralateral breast seems to be independent of tumour characteristics. -- Highlights: •There is no difference in distribution of MGD and BPE of contralateral breast on MRI. •High MGD is associated with ER positivity of the invasive breast cancer. •BPE of the contralateral breast on MRI is independent of tumor

  14. Homotypic Cell Cannibalism and Cannibalism Index-A Four Year Study in Inltrating Ductal Carcinoma Breast

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    Alok Mohan

    2016-01-01

    Full Text Available Background: Homotypic cell cannibalism is a hallmark of malignant lesions. It serves as an emerging indicator of both the anaplastic grade and invasiveness. Aim and Objectives: The present study was conducted to correlate tumour cytological grade with the incidences of cell cannibalism. Material and Methods: Three stained smears per case were submitted for cytological grading. The smears were then submitted for visually counting the number of examples of cell cannibalism and the cannibalism index was calculated. Results: Seventy cytological diagnosed cases of breast malignancies were assessed for the presence of cell cannibalism. The results were correlated with the cytological grade of carcinoma. The study revealed that cell cannibalism was encountered in 68.57% cases of breast carcinoma. 44.4% of grade I, 71.4% of grade II and 100% of grade III tumours grade. It was observed that grade I tumours had mean cannibalism per smear of 1.62/1000 tumour cells smear, grade II mean cannibalism per smear of 2.50/ 1000 tumour cells and grade III mean cannibalism per smear 4.90/1000 tumour cells. Tumour diathesis and metastasis were also found more in cannibalism positive cases. Conclusion: The phenomenon of cell cannibalism was encountered more in high grade tumours. Thus it can be designated as an emerging marker of anaplasia and aggressive tumour behaviour

  15. Inflamed Phylloides Tumour in a Girl: A Challenging Diagnosis in Paediatric Breast Lesions

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    Ilaria Testa

    2018-05-01

    Full Text Available Introduction: Phylloides tumours (PTs are rare fibroepithelial neoplasms that account for 0.3–0.9% of all breast tumours. These tumours typically occur in women aged 30–70 years. The occurrence of these tumours in older children and adolescents poses particular diagnostic and therapeutic problems. However, early diagnosis is mandatory because although most of the cases of PTs in children are benign, the borderline and malignant cases with potential negative outcomes cannot be excluded. Case presentation: A 12-year-old girl presented at the Paediatric Emergency Department for hyperaemia and warmth of the left breast that occurred a few days prior without fever. The girl experienced menarche 8 months previously. She experienced no previous trauma and she had no family history of breast cancer. On physical examination, the left breast was painful, enlarged and tender. The overlying skin was erythematous and warm. A breast ultrasonography (US revealed a large mass with features of an abscess, including a hyperechoic wall, scattered internal echoes and hypoechoic peripheral lacunae of apparent colliquative nature. After 4 days of unsuccessful antibiotic therapy, surgical drainage was performed due to the suspicion of a mammary abscess. At the surgical incision site, the lesion was not-well circumscribed and lacked a capsule. In addition, purulent material was not detected. Histological examination revealed that the tissue alterations were compatible with benign PT. With this diagnosis, the girl underwent definitive surgical removal of the lesion. The postoperative period passed without negative events. An US performed 6 months later revealed that no new mass was present at this time, suggesting no recurrence of the tumour. Conclusion: This case shows that in the presence of a clinical picture suggesting the inflammation of the breast in adolescent females, PT should be considered as a possible diagnosis and US-guided core biopsy should be

  16. Inflamed Phylloides Tumour in a Girl: A Challenging Diagnosis in Paediatric Breast Lesions.

    Science.gov (United States)

    Testa, Ilaria; Salvatori, Cristina; Prestipino, Marco; Laurenti, Maria Elena; Gerli, Paolo; Di Cara, Giuseppe; Principi, Nicola; Esposito, Susanna; Bertozzi, Mirko

    2018-05-11

    Introduction : Phylloides tumours (PTs) are rare fibroepithelial neoplasms that account for 0.3⁻0.9% of all breast tumours. These tumours typically occur in women aged 30⁻70 years. The occurrence of these tumours in older children and adolescents poses particular diagnostic and therapeutic problems. However, early diagnosis is mandatory because although most of the cases of PTs in children are benign, the borderline and malignant cases with potential negative outcomes cannot be excluded. Case presentation : A 12-year-old girl presented at the Paediatric Emergency Department for hyperaemia and warmth of the left breast that occurred a few days prior without fever. The girl experienced menarche 8 months previously. She experienced no previous trauma and she had no family history of breast cancer. On physical examination, the left breast was painful, enlarged and tender. The overlying skin was erythematous and warm. A breast ultrasonography (US) revealed a large mass with features of an abscess, including a hyperechoic wall, scattered internal echoes and hypoechoic peripheral lacunae of apparent colliquative nature. After 4 days of unsuccessful antibiotic therapy, surgical drainage was performed due to the suspicion of a mammary abscess. At the surgical incision site, the lesion was not-well circumscribed and lacked a capsule. In addition, purulent material was not detected. Histological examination revealed that the tissue alterations were compatible with benign PT. With this diagnosis, the girl underwent definitive surgical removal of the lesion. The postoperative period passed without negative events. An US performed 6 months later revealed that no new mass was present at this time, suggesting no recurrence of the tumour. Conclusion : This case shows that in the presence of a clinical picture suggesting the inflammation of the breast in adolescent females, PT should be considered as a possible diagnosis and US-guided core biopsy should be considered to confirm

  17. [Giant juvenile fibroadenoma - a benign and rare tumour of the breast in adolescent girls].

    Science.gov (United States)

    Hasanbegovic, Emir; Talman, Maj-Lis Møller; Hjalgrim, Lisa Lyngsie; Lausen, Iver Michael Gudme

    2014-03-03

    A rapidly growing mass in the breast may be stressful for both parents and child as the suspicion of malignancy arises. The purpose of this case report is to draw attention to the fact that most emerging lesions of the breast in girls during puberty are benign. This case report presents a ten-year-old girl with a rapidly growing tumour in the breast. The tumour turned out to be a giant juvenile fibroadenoma, which is rare and benign. Differential diagnosis, investigation and management are reviewed.

  18. AMP-guided tumour-specific nanoparticle delivery via adenosine A1 receptor.

    Science.gov (United States)

    Dai, Tongcheng; Li, Na; Han, Fajun; Zhang, Hua; Zhang, Yuanxing; Liu, Qin

    2016-03-01

    Active targeting-ligands have been increasingly used to functionalize nanoparticles for tumour-specific clinical applications. Here we utilize nucleotide adenosine 5'-monophosphate (AMP) as a novel ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for tumour-targeted imaging. We demonstrate that AMP-conjugated NPs (NPs-AMP) efficiently bind to and are following internalized into colon cancer cell CW-2 and breast cancer cell MDA-MB-468 in vitro. RNA interference and inhibitor assays reveal that the targeting effects mainly rely on the specific binding of AMP to adenosine A1 receptor (A1R), which is greatly up-regulated in cancer cells than in matched normal cells. More importantly, NPs-AMP specifically accumulate in the tumour site of colon and breast tumour xenografts and are further internalized into the tumour cells in vivo via tail vein injection, confirming that the high in vitro specificity of AMP can be successfully translated into the in vivo efficacy. Furthermore, NPs-AMP exhibit an active tumour-targeting behaviour in various colon and breast cancer cells, which is positively related to the up-regulation level of A1R in cancer cells, suggesting that AMP potentially suits for more extensive A1R-overexpressing cancer models. This work establishes AMP to be a novel tumour-targeting ligand and provides a promising strategy for future diagnostic or therapeutic applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

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    Giuseppe Perrone

    Full Text Available Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23% of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001; in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively. No relationship was evident with tumour size (T and regional lymph node (N status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004. Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

  20. Increased risk of breast cancer development after diagnosis of salivary gland tumour

    NARCIS (Netherlands)

    In der Maur, Caroline D.; Klokman, Willem J.; van Leeuwen, Floor E.; Tan, I. Bing; Rutgers, Emiel J. Th; Balm, Alfons J. M.

    2005-01-01

    The aim of this study was to evaluate whether patients with salivary gland tumours are at increased risk of developing breast cancer. A retrospective cohort study was performed. Female patients (n = 439) with a salivary gland tumour (major and minor) were included. The diagnosis was confirmed

  1. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

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    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  2. Risk profile for breast carcinoma and tumour histopathology of medical uninsured patients in Pakistan

    International Nuclear Information System (INIS)

    Raza, U.; Haque, S.U.

    2011-01-01

    Breast carcinoma is an unpredictable disease in the sense that some patients may die at early disease stage due to wide-spread metastasis within six months to one year, while others may survive longer. This study was aimed to evaluate the risk factors for breast carcinoma occurrence and histopathological features of breast carcinoma developed in the social and economical conditions of Pakistan. Methods: A total of 224 female breast cancer diagnosed patients with uncovered medical insurance visiting at the Oncology clinic of a teaching hospital at Karachi, Pakistan were selected for the study. Two hundred and twenty-four (224) healthy female subjects free of any cancer diagnosis were selected as control from different areas of the city. Information on stress, occupation, life history, and life style was obtained through personal interviews. Breast tumour pathology was evaluated for histological grade, lymph node metastasis and hormone receptor status by using standard methods. Student's t-test, Chi-square test and ANOVA were used for comparison. Results: Breast cancer patients in significantly high percentage reported early marriages, abortion occurrence, stressful life style, family cancer history and past disease suffering from diabetes and hypertension. Life style including aerosol chewing and fat rich food intake was significantly high among the patients (p<0.05). On histopathological analysis, patients at the age of 40 years and below were identified in significantly high percentage with tumour grade III, 1-3 lymph node metastasis and hormone receptor negative type. Increasing age was associated with low tumour grade and less percentage of lymph node metastasis. Significantly high percentage of patients were presented with hormone receptor positive tumour (p<0.05). Conclusion: The contributing factors for breast carcinoma occurrence were related to life history and life-style of the patients. Medical insurance uncovered patients at initial diagnosis were

  3. 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.

  4. Biochemical study on some tumour angiogenesis factors and inhibitors in breast cancer

    International Nuclear Information System (INIS)

    Mohamed, N.M.E

    2007-01-01

    This pilot study was undertaken to investigate the significance of some tumour angiogenic factors (e.g. MMP, ADAM-12 and VEGF) and tumour angiogenic inhibitors (endostatin and TIMP-1) in the aetiology of breast cancer and their responsiveness to cancer treatment as well . We also sought to assess the significance of these angiogenic and antiangiogenic factors in the prognosis and diagnosis of breast cancer. The cases were allocated into five groups: Normal control group (Gr.l), fibroadenoma (Gr.l l), breast cancer (invasive duct carcinoma type grade l l) (Gr.lll) , breast cancer + chemo hormonal therapy (Gr.IV), and breast cancer + chemo hormonal and radiotherapy (Gr.V).Results obtained from this study reported absence of matrix metalloproteinase-9 (MMP-9)activity in the urine and serum of normal subjects and fibroadenoma patients and its significant depression in the urine and serum of breast cancer patients treated with chemo hormonal therapy alone or followed by radiotherapy, compared to breast cancer group as reference. A significantly mild elevation in urinary MMP-2 activity and a non significant change in its activity in the serum of fibroadenoma patients, compared to the dramatic rise in the urine and serum of breast cancer patients were observed

  5. Pathobiological features of breast tumours in the State of Kuwait: a comprehensive analysis

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    Abdeen Suad

    2007-01-01

    Full Text Available Abstract Background Breast cancer accounts for 30.3% of all cancer types in Kuwaiti women. Death occurs in approximately 43% of these patients. Our goal was to conduct a comprehensive analysis of the pathobiological characteristics of the tumours in an attempt to determine any particular trend that could be present. Methods One hundred and sixty-six cases were included in this study. All the pathology reports and paraffin blocks pertaining to these cases were collected. Four micrometer sections were taken from each block, and immunostaining against Her-2, ER, and PgR was performed. Both the proportion and intensity of immunostaining were scored according to the Allred's method, and typing of the tumour was done according the WHO criteria regarding tumour classification. Grading of invasive carcinomas was done according to the modified Bloom-Richardson-Elston's method, and tumour stage was determined according to the criteria set by the American Joint Committee on Cancer. Results The mean age of the patients below 55 years was 40, as compared to 68 for those above 55 (p < 0.0001. More than half of the cases were in the right breast, and were surgically treated by total mastectomy with axillary clearance. The majority of the tumours had irregular (stellate margins, was invasive, and had a surrounding breast tissue of adenosis or fibrocystic type. Their mitotic index was 10–20 or >20 with a marked to moderate nuclear pleomorphism. They were mostly grade II or III, sized 2–5 or > 5 cm, had absent or scanty tumour lymphocytes, and were stage II or III. The in situ tumours were mainly ductal carcinoma (DCIS of which comedo and cribriform were the major histological subtypes. The major histological subtypes of the invasive tumours were ductal-not otherwise specified, lobular, and tubular/cribriform. In this study, we also found a significant (p < 0.05 association between over expression of Her-2, lack of expression of ER and some of the

  6. Analysis of the progression of fibroepithelial tumours of the breast by PCR-based clonality assay

    NARCIS (Netherlands)

    Kuijper, Arno; Buerger, H.; Simon, R.; Schaefer, K-L.; Croonen, A.; Boecker, W.; Wall, E. van der; Diest, P.J. van

    2002-01-01

    Fibroadenoma and phyllodes tumour of the breast are both fibroepithelial tumours. Although progression to epithelial malignancy has been described, the behaviour of most fibroadenomas is benign. Phyllodes tumours, on the other hand, can display locally destructive growth and can even metastasize. A

  7. Can cell kinetic parameters predict the response of tumours to radiotherapy?

    Science.gov (United States)

    McNally, N J

    1989-11-01

    Three potential predictive assays of the repopulation component in tumour response to therapy are considered. (1) The DNA index can easily be measured. It is of prognostic value for cancers of certain sites, aneuploidy being a bad prognostic indicator. It is not strictly an indicator of cell proliferation. (2) The in vitro labelling index is of predictive value in early stage operable breast cancer and in head and neck cancer. In the former a high pretreatment labelling index can identify patients who could benefit from adjuvant chemotherapy. (3) The tumour potential doubling time (Tpot) can be measured rapidly following in vivo labelling with bromodeoxyuridine or iododeoxyuridine. We have measured Tpot in over 100 solid tumours with a success rate of about 75 per cent. Nearly 50 per cent of the tumours have a pre-treatment potential doubling time of 5 days or less. These would be suitable candidates for accelerated fractionation.

  8. Can cell kinetic parameters predict the response of tumours to radiotherapy?

    International Nuclear Information System (INIS)

    McNally, N.J.

    1989-01-01

    Three potential predictive assays of the repopulation component in tumour response to therapy are considered. (1) The DNA index can easily be measured. It is of prognostic value for cancers of certain sites, aneuploidy being a bad prognostic indicator. It is not strictly an indicator of cell proliferation. (2) The in vitro labelling index is of predictive value in early stage operable breast cancer and in head and neck cancer. In the former a high pretreatment labelling index can identify patients who could benefit from adjuvant chemotherapy. (3) The tumour potential doubling time can be measured rapidly following in vivo labelling with bromodeoxyuridine or iododeoxyuridine. The authors measured T pot in over 100 solid tumours with a success rate of about 75%. Nearly 50% of the tumours have a pre-treatment potential doubling time of 5 days or less. These would be suitable candidates for accelerated fractionation. (author)

  9. Inflammatory breast cancer biology: the tumour microenvironment is key.

    Science.gov (United States)

    Lim, Bora; Woodward, Wendy A; Wang, Xiaoping; Reuben, James M; Ueno, Naoto T

    2018-04-27

    Inflammatory breast cancer (IBC) is a rare and aggressive disease that accounts for ~2-4% of all breast cancers. However, despite its low incidence rate, IBC is responsible for 7-10% of breast cancer-related mortality in Western countries. Thus, the discovery of robust biological targets and the development of more effective therapeutics in IBC are crucial. Despite major international efforts to understand IBC biology, genomic studies have not led to the discovery of distinct biological mechanisms in IBC that can be translated into novel therapeutic strategies. In this Review, we discuss these molecular profiling efforts and highlight other important aspects of IBC biology. We present the intrinsic characteristics of IBC, including stemness, metastatic potential and hormone receptor positivity; the extrinsic features of the IBC tumour microenvironment (TME), including various constituent cell types; and lastly, the communication between these intrinsic and extrinsic components. We summarize the latest perspectives on the key biological features of IBC, with particular emphasis on the TME as an important contributor to the aggressive nature of IBC. On the basis of the current understanding of IBC, we hope to develop the next generation of translational studies, which will lead to much-needed survival improvements in patients with this deadly disease.

  10. Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

    Science.gov (United States)

    Boneberg, E-M; Legler, D F; Hoefer, M M; Öhlschlegel, C; Steininger, H; Füzesi, L; Beer, G M; Dupont-Lampert, V; Otto, F; Senn, H-J; Fürstenberger, G

    2009-01-01

    Background: Angiogenesis and lymphangiogenesis are considered to play key roles in tumour growth, progression and metastasis. However, targeting tumour angiogenesis in clinical trials showed only modest efficacy. We therefore scrutinised the concept of tumour angiogenesis and lymphangiogenesis by analysing the expression of crucial markers involved in these processes in primary breast cancer. Methods: We analysed the expression of angiogenic, lymphangiogenic or antiangiogenic factors, their respective receptors and specific markers for endothelial and lymphendothelial cells by quantitative real-time RT-PCR in primary breast cancer and compared the expression profiles to non-cancerous, tumour-adjacent tissues and breast tissues from healthy women. Results: We found decreased mRNA amounts of major angiogenic and lymphangiogenic factors in tumour compared to healthy tissues, whereas antiangiogenic factors were upregulated. Concomitantly, angiogenic and lymphangiogenic receptors were downregulated in breast tumours. This antiangiogenic, antilymphangiogenic microenvironment was even more pronounced in aggressive tumours and accompanied by reduced amounts of endothelial and lymphatic endothelial cell markers. Conclusion: Primary breast tumours are not a site of highly active angiogenesis and lymphangiogenesis. Selection for tumour cells that survive with minimal vascular supply may account for this observation in clinical apparent tumours. PMID:19672262

  11. Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies

    International Nuclear Information System (INIS)

    Mant, Christine; Gillett, Cheryl; D'Arrigo, Corrado; Cason, John

    2004-01-01

    It has been reported that a human murine mammary tumour virus (MMTV)-like virus (HMLV), which may be an endogenous human retrovirus (HERV), occurs in the human breast cancer cell lines T47D and MCF-7 and, in 38% of human breast cancer biopsies. As the aetiology of most breast cancers remains unknown, it is important to verify these observations in differing breast cancer populations worldwide. Thus, we sought to determine the genetic relationships between HMLVs, MMTVs, and HERVs, and to investigate the association between HMLVs and breast cancer biopsies from South London, UK. Phylogenetic analyses of the env/pol region indicated that HMLVs are indistinct from MMTVs, and that MMTVS/HMLVs exhibit only low sequence homologies with HERVs. A search of the human genome confirmed that HMLVs are not endogenous. Using MMTV polymerase chain reaction (PCR) primers described previously, we amplified DNA from all cell lines except MCF-7 and from 7 of 44 (16%) breast cancer biopsies. A restriction fragment length polymorphism assay was designed to distinguish between HMLVs and MMTVs, and upon analyses, PCR amplicons appeared to be HMLVs. To confirm these findings, amplicons from the T47D cell line and from four randomly selected breast cancer patients were sequenced. Of 106 DNA sequences obtained, 103 were homologous with a short arm of human chromosome (Chr) 3 (3p13), two with Chr 4, and one with Chr 8. None of the sequences exhibited significant nucleotide homology with MMTVs, HMLVs, or with HERVs (all <50%). Thus, we conclude that (i) HMLVs are integral members of the MMTV family; (ii) MMTVs/HMLVs are genetically distinct from HERVs; (iii) MMTV/HMLV DNA is not present in human breast cancer cell lines or clinical biopsies in our locality

  12. Apoptotic Cell Death and the Proliferative Capacity of Human Breast Cancers

    Directory of Open Access Journals (Sweden)

    Gabriele A. Losa

    1998-01-01

    Full Text Available The proliferative capacity (%S‐phase fraction, DNA ploidy, apoptosis frequency (DNA fragmentation and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left‐skewed frequency distribution and an overall median value of 1.64%, whilst the median %S‐phase fraction was 8%. The median %DNA fragmentation and %S‐phase fraction were 1.96% and 16% in hyperdiploid tumours (n=29; DNA index >1.1 higher than in hypodiploid tumors (n=10; DNA index 0.96, 0.38% and 7.5%. DNA diploid tumours (n=71 had median %DNA fragmentation and %S‐phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg the median values in hyperdiploid (10.6 fmol/mg and diploid tumours (14.6 fmol/mg. This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S‐phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2 and diploid tumours (3.6. These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

  13. Background parenchymal enhancement in breast MRI before and after neoadjuvant chemotherapy: correlation with tumour response

    Energy Technology Data Exchange (ETDEWEB)

    Preibsch, H.; Wanner, L.; Bahrs, S.D.; Wietek, B.M.; Nikolaou, K.; Wiesinger, B. [University Hospital Tuebingen, Diagnostic and Interventional Radiology, Tuebingen (Germany); Siegmann-Luz, K.C. [Diagnostic Center for Breast Cancer and Screening Mammography Brandenburg Ost, Koenigs Wusterhausen (Germany); Oberlecher, E.; Hahn, M. [University Hospital Tuebingen, Department of Gynecology and Obstetrics, Tuebingen (Germany); Staebler, A. [University Hospital Tuebingen, Institute of Pathology and Neuropathology, Tuebingen (Germany)

    2016-06-15

    To correlate the decrease in background parenchymal enhancement (BPE) and tumour response measured with MRI in breast cancer patients treated with neoadjuvant chemotherapy (NAC). One hundred and forty-six MRI examinations of 73 patients with 80 biopsy-proven breast cancers who underwent breast MRI before and after NAC were retrospectively analysed. All images were reviewed by two blinded readers, who classified BPE into categories (BEC; 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) before and after NAC. Histopathological and morphological tumour responses were analysed and compared. The distribution of BEC 1/2/3/4 was 25/46/18/11 % before and 78/20/2/0 % after NAC. On average, BPE decreased by 0.87 BEC. Cohen's kappa showed substantial agreement (k = 0.73-0.77) before and moderate agreement (k = 0.43-0.60) after NAC and moderate agreement (k = 0.62-0.60) concerning the change in BEC. Correlating the change in BPE with tumour response, the average decrease in BEC was 1.3 in cases of complete remission, 0.83 in cases with partial response, 0.85 in cases with stable disease and 0.40 in cases with progressive disease. Correlation analysis showed a significant correlation between the decrease in BEC and tumour response (r = -0.24, p = 0.03). BPE decreased by, on average, 0.87 BEC following NAC for breast cancer. The degree of BPE reduction seemed to correlate with tumour response. (orig.)

  14. Biochemical signatures of in vitro radiation response in human lung, breast and prostate tumour cells observed with Raman spectroscopy

    International Nuclear Information System (INIS)

    Matthews, Q; Jirasek, A; Lum, J J; Brolo, A G

    2011-01-01

    This work applies noninvasive single-cell Raman spectroscopy (RS) and principal component analysis (PCA) to analyze and correlate radiation-induced biochemical changes in a panel of human tumour cell lines that vary by tissue of origin, p53 status and intrinsic radiosensitivity. Six human tumour cell lines, derived from prostate (DU145, PC3 and LNCaP), breast (MDA-MB-231 and MCF7) and lung (H460), were irradiated in vitro with single fractions (15, 30 or 50 Gy) of 6 MV photons. Remaining live cells were harvested for RS analysis at 0, 24, 48 and 72 h post-irradiation, along with unirradiated controls. Single-cell Raman spectra were acquired from 20 cells per sample utilizing a 785 nm excitation laser. All spectra (200 per cell line) were individually post-processed using established methods and the total data set for each cell line was analyzed with PCA using standard algorithms. One radiation-induced PCA component was detected for each cell line by identification of statistically significant changes in the PCA score distributions for irradiated samples, as compared to unirradiated samples, in the first 24-72 h post-irradiation. These RS response signatures arise from radiation-induced changes in cellular concentrations of aromatic amino acids, conformational protein structures and certain nucleic acid and lipid functional groups. Correlation analysis between the radiation-induced PCA components separates the cell lines into three distinct RS response categories: R1 (H460 and MCF7), R2 (MDA-MB-231 and PC3) and R3 (DU145 and LNCaP). These RS categories partially segregate according to radiosensitivity, as the R1 and R2 cell lines are radioresistant (SF 2 > 0.6) and the R3 cell lines are radiosensitive (SF 2 < 0.5). The R1 and R2 cell lines further segregate according to p53 gene status, corroborated by cell cycle analysis post-irradiation. Potential radiation-induced biochemical response mechanisms underlying our RS observations are proposed, such as (1) the

  15. Breast cancer detection using time reversal

    Science.gov (United States)

    Sheikh Sajjadieh, Mohammad Hossein

    Breast cancer is the second leading cause of cancer death after lung cancer among women. Mammography and magnetic resonance imaging (MRI) have certain limitations in detecting breast cancer, especially during its early stage of development. A number of studies have shown that microwave breast cancer detection has potential to become a successful clinical complement to the conventional X-ray mammography. Microwave breast imaging is performed by illuminating the breast tissues with an electromagnetic waveform and recording its reflections (backscatters) emanating from variations in the normal breast tissues and tumour cells, if present, using an antenna array. These backscatters, referred to as the overall (tumour and clutter) response, are processed to estimate the tumour response, which is applied as input to array imaging algorithms used to estimate the location of the tumour. Due to changes in the breast profile over time, the commonly utilized background subtraction procedures used to estimate the target (tumour) response in array processing are impractical for breast cancer detection. The thesis proposes a new tumour estimation algorithm based on a combination of the data adaptive filter with the envelope detection filter (DAF/EDF), which collectively do not require a training step. After establishing the superiority of the DAF/EDF based approach, the thesis shows that the time reversal (TR) array imaging algorithms outperform their conventional conterparts in detecting and localizing tumour cells in breast tissues at SNRs ranging from 15 to 30dB.

  16. 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

  17. Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

    International Nuclear Information System (INIS)

    Azmy, Iman AF; Balasubramanian, Saba P; Wilson, Anthony G; Stephenson, Timothy J; Cox, Angela; Brown, Nicola J; Reed, Malcolm WR

    2004-01-01

    Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study. Using a case–control study design, breast cancer patients (n = 709) and appropriate age-matched and sex-matched controls obtained from the Breast Screening Unit (n = 498) were genotyped for these TNF polymorphisms, using a high-throughput allelic discrimination method. Allele frequencies for both polymorphisms were similar in both breast cancer cases and controls. However, the -308 polymorphism was found to be associated with vascular invasion in breast tumours (P = 0.024). Comparison with other standard prognostic indices did not show any association for either genotype. We demonstrated no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF and susceptibility to breast cancer, in a large North European population. However, the -308 G>A polymorphism was found to be associated with the presence of vascular invasion in breast tumours

  18. Lidocaine and ropivacaine, but not bupivacaine, demethylate deoxyribonucleic acid in breast cancer cells in vitro

    NARCIS (Netherlands)

    Lirk, P.; Hollmann, M. W.; Fleischer, M.; Weber, N. C.; Fiegl, H.

    2014-01-01

    Lidocaine demethylates deoxyribonucleic acid (DNA) in breast cancer cells. This modification of epigenetic information may be of therapeutic relevance in the perioperative period, because a decrease in methylation can reactivate tumour suppressor genes and inhibit tumour growth. The objectives of

  19. MMP-1 expression has an independent prognostic value in breast cancer

    International Nuclear Information System (INIS)

    Boström, Pia; Söderström, Mirva; Vahlberg, Tero; Söderström, Karl-Ove; Roberts, Peter J; Carpén, Olli; Hirsimäki, Pirkko

    2011-01-01

    Breast cancer consists of a variety of tumours, which differ by their morphological features, molecular characteristics and outcome. Well-known prognostic factors, e.g. tumour grade and size, Ki-67, hormone receptor status, HER2 expression, lymph node status and patient age have been traditionally related to prognosis. Although the conventional prognostic markers are reliable in general, better markers to predict the outcome of an individual tumour are needed. Matrix metalloproteinase-1 (MMP-1) expression has been reported to inversely correlate with survival in advanced cancers. In breast cancer MMP-1 is often upregulated, especially in basal-type breast tumours. The purpose of this retrospective study was to analyse MMP-1 expression in breast cancer cells and in cancer associated stromal cells and to correlate the results with traditional prognostic factors including p53 and bcl-2, as well as to patient survival in breast cancer subtypes. Immunohistochemical analysis of MMP-1, ER, PR, Ki-67, HER2, bcl-2, p53 and CK5/6 expression was performed on 125 breast cancers. Statistical analyses were carried out using Kruskal-Wallis and Mann-Whitney -tests. In pairwise comparison Bonferroni-adjustment was applied. Correlations were calculated using Spearman rank-order correlation coefficients. Kaplan-Meier survival analyses were carried out to compare breast cancer-specific survival curves. Factors significantly associated with disease-specific survival in univariate models were included in multivariate stepwise. Positive correlations were found between tumour grade and MMP-1 expression in tumour cells and in stromal cells. P53 positivity significantly correlated with MMP-1 expression in tumour cells, whereas HER2 expression correlated with MMP-1 both in tumour cells and stromal cells. MMP-1 expression in stromal cells showed a significant association with luminal A and luminal B, HER2 overexpressing and triple-negative breast cancer subtypes. The most important finding of

  20. Is there a requirement for axillary lymph node dissection following identification of micro-metastasis or isolated tumour cells at sentinel node biopsy for breast cancer?

    LENUS (Irish Health Repository)

    Joyce, D P

    2012-02-29

    INTRODUCTION: Recent decades have seen a significant shift towards conservative management of the axilla. Increasingly, immunohistochemical analysis of sentinel nodes leads to the detection of small tumour deposits, the significance of which remains uncertain. The aims of this study are to examine patients whose sentinel lymph nodes are positive for macro-metastasis, micro-metastasis or isolated tumour cells (ITCs) and to determine the rate of further nodal disease after axillary lymph node dissection (ALND). METHODS: A retrospective analysis of all patients undergoing a sentinel lymph node biopsy (SLNB) between January 2007 and December 2010 in a tertiary referral breast unit was performed. Patients who underwent an axillary lymph node dissection for macro-metastasis, micro-metastasis or ITCs were identified. Demographics, histological data and the rate of further axillary disease were examined. RESULTS: In total, 664 breast cancer patients attended the symptomatic breast unit during the study period, 360 of whom underwent a SLNB. Seventy patients had a SLNB positive for macro-metastasis. All of these patients underwent ALND. A positive SLNB with either micro-metastasis or ITCs was identified in 58 patients. Only 41 of the 58 patients went on to have an ALND, due primarily to variations in surgeons\\' preferences. Nineteen patients with micro-metastasis underwent an ALND. Four patients had further axillary disease (21%). Twenty-two patients had ITCs identified, of whom only one had further disease (4.5%). No statistically significant difference was found between the two groups in terms of tumour size, grade, lymphovascular invasion or oestrogen receptor status. CONCLUSION: ALND should be considered in patients with micro-metastasis at SLNB. It should rarely be employed in the setting of SLNB positive for ITCs.

  1. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  2. 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.

  3. Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women.

    Science.gov (United States)

    Arko-Boham, Benjamin; Lomotey, Justice Tanihu; Tetteh, Emmanuel Nomo; Tagoe, Emmanuel Ayitey; Aryee, Nii Ayite; Owusu, Ewurama Ampadu; Okai, Isaac; Blay, Richard Michael; Clegg-Lamptey, Joe-Nat

    2017-01-01

    Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily metastasize and recur and often have unfavourable outcomes. The current study investigated candidate genes that may regulate tumour aggression in Ghanaian women. We hypothesize that increased expression and function of certain genes other than the widely-held view attributing breast cancer aggression in African populations to their younger population age may be responsible for the aggressive nature of tumours. Employing ELISA, we assayed for vimentin and death-associated protein kinase 1 (DAPK1) from thawed archived (stored at -80 °C) serum samples obtained from 40 clinically confirmed Ghanaian breast cancer patients and 40 apparently healthy controls. Patients' clinical records and tumour parameters matching the samples were retrieved from the database of the hospital. ANOVA was used to compare means of serum protein concentration among groups while Chi-square analysis was used for the categorical data sets with p -value ≤0.05 considered significant. Multiple logistic regression analysis was conducted to determine the association between protein concentration and tumour parameters. Of the 80 samples, 27 (33.8%) and 53 (66.2%) were from young (<35 years) and old (≥35 years), respectively. Vimentin and DAPK1 concentration were higher in patients than controls with higher levels in "young" age group than "old" age group. Vimentin concentration was highest in grade 3 tumours followed by grade 2 and 1 but that for DAPK1 was not significant. For vimentin, tumour area strongly correlated with tumour grade ( r  = 0.696, p  < 0.05) but weakly correlated with tumour stage ( r  = 0.420, p  < 0.05). Patient's age correlated with DAPK1 concentration ( r  = 0

  4. 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.

  5. Shear-wave elastography contributes to accurate tumour size estimation when assessing small breast cancers

    International Nuclear Information System (INIS)

    Mullen, R.; Thompson, J.M.; Moussa, O.; Vinnicombe, S.; Evans, A.

    2014-01-01

    Aim: To assess whether the size of peritumoural stiffness (PTS) on shear-wave elastography (SWE) for small primary breast cancers (≤15 mm) was associated with size discrepancies between grey-scale ultrasound (GSUS) and final histological size and whether the addition of PTS size to GSUS size might result in more accurate tumour size estimation when compared to final histological size. Materials and methods: A retrospective analysis of 86 consecutive patients between August 2011 and February 2013 who underwent breast-conserving surgery for tumours of size ≤15 mm at ultrasound was carried out. The size of PTS stiffness was compared to mean GSUS size, mean histological size, and the extent of size discrepancy between GSUS and histology. PTS size and GSUS were combined and compared to the final histological size. Results: PTS of >3 mm was associated with a larger mean final histological size (16 versus 11.3 mm, p < 0.001). PTS size of >3 mm was associated with a higher frequency of underestimation of final histological size by GSUS of >5 mm (63% versus 18%, p < 0.001). The combination of PTS and GSUS size led to accurate estimation of the final histological size (p = 0.03). The size of PTS was not associated with margin involvement (p = 0.27). Conclusion: PTS extending beyond 3 mm from the grey-scale abnormality is significantly associated with underestimation of tumour size of >5 mm for small invasive breast cancers. Taking into account the size of PTS also led to accurate estimation of the final histological size. Further studies are required to assess the relationship of the extent of SWE stiffness and margin status. - Highlights: • Peritumoural stiffness of greater than 3 mm was associated with larger tumour size. • Underestimation of tumour size by ultrasound was associated with peri-tumoural stiffness size. • Combining peri-tumoural stiffness size to ultrasound produced accurate tumour size estimation

  6. Mechanisms driving local breast cancer recurrence in a model of breast-conserving surgery.

    LENUS (Irish Health Repository)

    Smith, Myles J

    2012-02-03

    OBJECTIVE: We aimed to identify mechanisms driving local recurrence in a model of breast-conserving surgery (BCS) for breast cancer. BACKGROUND: Breast cancer recurrence after BCS remains a clinically significant, but poorly understood problem. We have previously reported that recurrent colorectal tumours demonstrate altered growth dynamics, increased metastatic burden and resistance to apoptosis, mediated by upregulation of phosphoinositide-3-kinase\\/Akt (PI3K\\/Akt). We investigated whether similar characteristics were evident in a model of locally recurrent breast cancer. METHODS: Tumours were generated by orthotopic inoculation of 4T1 cells in two groups of female Balb\\/c mice and cytoreductive surgery performed when mean tumour size was above 150 mm(3). Local recurrence was observed and gene expression was examined using Affymetrix GeneChips in primary and recurrent tumours. Differential expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR). Phosphorylation of Akt was assessed using Western immunoblotting. An ex vivo heat shock protein (HSP)-loaded dendritic cell vaccine was administered in the perioperative period. RESULTS: We observed a significant difference in the recurrent 4T1 tumour volume and growth rate (p < 0.05). Gene expression studies suggested roles for the PI3K\\/Akt system and local immunosuppression driving the altered growth kinetics. We demonstrated that perioperative vaccination with an ex vivo HSP-loaded dendritic cell vaccine abrogated recurrent tumour growth in vivo (p = 0.003 at day 15). CONCLUSION: Investigating therapies which target tumour survival pathways such as PI3K\\/Akt and boost immune surveillance in the perioperative period may be useful adjuncts to contemporary breast cancer treatment.

  7. Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT)

    Energy Technology Data Exchange (ETDEWEB)

    Brouwer, O.R. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands); Antoni van Leeuwenhoekhospital, Amsterdam (Netherlands); Vermeeren, L.; Valdes Olmos, R.A. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands); Ploeg, I.M.C. van der; Rutgers, E.J.T.; Oldenburg, H.S.A. [Antoni van Leeuwenhoek Hospital, Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Loo, C.E. [Antoni van Leeuwenhoek Hospital, Department of Radiology, Netherlands Cancer Institute, Amsterdam (Netherlands); Pereira-Bouda, L.M.; Smit, F. [Rijnland Hospital, Department of Nuclear Medicine, Leiderdorp (Netherlands); Neijenhuis, P. [Rijnland Hospital, Department of Surgery, Leiderdorp (Netherlands); Vrouenraets, B.C. [Sint Lucas Andreas Hospital, Department of Surgery, Amsterdam (Netherlands); Sivro-Prndelj, F. [Sint Lucas Andreas Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Jap-a-Joe, S.M.; Borgstein, P.J. [Onze Lieve Vrouwe Gasthuis, Department of Nuclear Medicine, Amsterdam (Netherlands)

    2012-07-15

    To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of {sup 99m}Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64 %). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34 %)). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or

  8. Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

    Science.gov (United States)

    Brouwer, O R; Vermeeren, L; van der Ploeg, I M C; Valdés Olmos, R A; Loo, C E; Pereira-Bouda, L M; Smit, F; Neijenhuis, P; Vrouenraets, B C; Sivro-Prndelj, F; Jap-a-Joe, S M; Borgstein, P J; Rutgers, E J Th; Oldenburg, H S A

    2012-07-01

    To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or

  9. Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

    Science.gov (United States)

    Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

    2017-11-01

    Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

    Directory of Open Access Journals (Sweden)

    Mennerich Detlev

    2007-01-01

    Full Text Available Abstract Background Stromelysin-3 (ST-3 is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. Methods The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Results Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. Conclusion These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated "early stage" breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour

  11. Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

    International Nuclear Information System (INIS)

    Kasper, Grit; Lehmann, Kerstin E; Reule, Matthias; Tschirschmann, Miriam; Dankert, Niels; Stout-Weider, Karen; Lauster, Roland; Schrock, Evelin; Mennerich, Detlev; Duda, Georg N

    2007-01-01

    Stromelysin-3 (ST-3) is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated 'early stage' breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour fibroblasts leads to the stimulation of the IGF-1R pathway in

  12. lmmunohistochemical study of effect of ionizing radiation on human malignant tumours

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  13. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer.

    Science.gov (United States)

    Glenn, Wendy K; Heng, Benjamin; Delprado, Warick; Iacopetta, Barry; Whitaker, Noel J; Lawson, James S

    2012-01-01

    The purpose of this investigation is to determine if Epstein Barr virus (EBV), high risk human papillomavirus (HPV), and mouse mammary tumour viruses (MMTV) co-exist in some breast cancers. All the specimens were from women residing in Australia. For investigations based on standard PCR, we used fresh frozen DNA extracts from 50 unselected invasive breast cancers. For normal breast specimens, we used DNA extracts from epithelial cells from milk donated by 40 lactating women. For investigations based on in situ PCR we used 27 unselected archival formalin fixed breast cancer specimens and 18 unselected archival formalin fixed normal breast specimens from women who had breast reduction surgery. Thirteen of these fixed breast cancer specimens were ductal carcinoma in situ (dcis) and 14 were predominantly invasive ductal carcinomas (idc). EBV sequences were identified in 68%, high risk HPV sequences in 50%, and MMTV sequences in 78% of DNA extracted from 50 invasive breast cancer specimens. These same viruses were identified in selected normal and breast cancer specimens by in situ PCR. Sequences from more than one viral type were identified in 72% of the same breast cancer specimens. Normal controls showed these viruses were also present in epithelial cells in human milk - EBV (35%), HPV, 20%) and MMTV (32%) of 40 milk samples from normal lactating women, with multiple viruses being identified in 13% of the same milk samples. We conclude that (i) EBV, HPV and MMTV gene sequences are present and co-exist in many human breast cancers, (ii) the presence of these viruses in breast cancer is associated with young age of diagnosis and possibly an increased grade of breast cancer.

  14. 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.

  15. [Assessment of current eating habits in women diagnosed with breast tumours and changes introduced after diagnosis].

    Science.gov (United States)

    Kucharska, Alicja; Królikowska, Ewa; Sińska, Beata

    Intrroduction: Incorrect eating habits are a significant risk factor for breast tumours. An appropriate diet is a vital part in the treatment of such a disorder. The aim of the study was to assess current eating habits in women diagnosed with breast tumours and the changes introduced after diagnosis. The survey was conducted among 200 women aged 59±11.2 with a diagnosed breast tumour. An original survey questionnaire was used to assess the respondents' dietary habits. Questions pertained to the frequency of consumption of certain food groups, changes in diet since the moment of diagnosis and sources of knowledge about nutrition. A number of current incorrect eating habits became apparent (namely, low frequency of eating wholemeal products, legumes, fish, vegetables, fruit and high frequency of eating sweets), as well as many beneficial changes introduced after the diagnosis (more frequent consumption of wholemeal products, poultry, vegetables and fruit and lower frequency of consumption of red meat, meat preserves, sweets, sweetened drinks and alcohol), with no difference in age, education or time elapsed since the diagnosis. Less than one third of respondents have received nutrition advice after their diagnosis. In spite of the beneficial changes in dietary habits there is a need for widely available, reliable nutrition education amongst all women diagnosed with a breast tumour.

  16. Aqp 9 and Brain Tumour Stem Cells

    Directory of Open Access Journals (Sweden)

    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.

  17. 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.

  18. Staging primary breast cancer. Are there tumour pathological features that correlate with a false-negative axillary ultrasound?

    International Nuclear Information System (INIS)

    Johnson, S.; Brown, S.; Porter, G.; Steel, J.; Paisley, K.; Watkins, R.; Holgate, C.

    2011-01-01

    Aim: To investigate whether the histopathological characteristics of primary breast cancer tumours could predict the likelihood of false-negative axillary ultrasound. Materials and methods: Screening and symptomatic patients were identified from pathology records and imaging and pathology records reviewed. True and false-negative axillary staging ultrasound groups were compared statistically in terms of tumour size, pathological type and grade, lymphovascular invasion, and oestrogen receptor (ER) status. Results: Of 155 women with normal ultrasounds, 45 (29%) were node positive at axillary surgery. Breast tumour size was significantly different with the average size smaller in the true-negative group: 21 versus 30 mm (p < 0.02). The histological type varied significantly between the groups, with more lobular carcinomas in the false-negative group [6/110 (5%) versus 6/45 (13%), p < 0.001]. The false-negative group was also more likely to show lymphovascular invasion in the breast [6/110 (5%) versus 14/45 (31%), p < 0.001]. There was no significant difference in tumour grade or ER status. Conclusion: The present study has found significant differences in tumour characteristics between women with true-negative and false-negative axillary staging ultrasound in terms of size, primary tumour histological type and presence of lymphovascular invasion. In particular, axillary ultrasound in primary lobular carcinoma may be less accurate and a negative result is more likely to be spurious than with primary ductal carcinomas.

  19. 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.

  20. 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)

  1. Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture.

    Science.gov (United States)

    Darbre, Philippa D; Bakir, Ayse; Iskakova, Elzira

    2013-11-01

    Aluminium (Al) has been measured in human breast tissue, nipple aspirate fluid and breast cyst fluid, and recent studies have shown that at tissue concentrations, aluminium can induce DNA damage and suspension growth in human breast epithelial cells. This paper demonstrates for the first time that exposure to aluminium can also increase migratory and invasive properties of MCF-7 human breast cancer cells. Long-term (32 weeks) but not short-term (1 week) exposure of MCF-7 cells to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate increased motility of the cells as measured by live cell imaging (cumulative length moved by individual cells), by a wound healing assay and by migration in real time through 8 μm pores of a membrane using xCELLigence technology. Long-term exposure (37 weeks) to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate also increased the ability of MCF-7 cells to invade through a matrigel layer as measured in real time using the xCELLigence system. Although molecular mechanisms remain to be characterized, the ability of aluminium salts to increase migratory and invasive properties of MCF-7 cells suggests that the presence of aluminium in the human breast could influence metastatic processes. This is important because mortality from breast cancer arises mainly from tumour spread rather than from the presence of a primary tumour in the breast. © 2013.

  2. Can breast cancer patients with HER2 dual-equivocal tumours be managed as HER2-negative disease?

    Science.gov (United States)

    Tong, Yiwei; Chen, Xiaosong; Fei, Xiaochun; Lin, Lin; Wu, Jiayi; Huang, Ou; He, Jianrong; Zhu, Li; Chen, Weiguo; Li, Yafen; Shen, Kunwei

    2018-01-01

    Increasing human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)/fluorescence in situ hybridisation (FISH) dual-equivocal breast tumours are reported after the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline update. The aim of this study is to investigate the clinico-pathologic characteristics, treatment patterns and disease outcome of these patients with HER2 dual-equivocal tumours. Patients with HER2 IHC 2+ and available FISH results were retrospectively analysed from the Comprehensive Breast Health Center, Shanghai Ruijin Hospital. The 2013 ASCO/CAP guideline was applied to define HER2-positive, dual-equivocal and -negative groups. Patient characteristics, systemic treatment patterns and survival were compared among these groups. Reverse transcriptase-polymerase chain reaction-based assays were applied to test HER2 mRNA expression level. Among 691 patients included, 133 (19.25%) were HER2 positive, 25 (3.62%) were HER2 dual-equivocal and 533 (77.13%) were HER2 negative. Univariate and multivariate analyses stated that HER2 dual-equivocal tumours shared more similarity with HER2-negative tumours, whereas HER2-positive tumours had rather different clinico-pathologic features. HER2 dual-equivocal tumours had similar HER2 mRNA levels compared with HER2-negative tumours (P = 0.26), which were much less compared with HER2-positive breast cancer. Besides, adjuvant systemic treatment patterns were comparable between HER2-negative and dual-equivocal tumours, and none of HER2 dual-equivocal patients received anti-HER2 treatment. There was no survival difference among these three groups (P = 0.43). HER2 dual-equivocal tumours share more similarity with HER2-negative disease in terms of clinico-pathologic features, HER2 mRNA levels, adjuvant systemic treatment patterns and disease outcome, which deserves further clinical evaluation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Near-infrared laser, time domain, breast tumour detection system

    International Nuclear Information System (INIS)

    Joblin, A.J.

    1996-01-01

    image resolution using this technique is poor, being worse that S mm, with currently available time resolved detection system capabilities. However it was also found that tumour bodies smaller in size than the system resolution parameter produced a measurable change in the signal, which could be used to detect small tumour bodies. So while high resolution images of the breast are not possible, simple measurements to detect the presence of breast disease may be possible. This will require further work to allow the signal from breast disease to be distinguished without error from the expected variations in signal due to the variability in normal breast characteristics

  4. Surveillance of women with a personal history of breast cancer by tumour subtype.

    Science.gov (United States)

    Benveniste, A P; Dryden, M J; Bedrosian, I; Morrow, P K; Bassett, R L; Yang, W

    2017-03-01

    To determine if the rate and timing of a second breast cancer event (SBCE) in women with a personal history of breast cancer varies by disease subtype or breast imaging method. A retrospective review was performed of women with a SBCE from January 2006 to December 2010 at a single institution. Data analysed included oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status of the primary and second breast cancers; mammographic and ultrasound (US) features from SBCE; and the time interval between both events. Of 207 patients diagnosed with a SBCE, the median age at first diagnosis was 50.6 years, range 24.8 to 80.2; at second diagnosis was 56.2 years, range 25.8 to 87.9. Eleven percent of SBCE were diagnosed >10 years after the primary cancer diagnosis. The median time between the first and second diagnosis for ER-positive patients was 2.7 years (range 0.7-17.4 years); and 1.9 years for ER-negative patients, (range 0.4-23.4 years; pbreast cancer (TNBC) had a shorter time between diagnoses than others (p=0.0003). At 3, 5, and 10 years, 85%, 92%, and 97% of ER-negative and 54%, 81%, and 95% of ER-positive tumours, respectively, had recurred. ER-negative tumours and TNBC were more likely to be visible at US. There may be a role for customised imaging surveillance of women with a personal history of breast cancer (PHBC) after 10 years. Further studies are necessary to determine if US may be valuable in the surveillance of patients with ER-negative and TNBC tumours. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  5. Dendrogenin A arises from cholesterol and histamine metabolism and shows cell differentiation and anti-tumour properties.

    Science.gov (United States)

    de Medina, Philippe; Paillasse, Michael R; Segala, Gregory; Voisin, Maud; Mhamdi, Loubna; Dalenc, Florence; Lacroix-Triki, Magali; Filleron, Thomas; Pont, Frederic; Saati, Talal Al; Morisseau, Christophe; Hammock, Bruce D; Silvente-Poirot, Sandrine; Poirot, Marc

    2013-01-01

    We previously synthesized dendrogenin A and hypothesized that it could be a natural metabolite occurring in mammals. Here we explore this hypothesis and report the discovery of dendrogenin A in mammalian tissues and normal cells as an enzymatic product of the conjugation of 5,6α-epoxy-cholesterol and histamine. Dendrogenin A was not detected in cancer cell lines and was fivefold lower in human breast tumours compared with normal tissues, suggesting a deregulation of dendrogenin A metabolism during carcinogenesis. We established that dendrogenin A is a selective inhibitor of cholesterol epoxide hydrolase and it triggered tumour re-differentiation and growth control in mice and improved animal survival. The properties of dendrogenin A and its decreased level in tumours suggest a physiological function in maintaining cell integrity and differentiation. The discovery of dendrogenin A reveals a new metabolic pathway at the crossroads of cholesterol and histamine metabolism and the existence of steroidal alkaloids in mammals.

  6. Pharmacoeconomics of bisphosphonates for skeletal-related event prevention in metastatic non-breast solid tumours.

    Science.gov (United States)

    Carter, John A; Joshi, Avani D; Kaura, Satyin; Botteman, Marc F

    2012-05-01

    Bisphosphonates reduce the risk of skeletal-related events (SREs; i.e. spinal cord compression, pathological fracture, radiation or surgery to the bone, and hypercalcaemia) in patients with metastatic cancer. A number of analyses have been conducted to assess the cost effectiveness of bisphosphonates in patients with bone metastases secondary to breast cancer, but few in other solid tumours. This is a review of cost-effectiveness analyses in patients with non-breast solid tumours and bone metastases. A literature search was conducted to identify cost-effectiveness analyses reporting the cost per QALY gained of bisphosphonates in patients with metastatic bone disease secondary to non-breast solid tumours. Four analyses met inclusion criteria. These included two in prostate cancer (one of which used a global perspective but expressed results in $US, and the other reported from a multiple country perspective: France, Germany, Portugal and the Netherlands). The remaining analyses were in lung cancer (in the UK, France, Germany, Portugal and the Netherlands), and renal cell carcinoma (in the UK, France and Germany). In each analysis, the cost effectiveness of zoledronic acid versus placebo was analysed. Zoledronic acid was found to be cost effective in all European countries across all three indications but not in the sole global prostate cancer analysis. Across countries and indications, assumptions regarding patient survival, drug cost and baseline utility (i.e. patient utility with metastatic disease but without an SRE) were the most robust drivers of modelled estimates. Assumptions of SRE-related costs were most often the second strongest cost driver. Further review indicated that particular attention should be paid to the inclusion or exclusion of nonsignificant survival benefits, whether health state utilities were elicited from community or patient samples or author assumptions, delineation between symptomatic and asymptomatic SREs, and the methods with which SRE

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

    Science.gov (United States)

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

    2011-04-01

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

  8. Which factors influence MRI-pathology concordance of tumour size measurements in breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Rominger, M.; Frauenfelder, T. [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Berg, D. [Urbankrankenhaus Berlin, Anesthesiology, Berlin (Germany); Ramaswamy, A. [University Hospital Marburg, Pathology, Marburg (Germany); Timmesfeld, N. [Philipps University Marburg, Institute for Medical Biometry and Epidemiology, Marburg (Germany)

    2016-05-15

    To assess MRI-pathology concordance and factors influencing tumour size measurement in breast cancer. MRI tumour size (greatest diameter in anatomical planes (MRI-In-Plane) and greatest diameter along main tumour axis (MRI-MPR)) of 115 consecutive breast lesions (59 invasive lobular carcinoma, 46 invasive ductal carcinoma, and 10 ductal carcinoma in situ) was retrospectively compared to size measured at histopathology (pT size (Path-TNM) and greatest tumour diameter as relevant for excision (Path-Diameter; reference standard)). Histopathological tumour types, preoperative palpability, surgical management, additional high-risk lesions, and BI-RADS lesion type (mass versus non-mass enhancements) were assessed as possible influencing factors. Systematic errors were most pronounced between MRI-MPR and Path-TNM (7.1 mm, limits of agreement (LoA) [-21.7; 35.9]), and were lowest between MRI-In-Plane and Path-Diameter (0.2 mm, LoA [-19.7; 20.1]). Concordance rate of MRI-In-Plane with Path-Diameter was 86 % (97/113), overestimation 9 % (10/113) and underestimation 5 % (6/113); BI-RADS mass lesions were overestimated in 7 % (6/81) versus 41 % (13/32) for non-mass enhancements. On multivariate analysis only BI-RADS lesion type significantly influenced MRI-pathology concordance (p < 0.001). 2/59 (3 %) ILC did not enhance. Concordance rate varies according to the execution of MRI and histopathological measurements. Beyond this only non-mass enhancement significantly predicted discordance. (orig.)

  9. Growth of MCF-7 breast cancer cells and efficacy of anti-angiogenic agents in a hydroxyethyl chitosan/glycidyl methacrylate hydrogel.

    Science.gov (United States)

    Wang, Hejing; Qian, Junmin; Zhang, Yaping; Xu, Weijun; Xiao, Juxiang; Suo, Aili

    2017-01-01

    Breast cancer negatively affects women's health worldwide. The tumour microenvironment plays a critical role in tumour initiation, proliferation, and metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures as monolayers on a flat solid surface lacking cell-cell and cell-matrix interactions. These experimental conditions deviate from the clinical situation. Improved experimental systems that can mimic the in vivo situation are required to discover new therapies, particularly for anti-angiogenic agents that mainly target intercellular factors and play an essential role in treating some cancers. Chitosan can be modified to construct three-dimensional (3D) tumour models. Here, we report an in vitro 3D tumour model using a hydroxyethyl chitosan/glycidyl methacrylate (HECS-GMA) hydrogel produced by a series of chitosan modifications. Parameters relating to cell morphology, viability, proliferation, and migration were analysed using breast cancer MCF-7 cells. In a xenograft model, secretion of angiogenesis-related growth factors and the anti-angiogenic efficacy of Endostar and Bevacizumab in cells grown in HECS-GMA hydrogels were assessed by immunohistochemistry. Hydroxyethyl chitosan/glycidyl methacrylate hydrogels had a highly porous microstructure, mechanical properties, swelling ratio, and morphology consistent with a 3D tumour model. Compared with a 2D monolayer culture, breast cancer MCF-7 cells residing in the HECS-GMA hydrogels grew as tumour-like clusters in a 3D formation. In a xenograft model, MCF-7 cells cultured in the HECS-GMA hydrogels had increased secretion of angiogenesis-related growth factors. Recombinant human endostatin (Endostar), but not Bevacizumab (Avastin), was an effective anti-angiogenic agent in HECS-GMA hydrogels. The HECS-GMA hydrogel provided a 3D tumour model that mimicked the in vivo cancer microenvironment and supported the growth of MCF7 cells better than traditional tissue culture plates. The HECS

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

    Directory of Open Access Journals (Sweden)

    Manuali Elisabetta

    2012-06-01

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

  11. 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)

  12. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Tim A D Smith

    Full Text Available The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK, CTP:phosphocholine cytidylyl transferase (CCT and PtdCho-phospholipase C (PLC were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U]glucose.This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.

  13. Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

    Science.gov (United States)

    Munisvaradass, Rusheni; Kumar, Suresh; Govindasamy, Chandramohan; Alnumair, Khalid S.; Mok, Pooi Ling

    2017-01-01

    Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non–transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours. PMID:28885562

  14. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours

    International Nuclear Information System (INIS)

    Tomlinson, Victoria AL; Newbery, Helen J; Wray, Naomi R; Jackson, Juliette; Larionov, Alexey; Miller, William R; Dixon, J Michael; Abbott, Catherine M

    2005-01-01

    The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α) making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis

  15. 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.

  16. 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.

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

    Science.gov (United States)

    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.

  18. 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

  19. 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.

  20. Protein tyrosine phosphatase µ (PTP µ or PTPRM, a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis.

    Directory of Open Access Journals (Sweden)

    Ping-Hui Sun

    Full Text Available BACKGROUND: PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells. DESIGN: Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models. RESULTS: A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK. CONCLUSIONS: Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.

  1. Parameter estimation of breast tumour using dynamic neural network from thermal pattern

    Directory of Open Access Journals (Sweden)

    Elham Saniei

    2016-11-01

    Full Text Available This article presents a new approach for estimating the depth, size, and metabolic heat generation rate of a tumour. For this purpose, the surface temperature distribution of a breast thermal image and the dynamic neural network was used. The research consisted of two steps: forward and inverse. For the forward section, a finite element model was created. The Pennes bio-heat equation was solved to find surface and depth temperature distributions. Data from the analysis, then, were used to train the dynamic neural network model (DNN. Results from the DNN training/testing confirmed those of the finite element model. For the inverse section, the trained neural network was applied to estimate the depth temperature distribution (tumour position from the surface temperature profile, extracted from the thermal image. Finally, tumour parameters were obtained from the depth temperature distribution. Experimental findings (20 patients were promising in terms of the model’s potential for retrieving tumour parameters.

  2. Growth of MCF-7 breast cancer cells and efficacy of anti-angiogenic agents in a hydroxyethyl chitosan/glycidyl methacrylate hydrogel

    OpenAIRE

    Wang, Hejing; Qian, Junmin; Zhang, Yaping; Xu, Weijun; Xiao, Juxiang; Suo, Aili

    2017-01-01

    Background Breast cancer negatively affects women?s health worldwide. The tumour microenvironment plays a critical role in tumour initiation, proliferation, and metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures as monolayers on a flat solid surface lacking cell?cell and cell?matrix interactions. These experimental conditions deviate from the clinical situation. Improved experimental systems that can mimic the in vivo situation are required to discover new thera...

  3. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours

    Directory of Open Access Journals (Sweden)

    Miller William R

    2005-09-01

    Full Text Available Abstract Background The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer. Methods eEF1A2 is highly similar (98% to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity. Conclusion eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis.

  4. Oestrogen and progesterone receptor assays in breast tumours. The Prince Henry's Hospital experience, 1983-1990.

    Science.gov (United States)

    Pearce, P T; Myles, K M; Funder, J W

    1993-08-16

    To present and analyse the results of eight years of experience (1983-1990) in breast tumour receptor analysis. All female primary breast tumour samples received (4683) were analysed for seasonal variation, patient age, relative risk index, oestrogen receptor (ER) and progesterone receptor (PR) status, ER and PR status as a function of age, ER and PR levels as a function of age, and ER and PR levels as a function of month of analysis. The assays were done at the Medical Research Centre, Prince Henry's Hospital, Melbourne, as a non-profit service to surgeons, oncologists and pathologists. The numbers of samples referred for assay increased progressively each year, from 473 in 1983 to 1097 in 1990, but the receptor status (ER +/-, PR +/-) appeared not to vary from year to year. ER+PR+ tumours were the most common in all age groups, steadily increasing from between 50% and 60% in premenopausal women to 70% or more in those aged over 80. In postmenopausal women, levels of ER in ER+ tumours were three times those in premenopausal women; PR levels in PR+ tumours, however, were bimodal, with higher levels in the age groups 35-49 and 70-89 years than in women aged 50-69 years. No significant seasonal variation was seen, and the overall patterns of receptor status are similar to those seen in Northern hemisphere studies.

  5. 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

  6. 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

  7. 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)

  8. Assessment of DNA methylation profiling and copy number variation as indications of clonal relationship in ipsilateral and contralateral breast cancers to distinguish recurrent breast cancer from a second primary tumour

    International Nuclear Information System (INIS)

    Huang, Katie T.; Mikeska, Thomas; Li, Jason; Takano, Elena A.; Millar, Ewan K A; Graham, Peter H.; Boyle, Samantha E.; Campbell, Ian G.; Speed, Terence P.; Dobrovic, Alexander; Fox, Stephen B.

    2015-01-01

    Patients with breast cancer have an increased risk of developing subsequent breast cancers. It is important to distinguish whether these tumours are de novo or recurrences of the primary tumour in order to guide the appropriate therapy. Our aim was to investigate the use of DNA methylation profiling and array comparative genomic hybridization (aCGH) to determine whether the second tumour is clonally related to the first tumour. Methylation-sensitive high-resolution melting was used to screen promoter methylation in a panel of 13 genes reported as methylated in breast cancer (RASSF1A, TWIST1, APC, WIF1, MGMT, MAL, CDH13, RARβ, BRCA1, CDH1, CDKN2A, TP73, and GSTP1) in 29 tumour pairs (16 ipsilateral and 13 contralateral). Using the methylation profile of these genes, we employed a Bayesian and an empirical statistical approach to estimate clonal relationship. Copy number alterations were analysed using aCGH on the same set of tumour pairs. There is a higher probability of the second tumour being recurrent in ipsilateral tumours compared with contralateral tumours (38 % versus 8 %; p <0.05) based on the methylation profile. Using previously reported recurrence rates as Bayesian prior probabilities, we classified 69 % of ipsilateral and 15 % of contralateral tumours as recurrent. The inferred clonal relationship results of the tumour pairs were generally concordant between methylation profiling and aCGH. Our results show that DNA methylation profiling as well as aCGH have potential as diagnostic tools in improving the clinical decisions to differentiate recurrences from a second de novo tumour. The online version of this article (doi:10.1186/s12885-015-1676-0) contains supplementary material, which is available to authorized users

  9. 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.)

  10. A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma

    Directory of Open Access Journals (Sweden)

    Scally John

    2003-12-01

    Full Text Available Abstract Background Mantle cell lymphoma (MCL is a rare variety of non-Hodgkin's lymphoma which originates from CD5+ B-cell population in the mantle zones of lymphoid follicles. Coexistence of such tumours in the axillary lymph nodes with invasive breast cancers without prior history of adjuvant chemotherapy or radiotherapy has not been previously reported in literature. Case report We report a rare case of breast cancer co-existing with stage I mantle cell lymphoma of the ipsilateral axillary lymph node detected fortuitously by population screening. Conclusion Though some studies have tried to prove breast carcinomas and lymphomas to share a common molecular or viral link, more research needs to be done to establish whether such a link truly exists.

  11. 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

  12. 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...

  13. Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy.

    Science.gov (United States)

    Duanmu, J; Cheng, J; Xu, J; Booth, C J; Hu, Z

    2011-04-26

    The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR. The TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume. To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model. We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers.

  14. Oestrogen receptors in breast tumours: associations with age, menopausal status and epidemiological and clinical features in 735 patients.

    Science.gov (United States)

    Elwood, J M; Godolphin, W

    1980-11-01

    Comparisons between oestrogen-receptor (RE)-positive or negative patients were made on a continuous series of 735 patients with primary breast tumours seen at the major treatment centre in British Columbia between 1975 and 1978. RE positivity was commoner in older patients, and was not associated with menopausal status independently of age. The concentration of receptor protein also increased with increasing age, but was not affected by menopausal status. Neither RE status nor quantity was associated with any of the epidemiological risk factors studied, which included parity, age at first birth, weight, family history and exposure to oestrogenic drugs and oral contraceptives. Patients with RE- tumours were more likely to present with symptoms other than a breast lump, pain or nipple inversion, and had less-differentiated tumours; they did not differ from RE+ patients in terms of stage, size of tumour, or interval from first symptom. These findings are discussed in terms of the biological origin and determinants of oestrogen receptors.

  15. Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women

    NARCIS (Netherlands)

    Arko-Boham, Benjamin; Lomotey, Justice Tanihu; Tetteh, Emmanuel Nomo; Tagoe, Emmanuel Ayitey; Aryee, Nii Ayite; Owusu, Ewurama Ampadu; Okai, Isaac; Blay, Richard Michael; Clegg-Lamptey, Joe-Nat

    2017-01-01

    Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily

  16. Correlation between the Histo-Pathological Grade and Tumour Uptake Analysis of Tc99m-MIBI in Breast Cancer Nodules

    International Nuclear Information System (INIS)

    Haider, Saima

    2006-01-01

    Full text: Breast Cancer is the most common malignancy among women in the world. X-Ray mammography is the best screening device, but radionuclide imaging such as Tc-99m MIBI Scintimammography promises to play an important role as an adjunctive functional imaging tool in breast malignancies. The aim of the study was to correlate the Histopathological grade and semi-quantitative analysis of tracer uptake in Tc-99m MIBI Scintimammography. Seven (7) female patients (mean age 47.5+10) with locally advanced breast cancer were imaged. Informed written consent was taken from each patient. Average of 950 MBq (0.3 mCi/kg) Tc-99m MIBI was injected intravenously in the contra lateral arm to the site of lesion. Static prone MIBI Scintimammoscans of the affected side was acquired 5-10 minutes post injection for 10 minutes. Similarly 10 minute static view of normal side was also done. The background subtracted lesions to normal ratios (LNR) were acquired. Histopathological grading of tumours was done according to Bloom Richardson grading system. All the tumours were infiltrating ductal carcinoma. The mean LNR value is higher in high-grade lesions while less in low-grade tumours. Higher un-differentiation of malignant tumour is related with aggressive nature of the disease. This would suggest that more aggressive tumours have higher uptake of Tc-99m MIBI and therefore greater invasiveness of malignancy. (author)

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  18. Role of endocrine disrupting chemicals on the tissue levels of AhR and sex steroid receptors in breast tumours

    Directory of Open Access Journals (Sweden)

    Sepideh Arbabi Bidgoli

    2016-09-01

    Full Text Available Breast cancer affects Iranian women at least one decade younger than their counterparts in other countries and the incidence of breast fibroadenoma is growing in the last two decades in Tehran. This study aimed to compare the AhR levels in premenopausal breast cancer and breast fibroadnemo with appropriate normal groups. Possible associations of AhR with lifestyle and reproductive risk factors and other fundamental genes of breast cancer and reproductive disorders were the other major goals of present study. To conduct the comparisons all possible reproductive, environmental and lifestyle risk factors of mentioned diseases were recorded in 100 breast cancer, 100 breast fibroadenoma and compared with 400 women in normal group from 2009 to 2011. AhR overexpression in epithelial cells of premenopausal patients emphasized the susceptibility of these cells to environmental induced reproductive disorders. The AhR overexpression was contributed to ER-/PgR- immunophenotype in malignant tissues. Weight gain (after 18 and after pregnancy, long term (>5yrs OCP consumption, smoking, severe stress ,history of ovarian cysts, hormonal deregulations, living near PAHs producing sources, were correlated with increased risk of breast cancer and reproductive disorders and were correlated with elevated tissue levels of AhR. It seems that increased risk of breast cancer and other reproductive tumours in Tehran may be the result of exposure to environmental endocrine disruptors. Long term exposure to environmental estrogens can increase the tissue levels of AhR and deregulate the expression pattern of sex steroid receptors and other genes in target tissues.

  19. 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

  20. 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.

  1. 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...

  2. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells

    International Nuclear Information System (INIS)

    Collins, Hilary M; Kundu, Tapas K; Heery, David M; Abdelghany, Magdy K; Messmer, Marie; Yue, Baigong; Deeves, Sian E; Kindle, Karin B; Mantelingu, Kempegowda; Aslam, Akhmed; Winkler, G Sebastiaan

    2013-01-01

    Post-translational modifications (PTMs) of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7. Cell viability/proliferation assays, cell cycle analysis by flow cytometry, immunodetection of specific histone and p53 acetylation marks, western blotting, siRNA and RT-qPCR. Although treatment with curcumin, garcinol or the garcinol derivative LTK-14 hampered MCF7 cell proliferation, differential effects of these compounds on histone modifications were observed. Garcinol treatment resulted in a strong reduction in H3K18 acetylation, which is required for S phase progression. Similar effects of garcinol on H3K18 acetylation were observed in the osteosarcoma cells lines U2OS and SaOS2. In contrast, global levels of acetylated H4K16 and trimethylated H4K20 in MCF7 cells were elevated after garcinol treatment. This was accompanied by upregulation of DNA damage signalling markers such as γH2A.X, H3K56Ac, p53 and TIP60. In contrast, exposure of MCF7 cells to curcumin resulted in increased global levels of acetylated H3K18 and H4K16, and was less effective in inducing DNA damage markers. In addition to its effects on histone modifications, garcinol was found to block CBP/p300-mediated acetylation of the C-terminal activation domain of p53, but resulted in enhanced acetylation of p53K120, and accumulation of p53 in the cytoplasmic compartment. Finally, we show that the elevation of H4K20Me3 levels by garcinol correlated with increased expression of SUV420H2, and was prevented by siRNA targeting of SUV420H2. In

  3. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells

    Directory of Open Access Journals (Sweden)

    Collins Hilary M

    2013-01-01

    Full Text Available Abstract Background Post-translational modifications (PTMs of histones and other proteins are perturbed in tumours. For example, reduced levels of acetylated H4K16 and trimethylated H4K20 are associated with high tumour grade and poor survival in breast cancer. Drug-like molecules that can reprogram selected histone PTMs in tumour cells are therefore of interest as potential cancer chemopreventive agents. In this study we assessed the effects of the phytocompounds garcinol and curcumin on histone and p53 modification in cancer cells, focussing on the breast tumour cell line MCF7. Methods Cell viability/proliferation assays, cell cycle analysis by flow cytometry, immunodetection of specific histone and p53 acetylation marks, western blotting, siRNA and RT-qPCR. Results Although treatment with curcumin, garcinol or the garcinol derivative LTK-14 hampered MCF7 cell proliferation, differential effects of these compounds on histone modifications were observed. Garcinol treatment resulted in a strong reduction in H3K18 acetylation, which is required for S phase progression. Similar effects of garcinol on H3K18 acetylation were observed in the osteosarcoma cells lines U2OS and SaOS2. In contrast, global levels of acetylated H4K16 and trimethylated H4K20 in MCF7 cells were elevated after garcinol treatment. This was accompanied by upregulation of DNA damage signalling markers such as γH2A.X, H3K56Ac, p53 and TIP60. In contrast, exposure of MCF7 cells to curcumin resulted in increased global levels of acetylated H3K18 and H4K16, and was less effective in inducing DNA damage markers. In addition to its effects on histone modifications, garcinol was found to block CBP/p300-mediated acetylation of the C-terminal activation domain of p53, but resulted in enhanced acetylation of p53K120, and accumulation of p53 in the cytoplasmic compartment. Finally, we show that the elevation of H4K20Me3 levels by garcinol correlated with increased expression of SUV420H2

  4. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

    Science.gov (United States)

    Asara, Yolande; Marchal, Juan A; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-08-12

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

  5. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Roberto Madeddu

    2013-08-01

    Full Text Available Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd, which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

  6. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Science.gov (United States)

    Asara, Yolande; Marchal, Juan A.; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A.; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782

  7. Biodistribution and SPECT imaging of 125/131I-crotoxin on mice bearing Ehrlich solid tumour

    International Nuclear Information System (INIS)

    Soares, Marcella Araugio; Santos, Raquel Gouvea dos; Silveira, Marina B.; Simal, Carlos

    2009-01-01

    The search of specific radiopharmaceuticals to be used in breast tumour diagnosis is relevant to complement the techniques applied in conventional medicine. Crotalus durissus terrificus venom (CV) and its main polypeptide, Crotoxin (Crtx), are natural source of several bioactive substances with therapeutical potential. The aim of this work was to evaluate the binding of Crtx with tumour targets in vivo, as well as, evaluate its applicability for breast tumours diagnosis. Crtx was labelled with 125/131 I using lactoperoxidase method and radiochemical analysis was performed by chromatography. 125 I-Crtx was used for biodistribution and pharmacokinetics studies on swiss mice bearing Ehrlich solid tumour, while 131 I-Crtx was used for single photon emission computed tomography (SPECT) imaging. Crtx presented specific binding sites on Ehrlich tumour cells and had a rapid blood clearance (T 1/2 = 201.1 min.). Intratumoral administration increased significantly the activity delivered into the tumour site (128-fold higher) and reduced the kidney burden (7.2-fold lower). 131 I-Crxt demonstrated to interact with tumour cells for until 72 hours allowing good quality images of tumour. Our results indicate the biotechnological potential of Crtx as template for radiopharmaceutical design for cancer diagnosis. (author)

  8. Pentoxifylline regulates the cellular adhesion and its allied receptors to extracellular matrix components in breast cancer cells.

    Science.gov (United States)

    Goel, Peeyush N; Gude, Rajiv P

    2014-02-01

    Pentoxifylline (PTX) is a methylxanthine derivative that improves blood flow by decreasing its viscosity. Being an inhibitor of platelet aggregation, it can thus reduce the adhesiveness of cancer cells prolonging their circulation time. This delay in forming secondary tumours makes them more prone to immunological surveillance. Recently, we have evaluated its anti-metastatic efficacy against breast cancer, using MDA-MB-231 model system. In view of this, we had ascertained the effect of PTX on adhesion of MDA-MB-231 cells to extracellular matrix components (ECM) and its allied receptors such as the integrins. PTX affected adhesion of breast cancer cells to matrigel, collagen type IV, fibronectin and laminin in a dose dependent manner. Further, PTX showed a differential effect on integrin expression profile. The experimental metastasis model using NOD-SCID mice showed lesser tumour island formation when treated with PTX compared to the control. These findings further substantiate the anti-adhesive potential of PTX in breast cancer and warrant further insights into the functional regulation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. 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.

  10. Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

    International Nuclear Information System (INIS)

    Shao, Chunlin; Folkard, Melvyn; Held, Kathryn D; Prise, Kevin M

    2008-01-01

    Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. The observation of bystander responses in breast tumour cells may offer new potential targets for radiation

  11. Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model.

    Science.gov (United States)

    Sugumaran, Abimanyu; Ponnusamy, Chandrasekar; Kandasamy, Palanivel; Krishnaswami, Venkateshwaran; Palanichamy, Rajaguru; Kandasamy, Ruckmani; Lakshmanan, Manikandan; Natesan, Subramanian

    2018-04-30

    Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59±6.12% at 24h), acceptable hemolytic potential, significant cytotoxicity (IC 50 =176±4.3ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84±568.46ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. 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.

  13. Egfr Amplification Specific Gene Expression in Phyllodes Tumours of the Breast

    Directory of Open Access Journals (Sweden)

    Konstantin Agelopoulos

    2007-01-01

    Full Text Available Background: Recently, we were able to show that amplifications of the epidermal growth factor receptor (egfr gene and the overexpression of EGFR were associated with the initiation and progression of phyllodes tumours. Methods: In order to gain further insights into regulation mechanisms associated with egfr amplifications and EGFR expression in phyllodes tumours, we performed global gene expression analysis (Affymetrix A133.2 on a series of 10 phyllodes tumours, of these three with and seven without amplifications of an important regulatory repeat in intron 1 of egfr (CA-SSR I. The results were verified and extended by means of immunohistochemistry using the tissue microarray method on an extensively characterized series of 58 phyllodes tumours with antibodies against caveolin-1, eps15, EGF, TGF-α, pErk, pAkt and mdm2. Results: We were able to show that the presence of egfr CA-SSR I amplifications in phyllodes tumours was associated with 230 differentially expressed genes. Caveolin-1 and eps15, involved in EGFR turnover and signalling, were regulated differentially on the RNA and protein level proportionally to egfr gene dosage. Further immunohistochemical analysis revealed that the expression of caveolin-1 and eps15 were also significantly correlated with the expression of pAkt (p < 0.05, pERK (p < 0.05, mdm2 (p < 0.01 and EGF (p < 0.001 for caveolin-1. Eps15 and pERK were further associated with tumour grade (p < 0.01 and p < 0.001, respectively. Conclusion: Our results show that amplifications within regulatory sequences of egfr are associated with the expression of eps15 and caveolin-1, indicating an increased turnover of EGFR. The interplay between EGFR and caveolin-1, eps15, pAkt, mdm2 and pERK therefore seems to present a major molecular pathway in carcinogenesis and progression of breast phyllodes tumours.

  14. New evidence for the origin of intracranial germ cell tumours from primordial germ cells

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Sehested, A; Juhler, M

    2006-01-01

    that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which...... germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children...... and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected...

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  16. 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).

  17. GATA3 expression in triple-negative breast cancers.

    Science.gov (United States)

    Byrne, David J; Deb, Siddhartha; Takano, Elena A; Fox, Stephen B

    2017-07-01

    GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types, including breast and urothelial carcinomas, making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. We investigated GATA3 protein expression in a 106 primary triple-negative breast carcinomas (100 basal-like, six non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to quantify mRNA expression in 22 triple-negative breast cancers (TNBCs) (20 primary and two cell lines), four luminal (three primary and one cell line) and five human epidermal growth factor receptor 2 (HER2) (four primary and one cell line) amplified tumours. In 98 TNBCs where IHC was assessable, 47 (48%) had a 1+ or greater staining with 20 (21%) having high GATA3 expression when using a weighted scoring. Our study has demonstrated that GATA3 expression is common in primary triple-negative breast carcinomas. It also suggests that although GATA3 is an oestrogen receptor (ER) regulated gene, it still proves useful in differentiating between primary and metastatic tumours in patients with a history of breast cancer regardless of its molecular subtype. © 2017 John Wiley & Sons Ltd.

  18. Tumour tissue microenvironment can inhibit dendritic cell maturation in colorectal cancer.

    LENUS (Irish Health Repository)

    Michielsen, Adriana J

    2011-01-01

    Inflammatory mediators in the tumour microenvironment promote tumour growth, vascular development and enable evasion of anti-tumour immune responses, by disabling infiltrating dendritic cells. However, the constituents of the tumour microenvironment that directly influence dendritic cell maturation and function are not well characterised. Our aim was to identify tumour-associated inflammatory mediators which influence the function of dendritic cells. Tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. Pre-treatment of monocyte derived dendritic cells with this tumour conditioned media inhibited the up-regulation of CD86, CD83, CD54 and HLA-DR in response to LPS, enhancing IL-10 while reducing IL-12p70 secretion. We examined if specific individual components of the tumour conditioned media (CCL2, CXCL1, CXCL5) could modulate dendritic cell maturation or cytokine secretion in response to LPS. VEGF was also assessed as it has a suppressive effect on dendritic cell maturation. Pre-treatment of immature dendritic cells with VEGF inhibited LPS induced upregulation of CD80 and CD54, while CXCL1 inhibited HLA-DR. Interestingly, treatment of dendritic cells with CCL2, CXCL1, CXCL5 or VEGF significantly suppressed their ability to secrete IL-12p70 in response to LPS. In addition, dendritic cells treated with a combination of CXCL1 and VEGF secreted less IL-12p70 in response to LPS compared to pre-treatment with either cytokine alone. In conclusion, tumour conditioned media strongly influences dendritic cell maturation and function.

  19. Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer

    Science.gov (United States)

    Suzuki, H; Toyota, M; Caraway, H; Gabrielson, E; Ohmura, T; Fujikane, T; Nishikawa, N; Sogabe, Y; Nojima, M; Sonoda, T; Mori, M; Hirata, K; Imai, K; Shinomura, Y; Baylin, S B; Tokino, T

    2008-01-01

    Although mutation of APC or CTNNB1 (β-catenin) is rare in breast cancer, activation of Wnt signalling is nonetheless thought to play an important role in breast tumorigenesis, and epigenetic silencing of Wnt antagonist genes, including the secreted frizzled-related protein (SFRP) and Dickkopf (DKK) families, has been observed in various tumours. In breast cancer, frequent methylation and silencing of SFRP1 was recently documented; however, altered expression of other Wnt antagonist genes is largely unknown. In the present study, we found frequent methylation of SFRP family genes in breast cancer cell lines (SFRP1, 7 out of 11, 64%; SFRP2, 11 out of 11, 100%; SFRP5, 10 out of 11, 91%) and primary breast tumours (SFRP1, 31 out of 78, 40%; SFRP2, 60 out of 78, 77%; SFRP5, 55 out of 78, 71%). We also observed methylation of DKK1, although less frequently, in cell lines (3 out of 11, 27%) and primary tumours (15 out of 78, 19%). Breast cancer cell lines express various Wnt ligands, and overexpression of SFRPs inhibited cancer cell growth. In addition, overexpression of a β-catenin mutant and depletion of SFRP1 using small interfering RNA synergistically upregulated transcriptional activity of T-cell factor/lymphocyte enhancer factor. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in breast cancer, and suggest that their loss of function contributes to activation of Wnt signalling in breast carcinogenesis. PMID:18283316

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    Marina Rios Araújo

    2012-08-01

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

  2. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

    International Nuclear Information System (INIS)

    Osin, Pinchas P; Lakhani, Sunil R

    1999-01-01

    Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

  3. Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2013-01-01

    Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

  4. Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models

    International Nuclear Information System (INIS)

    Phelan, J. P.; Reen, F. J.; Dunphy, N.; O'Connor, R.; O'Gara, F.

    2016-01-01

    The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1α subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor. HIF-1 overexpression is an early biomarker of tumour metastasis and is associated with tumour resistance to conventional therapies, and poor prognosis in a range of different cancers. Here we investigated the effects of bile acids on the cancer growth and migratory potential of cell lines where HIF-1α is known to be active under hypoxic conditions. HIF-1α status was investigated in A-549 lung, DU-145 prostate and MCF-7 breast cancer cell lines exposed to bile acids (CDCA and DCA). Cell adhesion, invasion, migration was assessed in DU-145 cells while clonogenic growth was assessed in all cell lines. Intracellular HIF-1α was destabilised in the presence of bile acids in all cell lines tested. Bile acids were not cytotoxic but exhibited greatly reduced clonogenic potential in two out of three cell lines. In the migratory prostate cancer cell line DU-145, bile acids impaired cell adhesion, migration and invasion. CDCA and DCA destabilised HIF-1α in all cells and significantly suppressed key cancer progression associated phenotypes; clonogenic growth, invasion and migration in DU-145 cells. These findings suggest previously unobserved roles for bile acids as physiologically relevant molecules targeting hypoxic tumour progression

  5. High-intensity focused ultrasound in the treatment of breast tumours.

    Science.gov (United States)

    Peek, Mirjam C L; Wu, Feng

    2018-01-01

    High-intensity focused ultrasound (HIFU) is a minimally invasive technique that has been used for the treatment of both benign and malignant tumours. With HIFU, an ultrasound (US) beam propagates through soft tissue as a high-frequency pressure wave. The US beam is focused at a small target volume, and due to the energy building up at this site, the temperature rises, causing coagulative necrosis and protein denaturation within a few seconds. HIFU is capable of providing a completely non-invasive treatment without causing damage to the directly adjacent tissues. HIFU can be either guided by US or magnetic resonance imaging (MRI). Guided imaging is used to plan the treatment, detect any movement during the treatment and monitor response in real-time. This review describes the history of HIFU, the HIFU technique, available devices and gives an overview of the published literature in the treatment of benign and malignant breast tumours with HIFU.

  6. Which techniques for an additional irradiation of the tumour bed in a breast cancer?

    International Nuclear Information System (INIS)

    Chenna, H.; Iraqi, M.; Ahmedou, M.M.; Berhil, H.; El Kacemi, H.; Hassouni, K.; Kebdani, T.; Benjaafar, N.; El Gueddari, B.K.

    2010-01-01

    The authors report a comparison of different techniques for an additional irradiation of the tumour bed, in terms of local control and aesthetic result in the case of a breast cancer. This additional irradiation has been delivered by electron beam in five fractions, high dose rate curie-therapy in two fractions, photon beam in five or six fractions, and low dose rate curie-therapy. The dose increase in the tumour bed allows the local control rate to be increased without compromising aesthetic results. However, the comparison of the different boost techniques does not reveal significant differences. Short communication

  7. Metastatic tumours to hypophysis: a report of three cases and review of literature

    Directory of Open Access Journals (Sweden)

    Tomaž Šmigoc

    2016-10-01

    Full Text Available Background. Metastatic tumours to pituitary are rare. The most frequent are metastases from breast and lung.Methods. In this paper, three cases of metastatic tumours to the pituitary are presented with panhypopituitarism as a common symptom: I a 60-year-old gentleman with metastasis of diffuse large B cell lymphoma, who presented with diabetes insipidus, II a 54-year-old lady with metastatic renal clear cell carcinoma and consequent disturbances in visual acuity, brain nerve paresis and III a 57-year-old lady with breast cancer metastasis, visual impairment and brain nerve paresis.Results. A transnasal endoscopic resection of the tumours was performed in all cases, followed by oncological treatment. All patients improved after the treatment.Conclusions. Despite the rarity of the disease, a metastatic tumour to the pituitary gland must be included in the differential diagnosis when symptoms such as diabetes insipidus, ophthalmoplegy due to brain nerve palsies, rapid course of the disease and headache are observed. In 20% to 30%, pituitary metastases are the first manifestation of a tumour of unknown origin. Surgical and adjuvant therapy may improve the quality of life. The survival and prognosis are generally poor.

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

  9. A simple method for assigning genomic grade to individual breast tumours

    International Nuclear Information System (INIS)

    Wennmalm, Kristian; Bergh, Jonas

    2011-01-01

    The prognostic value of grading in breast cancer can be increased with microarray technology, but proposed strategies are disadvantaged by the use of specific training data or parallel microscopic grading. Here, we investigate the performance of a method that uses no information outside the breast profile of interest. In 251 profiled tumours we optimised a method that achieves grading by comparing rank means for genes predictive of high and low grade biology; a simpler method that allows for truly independent estimation of accuracy. Validation was carried out in 594 patients derived from several independent data sets. We found that accuracy was good: for low grade (G1) tumors 83- 94%, for high grade (G3) tumors 74- 100%. In keeping with aim of improved grading, two groups of intermediate grade (G2) cancers with significantly different outcome could be discriminated. This validates the concept of microarray-based grading in breast cancer, and provides a more practical method to achieve it. A simple R script for grading is available in an additional file. Clinical implementation could achieve better estimation of recurrence risk for 40 to 50% of breast cancer patients

  10. A simple method for assigning genomic grade to individual breast tumours

    Directory of Open Access Journals (Sweden)

    Bergh Jonas

    2011-07-01

    Full Text Available Abstract Background The prognostic value of grading in breast cancer can be increased with microarray technology, but proposed strategies are disadvantaged by the use of specific training data or parallel microscopic grading. Here, we investigate the performance of a method that uses no information outside the breast profile of interest. Results In 251 profiled tumours we optimised a method that achieves grading by comparing rank means for genes predictive of high and low grade biology; a simpler method that allows for truly independent estimation of accuracy. Validation was carried out in 594 patients derived from several independent data sets. We found that accuracy was good: for low grade (G1 tumors 83- 94%, for high grade (G3 tumors 74- 100%. In keeping with aim of improved grading, two groups of intermediate grade (G2 cancers with significantly different outcome could be discriminated. Conclusion This validates the concept of microarray-based grading in breast cancer, and provides a more practical method to achieve it. A simple R script for grading is available in an additional file. Clinical implementation could achieve better estimation of recurrence risk for 40 to 50% of breast cancer patients.

  11. Progression of fibroadenoma to malignant phyllodes tumour in a 14-year female

    International Nuclear Information System (INIS)

    Faridi, S.H.; Aslam, M.; Siddiqui, B.; Ahmad, S.S.

    2018-01-01

    Phyllodes tumours are uncommon breast tumours which account for less than 1% of all breast neoplasms. High-grade malignant phyllodes tumour is a very rare but aggressive breast malignancy and forms approximately 15-30% of all phyllodes tumours. The transformation of a benign fibroadenoma into a malignant phyllodes tumour in a teenaged female is even rarer. We report here an interesting case of malignant phyllodes tumour in a 14-year female patient who was operated twice previously with the diagnosis of complex fibroadenoma in the same breast. There was a large tumour involving whole of the breast and infiltrating the skin. The patient was operated and total mastectomy was done. Diagnosis was confirmed after histopathological examination and immunohistochemistry of the resected specimen. Patient received adjuvant radiotherapy and there was no recurrence on 6-month follow-up. Owing to the rare occurrence of malignant phyllodes tumour in this age group along with previous operations for complex fibroadenoma, this case is being reported here. (author)

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

    Directory of Open Access Journals (Sweden)

    Gorges Tobias M

    2012-05-01

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

  13. Tumour characteristics and survival in patients with invasive interval breast cancer classified according to mammographic findings at the latest screening

    DEFF Research Database (Denmark)

    Vitak, B; Olsen, K E; Månson, J C

    1999-01-01

    with invasive interval cancer detected from May 1978 to August 1995 (n = 544). The tumours were evaluated with regard to age, radiological category, interval between the latest screen and diagnosis and tumour characteristics at the time of diagnosis. We investigated possible relationships between the survival...... screen and diagnosis were not genuine predictors of the prognosis in patients with invasive interval breast cancer. No certain prognostic difference existed between true interval cancers and overlooked or misinterpreted interval breast cancers, despite higher proportions of grade-I tumours, ER positive......The aim of this study was to investigate whether different mammographic categories of interval cancer classified according to findings at the latest screening are associated with different distributions of prognostic factors or with different survival rates. The series consisted of all patients...

  14. Effects of vitamin D-binding protein-derived macrophage-activating factor on human breast cancer cells.

    Science.gov (United States)

    Pacini, Stefania; Punzi, Tiziana; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco

    2012-01-01

    Searching for additional therapeutic tools to fight breast cancer, we investigated the effects of vitamin D-binding protein-derived macrophage activating factor (DBP-MAF, also known as GcMAF) on a human breast cancer cell line (MCF-7). The effects of DBP-MAF on proliferation, morphology, vimentin expression and angiogenesis were studied by cell proliferation assay, phase-contrast microscopy, immunohistochemistry and western blotting, and chorioallantoic membrane (CAM) assay. DBP-MAF inhibited human breast cancer cell proliferation and cancer cell-stimulated angiogenesis. MCF-7 cells treated with DBP-MAF predominantly grew in monolayer and appeared to be well adherent to each other and to the well surface. Exposure to DBP-MAF significantly reduced vimentin expression, indicating a reversal of the epithelial/mesenchymal transition, a hallmark of human breast cancer progression. These results are consistent with the hypothesis that the known anticancer efficacy of DBP-MAF can be ascribed to different biological properties of the molecule that include inhibition of tumour-induced angiogenesis and direct inhibition of cancer cell proliferation, migration and metastatic potential.

  15. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    Science.gov (United States)

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  16. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

    Full Text Available Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR. It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954 human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative. These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  17. A comparison of tumour size measurements with palpation, ultrasound and mammography in male breast cancer: first results of the prospective register study.

    Science.gov (United States)

    Streng, Martin; Ignatov, Atanas; Reinisch, Mattea; Costa, Serban-Dan; Eggemann, Holm

    2018-02-01

    Precise presurgical diagnosis of tumour size is essential for adequate treatment of male breast cancer (MBC). This study is aimed to compare the accuracy of clinical measurement (CE), ultrasound (US) and mammography (MG) for preoperative estimation of tumour size. This study was conducted as a prospective, multicentre register study. One hundred and twenty-nine male patients with invasive breast cancer were included. CE, US and MG were performed in 107, 110 and 75 patients, respectively, and the estimated tumour size was compared with the histopathological (HP) tumour size. All methods tended to underestimate the HP tumour size. None of the methods were significantly more accurate than the others in determining the maximal tumour diameter. The sensitivity within 5 mm tolerance for US was 65.5%, which was better than for MG (61.3%) and CE (56.6%). In the group of patients with pT2 tumours, MG showed significantly better accuracy than US. The measurements obtained with each method were significantly correlated with the HP measurements. The highest correlation coefficient was observed for MG (0.788), followed by US (0.741) and CE (0.671). Our data demonstrate that MG and US have similar accuracy with regard to tumour size estimation. US assessment showed the highest sensitivity in determining tumour size, followed by MG and CE. However, MG demonstrated a significant advantage for estimating the real tumour size for pT2 tumours compared to US or CE.

  18. Antigen-specific primed cytotoxic T cells eliminate tumour cells in vivo and prevent tumour development, regardless of the presence of anti-apoptotic mutations conferring drug resistance.

    Science.gov (United States)

    Jaime-Sánchez, Paula; Catalán, Elena; Uranga-Murillo, Iratxe; Aguiló, Nacho; Santiago, Llipsy; M Lanuza, Pilar; de Miguel, Diego; A Arias, Maykel; Pardo, Julián

    2018-05-09

    Cytotoxic CD8 + T (Tc) cells are the main executors of transformed and cancer cells during cancer immunotherapy. The latest clinical results evidence a high efficacy of novel immunotherapy agents that modulate Tc cell activity against bad prognosis cancers. However, it has not been determined yet whether the efficacy of these treatments can be affected by selection of tumoural cells with mutations in the cell death machinery, known to promote drug resistance and cancer recurrence. Here, using a model of prophylactic tumour vaccination based on the LCMV-gp33 antigen and the mouse EL4 T lymphoma, we analysed the molecular mechanism employed by Tc cells to eliminate cancer cells in vivo and the impact of mutations in the apoptotic machinery on tumour development. First of all, we found that Tc cells, and perf and gzmB are required to efficiently eliminate EL4.gp33 cells after LCMV immunisation during short-term assays (1-4 h), and to prevent tumour development in the long term. Furthermore, we show that antigen-pulsed chemoresistant EL4 cells overexpressing Bcl-X L or a dominant negative form of caspase-3 are specifically eliminated from the peritoneum of infected animals, as fast as parental EL4 cells. Notably, antigen-specific Tc cells control the tumour growth of the mutated cells, as efficiently as in the case of parental cells. Altogether, expression of the anti-apoptotic mutations does not confer any advantage for tumour cells neither in the short-term survival nor in long-term tumour formation. Although the mechanism involved in the elimination of the apoptosis-resistant tumour cells is not completely elucidated, neither necroptosis nor pyroptosis seem to be involved. Our results provide the first experimental proof that chemoresistant cancer cells with mutations in the main cell death pathways are efficiently eliminated by Ag-specific Tc cells in vivo during immunotherapy and, thus, provide the molecular basis to treat chemoresistant cancer cells with CD8 Tc

  19. Biodistribution and SPECT imaging of {sup 125/131}I-crotoxin on mice bearing Ehrlich solid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Marcella Araugio; Santos, Raquel Gouvea dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: marcellaaraugio@yahoo.com.br, e-mail: santosr@cdtn.br; Silveira, Marina B.; Simal, Carlos [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina; Dias, Consuelo L. Fortes [Fundacao Ezequiel Dias (FUNED), Belo Horizonte, MG (Brazil)

    2009-07-01

    The search of specific radiopharmaceuticals to be used in breast tumour diagnosis is relevant to complement the techniques applied in conventional medicine. Crotalus durissus terrificus venom (CV) and its main polypeptide, Crotoxin (Crtx), are natural source of several bioactive substances with therapeutical potential. The aim of this work was to evaluate the binding of Crtx with tumour targets in vivo, as well as, evaluate its applicability for breast tumours diagnosis. Crtx was labelled with {sup 125/131}I using lactoperoxidase method and radiochemical analysis was performed by chromatography. {sup 125}I-Crtx was used for biodistribution and pharmacokinetics studies on swiss mice bearing Ehrlich solid tumour, while {sup 131}I-Crtx was used for single photon emission computed tomography (SPECT) imaging. Crtx presented specific binding sites on Ehrlich tumour cells and had a rapid blood clearance (T{sub 1/2}= 201.1 min.). Intratumoral administration increased significantly the activity delivered into the tumour site (128-fold higher) and reduced the kidney burden (7.2-fold lower). {sup 131}I-Crxt demonstrated to interact with tumour cells for until 72 hours allowing good quality images of tumour. Our results indicate the biotechnological potential of Crtx as template for radiopharmaceutical design for cancer diagnosis. (author)

  20. 3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response.

    Science.gov (United States)

    Gangadhara, Sharath; Smith, Chris; Barrett-Lee, Peter; Hiscox, Stephen

    2016-06-01

    The Her2 receptor is overexpressed in up to 25 % of breast cancers and is associated with a poor prognosis. Around half of Her2+ breast cancers also express the estrogen receptor and treatment for such tumours can involve both endocrine and Her2-targeted therapies. However, despite preclinical data supporting the effectiveness of these agents, responses can vary widely in the clinical setting. In light of the increasing evidence pointing to the interplay between the tumour and its extracellular microenvironment as a significant determinant of therapeutic sensitivity and response here we investigated the impact of 3D matrix culture of breast cancer cells on their therapeutic sensitivity. A 3D Matrigel-based culture system was established and optimized for the growth of ER+/Her2+ breast cancer cell models. Growth of cells in response to trastuzumab and endocrine agents in 3D culture versus routine monolayer culture were assessed using cell counting and Ki67 staining. Endogenous and trastuzumab-modulated signalling pathway activity in 2D and 3D cultures were assessed using Western blotting. Breast cancer cells in 3D culture displayed an attenuated response to both endocrine agents and trastuzumab compared with cells cultured in traditional 2D monolayers. Underlying this phenomenon was an apparent matrix-induced shift from AKT to MAPK signalling; consequently, suppression of MAPK in 3D cultures restores therapeutic response. These data suggest that breast cancer cells in 3D culture display a reduced sensitivity to therapeutic agents which may be mediated by internal MAPK-mediated signalling. Targeting of adaptive pathways that maintain growth in 3D culture may represent an effective strategy to improve therapeutic response clinically.

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

    Science.gov (United States)

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

    2014-12-01

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

  2. Targeting Common but Complex Proteoglycans on Breast Cancer Cells and Stem Cells Using Evolutionary Refined Malaria Proteins

    Science.gov (United States)

    2016-08-01

    T24 Bladder transitional cell carcinoma ++ UM-UC-6 Bladder transitional cell carcinoma +++ Cancer of mesenchymal lineage CW9019 Rhabdomyosarcoma...Expression (median) nd Bladder cancer (n=32) -3 -2 321-1 0 BCAN CA9 CCR10 CD44 THBD GPC3 GPC5 CSPG5 PODXL2 PTPRG S100A9 SDC1 SDC4 TGFBR3 TMEFF1 TMEFF2...in various other tumours including breast cancers . CCR10 Chemokine receptor 10 Not known Chemokine receptor . Overexpressed in lymphoma

  3. Alpha particles induce expression of immunogenic markers on tumour cells

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2018-02-01

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

  5. Detection of apoptotic cells in tumour paraffin sections

    International Nuclear Information System (INIS)

    Pizem, J.; Coer, A.

    2003-01-01

    Apoptosis is a distinct form of cell death characterised by specific morphological features and regulated by complex molecular mechanisms. Its deregulation is fundamental for tumour growth and progression and, moreover, anticancer therapies suppress tumour growth mainly by induction of apoptosis. Since the extent of apoptosis in a tumour may have prognostic as well as therapeutic implications, much effort has been invested in developing specific methods that can be routinely used to detect apoptotic cells in archival formalin- fixed paraffin-embedded tissue. Complex molecular pathways are involved in the regulation of apoptosis. Pro-apoptotic signals trigger activation of caspases that specifically cleave target proteins. Cleavage of proteins (caspase substrates) is responsible for morphological changes of apoptotic cells and DNA fragmentation. In the last decade, detection of apoptotic cells in formalin-fixed tumour tissue sections has been based mainly on morphology and characteristic DNA fragmentation. Recently, specific antibodies to activated caspases and cleaved target proteins (including cytokeratin 18, actin and PARP) have been produced that enable accurate detection of apoptosis in paraffin sections. (author)

  6. In vitro and in vivo MMP gene expression localisation by In Situ-RT-PCR in cell culture and paraffin embedded human breast cancer cell line xenografts

    International Nuclear Information System (INIS)

    Haupt, Larisa M; Thompson, Erik W; Trezise, Ann EO; Irving, Rachel E; Irving, Michael G; Griffiths, Lyn R

    2006-01-01

    Members of the matrix metalloproteinase (MMP) family of proteases are required for the degradation of the basement membrane and extracellular matrix in both normal and pathological conditions. In vitro, MT1-MMP (MMP-14, membrane type-1-MMP) expression is higher in more invasive human breast cancer (HBC) cell lines, whilst in vivo its expression has been associated with the stroma surrounding breast tumours. MMP-1 (interstitial collagenase) has been associated with MDA-MB-231 invasion in vitro, while MMP-3 (stromelysin-1) has been localised around invasive cells of breast tumours in vivo. As MMPs are not stored intracellularly, the ability to localise their expression to their cells of origin is difficult. We utilised the unique in situ-reverse transcription-polymerase chain reaction (IS-RT-PCR) methodology to localise the in vitro and in vivo gene expression of MT1-MMP, MMP-1 and MMP-3 in human breast cancer. In vitro, MMP induction was examined in the MDA-MB-231 and MCF-7 HBC cell lines following exposure to Concanavalin A (Con A). In vivo, we examined their expression in archival paraffin embedded xenografts derived from a range of HBC cell lines of varied invasive and metastatic potential. Mouse xenografts are heterogenous, containing neoplastic human parenchyma with mouse stroma and vasculature and provide a reproducible in vivo model system correlated to the human disease state. In vitro, exposure to Con A increased MT1-MMP gene expression in MDA-MB-231 cells and decreased MT1-MMP gene expression in MCF-7 cells. MMP-1 and MMP-3 gene expression remained unchanged in both cell lines. In vivo, stromal cells recruited into each xenograft demonstrated differences in localised levels of MMP gene expression. Specifically, MDA-MB-231, MDA-MB-435 and Hs578T HBC cell lines are able to influence MMP gene expression in the surrounding stroma. We have demonstrated the applicability and sensitivity of IS-RT-PCR for the examination of MMP gene expression both in vitro and in

  7. Improved contrast deep optoacoustic imaging using displacement-compensated averaging: breast tumour phantom studies

    Energy Technology Data Exchange (ETDEWEB)

    Jaeger, M; Preisser, S; Kitz, M; Frenz, M [Institute of Applied Physics, University of Bern, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Ferrara, D; Senegas, S; Schweizer, D, E-mail: frenz@iap.unibe.ch [Fukuda Denshi Switzerland AG, Reinacherstrasse 131, CH-4002 Basel (Switzerland)

    2011-09-21

    For real-time optoacoustic (OA) imaging of the human body, a linear array transducer and reflection mode optical irradiation is usually preferred. Such a setup, however, results in significant image background, which prevents imaging structures at the ultimate depth determined by the light distribution and the signal noise level. Therefore, we previously proposed a method for image background reduction, based on displacement-compensated averaging (DCA) of image series obtained when the tissue sample under investigation is gradually deformed. OA signals and background signals are differently affected by the deformation and can thus be distinguished. The proposed method is now experimentally applied to image artificial tumours embedded inside breast phantoms. OA images are acquired alternately with pulse-echo images using a combined OA/echo-ultrasound device. Tissue deformation is accessed via speckle tracking in pulse echo images, and used to compensate in the OA images for the local tissue displacement. In that way, OA sources are highly correlated between subsequent images, while background is decorrelated and can therefore be reduced by averaging. We show that image contrast in breast phantoms is strongly improved and detectability of embedded tumours significantly increased, using the DCA method.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  9. MR imaging of the skin and nipple of the breast: differentiation between tumour recurrence and post-treatment change

    International Nuclear Information System (INIS)

    Ralleigh, G.; Walker, A.E.; Hall-Craggs, M.A.; Lakhani, S.R.; Saunders, C.

    2001-01-01

    Contrast-enhanced MR imaging of the breast has been found to be valuable in the assessment of local recurrence of previously treated breast cancer. We looked specifically at the appearances of the skin and nipple of the treated breast in order to describe the appearances of post-treatment change and recurrence in this region. Thirty-nine women treated for breast cancer had MR imaging of one or both breasts reviewed retrospectively with particular attention to the nipple and skin. The skin and chest wall were assessed for patients with mastectomies. All available histology of the skin and/or nipple, obtained following MR imaging, was reviewed. In patients who did not undergo surgery following MR imaging, clinical follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR imaging, which correlated with histology demonstrating tumour recurrence within the skin and/or nipple. Of the remaining 33 patients, changes of linear or diffuse enhancement were seen in the skin and/or nipple of 15 patients. These changes were shown to be benign post-treatment changes at surgery/biopsy in 4 cases or by clinical follow-up in the remainder. In this article we demonstrate differing patterns of contrast enhancement within the skin and nipple in recurrent breast carcinoma vs post-treatment changes. This suggests that contrast-enhanced MR imaging of the breast may be a useful tool in differentiating tumour recurrence from post-treatment changes within the skin and nipple. (orig.)

  10. Testicular germ cell tumours in dogs are predominantly of spermatocytic seminoma type and are frequently associated with somatic cell tumours

    DEFF Research Database (Denmark)

    Bush, J M; Gardiner, D W; Palmer, J S

    2011-01-01

    Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated...... in canine TGCT. None of the canine TGCT evaluated demonstrated the presence of carcinoma in situ cells, a standard feature of human classical seminomas, suggesting that classical seminomas either do not occur in dogs or are rare in occurrence. Canine spermatocytic seminomas may provide a useful model...... and characterized using human classification criteria. Histopathological and immunohistological analysis of PLAP, KIT, DAZ and DMRT1 expression revealed that canine seminomas closely resemble human spermatocytic seminomas. In addition, a relatively frequent concomitant presence of somatic cell tumours was noted...

  11. Mitochondrial modulation of oxygen-dependent radiosensitivity in some human tumour cell lines.

    LENUS (Irish Health Repository)

    Anoopkumar-Dukie, S

    2009-10-01

    Oxygen-dependent radiosensitivity of tumour cells reflects direct oxidative damage to DNA, but non-nuclear mechanisms including signalling pathways may also contribute. Mitochondria are likely candidates because not only do they integrate signals from each of the main kinase pathways but mitochondrial kinases responsive to oxidative stress communicate to the rest of the cell. Using pharmacological and immunochemical methods, we tested the role of mitochondrial permeability transition (MPT) and the Bcl-2 proteins in oxygen-dependent radiosensitivity. Drug-treated or untreated cervical cancer HeLa, breast cancer MCF-7 and melanoma MeWo cell lines were irradiated at 6.2 Gy under normoxic and hypoxic conditions then allowed to proliferate for 7 days. The MPT blocker cyclosporin A (2 microM) strongly protected HeLa but not the other two lines against oxygen-dependent radiosensitivity. By contrast, bongkrekic acid (50 microM), which blocks MPT by targeting the adenine nucleotide transporter, had only marginal effect and calcineurin inhibitor FK-506 (0.1 microM) had none. Nor was evidence found for the modulation of oxygen-dependent radiosensitivity by Bax\\/Bcl-2 signalling, mitochondrial ATP-dependent potassium (mitoK(ATP)) channels or mitochondrial Ca(2+) uptake. In conclusion, calcineurin-independent protection by cyclosporin A suggests that MPT but not mitoK(ATP) or the mitochondrial apoptosis pathway plays a causal role in oxygen-dependent radiosensitivity of HeLa cells. Targeting MPT may therefore improve the effectiveness of radiotherapy in some solid tumours.

  12. 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.

  13. Selection of viable cell subpopulations from murine tumours using FACS

    International Nuclear Information System (INIS)

    Chaplin, D.J.; Durand, R.E.; Olive, P.L.

    1985-01-01

    The authors developed a technique which enables isolation of viable tumour cells subpopulation as a function of their distance from the blood supply. The basis for this separation procedure is that the fluorochrome, Hoechst 33342, as a result of its high avidity for cellular DNA, exhibits a marked diffusion/consumption gradient when it has to pass through several cell layers. As a result intravenous injection of Hoechst 33342 into tumour bearing animals, results in a heterogeneous straining pattern within the tumour with cells close to blood vessels being brightly fluorescent while those more distant are less intensely stained. Since these differences in staining intensity persist after tumour disaggregation, cells can be sorted into subpopulations on the basis of their fluorescence intensity using a fluorescence activated cell sorter. This technique offers the unique possibility of identifying the location of those cell subpopulations resistant to treatment with either radiation or chemotherapeutic drugs

  14. Effect of aspirin on tumour cell colony formation and evolution.

    Science.gov (United States)

    Wodarz, Dominik; Goel, Ajay; Boland, C Richard; Komarova, Natalia L

    2017-09-01

    Aspirin is known to reduce the risk of colorectal cancer (CRC) incidence, but the underlying mechanisms are not fully understood. In a previous study, we quantified the in vitro growth kinetics of different CRC tumour cell lines treated with varying doses of aspirin, measuring the rate of cell division and cell death. Here, we use these measured parameters to calculate the chances of successful clonal expansion and to determine the evolutionary potential of the tumour cell lines in the presence and absence of aspirin. The calculations indicate that aspirin increases the probability that a single tumour cell fails to clonally expand. Further, calculations suggest that aspirin increases the evolutionary potential of an expanding tumour cell colony. An aspirin-treated tumour cell population is predicted to result in the accumulation of more mutations (and is thus more virulent and more difficult to treat) than a cell population of the same size that grew without aspirin. This indicates a potential trade-off between delaying the onset of cancer and increasing its evolutionary potential through chemoprevention. Further work needs to investigate to what extent these findings apply to in vivo settings, and to what degree they contribute to the epidemiologically documented aspirin-mediated protection. © 2017 The Author(s).

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    2016-08-01

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

  17. Lipid accumulation in human breast cancer cells injured by iron depletors.

    Science.gov (United States)

    De Bortoli, Maida; Taverna, Elena; Maffioli, Elisa; Casalini, Patrizia; Crisafi, Francesco; Kumar, Vikas; Caccia, Claudio; Polli, Dario; Tedeschi, Gabriella; Bongarzone, Italia

    2018-04-03

    Current insights into the effects of iron deficiency in tumour cells are not commensurate with the importance of iron in cell metabolism. Studies have predominantly focused on the effects of oxygen or glucose scarcity in tumour cells, while attributing insufficient emphasis to the inadequate supply of iron in hypoxic regions. Cellular responses to iron deficiency and hypoxia are interlinked and may strongly affect tumour metabolism. We examined the morphological, proteomic, and metabolic effects induced by two iron chelators-deferoxamine (DFO) and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT)-on MDA-MB-231 and MDA-MB-157 breast cancer cells. These chelators induced a cytoplasmic massive vacuolation and accumulation of lipid droplets (LDs), eventually followed by implosive, non-autophagic, and non-apoptotic death similar to methuosis. Vacuoles and LDs are generated by expansion of the endoplasmic reticulum (ER) based on extracellular fluid import, which includes unsaturated fatty acids that accumulate in LDs. Typical physiological phenomena associated with hypoxia are observed, such as inhibition of translation, mitochondrial dysfunction, and metabolic remodelling. These survival-oriented changes are associated with a greater expression of epithelial/mesenchymal transcription markers. Iron starvation induces a hypoxia-like program able to scavenge nutrients from the extracellular environment, and cells assume a hypertrophic phenotype. Such survival strategy is accompanied by the ER-dependent massive cytoplasmic vacuolization, mitochondrial dysfunctions, and LD accumulation and then evolves into cell death. LDs containing a greater proportion of unsaturated lipids are released as a consequence of cell death. The consequence of the disruption of iron metabolism in tumour tissue and the effects of LDs on intercellular communication, cancer-inflammation axis, and immunity remain to be explored. Considering the potential benefits, these are crucial

  18. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    International Nuclear Information System (INIS)

    Peres, Elodie A.; Valable, Samuel; Guillamo, Jean-Sebastien; Marteau, Lena; Bernaudin, Jean-Francois; Roussel, Simon; Lechapt-Zalcman, Emmanuele; Bernaudin, Myriam; Petit, Edwige

    2011-01-01

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  19. Tumour 18 F-FDG Uptake on preoperative PET/CT may predict axillary lymph node metastasis in ER-positive/HER2-negative and HER2-positive breast cancer subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin You; Lee, Suck Hong; Kim, Suk [Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Department of Radiology, Seo-gu, Busan (Korea, Republic of); Kang, Taewoo [Pusan National University Hospital, Busan Cancer Center, Busan (Korea, Republic of); Bae, Young Tae [Pusan National University Hospital, Department of Surgery, Busan (Korea, Republic of)

    2015-04-01

    To evaluate the association between tumour FDG uptake on preoperative PET/CT and axillary lymph node metastasis (ALNM) according to breast cancer subtype. The records of 671 patients with invasive breast cancer who underwent {sup 18} F-FDG PET/CT and surgery were reviewed. Using immunohistochemistry, tumours were divided into three subtypes: oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive, and triple-negative. Tumour FDG uptake, expressed as maximum standardized uptake value (SUV{sub max}), and clinicopathological variables were analysed. ALNM was present in 187 of 461 ER-positive/HER2-negative, 54 of 97 HER2-positive, and 38 of 113 triple-negative tumours. On multivariate analysis, high tumour SUV{sub max} (≥4.25) (P < 0.001), large tumour size (>2 cm) (P = 0.003) and presence of lymphovascular invasion (P < 0.001) were independent variables associated with ALNM. On subset analyses, tumour SUV{sub max} maintained independent significance for predicting ALNM in ER-positive/HER2-negative (adjusted odds ratio: 3.277, P < 0.001) and HER2-positive tumours (adjusted odds ratio: 14.637, P = 0.004). No association was found for triple-negative tumours (P = 0.161). Tumour SUV{sub max} may be an independent prognostic factor for ALNM in patients with invasive breast cancer, especially in ER-positive/HER2-negative and HER2-positive subtypes, but not in those with triple-negative subtype. (orig.)

  20. Early dissemination seeds metastasis in breast cancer

    Science.gov (United States)

    Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

    2016-01-01

    Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

  1. ATM induction insufficiency in a radiosensitive breast-cancer patient

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.H.; Marr, P.J.; Kearsley, J.H.; Papadatos, G.; Lee, C.S.; University of Sydney, Camperdown, NSW

    2002-01-01

    ATM induction insufficiency in a radiosensitive breast-cancer patient The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology. Copyright (2002) Blackwell Science Pty Ltd

  2. Tumour metastasis as an adaptation of tumour cells to fulfil their phosphorus requirements.

    Science.gov (United States)

    de Carvalho, Carla C C R; Caramujo, Maria José

    2012-05-01

    Inorganic phosphate (Pi) is a vital component of nucleotides, membrane phospholipids, and phosphorylated intermediates in cellular signalling. The Growth Rate Hypothesis (GRH) states that fast growing organisms should be richer in phosphorus (relatively low C:P and N:P cell content) than slow developing organisms as a result of high ribosome biogenesis. Cells that proliferate rapidly, such as cancer cells, require a high amount of ribosomes and other P-rich RNA components that are necessary to manufacture proteins. The GRH hypothesis may be applied to cancer predicting that tumour cells are richer in phosphorus than the surrounding tissue, and that they resort to metastasis in order to meet their nutrient demands. Considering that the cells most P-deprived should be located in the inner parts of the tumour we propose that changes in the membrane of these cells favour the detachment of the more peripheral cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Role of tumour initiating cells in the radiation resistance of osteosarcoma

    International Nuclear Information System (INIS)

    Klymenko, Olena

    2014-01-01

    In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

  4. Role of tumour initiating cells in the radiation resistance of osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Klymenko, Olena

    2014-02-26

    In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-01-01

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

  6. Optical diagnostics of tumour cells at different stages of pathology development

    Energy Technology Data Exchange (ETDEWEB)

    Shcheglova, L S; Maryakhina, V S [Orenburg State University, Orenburg (Russian Federation); Abramova, L L [Orenburg State Agrarian University, Orenburg (Russian Federation)

    2013-11-30

    The differences in optical and biophysical properties between the cells of mammary gland tumour extracted from tumours of different diameter are described. It is shown that the spectral and spectrokinetic properties of fluorescent probes in the cells extracted from the tumours 1 – 3 cm in diameter are essentially different. Thus, the extinction coefficient of rhodamine 6G gradually increases with the pathology development. At the same time the rate of interaction of the triplet states of molecular probes with the oxygen, diluted in the tumour cells cytoplasm, decreases with the growth of the tumour capsule diameter. The observed regularities can be due to the changes in the cell structure, biochemical and biophysical properties. The reported data may be useful for developing optical methods of diagnostics of biotissue pathological conditions. (optical methods in biology and medicine)

  7. Cell Proliferation (KI-67) Expression Is Associated with Poorer Prognosis in Nigerian Compared to British Breast Cancer Women

    Science.gov (United States)

    Agboola, Ayodeji O. J.; Banjo, Adekumbiola A. F.; Anunobi, Charles C.; Salami, Babatunde; Agboola, Mopelola Deji; Musa, Adewale A.; Nolan, Christopher C.; Rakha, Emad A.; Ellis, Ian O.; Green, Andrew R.

    2013-01-01

    Background. Black women with breast cancer (BC) in Nigeria have higher mortality rate compared with British women. This study investigated prognostic features of cell proliferation biomarker (Ki-67) in Nigerian breast cancer women. Materials and Methods. The protein expression of Ki-67 was investigated in series of 308 Nigerian women, prepared as a tissue microarray (TMA), using immunohistochemistry. Clinic-pathological parameters, biomarkers, and patient outcome of tumours expressing Ki-67 in Nigerian women were correlated with UK grade-matched series. Results. A significantly larger proportion of breast tumours from Nigerian women showed high Ki-67 expression. Those tumours were significantly correlated with negative expression of the steroid hormone receptors (ER and PgR), p21, p27, E-cadherin, BRCA-1, and Bcl-2 (all P < 0.001), but positively associated with EGFR (P = 0.003), p53, basal cytokeratins: CK56, CK14, triple negative, and basal phenotype using Nielsen's classification (all P < 0.001) compared to UK women. Multivariate analyses showed that race was also associated with BCSS independent of tumour size, lymph node status, and ER status. Conclusion. Ki-67 expression was observed to have contributed to the difference in the BCSS in Nigerian compared with British BC women. Therefore, targeting Ki-67 in the indigenous black women with BC might improve the patient outcome in the black women with BC. PMID:23691362

  8. Estrogen regulation of TRPM8 expression in breast cancer cells

    International Nuclear Information System (INIS)

    Chodon, Dechen; Guilbert, Arnaud; Dhennin-Duthille, Isabelle; Gautier, Mathieu; Telliez, Marie-Sophie; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2010-01-01

    The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer. RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques. TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E 2 , 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca 2+ entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER + ) status of the tumours. Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha

  9. The choice of radiopharmaceutical to image breast cancer

    International Nuclear Information System (INIS)

    Capriotti, G.; Scopinaro, F.; Signore, A.; Wiele, C. van de

    2004-01-01

    Breast function and development are regulated by a network of local and systemic signals which can exert either stimulatory or inhibitory effects. Many of these signals are mediated by topically produced hormones and cytokines, which are both believed to be part of complex feedback loops. These local feedback loops also play an integral part in the vascularization and invasion of malignant breast tumours. More specifically, it has been demonstrated that the disruption of physiological negative feedback loops in breast tissue may result in the loss of cell cycle control and eventually leading to local breakdown of the adjacent stroma implying interactions between breast tumour cells and their stromal environment. Novel anticancer strategies selectively interacting with breast tumour vascularization and metastasis, include blocking monoclonal antibodies, peptide hormone antagonists, peptide/toxin fusion proteins and inhibitors of signal transduction. As most of these novel drugs are cytostatic, objective response as measured by morphological imaging modalities, e.g., Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) cannot be utilized as a surrogate marker for drug development, nor for clinical decision- making. Accordingly, in order to maximize the benefit from these new treatment paradigms, novel objective markers of therapeutic success are mandatory. This editorial focuses on recently developed radioligands for SPECT imaging as potential markers for the in vivo assessment of ongoing angiogenesis and metastasis in patients suffering from breast carcinoma

  10. Characterization of TRPS1 and ERAS as oncogenes implicated in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Gonzalez, L.

    2015-07-01

    New high throughput technologies have made possible to identify putative oncogenes in breast cancer. In this project we aim to relate and characterise two novel putative oncogenes, ERAS and TRPS1, in their role in human breast cancer. TRPS1, an atypical GATA factor, modulates cell proliferation and controls cell cycle progression through repression of GATA-regulated genes, therefore acting as a tumour suppressor gene. Conversely, TRPS1 expression has been shown to be significantly elevated in luminal and in a lesser extent in basal breast cancer cells, presenting roles both as an oncogene and as a tumour suppressor gene in breast cancer development. The aim of this project is therefore to determine the characteristics of TRPS1 either as a putative novel human oncogene or as a tumour suppressor gene in breast cancer cells. To this aim, we have cloned a novel isoform of TRPS1 and introduced it into several breast cancer cell lines. Our results show that overexpression of this isoform of TRPS1 results in variations in motility in non-carcinogenic cell lines, as well as in a series of EMT-like changes such as the down-regulation of the EMT marker E-cadherin, both of which can be associated to an increase in malignancy, suggesting an oncogenic behaviour for TRPS1. Furthermore, our results suggest that constitutively active members of the RAS protein family induce the expression of TRPS1, establishing a relationship between both genes. We can conclude that the effects of TRPS1 overexpression are moderate, inducing some changes but not fully transforming the cells. Therefore we cannot confirm that TRPS1 is a putative oncogene in breast cancer. (Author)

  11. Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo.

    LENUS (Irish Health Repository)

    Tan, B

    2012-02-03

    BACKGROUND: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown. METHODS: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg\\/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly. RESULTS: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016). CONCLUSION: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

  12. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    Directory of Open Access Journals (Sweden)

    de Souza Emanuel M

    2009-03-01

    Full Text Available Abstract Background ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. Methods First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP. Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. Results The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM; tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC was 76.2% compared with 25.5% in invasive ductal carcinoma

  13. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Seniski, Gerusa G; Zanata, Silvio M; Costa, Fabrício F; Klassen, Giseli; Camargo, Anamaria A; Ierardi, Daniela F; Ramos, Edneia AS; Grochoski, Mariana; Ribeiro, Enilze SF; Cavalli, Iglenir J; Pedrosa, Fabio O; Souza, Emanuel M de

    2009-01-01

    ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was

  14. MRI fused with prone FDG PET/CT improves the primary tumour staging of patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Velloso, Maria J.; Ribelles, Maria J.; Rodriguez, Macarena; Sancho, Lidia; Prieto, Elena [Clinica Universidad de Navarra, Department of Nuclear Medicine, Pamplona (Spain); Fernandez-Montero, Alejandro [Clinica Universidad de Navarra, Department of Occupational Medicine, Pamplona (Spain); Santisteban, Marta [Clinica Universidad de Navarra, Department of Oncology, Pamplona (Spain); Rodriguez-Spiteri, Natalia; Martinez-Regueira, Fernando [Clinica Universidad de Navarra, Department of Surgery, Pamplona (Spain); Idoate, Miguel A. [Clinica Universidad de Navarra, Department of Pathology, Pamplona (Spain); Elizalde, Arlette; Pina, Luis J. [Clinica Universidad de Navarra, Department of Radiology, Pamplona (Spain)

    2017-08-15

    Our aim was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in primary tumour staging of patients with breast cancer. This retrospective study evaluated 45 women with 49 pathologically proven breast carcinomas. MRI and prone PET-CT scans with time-of-flight and point-spread-function reconstruction were performed with the same dedicated breast coil. The studies were assessed by a radiologist and a nuclear medicine physician, and evaluation of fused images was made by consensus. The final diagnosis was based on pathology (90 lesions) or follow-up ≥ 24 months (17 lesions). The study assessed 72 malignant and 35 benign lesions with a median size of 1.8 cm (range 0.3-8.4 cm): 31 focal, nine multifocal and nine multicentric cases. In lesion-by-lesion analysis, sensitivity, specificity, positive and negative predictive values were 97%, 80%, 91% and 93% for MRI, 96%, 71%, 87%, and 89% for prone PET, and 97%. 94%, 97% and 94% for MRI fused with PET. Areas under the curve (AUC) were 0.953, 0.850, and 0.983, respectively (p < 0.01). MRI fused with FDG-PET is more accurate than FDG-PET in primary tumour staging of breast cancer patients and increases the specificity of MRI. (orig.)

  15. Recent advances in technologies for the detection of occult metastatic cells in bone marrow of breast cancer patients

    International Nuclear Information System (INIS)

    Braun, Stephan; Harbeck, Nadia

    2001-01-01

    Approximately half of breast cancer patients with stage I–III disease will suffer metastatic disease despite resection with tumour-free margins. In 30–40% of these patients, individual carcinoma cells can already be detected at the time of primary therapy in cytological bone marrow preparations using immunocytochemistry. Numerous prospective clinical studies have shown that the presence of occult metastatic cells in bone marrow is prognostically relevant to patient survival. Only a few studies failed to do so, thus stimulating a critical discussion on the methodology and clinical value of bone marrow analysis. The potential for obtaining improved prognostic information on patient outcome, for monitoring tumour cell eradication during adjuvant and palliative systemic therapy, and for specifically targeting tumour biological therapies are intriguing clinical opportunities that may be afforded by bone marrow analysis. Standardized and robust methodology is a prerequisite for clinical application of these techniques, however

  16. Epidermal Langerhans' cell induction of immunity against an ultraviolet-induced skin tumour

    International Nuclear Information System (INIS)

    Cavanagh, L.L.; Sluyter, R.; Henderson, K.G.; Barnetson, R.St.C.; Halliday, G.M.

    1996-01-01

    Lanerghans' cells (LC) have been shown experimentally to induce immune response against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced anti-tumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia + EC and was tumour specific. Thus Ia + epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation. (author)

  17. Neglected giant fibroadenoma of the breast presenting like a fungating breast cancer in a premenarchal Nigerian teenager.

    Science.gov (United States)

    Arowolo, O A; Akinkuolie, A A; Adisa, A O; Obonna, G C; Olasode, B J

    2012-01-01

    Giant fibroadenoma of the breast is a type of rare benign breast tumour which can grow to a giant size, It is even rarer for this benign tumour to grow rapidly, ulcerate spontaneously and present like a fungating breast tumour in a way mimicking breast cancer. Carcinoma of the breast on the other hand has been on the increase so much that it has assumed an epidemiological dimension. In developing country such as Nigeria late presentation of breast cancer has remained a rule rather than exception and it is very common for patient to present with fungating breast lesion. This is a case presentation of a 14 year old premenarchal girl presenting with a massive ulcerating and fungating left breast mass that was initially thought to be a fungating locally advanced breast carcinoma on clinical examination. Further examination of the morphology of the resected surgical specimen and histological examination confirmed it to be giant fibroadenoma of the breast. The giant fungating breast tumour successfully managed by partial mastectomy and breast reconstruction with an excellent result and a high degree of patient satisfaction was achieved. Though a rare clinical entity benign breast tumour can present like a fungating breast cancer and this must be bore in mind especially in young adolescent patients presenting with ulcerating breast tumour.

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

    Science.gov (United States)

    Borges, Ana; Sousa, Inês; Castro, Luis

    2017-06-01

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

  19. Carcinoma in situ testis, the progenitor of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Rajpert-De Meyts, E; Daugaard, G

    2005-01-01

    Testicular germ cell tumours (TGCT), including seminomas, embryonal carcinomas, teratomas and yolk sac tumours, have a common precursor, the carcinoma in situ (CIS) cell. Recent gene expression studies displaying close similarity of CIS cells to embryonic stem cells support the longstanding theory...... should be made to obtain diagnosis at the CIS stage, as intervention is possible before an invasive tumour develops, thus reducing the necessity for intensive therapy. CIS may be suspected in patients with an assumed extragonadal GCT or cryptorchidism, and in intersex patients and selected cases...

  20. Inhibition of growth of human breast cancer cells in culture by neutron capture using liposomes containing 10B.

    Science.gov (United States)

    Yanagië, H; Kobayashi, H; Takeda, Y; Yoshizaki, I; Nonaka, Y; Naka, S; Nojiri, A; Shinnkawa, H; Furuya, Y; Niwa, H; Ariki, K; Yasuhara, H; Eriguchi, M

    2002-03-01

    Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4 microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation.

  1. Analysis of the effects of exposure to acute hypoxia on oxidative lesions and tumour progression in a transgenic mouse breast cancer model

    Directory of Open Access Journals (Sweden)

    Lunt Sarah

    2008-05-01

    Full Text Available Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG lesions in the transgenic polyomavirus middle T (PyMT breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs, demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

  2. [Primary pigmented breast adenocarcinoma in a male patient].

    Science.gov (United States)

    Dauendorffer, J-N; Pages, C; Abd Alsamad, I; Bagot, M; Fraitag, S

    2013-01-01

    Pigmented mammary tumours are rare. Herein, we report the third case of primary pigmented breast adenocarcinoma in a male patient with clinical mimicking of nodular melanoma of the nipple. A male patient presented with a pigmented nodule of the right nipple. Histological examination of the lesion showed dermal and subcutaneous adenocarcinomatous proliferation. The perilesional stroma contained melanin both inside and outside macrophages, leading us to conclude on primary pigmented breast adenocarcinoma clinically mimicking nodular melanoma of the nipple. Local production of melanin by neoplastic cells in the mammary carcinoma was postulated as the cause of hyperpigmentation of the tumour. Other possible causes are transfer of melanin from overlying melanocytes of the pigmented areolar epidermis to the underlying neoplastic cells, or melanin synthesis by intratumoral melanocytes migrating from the epidermis (which strikes us as the most convincing interpretation for the reported case). Breast adenocarcinoma is a rare tumour in men and may present clinically as a pigmented lesion of the nipple, resulting in the problem of differential diagnosis with primary or metastasised nodular melanoma. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  3. 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

  4. Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT)

    NARCIS (Netherlands)

    Brouwer, O. R.; Vermeeren, L.; van der Ploeg, I. M. C.; Valdés Olmos, R. A.; Loo, C. E.; Pereira-Bouda, L. M.; Smit, F.; Neijenhuis, P.; Vrouenraets, B. C.; Sivro-Prndelj, F.; Jap-A-Joe, S. M.; Borgstein, P. J.; Rutgers, E. J. Th; Oldenburg, H. S. A.

    2012-01-01

    To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were

  5. PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours.

    Science.gov (United States)

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

    2017-11-01

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

  6. 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)

  7. Size, node status and grade of breast tumours: association with mammographic parenchymal patterns

    Energy Technology Data Exchange (ETDEWEB)

    Sala, E.; Solomon, L.; McCann, J. [Department of Community Medicine, Strangeways Research Laboratory, Worts Causeway, Cambridge (United Kingdom); Warren, R. [Cambridge and Huntingdon Breast Screening Service, Rosie Maternity Hospital, Robinson Way, Cambridge (United Kingdom); Duffy, S. [MRC-Biostatistics Unit, Institute of Public Health, Cambridge (United Kingdom); Luben, R. [Department of Clinical Gerontology, Strangeways Research Laboratory, Cambridge (United Kingdom); Day, N. [Department of Community Medicine, Institute of Public Health, Robinson Way, Cambridge, CB2 2SR (United Kingdom)

    2000-01-01

    A case-control study was designed to assess the association of mammographic parenchymal patterns with the risk of in-situ and invasive breast cancer. In addition, the relationship between tumour characteristics and mammographic patterns were also investigated. A total of 875 patients with breast cancer were selected and matched with 2601 controls. Mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification, and statistical analysis was by conditional logistic regression. Relative to the N1 pattern, the odds ratios of having an invasive breast cancer associated with the P2 and DY patterns were 1.8 and 1.4, respectively. In addition, the odd ratios of having an invasive grade 3 breast cancer associated with the P2 and DY patterns were 2.8 and 3.9, respectively. Relative to the combined N1/P1 pattern, the odd ratios of having a breast cancer smaller than 14 mm, 15-29 mm, or larger than 30 mm associated with the combined high-risk P2/DY pattern (P2 + DY) were 1.2, 1.6, and 2.0, respectively. Finally, women with the P2/DY pattern were twice as likely to have a breast cancer which had already spread to the axillary nodes, compared to women with women with the N1/P1 pattern (odds ratios of 2.1 and 1.4, respectively). Our results confirm previous findings suggesting that mammographic parenchymal patterns may serve as indicators of risk for breast cancer. Our results also suggest that mammographic parenchymal patterns are associated with the stage at which breast cancer is detected. (orig.)

  8. Size, node status and grade of breast tumours: association with mammographic parenchymal patterns

    International Nuclear Information System (INIS)

    Sala, E.; Solomon, L.; McCann, J.; Warren, R.; Duffy, S.; Luben, R.; Day, N.

    2000-01-01

    A case-control study was designed to assess the association of mammographic parenchymal patterns with the risk of in-situ and invasive breast cancer. In addition, the relationship between tumour characteristics and mammographic patterns were also investigated. A total of 875 patients with breast cancer were selected and matched with 2601 controls. Mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification, and statistical analysis was by conditional logistic regression. Relative to the N1 pattern, the odds ratios of having an invasive breast cancer associated with the P2 and DY patterns were 1.8 and 1.4, respectively. In addition, the odd ratios of having an invasive grade 3 breast cancer associated with the P2 and DY patterns were 2.8 and 3.9, respectively. Relative to the combined N1/P1 pattern, the odd ratios of having a breast cancer smaller than 14 mm, 15-29 mm, or larger than 30 mm associated with the combined high-risk P2/DY pattern (P2 + DY) were 1.2, 1.6, and 2.0, respectively. Finally, women with the P2/DY pattern were twice as likely to have a breast cancer which had already spread to the axillary nodes, compared to women with women with the N1/P1 pattern (odds ratios of 2.1 and 1.4, respectively). Our results confirm previous findings suggesting that mammographic parenchymal patterns may serve as indicators of risk for breast cancer. Our results also suggest that mammographic parenchymal patterns are associated with the stage at which breast cancer is detected. (orig.)

  9. Rapid and non-enzymatic in vitro retrieval of tumour cells from surgical specimens.

    Directory of Open Access Journals (Sweden)

    Brigitte Mack

    Full Text Available The study of tumourigenesis commonly involves the use of established cell lines or single cell suspensions of primary tumours. Standard methods for the generation of short-term tumour cell cultures include the disintegration of tissue based on enzymatic and mechanical stress. Here, we describe a simple and rapid method for the preparation of single cells from primary carcinomas, which is independent of enzymatic treatment and feeder cells. Tumour biopsies are processed to 1 mm(3 cubes termed explants, which are cultured 1-3 days on agarose-coated well plates in specified medium. Through incisions generated in the explants, single cells are retrieved and collected from the culture supernatant and can be used for further analysis including in vitro and in vivo studies. Collected cells retain tumour-forming capacity in xenotransplantation assays, mimic the phenotype of the primary tumour, and facilitate the generation of cell lines.

  10. Is cell survival a determinant of the in situ response of 9L tumours

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Wallen, C.A.

    1980-01-01

    The influence of growth rate, location, size and potential lethal damage (PLD) recovery on the cellular radiosensitivity and the tumour response was studied in 9L/Ro and 9L/SF rat tumours. The median day of death of rats bearing the intracerebral (i.c.) 9L/Ro tumours was 16-18 days; for i.c. 9L/SF tumours it was 23-25 days. The doubling time of 9L/Ro cells was slightly faster than for 9L/SF cells both in culture and in the brain. The cellular radiosensitivity of both i.c. tumour cell sublines was identical. However, subcutaneous (s.c.) 9L/Ro tumour cells were more resistant. There was no evidence of a substantial hypoxic fraction in either site. When i.c. 9L/Ro and 9L/SF tumours of similar size were treated with fractionated doses of BCNU, X-rays or combinations of the two, the responses of the two tumours were essentially identical. The rate of recovery from radiation-induced PLD was identical in the two sublines and the two sites. Increase in life-span of rats bearing i.c. 9L/Ro tumours appeared to be correlated with the tumour cell kill measured after completion of PLD recovery rather than with the tumour cell kill determined immediately after irradiation. (author)

  11. Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency

    International Nuclear Information System (INIS)

    Gervais, Alban; Levêque, Jean; Bouet-Toussaint, Françoise; Burtin, Florence; Lesimple, Thierry; Sulpice, Laurent; Patard, Jean-Jacques; Genetet, Noelle; Catros-Quemener, Véronique

    2005-01-01

    Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs. The IL-4/GM-CSF (granulocyte–macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells. Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR - Lin - cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-γ production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR - Lin - cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed

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

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015) ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.265, year: 2015

  13. Simultaneous CXCL12 and ESR1 CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer

    International Nuclear Information System (INIS)

    Ramos, Edneia AS; Klassen, Giseli; Camargo, Anamaria A; Braun, Karin; Slowik, Renata; Cavalli, Iglenir J; Ribeiro, Enilze MSF; Pedrosa, Fábio de O; Souza, Emanuel M de; Costa, Fabrício F

    2010-01-01

    CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. CXCL12 promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (ESR1) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the CXCL12 promoter and ESR1 in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data. First, we analysed CXCL12 expression in breast tumour cell lines by RT-PCR. We also used 5-aza-2'-deoxycytidine (5-aza-CdR) treatment and DNA bisulphite sequencing to study the promoter methylation for a specific region of CXCL12 in breast tumour cell lines. We evaluated CXCL12 and ESR1 methylation in primary tumour samples by methylation-specific PCR (MSP). Finally, promoter hypermethylation of these genes was analysed using Fisher's exact test and correlated with clinicopathological data using the Chi square test, Kaplan-Meier survival analysis and Cox regression analysis. CXCL12 promoter hypermethylation in the first region (island 2) and second region (island 4) was correlated with lack of expression of the gene in tumour cell lines. In the primary tumours, island 2 was hypermethylated in 14.5% of the samples and island 4 was hypermethylated in 54% of the samples. The ESR1 promoter was hypermethylated in 41% of breast tumour samples. In addition, the levels of ERα protein expression diminished with increased frequency of ESR1 methylation (p < 0.0001). This study also demonstrated that CXCL12 island 4 and ESR1 methylation occur simultaneously at a high frequency (p = 0.0220). This is the first study showing a simultaneous involvement of epigenetic regulation for both CXCL12 and ESR1 genes in Brazilian women. The methylation status of both genes was significantly correlated with histologically advanced

  14. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade.

    Science.gov (United States)

    Ouzounova, Maria; Lee, Eunmi; Piranlioglu, Raziye; El Andaloussi, Abdeljabar; Kolhe, Ravindra; Demirci, Mehmet F; Marasco, Daniela; Asm, Iskander; Chadli, Ahmed; Hassan, Khaled A; Thangaraju, Muthusamy; Zhou, Gang; Arbab, Ali S; Cowell, John K; Korkaya, Hasan

    2017-04-06

    It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and promoting tumour cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumour-bearing animals enhance metastatic growth of already disseminated tumour cells. MDSC-induced 'metastatic gene signature' derived from murine syngeneic model predicts poor patient survival in the majority of human solid tumours. Thus spatiotemporal MDSC infiltration may have clinical implications in tumour progression.

  15. Prospective MRI assessment for invasive lobular breast cancer. Correlation with tumour size at histopathology and influence on surgical management

    International Nuclear Information System (INIS)

    Muttalib, M.; Ibrahem, R.; Khashan, A.S.; Hajaj, M.

    2014-01-01

    Aim: To evaluate the performance of breast magnetic resonance imaging (MRI) in determining the size of invasive lobular carcinoma (ILC) compared to histopathology, and its influence on breast surgical management. Materials and methods: Prospective evaluation was undertaken of standardized contrast-enhanced MRI images of 51 consecutive women over an 18 month period with pure ILC or with lobular features as the dominant subtype on breast core biopsy. Image interpretation was performed by one consultant radiologist (M.H.). The lesion size at MRI was compared with the size at final histopathology after surgical excision using a Bland–Altman agreement plot. Results: Of the 51 prospectively imaged consecutive women, seven were excluded as they had diffuse ILC. The remaining 44 patients had a mean histological tumour size of 34.9 mm (range 4–77 mm). MRI underestimated tumour size in 26 (59.1%) cases. In 21 (47.7%) patients, this discrepancy was small, ranging up to 16 mm. The largest underestimation occurred in five (11.4%) cases with a difference ranging between 31 and 48 mm. Fifteen (34.1%) tumours were overestimated by MRI where the discrepancy ranged up to 22 mm. In three (6.8%) patients MRI and histological size matched. The Bland–Altman agreement plot demonstrated that in 95% of cases the size at histopathology will be between 0.36 and 2.31 times the MRI size at extremes. MRI correlated better with histopathology in tumours up to T2 (<5 cm) size leading to a change in surgical management for nine of the 44 (20.5%) patients. Conclusion: MRI enables surgical management decisions to be made with increased confidence in patients with ILC up to T2 size

  16. Multi-modality treatment in males with advanced malignant germ cell tumours

    International Nuclear Information System (INIS)

    Fossaa, S.D.; Klepp, O.; Ous, S.; Lien, H.; Stenwig, J.T.; Abeler, V.; Eliasson, G.; Hoest, H.

    1984-01-01

    After chemotherapy with cis-platinum, vinblastine and bleomycin, 33 surgical prosedures were performed in 29 patients with advanced malignant germ-cell tumours. The tumour masses could be completely resected macroscopially in 26 patients. Patients with fibros/necrosis or completely resected mature teratoma had an excellent prognosis, whereas only 5 of the 11 patients with vital malignant tumour survived in spite of second-line treatment with chemotherapy/radiotherapy. Preoperatively elevated serum levels of AFP, β-HCG and/or LDH indicated the presence of residual germ cell tumour. Eight of 14 patients were rendered tumour-free by radiotherapy given as second- or third-line treatment. In general, tumour masses, remaining after cis-platinum-based induction chemotherapy should be resected as completely as possible even in the case of mature teratoma or fibrosis/necrosis. Radiotherapy should be considered as second -and thirdline treatment

  17. A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44.

    Science.gov (United States)

    Babina, Irina S; McSherry, Elaine A; Donatello, Simona; Hill, Arnold D K; Hopkins, Ann M

    2014-02-10

    Most breast cancer-related deaths result from metastasis, a process involving dynamic regulation of tumour cell adhesion and migration. The adhesion protein CD44, a key regulator of cell migration, is enriched in cholesterol-enriched membrane microdomains termed lipid rafts. We recently reported that raft affiliation of CD44 negatively regulates interactions with its migratory binding partner ezrin. Since raft affiliation is regulated by post-translational modifications including palmitoylation, we sought to establish the contribution of CD44 palmitoylation and lipid raft affiliation to cell migration. Recovery of CD44 and its binding partners from raft versus non-raft membrane microdomains was profiled in non-migrating and migrating breast cancer cell lines. Site-directed mutagenesis was used to introduce single or double point mutations into both CD44 palmitoylation sites (Cys286 and Cys295), whereupon the implications for lipid raft recovery, phenotype, ezrin co-precipitation and migratory behaviour was assessed. Finally CD44 palmitoylation status and lipid raft affiliation was assessed in primary cultures from a small panel of breast cancer patients. CD44 raft affiliation was increased during migration of non-invasive breast cell lines, but decreased during migration of highly-invasive breast cells. The latter was paralleled by increased CD44 recovery in non-raft fractions, and exclusive non-raft recovery of its binding partners. Point mutation of CD44 palmitoylation sites reduced CD44 raft affiliation in invasive MDA-MB-231 cells, increased CD44-ezrin co-precipitation and accordingly enhanced cell migration. Expression of palmitoylation-impaired (raft-excluded) CD44 mutants in non-invasive MCF-10a cells was sufficient to reversibly induce the phenotypic appearance of epithelial-to-mesenchymal transition and to increase cell motility. Interestingly, cell migration was associated with temporal reductions in CD44 palmitoylation in wild-type breast cells. Finally

  18. Brain tumour stem cells: implications for cancer therapy and regenerative medicine.

    Science.gov (United States)

    Sanchez-Martin, Manuel

    2008-09-01

    The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.

  19. Radiation-induced apoptosis and cell cycle checkpoints in human colorectal tumour cell lines

    International Nuclear Information System (INIS)

    Playle, L.C.

    2001-03-01

    The p53 tumour suppressor gene is mutated in 75% of colorectal carcinomas and is critical for DNA damage-induced G1 cell cycle arrest. Data presented in this thesis demonstrate that after treatment with Ionizing Radiation (IR), colorectal tumour cell lines with mutant p53 are unable to arrest at G1 and undergo cell cycle arrest at G2. The staurosporine derivative, UCN-01, was shown to abrogate the IR-induced G2 checkpoint in colorectal tumour cell lines. Furthermore, in some cell lines, abrogation of the G2 checkpoint was associated with radiosensitisation. Data presented in this study demonstrate that 2 out of 5 cell lines with mutant p53 were sensitised to IR by UCN-01. In order to determine whether radiosensitisation correlated with lack of functional p53, transfected derivatives of an adenoma-derived cell line were studied, in which endogenous wild type p53 was disrupted by expression of a dominant negative p53 mutant protein (and with a vector control). In both these cell lines UCN-01 abrogated the G2 arrest however this was not associated with radiosensitisation, indicating that radiosensitisation is a cell type-specific phenomenon. Although 2 colorectal carcinoma cell lines, with mutant p53, were sensitised to IR by UCN-01, the mechanisms of p53-independent IR-induced apoptosis in the colon are essentially unknown. The mitogen-activated protein kinase (MAPK) pathways (that is the JNK, p38 and ERK pathways) have been implicated in apoptosis in a range of cell systems and in IR-induced apoptosis in some cell types. Data presented in this study show that, although the MAPKs can be activated by the known activator anisomycin, there is no evidence of a role for MAPKs in IR-induced apoptosis in colorectal tumour cell lines, regardless of p53 status. In summary, some colorectal tumour cell lines with mutant p53 can be sensitised to IR-induced cell death by G2 checkpoint abrogation and this may be an important treatment strategy, however mechanisms of IR-induced p53

  20. Dermatofibroma-like granular cell tumour: a potential diagnostic pitfall

    Directory of Open Access Journals (Sweden)

    Jiri Soukup

    2016-11-01

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

  1. Phyto-oestrogens and breast cancer chemoprevention

    International Nuclear Information System (INIS)

    Limer, Jane L; Speirs, Valerie

    2004-01-01

    Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

  2. 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.)

  3. Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism.

    Science.gov (United States)

    Fais, S

    2010-05-01

    This review presents a possible new approach against cancer, as represented by inhibition of proton pumps, a mechanism used by tumour cells to avoid intracellular accumulation of toxic substances. Proton pump inhibitors (PPIs) belong to a family of pro-drugs that are currently used in the treatment of peptic diseases needing acidity to be activated. PPIs target the acidic tumour mass, where they are metabolized, thus blocking proton traffic. Proton pump inhibition triggers a rapid cell death as a result of intracellular acidification, caspase activation and early accumulation of reactive oxygen species into tumour cells. As a whole, the devastating effect of PPIs on tumour cells suggest the triggering of a fatal cell toxification. Many human tumours, including melanoma, osteosarcoma, lymphomas and various adenocarcinomas are responsive to PPIs. This appears highly conceivable, in as much as almost all human tumours are acidic and express high levels of proton pumps. Paradoxically, metastatic tumours appear to be more responsive to PPIs being more acidic than the majority of primary tumours. However, two clinical trials test the effectiveness of PPIs in chemosensitizing melanoma and osteosarcoma patients. Indeed, tumour acidity represents a very potent mechanism of chemoresistance. A majority of cytotoxic agents, being weak bases, are quickly protonated outside and do not enter the cells, thus preventing drugs to reach specific cellular targets. Clinical data will provide the proof of concept on the use of PPIs as a new class of antitumour agent with a very low level of systemic toxicity as compared with standard chemotherapeutic agents.

  4. Modelling radiation-induced cell death and tumour re-oxygenation: local versus global and instant versus delayed cell death

    International Nuclear Information System (INIS)

    Gago-Arias, Araceli; Espinoza, Ignacio; Sánchez-Nieto, Beatriz; Aguiar, Pablo; Pardo-Montero, Juan

    2016-01-01

    The resistance of hypoxic cells to radiation, due to the oxygen dependence of radiosensitivity, is well known and must be taken into account to accurately calculate the radiation induced cell death. A proper modelling of the response of tumours to radiation requires deriving the distribution of oxygen at a microscopic scale. This usually involves solving the reaction-diffusion equation in tumour voxels using a vascularization distribution model. Moreover, re-oxygenation arises during the course of radiotherapy, one reason being the increase of available oxygen caused by cell killing, which can turn hypoxic tumours into oxic. In this work we study the effect of cell death kinetics in tumour oxygenation modelling, analysing how it affects the timing of re-oxygenation, surviving fraction and tumour control. Two models of cell death are compared, an instantaneous cell killing, mimicking early apoptosis, and a delayed cell death scenario in which cells can die shortly after being damaged, as well as long after irradiation. For each of these scenarios, the decrease in oxygen consumption due to cell death can be computed globally (macroscopic voxel average) or locally (microscopic). A re-oxygenation model already used in the literature, the so called full re-oxygenation, is also considered. The impact of cell death kinetics and re-oxygenation on tumour responses is illustrated for two radiotherapy fractionation schemes: a conventional schedule, and a hypofractionated treatment. The results show large differences in the doses needed to achieve 50% tumour control for the investigated cell death models. Moreover, the models affect the tumour responses differently depending on the treatment schedule. This corroborates the complex nature of re-oxygenation, showing the need to take into account the kinetics of cell death in radiation response models. (paper)

  5. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina

    2016-01-01

    Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40...... oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell......-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were...

  6. Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

    Science.gov (United States)

    Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

    Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

  7. Ribosomal protein S6 phosphorylation and morphological changes in response to the tumour promoter 12-O-tetradecanoylphorbol 13-acetate in primary human tumour cells, established and transformed cell lines

    DEFF Research Database (Denmark)

    Rance, A J; Thönnes, M; Issinger, O G

    1985-01-01

    lifespan (fibroblasts, primary human tumour cells) can be mimicked by unknown steps also associated with immortalization (establishment function) and the transformed state of the tumour cells. Another interesting observation were morphological changes of the established and SV40-transformed cells which...

  8. Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts

    International Nuclear Information System (INIS)

    Olsen, Charlotta J; Moreira, José; Lukanidin, Eugene M; Ambartsumian, Noona S

    2010-01-01

    Tumour phenotype is regulated in a complex fashion as a result of interactions between malignant cells and the tumour stroma. Fibroblasts are the most abundant and perhaps most active part of the tumour stroma. A better understanding of the changes that occur in fibroblasts in response to the presence of malignant cells may lead to the development of new strategies for cancer treatment. We explored the effects of fibroblasts on the growth and invasion of mammary carcinoma tumour cells in vitro and in vivo. In order to analyse secreted factors that affect invasive abilities of breast cancer cells we co-cultured human mammary fibroblasts (HMF3s) and cancer cells (MCF7S1) in three-dimensional (3D) growth conditions devoid of heterogeneous cell-cell contact. To study the possible influence of fibroblasts on MCF7S1 cancer cell growth in vivo we co-injected HMF3s and MCF7S1 cells in Balb/c nu/nu mice. In 3D co-culture both HMF3s and MCF7S1 cells demonstrated enhanced invasion into a Matrigel matrix. This was correlated with enhanced expression of the metastasis promoting S100A4 protein in fibroblasts, stimulation of the matrix metalloproteinase (MMP)-2 activity, and enhanced secretion of a range of different cytokines. Orthotopic injection of oestrogen-dependent MCF7S1 cancer cells together with fibroblasts showed stimulation of tumour growth in mice without an external oestrogen supply. The resulting tumours were characterized by increased development of extracellular matrix, as well as an increase of murine S100A4 concentration and activity of MMP-2 in the tumour interstitial fluid. Stimulation of the invasive phenotype of tumour cells in 3D co-cultures with fibroblasts could be correlated with increased production of S100A4 and MMP-2. We propose that enhanced development of mouse host-derived tumour stroma in a MCF7S1 co-injection xenograft model leads to oestrogen independency and is triggered by the initial presence of human fibroblasts

  9. Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer.

    Science.gov (United States)

    Yu, Huixin; Hendrikx, Jeroen J M A; Rottenberg, Sven; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R

    2016-03-01

    In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir.

  10. Risk and prognostic significance of metachronous contralateral testicular germ cell tumours

    NARCIS (Netherlands)

    Schaapveld, M.; van den Belt-Dusebout, A. W.; Gietema, J. A.; de Wit, R.; Horenblas, S.; Witjes, J. A.; Hoekstra, H. J.; Kiemeney, L. A. L. M.; Louwman, W. J.; Ouwens, G. M.; Aleman, B. M. P.; van Leeuwen, F. E.

    2012-01-01

    BACKGROUND: Testicular germ cell tumour (TGCT) patients are at increased risk of developing a contralateral testicular germ cell tumour (CTGCT). It is unclear whether TGCT treatment affects CTGCT risk. METHODS: The risk of developing a metachronous CTGCT (a CTGCT diagnosed >= 6 months after a

  11. Giant Cell Tumour of the Distal Ulna: A Rare Presentation

    Directory of Open Access Journals (Sweden)

    Ruben Jaya Kumar

    2011-07-01

    Full Text Available Giant-cell tumour (GCT of bone, a primary yet locally aggressive benign tumour, commonly affects patients between the ages of 20 and 40 years, with the peak incidence occurring in the third decade. Women are affected slightly more than men. The distal end of the ulna is an extremely uncommon site for primary bone tumours in general and giant cell tumours in particular. Wide resection of the distal ulna is the recommended treatment for GCT in such locations. Radio-ulna convergence and dorsal displacement of the ulna stump are known complications following ulna resection proximal to the insertion of the pronator quadratus. This leads to reduction in grip power and forearm rotatory motion. Stabilization of the ulna stump with extensor carpi ulnaris (ECU tendon after wide resection of the tumour has been described in the literature. We report a case of GCT of distal end of ulna treated with wide resection and stabilization with ECU tendon.

  12. Tumour-cell killing by X-rays and immunity quantitated in a mouse model system

    International Nuclear Information System (INIS)

    Porteous, D.D.; Porteous, K.M.; Hughes, M.J.

    1979-01-01

    As part of an investigation of the interaction of X-rays and immune cytotoxicity in tumour control, an experimental mouse model system has been used in which quantitative anti-tumour immunity was raised in prospective recipients of tumour-cell suspensions exposed to varying doses of X-rays in vitro before injection. Findings reported here indicate that, whilst X-rays kill a proportion of cells, induced immunity deals with a fixed number dependent upon the immune status of the host, and that X-rays and anti-tumour immunity do not act synergistically in tumour-cell killing. The tumour used was the ascites sarcoma BP8. (author)

  13. A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.

    Science.gov (United States)

    Frascoli, Federico; Flood, Emelie; Kim, Peter S

    2017-06-01

    We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  14. Protective immunity to UV radiation-induced skin tumours induced by skin grafts and epidermal cells

    International Nuclear Information System (INIS)

    Ronald Sluyter; Kylie S Yuen; Gary M Halliday

    2001-01-01

    There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naive recipients could induce protective antitumour immunity, probably because the grafting stimulated the tumour Ag-loaded DC to migrate to local lymph nodes. This suggests that cutaneous APC can present tumour Ag to induce protective antitumour immunity. Previously, it has been shown that immunization of mice with MHC class II+ epidermal cells (EC) pulsed with tumour extracts could induce delayed-type hypersensitivity against tumour cells. Here, this same immunization protocol could induce protective immunity against a minimum tumorigenic dose of UVR-induced fibrosarcoma cells, but not higher doses. Epidermal cells obtained from semiallogeneic donors and pulsed with tumour extract could also induce protective immunity. However, presentation of BSA Ag from the culture medium was found to contribute to this result using semiallogeneic EC. The results suggest that LC overlying skin tumours may be able to induce protective immunity to UVR-induced tumours if stimulated to migrate from the skin. Copyright (2001) Australasian Society of Immunology Inc

  15. Assessment of the proliferation status of glioblastoma cell and tumour tissue after nanoplatinum treatment

    DEFF Research Database (Denmark)

    Kutwin, Marta; Sawosz, Ewa; Jaworski, Slawomir

    2017-01-01

    nanoparticles (NP-Pt). The aim of the study was to evaluate and compare the antiproliferative properties of NP-Pt and cisplatin against U87 and U118 glioma cell lines and U87 tumour tissue. NP-Pt and cisplatin were incubated with U87 and U118 glioma cells or administered directly into glioma tumour tissue. Cell...... and the migration of cancer cells but also downregulated the level of PCNA protein expression in tumour tissue. Furthermore, NP-Pt caused oxidative DNA damage in tumour tissue to a higher degree than cisplatin. Consequently, NP-Pt can be considered as an effective inhibitor of glioblastoma tumour cell proliferation....... However, the mechanism of action and potential side effects need to be elucidated further...

  16. Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kolberg, Hans-Christian; Akpolat-Basci, Leyla; Stephanou, Miltiades [Marienhospital Bottrop gGmbH, Department of Gynecology and Obstetrics, Bottrop (Germany); Loevey, Gyoergy [BORAD, Bottrop (Germany); Fasching, Peter A. [University of Erlangen, Erlangen (Germany); Untch, Michael [Helios Klinikum Berlin-Buch, Berlin (Germany); Liedtke, Cornelia [University Hospital Schleswig-Holstein/Campus Luebeck, Luebeck (Germany); Bulsara, Max [University of Notre Dame, Fremantle (Australia); University College, London (United Kingdom); Vaidya, Jayant S. [University College, London (United Kingdom)

    2017-01-15

    The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT). In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared. Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5-year Kaplan-Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5-99.2), EBRT 9 events (81.7%, 95%CI 67.6-90.1), hazard ratio (HR) 0.19 (0.04-0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3-95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5-98.4), EBRT 12 events (69.0%, 49.1-82.4), HR 0.23 (0.06-0.80), log rank p = 0.012. IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost. (orig.) [German] Die intraoperative Radiotherapie (TARGIT-IORT) als vorgezogener Boost im Rahmen der brusterhaltenden Therapie (BET) ist seit 1998 Gegenstand der wissenschaftlichen Diskussion. Wir praesentieren Daten zum Einsatz der IORT bei der BET nach neoadjuvanter Therapie (NACT). In diese retrospektive Analyse

  17. Endogenous myoglobin in human breast cancer is a hallmark of luminal cancer phenotype.

    Science.gov (United States)

    Kristiansen, G; Rose, M; Geisler, C; Fritzsche, F R; Gerhardt, J; Lüke, C; Ladhoff, A-M; Knüchel, R; Dietel, M; Moch, H; Varga, Z; Theurillat, J-P; Gorr, T A; Dahl, E

    2010-06-08

    We aimed to clarify the incidence and the clinicopathological value of non-muscle myoglobin (Mb) in a large cohort of non-invasive and invasive breast cancer cases. Matched pairs of breast tissues from 10 patients plus 17 breast cell lines were screened by quantitative PCR for Mb mRNA. In addition, 917 invasive and 155 non-invasive breast cancer cases were analysed by immunohistochemistry for Mb expression and correlated to clinicopathological parameters and basal molecular characteristics including oestrogen receptor-alpha (ERalpha)/progesteron receptor (PR)/HER2, fatty acid synthase (FASN), hypoxia-inducible factor-1alpha (HIF-1alpha), HIF-2alpha, glucose transporter 1 (GLUT1) and carbonic anhydrase IX (CAIX). The spatial relationship of Mb and ERalpha or FASN was followed up by double immunofluorescence. Finally, the effects of estradiol treatment and FASN inhibition on Mb expression in breast cancer cells were analysed. Myoglobin mRNA was found in a subset of breast cancer cell lines; in microdissected tumours Mb transcript was markedly upregulated. In all, 71% of tumours displayed Mb protein expression in significant correlation with a positive hormone receptor status and better prognosis. In silico data mining confirmed higher Mb levels in luminal-type breast cancer. Myoglobin was also correlated to FASN, HIF-2alpha and CAIX, but not to HIF-1alpha or GLUT1, suggesting hypoxia to participate in its regulation. Double immunofluorescence showed a cellular co-expression of ERalpha or FASN and Mb. In addition, Mb levels were modulated on estradiol treatment and FASN inhibition in a cell model. We conclude that in breast cancer, Mb is co-expressed with ERalpha and co-regulated by oestrogen signalling and can be considered a hallmark of luminal breast cancer phenotype. This and its possible new role in fatty acid metabolism may have fundamental implications for our understanding of Mb in solid tumours.

  18. A diagnostic dilemma in breast pathology – benign fibroadenoma with multinucleated stromal giant cells

    Directory of Open Access Journals (Sweden)

    Tobbia Igdam

    2008-08-01

    Full Text Available Abstract Fibroadenomas are common benign breast tumours that display a characteristic pathological morphology, although several epithelial and stromal variations exist. A very rare histological finding is the presence of multinucleated giant cells throughout the stroma of a benign fibroadenoma. Cells of this type, which are more commonly found incidentally within the interlobular stroma of breast tissue, are benign and should not be mistaken for malignant cells on microscopic examination. Unfortunately a lack of awareness of this pathological entity can lead to diagnostic confusion amongst pathologists resulting in the multinucleate giant cells being mistaken for highly mitotic cells and consequently the fibroadenoma being mistaken for a malignant lesion. This may have serious implications for the subsequent management of the patient. The presence of this unusual cell type in the stroma does not alter the prognosis of otherwise benign lesion. We encountered two such cases at our institution in a six month period recently. We present their histories along with relevant radiological, microscopic and immunohistochemical features, followed by a discussion of this unusual pathological entity.

  19. A biophysical approach to the optimisation of dendritic-tumour cell electrofusion

    International Nuclear Information System (INIS)

    Sukhorukov, Vladimir L.; Reuss, Randolph; Endter, Joerg M.; Fehrmann, Steffen; Katsen-Globa, Alisa; Gessner, Petra; Steinbach, Andrea; Mueller, Kilian J.; Karpas, Abraham; Zimmermann, Ulrich; Zimmermann, Heiko

    2006-01-01

    Electrofusion of tumour and dendritic cells (DCs) is a promising approach for production of DC-based anti-tumour vaccines. Although human DCs are well characterised immunologically, little is known about their biophysical properties, including dielectric and osmotic parameters, both of which are essential for the development of efficient electrofusion protocols. In the present study, human DCs from the peripheral blood along with a tumour cell line used as a model fusion partner were examined by means of time-resolved cell volumetry and electrorotation. Based on the biophysical cell data, the electrofusion protocol could be rapidly optimised with respect to the sugar composition of the fusion medium, duration of hypotonic treatment, frequency range for stable cell alignment, and field strengths of breakdown pulses triggering membrane fusion. The hypotonic electrofusion consistently gave a tumour-DC hybrid rate of up to 19%, as determined by counting dually labelled fluorescent hybrids in a microscope. This fusion rate is nearly twice as high as that usually reported in the literature for isotonic media. The experimental findings and biophysical approach presented here are generally useful for the development of efficient electrofusion protocols, especially for rare and valuable human cells

  20. Menopausal status dependence of the timing of breast cancer recurrence after surgical removal of the primary tumour

    International Nuclear Information System (INIS)

    Demicheli, Romano; Bonadonna, Gianni; Hrushesky, William JM; Retsky, Michael W; Valagussa, Pinuccia

    2004-01-01

    Information on the metastasis process in breast cancer patients undergoing primary tumour removal may be extracted from an analysis of the timing of clinical recurrence. The hazard rate for local-regional and/or distant recurrence as the first event during the first 4 years after surgery was studied in 1173 patients undergoing mastectomy alone as primary treatment for operable breast cancer. Subset analyses were performed according to tumour size, axillary nodal status and menopausal status. A sharp two-peaked hazard function was observed for node-positive pre-menopausal patients, whereas results from node-positive post-menopausal women always displayed a single broad peak. The first narrow peak among pre-menopausal women showed a very steep rise to a maximum about 8–10 months after mastectomy. The second peak was considerably broader, reaching its maximum at 28–30 months. Post-menopausal patients displayed a wide, nearly symmetrical peak with maximum risk at about 18–20 months. Peaks displayed increasing height with increasing axillary lymph node involvement. No multi-peaked pattern was evident for either pre-menopausal or post-menopausal node-negative patients; however, this finding should be considered cautiously because of the limited number of events. Tumour size influenced recurrence risk but not its timing. Findings resulting from the different subsets of patients were remarkably coherent and each observed peak maintained the same position on the time axis in all analysed subsets. The risk of early recurrence for node positive patients is dependent on menopausal status. The amount of axillary nodal involvement and the tumour size modulate the risk value at any given time. For pre-menopausal node-positive patients, the abrupt increase of the first narrow peak of the recurrence risk suggests a triggering event that synchronises early risk. We suggest that this event is the surgical removal of the primary tumour. The later, broader, more symmetrical risk

  1. MRI of intracranial germ cell tumours

    International Nuclear Information System (INIS)

    Sumida, M.; Uozumi, T.; Kiya, K.; Mukada, K.; Arita, K.; Kurisu, K.; Sugiyama, K.; Onda, J.; Satoh, H.; Ikawa, F.; Migita, K.

    1995-01-01

    We reviewed MRI findings in proven intracranial germ cell tumours in 22 cases, 12 of whom received Gd-DTPA. On T1-weighted images, the signal intensity of the tumour parenchyma was moderately low in 19 cases and isointense in 3; on T2-weighted images, it was high in all cases. Regions of different intensity thought to be cysts were found in 17 (77 %): 7 of 12 patients with germinoma (58 %) and in all other cases. Of the 13 patients with pineal lesions T1-weighted sagittal images showed the aqueduct to be obstructed in 5, stenotic in 7 and normal in 1. Strong contrast enhancement was observed in all 12 cases. Of the 14 patients with suprasellar lesions, 5 were found to have an intrasellar extension, and in 3 of these, the normal pituitary gland, which could be distinguished from the tumour, was displaced anteriorly. Ten patients (45 %) had multiple lesions. (orig.)

  2. Development of pyridine-containing macrocyclic copper(II) complexes: potential role in the redox modulation of oxaliplatin toxicity in human breast cells.

    Science.gov (United States)

    Fernandes, Ana S; Costa, Judite; Gaspar, Jorge; Rueff, José; Cabral, M Fátima; Cipriano, Madalena; Castro, Matilde; Oliveira, Nuno G

    2012-09-01

    The unique redox and catalytic chemistry of Cu has justified the development of novel Cu complexes for different therapeutic uses including cancer therapy. In this work, four pyridine-containing aza-macrocyclic copper(II) complexes were prepared (CuL1-CuL4) varying in ring size and/or substituents and their superoxide scavenging activity evaluated. CuL3, the most active superoxide scavenger, was further studied as a modulator of the cytotoxicity of oxaliplatin in epithelial breast MCF10A cells and in MCF7 breast cancer cells. Our results show that CuL3 enhances the therapeutic window of oxaliplatin, by both protecting non-tumour cells and increasing its cytotoxic effect in breast carcinoma cells. CuL3 is thus a promising complex to be further studied and to be used as a lead compound for the optimization of novel chemotherapy sensitizers.

  3. In silico design and performance of peptide microarrays for breast cancer tumour-auto-antibody testing

    Directory of Open Access Journals (Sweden)

    Andreas Weinhäusel

    2012-06-01

    Full Text Available The simplicity and potential of minimally invasive testing using sera from patients makes auto-antibody based biomarkers a very promising tool for use in cancer diagnostics. Protein microarrays have been used for the identification of such auto-antibody signatures. Because high throughput protein expression and purification is laborious, synthetic peptides might be a good alternative for microarray generation and multiplexed analyses. In this study, we designed 1185 antigenic peptides, deduced from proteins expressed by 642 cDNA expression clones found to be sero-reactive in both breast tumour patients and controls. The sero-reactive proteins and the corresponding peptides were used for the production of protein and peptide microarrays. Serum samples from females with benign and malignant breast tumours and healthy control sera (n=16 per group were then analysed. Correct classification of the serum samples on peptide microarrays were 78% for discrimination of ‘malignant versus healthy controls’, 72% for ‘benign versus malignant’ and 94% for ‘benign versus controls’. On protein arrays, correct classification for these contrasts was 69%, 59% and 59%, respectively. The over-representation analysis of the classifiers derived from class prediction showed enrichment of genes associated with ribosomes, spliceosomes, endocytosis and the pentose phosphate pathway. Sequence analyses of the peptides with the highest sero-reactivity demonstrated enrichment of the zinc-finger domain. Peptides’ sero-reactivities were found negatively correlated with hydrophobicity and positively correlated with positive charge, high inter-residue protein contact energies and a secondary structure propensity bias. This study hints at the possibility of using in silico designed antigenic peptide microarrays as an alternative to protein microarrays for the improvement of tumour auto-antibody based diagnostics.

  4. Generation of IgE-based immunotherapies against HER-2 overexpressing tumours

    International Nuclear Information System (INIS)

    Knittelfelder, R.

    2010-01-01

    In combination with chemotherapy or radiation, passive immunotherapy with monoclonal antibodies is state of the art in cancer therapy. For this purpose, two properties of antibodies are harnessed: i) via the Fab fragment they bind a specific tumour antigen and ii) via the Fc portion they recruit effector cells and activate the complement system. One of these antibodies is trastuzumab (Herceptin), a growth-inhibitory humanized monoclonal IgG1 antibody recognizing the tumour antigen HER-2, which is overexpressed in 30% of human breast cancers. Interestingly, all antibodies applied for passive immunotherapy are so far exclusively of the IgG subclass. In contrast, antibodies of the IgE subclass are best-known for their detrimental function in type I hypersensitivity. It is little-known that IgE has anti-tumour capacity which could be exploited for immunotherapy of cancer. Thus, the aim of this doctoral thesis was to examine alternative strategies for cancer treatment based on IgE antibodies, and to compare their efficacy with that of IgG. The oral immunization route is well suited for the induction of a Th2 immunity including high affine IgE responses to administered antigens. Therefore, the establishment of an IgE dependent food allergy model in mice is described, which we applied also for our cancer studies. When mice were fed with different concentrations of ovalbumin under concomitant anti-acid medication, an antigen-specific IgE induction in a Th2 environment could be achieved. This oral vaccination regimen was also used for feeding HER-2 mimotopes, i.e. epitope-mimics of the anti-HER-2 IgG antibody trastuzumab. Indeed, these mimotopes induced IgE antibodies recognizing the tumour antigen which were able to bind HER-2 overexpressing breast cancer cells and led to tumour cell lysis. Complementary to this active immunotherapeutic approach a trastuzumab-like IgE antibody for passive immunotherapy was constructed. We could show that this trastuzumab IgE exhibited the

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  6. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression.

    Science.gov (United States)

    Estrada, Marta F; Rebelo, Sofia P; Davies, Emma J; Pinto, Marta T; Pereira, Hugo; Santo, Vítor E; Smalley, Matthew J; Barry, Simon T; Gualda, Emilio J; Alves, Paula M; Anderson, Elizabeth; Brito, Catarina

    2016-02-01

    3D cell tumour models are generated mainly in non-scalable culture systems, using bioactive scaffolds. Many of these models fail to reflect the complex tumour microenvironment and do not allow long-term monitoring of tumour progression. To overcome these limitations, we have combined alginate microencapsulation with agitation-based culture systems, to recapitulate and monitor key aspects of the tumour microenvironment and disease progression. Aggregates of MCF-7 breast cancer cells were microencapsulated in alginate, either alone or in combination with human fibroblasts, then cultured for 15 days. In co-cultures, the fibroblasts arranged themselves around the tumour aggregates creating distinct epithelial and stromal compartments. The presence of fibroblasts resulted in secretion of pro-inflammatory cytokines and deposition of collagen in the stromal compartment. Tumour cells established cell-cell contacts and polarised around small lumina in the interior of the aggregates. Over the culture period, there was a reduction in oestrogen receptor and membranous E-cadherin alongside loss of cell polarity, increased collective cell migration and enhanced angiogenic potential in co-cultures. These phenotypic alterations, typical of advanced stages of cancer, were not observed in the mono-cultures of MCF-7 cells. The proposed model system constitutes a new tool to study tumour-stroma crosstalk, disease progression and drug resistance mechanisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Elevated mammaglobin (h-MAM) expression in breast cancer is associated with clinical and biological features defining a less aggressive tumour phenotype

    International Nuclear Information System (INIS)

    Núñez-Villar, MJ; Martínez-Arribas, F; Pollán, M; Lucas, AR; Sánchez, J; Tejerina, A; Schneider, J

    2003-01-01

    Mammaglobin (h-MAM) is expressed mainly by breast epithelial cells, and this feature has been used to detect circulating breast cancer cells and occult metastases in sentinel axillary lymph nodes of breast cancer patients. However, the biological role of mammaglobin is completely unknown. We studied 128 fresh-frozen breast cancer specimens by means of reverse transcriptase–polymerase chain reaction and quantified their h-MAM mRNA expression. This was then correlated with histological and nuclear grade, oestrogen and progesterone receptor expression, c-erb-B2 and mutant p53 expression, as well as with cellular proliferation measured by means of the Ki67 labelling index, DNA ploidy and S-phase, and finally with the presence or not of invaded axillary nodes in the mastectomy specimen. In the univariate analysis, high h-MAM expression (above the median for the whole group) correlated significantly (P < 0.05) with oestrogen and progesterone receptor expression, diploid DNA content, low Ki67 labelling index, low nuclear grade and almost significantly (P = 0.058) with the absence of axillary nodal invasion in the mastectomy specimen. In a final, multivariate model, only progesterone receptor expression, diploid DNA content and absence of nodal invasion were found to be independently associated with high h-MAM expression. All of the features associated with mammaglobin expression reflect, without exception, a less aggressive tumour phenotype. Further studies are needed to clarify whether this is attributable to h-MAM expression itself, or to another mechanism of which mammaglobin expression forms part

  8. POMB/ACE chemotherapy for mediastinal germ cell tumours.

    Science.gov (United States)

    Bower, M; Brock, C; Holden, L; Nelstrop, A; Makey, A R; Rustin, G J; Newlands, E S

    1997-05-01

    Mediastinal germ cell tumours (MGCT) are rare and most published series reflect the experiences of individual institutions over many years. Since 1979, we have treated 16 men (12 non-seminomatous germ cell tumours and 4 seminomas) with newly diagnosed primary MGCT with POMB/ACE chemotherapy and elective surgical resection of residual masses. This approach yielded complete remissions in 15/16 (94%) patients. The median follow-up was 6.0 years and no relapses occurred more than 2 years after treatment. The 5 year overall survival in the non-seminomatous germ cell tumours (NSGCT) is 73% (95% confidence interval 43-90%). One patient with NSGCT developed drug-resistant disease and died without achieving remission and 2 patients died of relapsed disease. In addition, 4 patients with bulky and/or metastatic seminoma were treated with POMB/ACE. One died of treatment-related neutropenic sepsis in complete remission and one died of relapsed disease. Finally, 4 patients (2 NSGCT and 2 seminomas) referred at relapse were treated with POMB/ACE and one was successfully salvaged. The combination of POMB/ACE chemotherapy and surgery is effective management for MGCT producing high long-term survival rates.

  9. Expression of MLN64 influences cellular matrix adhesion of breast cancer cells, the role for focal adhesion kinase.

    Science.gov (United States)

    Cai, Wei; Ye, Lin; Sun, Jiabang; Mansel, Robert E; Jiang, Wen G

    2010-04-01

    The metastatic lymph node 64 (MLN64) gene was initially identified as highly expressed in the metastatic lymph node from breast cancer. It is localized in q12-q21 of the human chromosome 17 and is often co-amplified with erbB-2. However, the role played by MLN64 in breast cancer remains unclear. In the present study, the expression of MLN64 was examined in a breast cancer cohort using quantitative real-time PCR and immunohistochemical staining. It demonstrated that MLN64 was highly expressed in breast tumours compared to corresponding background tissues at both transcript level and protein level. The elevated level of MLN64 transcripts was correlated with the poor prognosis and overall survival of the patients. A panel of breast cancer cell sublines was subsequently developed by knockdown of MLN64 expression. Loss of MLN64 expression in MCF-7 cells resulted in a significant reduction of cell growth (absorbance for MCF-7DeltaMLN64 being 0.87+/-0.07, Padhesion assay, MDA-MB-231DeltaMLN64 cells showed a significant increase in adhesion (86+/-14), padhesion kinase (FAK) in MDA-MB-231DeltaMLN64 cells using Western blot analysis and immunofluorescent staining of FAK. Moreover, addition of FAK inhibitor to these cells diminished the effect of MLN64 on cell-matrix adhesion, suggesting that FAK contributed to the increased adhesion in MDA-MB-231DeltaMLN64 cells. In conclusion, MLN64 is overexpressed in breast cancer, and its level correlates with poor prognosis and patient survival. MLN64 contributes to the development and progression of breast cancer through the regulation of cell proliferation and adhesive capacity.

  10. 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)

  11. Chemosensitivity and radiosensitivity testing of freshly explanted human tumour cells in vitro

    International Nuclear Information System (INIS)

    Wells, J.

    1977-10-01

    In this thesis, in vitro testing for the chemosensitivity and radiosensitivity of freshly explanted human tumour cells is described. The cells were incubated with anti-tumour drugs and either a 6-day growth test performed or a clonal growth test as a measure of survival of cell reproductive capacity. It was shown that if one aims to develop a suitable in vitro method for predicting the subsequent response of human tumour cells in situ to cytotoxic chemotherapy, the test procedure must be initiated before the explanted cells have undergone significant growth in vitro. The survival of the reproductive capacity of tumour cell explants following X-radiation was also studied. Using a 'feeder' layer technique, values for the survival curve parameter Dsub(q) were in the range 400-610 rad and the values for D 0 were in the range 120-160 rad. The shape of the X-ray survival curves did not change when cells were retested after repeated subculturing in vitro. Therefore, unlike chemosensitivity measured by the same biological end-point, radiosensitivity apparently does not change once cells have reached their maximum growth potential. (UK)

  12. Developing Anti-HER2 Vaccines: Breast Cancer Experience.

    Science.gov (United States)

    Al-Awadhi, Aydah; Murray, James Lee; Ibrahim, Nuhad K

    2018-04-25

    Breast cancer accounts for more than one million new cases annually and is the leading cause of death in women globally. HER2 overexpression induces cellular and humoral immune responses against the HER2 protein and is associated with higher tumour proliferation rates. Trastuzumab-based therapies are effectively and widely used as standard of care in HER2-amplified/overexpressed breast cancer patients; one cited mechanism of action is the induction of passive immunity and antibody-dependent cellular cytotoxicity against malignant breast cancer cells. These findings drove the efforts to generate antigen-specific immunotherapy to trigger the patient's immune system to target HER2-overexpressing tumour cells, which led to the development of various vaccines against the HER2 antigen. This manuscript discusses the various anti-HER2 vaccine formulations and strategies and their potential role in the metastatic and adjuvant settings. This article is protected by copyright. All rights reserved. © 2018 UICC.

  13. SPECTRUM OF NEUROENDOCRINE TUMOURS- A TERTIARY CARE CENTRE EXPERIENCE

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2011-12-01

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

  15. TOX3 mutations in breast cancer.

    Directory of Open Access Journals (Sweden)

    James Owain Jones

    Full Text Available TOX3 maps to 16q12, a region commonly lost in breast cancers and recently implicated in the risk of developing breast cancer. However, not much is known of the role of TOX3 itself in breast cancer biology. This is the first study to determine the importance of TOX3 mutations in breast cancers. We screened TOX3 for mutations in 133 breast tumours and identified four mutations (three missense, one in-frame deletion of 30 base pairs in six primary tumours, corresponding to an overall mutation frequency of 4.5%. One potentially deleterious missense mutation in exon 3 (Leu129Phe was identified in one tumour (genomic DNA and cDNA. Whilst copy number changes of 16q12 are common in breast cancer, our data show that mutations of TOX3 are present at low frequency in tumours. Our results support that TOX3 should be further investigated to elucidate its role in breast cancer biology.

  16. 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.)

  17. Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

    International Nuclear Information System (INIS)

    Fonseca, Fernando LA; Sant Ana, Aleksandra VL; Bendit, Israel; Arias, Vitor; Costa, Luciano J; Pinhal, Aparecida A; Giglio, Auro del

    2005-01-01

    Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment

  18. Giant fibroadenoma presenting like fungating breast cancer in a ...

    African Journals Online (AJOL)

    Background: Giant fibroadenoma of the breast is a rare benign breast tumour which seldom grows to a giant size, it is even rarer for this benign tumour to grow rapidly, ulcerate spontaneously and present like a fungating breast tumour in a way mimicking breast cancer. Case presentation: This is a presentation of a 14 year ...

  19. Occult Leydig Cell Tumour Presenting as Bilateral Gynaecomastia. Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    A. B. Patel

    2005-01-01

    Full Text Available Gynaecomastia is the most common benign breast disorder in men. Among the various causes, testicular malignancies are an uncommon, life-threatening condition requiring prompt diagnosis and treatment. The case of a 28-year-old man is discussed, who presented with a 6-month history of painful bilateral gynaecomastia with no abnormality on clinical or biochemical examination. The patient's symptoms spontaneously resolved within 4 weeks. He then represented 10 years later with similar symptoms and an associated secondary hypogonadism. Ultrasound imaging revealed a clinically occult, hypoechoic mass in the left testis (Leydig cell tumour on histology. Clinical and hormonal findings normalized following surgical excision. This report underlines the importance in clinical practice of ultrasonographic evaluation of the testis, in all patients with gynaecomastia, despite unremarkable findings on physical examination.

  20. Metastatic tumours to the thyroid gland: report of 3 cases and brief review of the literature

    International Nuclear Information System (INIS)

    Vardar, Enver; Erkan, Nazif; Bayol, Umit; Yılmaz, Cengiz; Dogan, Murat

    2010-01-01

    Metastases to the thyroid are encountered rarely in clinical practice, but the number of cases seems to have increased in recent years. The reason of this increase may be a more frequent use of fine-needle aspiration biopsy (FNAB) and the use of more sophisticated, complicated imaging techniques in patients with thyroid masses. Also, in addition to these reasons, the use of more organo-specific immunohistochemical antibodies in the examination of surgical specimens may affect the differential diagnosis of malignant tumours. Three metastatic tumours to thyroid were found in the retrospective review of malignant thyroid tumours diagnosed between January 1993 and December 2007. The primary tumours were clear cell carcinoma of the kidney, squamous cell carcinoma of the lung and breast carcinoma-ductal type. A detailed clinical history, careful histological examination and essential immunohistochemistry helped in attaining the correct diagnosis

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

    Directory of Open Access Journals (Sweden)

    Hiroaki Haga

    2015-01-01

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

  2. Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms

    Directory of Open Access Journals (Sweden)

    Miroslava Bilecova-Rabajdova

    2014-01-01

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

  3. Giant desmoid tumour of the thorax following latissimus dorsi and implant breast reconstruction: case report and review of the literature

    LENUS (Irish Health Repository)

    Collins, AM

    2017-03-01

    The case of a giant thoracic desmoid tumour in a 44-year-old woman, who presented two years following a breast reconstruction with a latissimus dorsi (LD) flap and implant, is reported. Clinical findings included a rapidly growing, painless mass. Computed tomography (CT) suggested skin and intercostal soft tissue invasion. The tumour was resected en bloc with the LD muscle, implant capsule and underlying rib segments. The resultant thoracic and abdominal wall defects were reconstructed with Dualmesh® and polypropylene meshes respectively. There was no evidence of recurrence at thirty-six months follow-up.

  4. Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival

    International Nuclear Information System (INIS)

    Haaf, Anette ten; Bektas, Nuran; Serenyi, Sonja von; Losen, Inge; Arweiler, Elfriede Christel; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2009-01-01

    The transcription factor GLI1, a member of the GLI subfamily of Krüppel-like zinc finger proteins is involved in signal transduction within the hedgehog pathway. Aberrant hedgehog signalling has been implicated in the development of different human tumour entities such as colon and lung cancer and increased GLI1 expression has been found in these tumour entities as well. In this study we questioned whether GLI1 expression might also be important in human breast cancer development. Furthermore we correlated GLI1 expression with histopathological and clinical data to evaluate whether GLI1 could represent a new prognostic marker in breast cancer treatment. Applying semiquantitative realtime PCR analysis and immunohistochemistry (IHC) GLI1 expression was analysed in human invasive breast carcinomas (n = 229) in comparison to normal human breast tissues (n = 58). GLI1 mRNA expression was furthermore analysed in a set of normal (n = 3) and tumourous breast cell lines (n = 8). IHC data were statistically interpreted using SPSS version 14.0. Initial analysis of GLI1 mRNA expression in a small cohort of (n = 5) human matched normal and tumourous breast tissues showed first tendency towards GLI1 overexpression in human breast cancers. However only a small sample number was included into these analyses and values for GLI1 overexpression were statistically not significant (P = 0.251, two-tailed Mann-Whitney U-test). On protein level, nuclear GLI1 expression in breast cancer cells was clearly more abundant than in normal breast epithelial cells (P = 0.008, two-tailed Mann-Whitney U-test) and increased expression of GLI1 protein in breast tumours significantly correlated with unfavourable overall survival (P = 0.019), but also with higher tumour stage (P < 0.001) and an increased number of tumour-positive axillar lymph nodes (P = 0.027). Interestingly, a highly significant correlation was found between GLI1 expression and the expression of SHH, a central upstream molecule of

  5. In vivo cell kinetics in breast carcinogenesis

    International Nuclear Information System (INIS)

    Bai, Maria; Agnantis, Niki J; Kamina, Sevasti; Demou, Asimina; Zagorianakou, Panayiota; Katsaraki, Aphroditi; Kanavaros, Panayiotis

    2001-01-01

    Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumours. In the present study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis. A total of 32 areas of apparently normal epithelium and 135 ductal proliferative and neoplastic lesions were studied. More than one epithelial lesion per case were analyzed. The apoptotic index (AI) and the proliferative index (PI) were expressed as the percentage of TdT-mediated dUTP-nick end-labelling (TUNEL) and Ki-67-positive cells, respectively. The PI/AI (P/A index) was calculated for each case. The AIs and PIs were significantly higher in hyperplasia than in apparently normal epithelium (P = 0.04 and P = 0.0005, respectively), in atypical hyperplasia than in hyperplasia (P = 0.01 and P = 0.04, respectively) and in invasive carcinoma than in in situ carcinoma (P < 0.001 and P < 0.001, respectively). The two indices were similar in atypical hyperplasia and in in situ carcinoma. The P/A index increased significantly from normal epithelium to hyperplasia (P = 0.01) and from preinvasive lesions to invasive carcinoma (P = 0.04) whereas it was decreased (non-significantly) from hyperplasia to preinvasive lesions. A strong positive correlation between the AIs and the PIs was found (r = 0.83, P < 0.001). These findings suggest accelerating cell turnover along the continuum of breast carcinogenesis. Atypical hyperplasias and in situ carcinomas might be kinetically similar lesions. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma the net growth of epithelial cells results from a growth imbalance in favour of proliferation. In the transition from hyperplasia

  6. Breast cancer recurrence after reoperation for surgical bleeding

    DEFF Research Database (Denmark)

    Pedersen, Rikke Nørgaard; Bhaskaran, K; Heide-Jørgensen, U

    2017-01-01

    BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group...... database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from...

  7. NANOG priming before full reprogramming may generate germ cell tumours

    Directory of Open Access Journals (Sweden)

    I Grad

    2011-11-01

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

  8. Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung.

    Directory of Open Access Journals (Sweden)

    Charlotte T A H Wetzels

    Full Text Available BACKGROUND: A new virus called the Merkel Cell Polyomavirus (MCPyV has recently been found in Merkel Cell Carcinoma (MCC. MCC is a rare aggressive small cell neuroendocrine carcinoma primarily derived from the skin, morphologically indistinguishable from small cell lung carcinoma (SCLC. So far the actual presence of the virus in MCC tumour cells on a morphological level has not been demonstrated, and the presence of MCPyV in other small cell neuroendocrine carcinomas has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: We investigated MCC tissue samples from five patients and SCLCs from ten patients for the presence of MCPyV-DNA by PCR and sequencing. Electron microscopy was used to search ultrastructurally for morphological presence of the virus in MCPyV-DNA positive samples. MCPyV was detected in two out of five primary MCCs. In one MCC patient MCPyV-DNA was detected in the primary tumour as well as in the metastasis, strongly suggesting integration of MCPyV in the cellular DNA of the tumour in this patient. In the primary MCC of another patient viral particles in tumour cell nuclei and cytoplasm were identified by electron microscopy, indicating active viral replication in the tumour cells. In none of the SCLCs MCPyV-DNA was detected. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that MCPyV is an oncogenic polyomavirus in humans, and is potentially causally related to the development of MCC but not to the morphological similar SCLC.

  9. GRANULAR CELL TUMOUR OF THE LARYNX – A CASE REPORT

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... cell tumour involving the right vocal cord diagnosed after direct laryngoscopy and biopsy. She was treated ... She had no associated weight loss, dysphagia, odynophagia or dyspnoea. She occasionally took ... A provisional diagnosis of a right vocal cord tumour was made and patient worked up for direct.

  10. Up-regulated proteins in the fluid bathing the tumour cell microenvironment as potential serological markers for early detection of cancer of the breast

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Bunkenborg, Jakob

    2010-01-01

    -based proteomics in combination with mass spectrometry and immunohistochemistry (IHC) of the tumour interstitial fluids (TIF) and normal interstitial fluids (NIF) collected from 69 prospective breast cancer patients. The goal of this study was to identify abundant cancer up-regulated proteins that are externalised...... in the TIF, some of which were confirmed by IHC. In the second phase, we carried out a systematic computer assisted analysis of the 2D gels of the remaining 68 TIF samples in order to identify TIF 46 up-regulated proteins that were deregulated in 90% or more of all the available TIFs, thus representing...

  11. Saponins extracted from by-product of Asparagus officinalis L. suppress tumour cell migration and invasion through targeting Rho GTPase signalling pathway.

    Science.gov (United States)

    Wang, Jieqiong; Liu, Yali; Zhao, Jingjing; Zhang, Wen; Pang, Xiufeng

    2013-04-01

    The inedible bottom part (~30-40%) of asparagus (Asparagus officinalis L.) spears is usually discarded as waste. However, since this by-product has been reported to be rich in many bioactive phytochemicals, it might be utilisable as a supplement in foods or natural drugs for its therapeutic effects. In this study it was identifed that saponins from old stems of asparagus (SSA) exerted potential inhibitory activity on tumour growth and metastasis. SSA suppressed cell viability of breast, colon and pancreatic cancers in a concentration-dependent manner, with half-maximum inhibitory concentrations ranging from 809.42 to 1829.96 µg mL(-1). However, SSA was more functional in blocking cell migration and invasion as compared with its cytotoxic effect, with an effective inhibitory concentration of 400 µg mL(-1). A mechanistic study showed that SSA markedly increased the activities of Cdc42 and Rac1 and decreased the activity of RhoA in cancer cells. SSA inhibits tumour cell motility through modulating the Rho GTPase signalling pathway, suggesting a promising use of SSA as a supplement in healthcare foods and natural drugs for cancer prevention and treatment. © 2012 Society of Chemical Industry.

  12. Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

    Science.gov (United States)

    Linedale, Richard; Schmidt, Campbell; King, Brigid T; Ganko, Annabelle G; Simpson, Fiona; Panizza, Benedict J; Leggatt, Graham R

    2017-01-01

    Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

  13. Elevated frequencies of CD8 T cells expressing PD-1, CTLA-4 and Tim-3 within tumour from perineural squamous cell carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Richard Linedale

    Full Text Available Perineural spread of tumour cells along cranial nerves is a severe complication of primary cutaneous squamous cell carcinomas of the head and neck region. While surgical excision of the tumour is the treatment of choice, removal of all the tumour is often complicated by the neural location and recurrence is frequent. Non-invasive immune treatments such as checkpoint inhibitor blockade may be useful in this set of tumours although little is understood about the immune response to perineural spread of squamous cell carcinomas. Immunohistochemistry studies suggest that perineural tumour contains a lymphocyte infiltrate but it is difficult to quantitate the different proportions of immune cell subsets and expression of checkpoint molecules such as PD-1, Tim-3 and CTLA-4. Using flow cytometry of excised perineural tumour tissue, we show that a T cell infiltrate is prominent in addition to less frequent B cell, NK cell and NKT cell infiltrates. CD8 T cells are more frequent than other T cells in the tumour tissue. Amongst CD8 T cells, the frequency of Tim-3, CTLA-4 and PD-1 expressing cells was significantly greater in the tumour relative to the blood, a pattern that was repeated for Tim-3, CTLA-4 and PD-1 amongst non-CD8 T cells. Using immunohistochemistry, PD-1 and PD-L1-expression could be detected in close proximity amongst perineural tumour tissue. The data suggest that perineural SCC contains a mixture of immune cells with a predominant T cell infiltrate containing CD8 T cells. Elevated frequencies of tumour-associated Tim-3+, CTLA-4+ and PD-1+ CD8 T cells suggests that a subset of patients may benefit from local antibody blockade of these checkpoint inhibitors.

  14. Giant fibroadenoma presenting like fungating breast cancer in a Nigerian teenager.

    Science.gov (United States)

    Arowolo, O A; Akinkuolie, A A; Adisa, A O; Obonna, G C; Olasode, B J

    2013-03-01

    Giant fibroadenoma of the breast is a rare benign breast tumour which seldom grows to a giant size, it is even rarer for this benign tumour to grow rapidly, ulcerate spontaneously and present like a fungating breast tumour in a way mimicking breast cancer. This is a presentation of a 14 year old premenarchal girl with a massive ulcerating and fungating left breast mass that was initially thought to be a fungating locally advanced breast carcinoma on clinical examination. Further examination of the morphology of the resected surgical specimen and histological examination confirmed it to be giant fibroadenoma of the breast. It was successfully managed by partial mastectomy and breast reconstruction with an excellent result and a high degree of patient satisfaction was achieved. Though a rare clinical entity benign breast tumour can present like a fungating breast cancer and this must be bore in mind especially in young adolescent patients presenting with ulcerating breast tumour.

  15. Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

    International Nuclear Information System (INIS)

    Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, Pierre; Brunet-Lecomte, Patrick

    1999-01-01

    Glutathione S-transferase (GST)M1, a member of the μ class GST gene family, has been shown to be polymorphic because of a partial gene deletion. This results in a failure to express the GSTM1 gene in 50-60% of individuals. Several studies have demonstrated a possible link with the GSTM1-null genotype and susceptibility to cancer. Furthermore, a GSTM1 isoenzyme has been positively associated with protective effect against mutagenic drugs, such as alkylating agents and anthracyclines. To determine whether GSTM1 polymorphisms are associated with tumour characteristics and survival in advanced breast cancer patients, and whether it may constitute a prognostic factor. We genotyped 92 patients receiving primary chemotherapy, which included cyclophosphamide, doxorubicine and 5-fluorouracil. The relationships between allelism at GSTM1 and clinicopathological parameters including age, menopausal status, tumour size, grade hormone receptors, involved nodes and p53 gene mutations were analysed. Of the patients with GSTM1-positive genotype, tissue samples obtained before and after treatment were available from 28 cases, allowing RNA extraction and GSTM1 expression by reverse transcription polymerase chain reaction. Relationships with clinical response to chemotherapy, and disease-free and overall survival were also evaluated. The data obtained was analysed using logistic regression to estimate the odds ratio and 95% confidence interval. Of 92 patients, 57.6% (n = 53) were classified as heritably GSTM1-deficient, and 42.4% (n = 39) were of the GSTM1-positive genotype. There were no statistically significant relationships between GSTM1-null genotype and the clinicopathological parameters analysed. No relationship was observed between GSTM1 RNA expression and objective clinical response to chemotherapy. Objective clinical response to chemotherapy was related only to clinical tumour size (P = 0.0177) and to the absence of intraductal carcinoma (P = 0.0013). GSTM1-null genotype

  16. Response of clonogenic cells of mice solid tumour NKLy/LL to N-methyl-N-nitrosourea

    International Nuclear Information System (INIS)

    Chan Tik Kan; Afanas'ev, G.G.; Pelevina, I.I.

    1979-01-01

    By cloning in vitro the cells of NKLy/LL solid tumour of mice it has been shown that the curve of clonogenic cell survival versus N-methyl-N-nitrosourea (MNU) dose in the 12.5-200.0 mg/kg interval is exponential and characterized by Dsub(o)=29.15 mg/kg dose value. Large size tumours (15.0-17.0 g) are characterized by higher death rate of clonogenic cells (survivor fraction approximately 0.5%) than in 1.0-7.0 g tumours (survivor fraction 2-4%). That is, evidently, related to higher sensitivity of the resting tumour cells to MNU

  17. Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis

    DEFF Research Database (Denmark)

    Madsen, Chris D; Pedersen, Jesper Thorhauge; Venning, Freja A

    2015-01-01

    , which can be prevented by simultaneous depletion of HIF-1α. Treatment with the PHD inhibitor DMOG in an orthotopic breast cancer model significantly decreases spontaneous metastases to the lungs and liver, associated with decreased tumour stiffness and fibroblast activation. PHD2 depletion in CAFs co......-injected with tumour cells similarly prevents CAF-induced metastasis to lungs and liver. Our data argue that reversion of CAFs towards a less active state is possible and could have important clinical implications....

  18. A core invasiveness gene signature reflects epithelial-to-mesenchymal transition but not metastatic potential in breast cancer cell lines and tissue samples.

    Directory of Open Access Journals (Sweden)

    Melike Marsan

    Full Text Available INTRODUCTION: Metastases remain the primary cause of cancer-related death. The acquisition of invasive tumour cell behaviour is thought to be a cornerstone of the metastatic cascade. Therefore, gene signatures related to invasiveness could aid in stratifying patients according to their prognostic profile. In the present study we aimed at identifying an invasiveness gene signature and investigated its biological relevance in breast cancer. METHODS & RESULTS: We collected a set of published gene signatures related to cell motility and invasion. Using this collection, we identified 16 genes that were represented at a higher frequency than observed by coincidence, hereafter named the core invasiveness gene signature. Principal component analysis showed that these overrepresented genes were able to segregate invasive and non-invasive breast cancer cell lines, outperforming sets of 16 randomly selected genes (all P<0.001. When applied onto additional data sets, the expression of the core invasiveness gene signature was significantly elevated in cell lines forced to undergo epithelial-mesenchymal transition. The link between core invasiveness gene expression and epithelial-mesenchymal transition was also confirmed in a dataset consisting of 2420 human breast cancer samples. Univariate and multivariate Cox regression analysis demonstrated that CIG expression is not associated with a shorter distant metastasis free survival interval (HR = 0.956, 95%C.I. = 0.896-1.019, P = 0.186. DISCUSSION: These data demonstrate that we have identified a set of core invasiveness genes, the expression of which is associated with epithelial-mesenchymal transition in breast cancer cell lines and in human tissue samples. Despite the connection between epithelial-mesenchymal transition and invasive tumour cell behaviour, we were unable to demonstrate a link between the core invasiveness gene signature and enhanced metastatic potential.

  19. Cell kinetics of hypoxic cells in a murine tumour in vivo: flow cytometric determination of the radiation-induced blockage of cell cycle progression

    International Nuclear Information System (INIS)

    Rutgers, D.H.; Niessen, D.P.P.; Linden, P.M. van der

    1987-01-01

    Cells from the small cell population of viable cells in the large necrotic centre of murine M8013 tumours were investigated with respect to their cell kinetics. Flow cytometry (FCM) of this part of subcutaneously transplanted tumours revealed the presence of tumour cells with G1,S and G2 + M phase DNA-contents. These severely hypoxic cells could have stopped cell cycle progression due to the nutritional deprivation, irrespective of their position within the cell cycle. Labelling methods, used to disclose the cell kinetics of this cell population, are hampered by the absence of a transport system in these large necrotic areas. Therefore FCM was used to monitor radiation induced changes in the cell cycle distribution. From this investigation it was concluded that hypoxic cells in the necrotic centre of the M8013 tumour progress through the cell cycle. As well as a cell population with a cell cycle time (Tsub(c)) of approximately 84 hr, a subpopulation with a Tsub(c) of approximately 21 hr occurred. (author)

  20. 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 ...

  1. EpCAM as multi-tumour target for near-infrared fluorescence guided surgery

    International Nuclear Information System (INIS)

    Driel, P. B. A. A. van; Boonstra, M. C.; Prevoo, H. A. J. M.; Giessen, M. van de; Snoeks, T. J. A.; Tummers, Q. R. J. G.; Keereweer, S.; Cordfunke, R. A.; Fish, A.; Eendenburg, J. D. H. van; Lelieveldt, B. P. F.; Dijkstra, J.; Velde, C. J. H. van de; Kuppen, P. J. K.; Vahrmeijer, A. L.; Löwik, C. W. G. M.; Sier, C. F. M.

    2016-01-01

    Evaluation of resection margins during cancer surgery can be challenging, often resulting in incomplete tumour removal. Fluorescence-guided surgery (FGS) aims to aid the surgeon to visualize tumours and resection margins during surgery. FGS relies on a clinically applicable imaging system in combination with a specific tumour-targeting contrast agent. In this study EpCAM (epithelial cell adhesion molecule) is evaluated as target for FGS in combination with the novel Artemis imaging system. The NIR fluorophore IRDye800CW was conjugated to the well-established EpCAM specific monoclonal antibody 323/A3 and an isotype IgG1 as control. The anti-EpCAM/800CW conjugate was stable in serum and showed preserved binding capacity as evaluated on EpCAM positive and negative cell lines, using flow cytometry and cell-based plate assays. Four clinically relevant orthotopic tumour models, i.e. colorectal cancer, breast cancer, head and neck cancer, and peritonitis carcinomatosa, were used to evaluate the performance of the anti-EpCAM agent with the clinically validated Artemis imaging system. The Pearl Impulse small animal imaging system was used as reference. The specificity of the NIRF signal was confirmed using bioluminescence imaging and green-fluorescent protein. All tumour types could clearly be delineated and resected 72 h after injection of the imaging agent. Using NIRF imaging millimetre sized tumour nodules were detected that were invisible for the naked eye. Fluorescence microscopy demonstrated the distribution and tumour specificity of the anti-EpCAM agent. This study shows the potential of an EpCAM specific NIR-fluorescent agent in combination with a clinically validated intraoperative imaging system to visualize various tumours during surgery

  2. Magnetic resonance imaging aspects of giant-cell tumours of bone

    International Nuclear Information System (INIS)

    Pereira, Helcio Mendoncça; Marchiori, Edson; Severo, Alessandro

    2014-01-01

    This study aimed to describe the magnetic resonance imaging (MRI) features of giant-cell tumours of bone. We analysed the clinical and MRI features of patients diagnosed with giant-cell tumours of bone confirmed by histopathology at our institution between 2010 and 2012. The peak incidence was between the second and third decades of life. There was no gender predominance. The most frequent locations were the knee and wrist. Pain and swelling were the prevailing symptoms. Fifty-one per cent of the patients were found to have associated secondary aneurysmal bone cysts on histopathology. On MRI, lesions demonstrated signal intensity equal to that of skeletal muscle on T1-weighted images and low signal intensity on T2-weighted images in 90% of cases. In gadolinium-enhanced T1-weighted images, 76.6% of cases demonstrated heterogeneous enhancement. We observed cystic components involving more than 50% of the lesion in 17 cases (56.6%). There was extra-osseous involvement in 13 cases (43.3%). MRI offers a valuable diagnostic tool for giant-cell tumours of bone. Contrast-enhanced MRI can distinguish between cystic and solid components of the tumour. MRI is also the imaging modality of choice for evaluation of soft-tissue involvement, offering a complete preoperative diagnosis.

  3. Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Hald, Jeppe; Rasmussen, N; Claesson, Mogens Helweg

    1995-01-01

    Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition...

  4. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with 18F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients.

    Science.gov (United States)

    Lemarignier, Charles; Martineau, Antoine; Teixeira, Luis; Vercellino, Laetitia; Espié, Marc; Merlet, Pascal; Groheux, David

    2017-07-01

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an 18 F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV max and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV max and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV max and TLG were able to predict response to NAC, TFs failed.

  5. Relationship between tumour size and response to neoadjuvant ...

    African Journals Online (AJOL)

    2018-03-16

    Mar 16, 2018 ... Introduction. Efforts to improve response of breast tumours to chemotherapy and maximize the benefit-to-adverse events ratio of chemotherapy include molecular subtyping to classify tumours, combined and cyclical use of chemotherapy and surgical de-bulking to stimulate proliferation. Molecular ...

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

    Science.gov (United States)

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

    2011-11-01

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

  7. Chemokine receptor expression in tumour islets and stroma in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Ohri, Chandra M; Shikotra, Aarti; Green, Ruth H; Waller, David A; Bradding, Peter

    2010-01-01

    We have previously demonstrated that tumour islet infiltration by macrophages is associated with extended survival (ES) in NSCLC. We therefore hypothesised that patients with improved survival would have high tumour islet expression of chemokine receptors known to be associated with favourable prognosis in cancer. This study investigated chemokine receptor expression in the tumour islets and stroma in NSCLC. We used immunohistochemistry to identify cells expressing CXCR1, CXCR2, CXCR3, CXCR4, CXCR5 and CCR1 in the tumour islets and stroma in 20 patients with surgically resected NSCLC. Correlations were made with macrophage and mast cell expression. There was increased expression of CXCR2, CXCR3, and CCR1 in the tumour islets of ES compared with poor survival (PS) patients (p = 0.007, 0.01, and 0.002, respectively). There was an association between 5 year survival and tumour islet CXCR2, CXCR3 and CCR1 density (p = 0.02, 0.003 and <0.001, respectively) as well as stromal CXCR3 density (p = 0.003). There was a positive correlation between macrophage density and CXCR3 expression (r s = 0.520, p = 0.02) and between mast cell density and CXCR3 expression (r s = 0.499, p = 0.03) in the tumour islets. Above median expression of CXCR2, CXCR3 and CCR1 in the tumour islets is associated with increased survival in NSCLC, and expression of CXCR3 correlates with increased macrophage and mast cell infiltration in the tumour islets

  8. History of myeloid derived suppressor cells (MDSCs) in the macro- and micro-environment of tumour-bearing hosts

    Science.gov (United States)

    Talmadge, James E.; Gabrilovich, Dmitry I.

    2015-01-01

    Tumour-induced granulocytic hyperplasia is associated with tumour vasculogenesis and escape from immunity via T-cell suppression. Initially, these myeloid cells were identified as granulocytes or monocytes; however, recent studies revealed that this hyperplasia was associated with populations of multi-potent progenitor cells identified as myeloid-derived suppressor cells (MDSCs). The discovery and study of MDSCs have provided a wealth of information regarding tumour pathobiology, extended our understanding of neoplastic progression, and modified our approaches to immune adjuvant therapy. In this perspective, we discuss the history of MDSCs, their influence on tumour progression and metastasis, and the crosstalk between tumour cells, MDSCs, and the host macroenvironment. PMID:24060865

  9. 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

  10. Ultrasound-guided diffuse optical tomography (DOT) of invasive breast carcinoma: Does tumour total haemoglobin concentration contribute to the prediction of axillary lymph node status?

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Qingli, E-mail: qinglizhu@gmail.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Xiao, Mengsu, E-mail: xiaomengsu_2000@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); You, Shanshan, E-mail: shanshan_0531@sina.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Zhang, Jing, E-mail: zhang.jing1029@163.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Jiang, Yuxin, E-mail: yuxinjiangxh@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Lai, Xingjian, E-mail: lxjpumch@yahoo.com.cn [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China); Dai, Qing, E-mail: qingdai_2000@yahoo.com [Department of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1, Dongcheng District, Beijing 100730 (China)

    2012-11-15

    Objectives: To prospectively study the ultrasound-guided near-infrared diffuse optical tomography (DOT) findings of the total haemoglobin concentration (THC) detected in invasive breast carcinomas and its contribution to the prediction of axillary lymph node (LN) status. Methods: A total of 195 invasive breast carcinomas were prospectively studied with DOT before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Tumour size and THC level were correlated with LN status by a logistic regression analysis. Results: One hundred twenty-four patients (63.59%) was LN(-) and 71 (36.41%) was LN(+). The average THC was significantly higher in the LN(+) group than in the LN(-) group (252.94 {+-} 69.19 {mu}mol/L versus 203.86 {+-} 83.13 {mu}mol/L, P = 0.01). A multivariate analysis showed an independent relationship between the probability of axillary metastasis, elevated THC level (P = 0.01), and tumour size (P = 0.001). The odds ratio with THC {>=} 140 {mu}mol/L was 13.651 (1.781-104.560), whereas that of tumour size with a 1 cm increment was only 1.777 (1.283-2.246). Conclusions: The THC level and the tumour size are independent and preoperative predictors of axillary nodal status; these variables may improve the diagnosis of patients with lymph node metastasis.

  11. Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype

    DEFF Research Database (Denmark)

    da Silveira, W A; Palma, P V B; Sicchieri, R D

    2017-01-01

    Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis...... of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies....... and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression...

  12. Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma.

    Science.gov (United States)

    Mario Gonzalez-Meljem, Jose; Haston, Scott; Carreno, Gabriela; Apps, John R; Pozzi, Sara; Stache, Christina; Kaushal, Grace; Virasami, Alex; Panousopoulos, Leonidas; Neda Mousavy-Gharavy, Seyedeh; Guerrero, Ana; Rashid, Mamunur; Jani, Nital; Goding, Colin R; Jacques, Thomas S; Adams, David J; Gil, Jesus; Andoniadou, Cynthia L; Martinez-Barbera, Juan Pedro

    2017-11-28

    Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2- cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis. We show that expression of oncogenic β-catenin in Hesx1+ embryonic precursors also results in stem cell clusters and paracrine tumours. We reveal that human and mouse clusters are analogous and share a common signature of senescence and SASP. Finally, we show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potential. Together, we provide evidence that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in vivo in an age-dependent fashion.

  13. A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Wen-Lin; Das, Debopriya; Ziyad, Safiyyah; Bhattacharya, Sanchita; Gibb, William J.; Heiser, Laura M.; Sadanandam, Anguraj; Fontenay, Gerald V.; Hu, Zhi; Wang, Nicholas J.; Bayani, Nora; Feiler, Heidi S.; Neve, Richard M.; Wyrobek, Andrew J.; Spellman, Paul T.; Marton, Laurence J.; Gray, Joe W.

    2009-11-14

    Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity. A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity. The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response. A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signaling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.

  14. 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

  15. Targeting single-walled carbon nanotubes for the treatment of breast cancer using photothermal therapy

    Science.gov (United States)

    Neves, Luís F. F.; Krais, John J.; Van Rite, Brent D.; Ramesh, Rajagopal; Resasco, Daniel E.; Harrison, Roger G.

    2013-09-01

    This paper focuses on the targeting of single-walled carbon nanotubes (SWNTs) for the treatment of breast cancer with minimal side effects using photothermal therapy. The human protein annexin V (AV) binds specifically to anionic phospholipids expressed externally on the surface of tumour cells and endothelial cells that line the tumour vasculature. A 2 h incubation of the SWNT-AV conjugate with proliferating endothelial cells followed by washing and near-infrared (NIR) irradiation at a wavelength of 980 nm was enough to induce significant cell death; there was no significant cell death with irradiation or the conjugate alone. Administration of the same conjugate i.v. in BALB/c female mice with implanted 4T1 murine mammary at a dose of 0.8 mg SWNT kg-1 and followed one day later by NIR irradiation of the tumour at a wavelength of 980 nm led to complete disappearance of implanted 4T1 mouse mammary tumours for the majority of the animals by 11 days since the irradiation. The combination of the photothermal therapy with the immunoadjuvant cyclophosphamide resulted in increased survival. The in vivo results suggest the SWNT-AV/NIR treatment is a promising approach to treat breast cancer.

  16. Increase in the fraction of necrotic, not apoptotic, cells in SiHa xenograft tumours shortly after irradiation

    International Nuclear Information System (INIS)

    Olive, P.L.; Vikse, C.M.; Vanderbyl, S.

    1999-01-01

    Background and purpose: Approximately 18% of the cells recovered by rapid mechanical dissociation of SiHa xenograft tumours contain large numbers of DNA strand breaks. The number of damaged cells increases to 30-40% 4-6 h after exposure to 5 or 15 Gy, returning to normal levels by 12 h. This observation is reminiscent of the rate of production of apoptotic cells in other murine and human xenograft tumours. The nature of this damage, rate of development and relation to cell proliferation rate were therefore examined in detail.Materials and methods: SiHa human cervical carcinoma cells were grown as xenograft tumours in SCID mice. Single-cell suspensions were prepared as a function of time after irradiation of the mouse and examined for DNA damage using the alkaline comet assay. Cell cycle progression was measured by flow cytometry evaluation of anti-bromodeoxyuridine-labelled tumour cells.Results: Significant numbers of apoptotic cells could not be detected in irradiated SiHa tumours using an end-labelling assay, electron microscopy, or histological examination of thin sections. Instead, xenograft cells exhibiting extensive DNA damage in the comet assay were predominantly necrotic cells. The increase in the proportion of heavily damaged cells 4-6 h after irradiation could be the result of an interplay between several factors including loss of viable cells and change in production or loss of necrotic cells. Analysis of the progression of BrdUrd-labelled cells confirmed that while 35% of cells from untreated SiHa tumours had divided and entered G 1 phase by 6 h after BrdUrd injection, none of the labelled cells from tumours exposed to 5 or 15 Gy had progressed to G 1 .Conclusions: The increase in the percentage of SiHa tumour cells with extensive DNA damage 4-6 h after irradiation is attributable to necrosis, not apoptosis. Cell cycle progression and cell loss are likely to influence the kinetics of appearance of both apoptotic and necrotic cells in irradiated tumours

  17. High-mobility group box 1 released by autophagic cancer-associated fibroblasts maintains the stemness of luminal breast cancer cells.

    Science.gov (United States)

    Zhao, Xi-Long; Lin, Yong; Jiang, Jun; Tang, Zhuo; Yang, Shuai; Lu, Lu; Liang, Yan; Liu, Xue; Tan, Jiao; Hu, Xu-Gang; Niu, Qin; Fu, Wen-Juan; Yan, Ze-Xuan; Guo, De-Yu; Ping, Yi-Fang; Wang, Ji Ming; Zhang, Xia; Kung, Hsiang-Fu; Bian, Xiu-Wu; Yao, Xiao-Hong

    2017-11-01

    Cancer stem cells/cancer-initiating cells (CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer-associated fibroblasts (CAFs) are major components of the niche of breast cancer-initiating cells (BCICs), and their interactions may profoundly affect breast cancer progression. Autophagy has been considered to be a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance has not been determined. In this study, we found that the presence of CAFs containing high levels of microtubule-associated protein 1 light chain 3 (LC3II), a marker of autophagosomes, was associated with more aggressive luminal human breast cancer. CAFs in human luminal breast cancer tissues with high autophagy activity enriched BCICs with increased tumourigenicity. Mechanistically, autophagic CAFs released high-mobility group box 1 (HMGB1), which activated its receptor, Toll-like receptor (TLR) 4, expressed by luminal breast cancer cells, to enhance their stemness and tumourigenicity. Furthermore, immunohistochemistry of 180 luminal breast cancers revealed that high LC3II/TLR4 levels predicted an increased relapse rate and a poorer prognosis. Our findings demonstrate that autophagic CAFs play a critical role in promoting the progression of luminal breast cancer through an HMGB1-TLR4 axis, and that both autophagy in CAFs and TLR4 on breast cancer cells constitute potential therapeutic targets. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  18. Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines

    International Nuclear Information System (INIS)

    Aloj, Luigi; Zannetti, Antonella; Caraco, Corradina; Del Vecchio, Silvana; Salvatore, Marco

    2004-01-01

    We have previously shown a correlation between the absence of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) uptake and overexpression of the anti-apoptotic protein Bcl-2 in human breast carcinoma. To establish a direct cause-effect relationship between Bcl-2 overexpression and reduced 99m Tc-MIBI uptake, MCF-7 and T47D breast cancer cell lines were stably transfected with the human Bcl-2 gene to increase intracellular protein levels and tested for 99m Tc-MIBI uptake. All clones overexpressing Bcl-2 showed a dramatic reduction of 99m Tc-MIBI uptake as compared with mock transfected control cells. Tracer uptake was promptly and partially restored by induction of apoptosis with staurosporine treatment. After 4.5 h of staurosporine treatment, a tenfold increase in 99m Tc-MIBI uptake was observed in treated as compared with untreated Bcl-2 overexpressing cells. Our findings provide a rational basis for the development of an in vivo test to detect Bcl-2 overexpression in human tumours. (orig.)

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  1. RECIST response and variation of circulating tumour cells in phase 1 trials: A prospective multicentric study.

    Science.gov (United States)

    Massard, Christophe; Borget, Isabelle; Farace, Françoise; Aspeslagh, Sandrine; Le Deley, Marie-Cécile; Le Tourneau, Christophe; Bidard, François-Clement; Pierga, Jean-Yves; Dieras, Veronique; Hofman, Paul; Spano, Jean-Philippe; Ferte, Charles; Lacroix, Ludovic; Soria, Jean-Charles

    2017-09-01

    Circulating tumour cell (CTC) counting could be a new biomarker for better evaluation of tumour response to molecules tested in phase I trials. Consenting patients with advanced metastatic cancer referred to various phase I units were enrolled prospectively in this study. CTCs from 7.5 ml of whole blood drawn at baseline and after starting experimental therapy were counted using the CellSearch system, and tumour response was assessed using RECIST 1.1 criteria at baseline and 2 months after treatment initiation. Between March 2010 and May 2013, a total of 326 patients were enrolled, among whom 214 were evaluable (49% male, median age = 56; main cancer types: lung [28], colon [53], ovarian [18], breast [28]). At baseline, we detected ≥1 CTC/7.5 ml in 113/214 patients (53%), and at day 30, we observed ≥1 CTC/7.5 ml in 103/214 patients (48%). Two months after treatment initiation, 11 (5%) of the 214 patients were classified as having a partial response, with no CTCs in 9 of them or a decrease in the CTC count after therapy. In contrast, among the 104 patients (49%) classified as having progressive disease, 38 patients had a higher CTC count. The remaining 99 patients (49%), 33 of whom (33%) had a lower CTC count, were classified as having stable disease. The sensitivity and specificity of CTC variation for predicting progressive disease were 41% (32-51%) and 80% (73-88%) respectively. An early CTC change following therapy does not correlate with RECIST response in patients with advanced cancer enrolled in phase I trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Evaluation of the radioinduced damage, repair capacity and cell death on human tumorigenic (T-47D and MCF-7) and nontumorigenic (MCF-10) cell lines of breast

    International Nuclear Information System (INIS)

    Valdoge, Flavia Gomes Silva

    2008-01-01

    Breast cancer is one of the most common malignancies that account women, representing about one in three of all female neoplasm. Approximately, 90% of cases are considered sporadic, attributed to somatic events and about 10% have a family history and this only 4 - 5 % is due to hereditary factors. In the clinic, ionizing radiation is a major tool utilized in the control of tumour growth, besides surgery and chemotherapy. There is, however, little information concerning cellular response to the action of ionizing radiation in the target cells, i.e., cell lines originating from breast cancer. The present study proposed to analyze the radiosensitivity of the human tumorigenic (T-47D and MCF-7) and non tumorigenic (MCF-10) cell lines, originating from breast and submitted to various doses (0.5 to 30 Gy) of 60 Co rays (0.72 - 1.50 Gy/min). For this purpose, DNA radioinduced damage, repair capacity and cell death were utilized as parameters of radiosensitivity by micronucleus, single cell gel electrophoresis (Comet assay) and cell viability techniques. The data obtained showed that tumorigenic cell lines were more radiosensitive than non tumorigenic breast cells in all assays here utilized. The T-47D cell line was presenting the highest amount of radioinduced damage, a more accelerated proliferation rate and a higher rate of cell death. The three cell lines presented a relatively efficient repair capacity, since one hour after the irradiation all of them showed a considerable reduction of radioinduced damage. The techniques employed showed to be secure, sensitive and reproducible, allowing to quantify and evaluate DNA damage, repair capacity and cell death in the three human breast cell lines. (author)

  3. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with {sup 18}F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lemarignier, Charles; Groheux, David [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France); Martineau, Antoine; Vercellino, Laetitia; Merlet, Pascal [Saint-Louis Hospital, Assistance Publique - Hopitaux de Paris, Department of Nuclear Medicine, Paris (France); Teixeira, Luis; Espie, Marc [Saint-Louis Hospital, Breast Diseases Unit, Paris (France); University Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris (France)

    2017-07-15

    The study was designed to evaluate 1) the relationship between PET image textural features (TFs) and SUVs, metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour characteristics in a large prospective and homogenous cohort of oestrogen receptor-positive (ER+) breast cancer (BC) patients, and 2) the capability of those parameters to predict response to neoadjuvant chemotherapy (NAC). 171 consecutive patients with large or locally advanced ER+ BC without distant metastases underwent an {sup 18}F-FDG PET examination before NAC. The primary tumour was delineated with an adaptive threshold segmentation method. Parameters of volume, intensity and texture (entropy, homogeneity, contrast and energy) were measured and compared with tumour characteristics determined on pre-treatment breast biopsy (Wilcoxon rank-sum test). The correlation between PET-derived parameters was determined using Spearman's coefficient. The relationship between PET features and pathological findings was determined using the Wilcoxon rank-sum test. Spearman's coefficients between SUV{sub max} and TFs were 0.43, 0.24, -0.43 and -0.15 respectively for entropy, homogeneity, energy and contrast; they were higher between MTV and TFs: 0.99, 0.86, -0.99 and -0.87. All TFs showed a significant association with the histological type (IDC vs. ILC; 0.02 < P < 0.03) but didn't with immunohistochemical characteristics. SUV{sub max} and TLG predicted the pathological response (P = 0.0021 and P = 0.02 respectively); TFs didn't (P: 0.27, 0.19, 0.94, 0.19 respectively for entropy, homogeneity, energy and contrast). The correlation of TFs was poor with SUV parameters and high with MTV. TFs showed a significant association with the histological type. Finally, while SUV{sub max} and TLG were able to predict response to NAC, TFs failed. (orig.)

  4. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    Science.gov (United States)

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

  5. Region of the eye. Strategy for the management of malignant tumours of the orbit

    International Nuclear Information System (INIS)

    Freeman, J.E.

    1984-01-01

    The strategy for the management of the various malignant tumours of the orbit was tabulated and also illustrated in diagrams. Table 1. Strategy for retinoblastoma; Table 2. Strategy for malignant melanoma: (a) intra-ocular, (b) epibulbar; Table 3. Strategy for squamous cell carcinoma: (a) conjunctival, (b) palpebral; Table 4. Strategy for basal cell carcinoma: (a) palpebral, (b) intra-orbital; Table 5. Strategy for rhabdomyosarcoma (and embryoma) of the orbit; Table 6. Strategy for lymphosarcoma of the orbit; Table 7. Strategy for other tumours of the orbit or adnexa: (A) hystiocytosis X, (B) adenocarcinoma of the lachrymal gland, (C) optic nerve glioma, (D) para-nasal sinus tumours involving orbit; Table 8. Strategy for systemic or metastatic disease involving the orbit or contents: (a) intra-ocular [(i) leukaemia, (ii) carcinoma of the breast or of the bronchus], (b) orbital or peri-orbital [(i) leukaemia, (ii) neuroblastoma, (iii) histiocytosis X, (iv) lymphoma

  6. Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

    Directory of Open Access Journals (Sweden)

    Rust Steven

    2013-02-01

    Full Text Available Abstract Background The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a ‘triple negative’ breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. Methods The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other ‘triple negative’ breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Results All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated

  7. Cyclin D1, Id1 and EMT in breast cancer

    International Nuclear Information System (INIS)

    Tobin, Nicholas P; Sims, Andrew H; Lundgren, Katja L; Lehn, Sophie; Landberg, Göran

    2011-01-01

    Cyclin D1 is a well-characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in 'inhibitor of differentiation 1' (ID1) gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT). Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. Protein and gene expression of ID1, CCND1 and EMT markers were determined in MDA-MB-231 and ZR75 cells by western blot and qPCR. Cell migration and promoter occupancy were monitored by transwell and ChIP assays, respectively. Gene expression was analysed from publicly available datasets. The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1-independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1 low /ID1 high tumours displayed increased expression of EMT markers and were associated with reduced recurrence free survival. Finally, a greater percentage of CCND1 low /ID1 high tumours were found in the EMT-like 'claudin-low' subtype of breast cancer than in other subtypes. These results indicate that increased migration of MDA-MB-231 cells following cyclin D1 silencing can be mediated by Id

  8. Iodide transport and breast cancer.

    Science.gov (United States)

    Poole, Vikki L; McCabe, Christopher J

    2015-10-01

    Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer. © 2015 Society for Endocrinology.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Interleukin-2 and its receptor complex (α, β and γ chains) in in situ and infiltrative human breast cancer: an immunohistochemical comparative study

    International Nuclear Information System (INIS)

    García-Tuñnón, Ignacio; Ricote, Mónica; Ruiz, Antonio; Fraile, Benito; Paniagua, Ricardo; Royuela, Mar

    2004-01-01

    The presence and distribution of interleukin-2 (IL-2) and its receptor complex (Rα, Rβ, Rγ) were studied in 52 women who were clinically and histopathologically diagnosed with breast tumours (17 in situ and 35 infiltrating), and in 13 women with benign fibrocystic lesions in the breast. Immunohistochemistry with antibodies against IL-2, IL-2Rα, IL-2Rβ and IL-2Rγ was used. A comparative semiquantitative immunohistochemical study between the three breast groups (fibrocystic lesions, in situ tumours and infiltrating tumours) was performed. IL-2 and its three receptor chains were immunodetected in the cytoplasm of epithelial cells. The three receptor chains were also detected on the cell surface. In fibrocystic lesions, immunoreactions to IL-2 (38.5% of cases), IL-2Rα (53.8%) and IL-2Rβ (30.8%) were very weak, whereas immunoreaction to IL-2Rγ (46.1%) was somewhat more intense. In in situ tumours, the percentages of cases that immunostained positively for IL-2 and its three receptor chains were similar to those observed in fibrocystic lesions, but immunostainings of the four antibodies were more intense. In infiltrative tumours, the percentages of positively stained cases and also immunostaining intensities were approximately twice that found for in situ tumours. Within infiltrating tumours, the percentage of cases showing immunoreaction to IL-2 and their three receptor chains was higher in the patients with lymph node infiltration at the time of surgery. The development of breast tumour is associated with an increased expression of IL-2 and its three receptor chains, and this expression also seems to be associated with the malignancy of the tumour

  11. Computed tomography evaluation of mast cell tumours; Avaliacao por tomografia computadorizada dos mastocitomas

    Energy Technology Data Exchange (ETDEWEB)

    Lorigados, Carla Aparecida Batista; Matera, Julia Maria; Macedo, Thais; Pinto, Ana Carolina Brandao Fonseca, E-mail: clorigados@usp.br [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia. Dept. de Cirurgia

    2012-07-01

    The mast cell tumours are common tumours of the canine skin. Computed tomography (CT) has assumed an important role in tumours evaluation and staging. The aim of this study was to evaluate the role of CT as a method of assessing characteristics of mast cell tumors. Ten dogs with mast cell tumor were evaluated. CT was performed before and after the intravenous injection of hydro soluble ionic iodine. Attenuation, contrast enhancement, cleavage with adjacent tissues and the unidimensional measurement of each lesion was determined in it maximum diameter, in transversal plane. Concerning the attenuation characteristic, 50% were homogeneous and 50% heterogeneous. The contrast enhancement was homogeneous in 50% of cases, heterogeneous in 40% and peripheral in 10%. Fifty percent of the tumours showed loss of plane of cleavage and 30% partial loss. This information can help in directing the patients that will be undergoing chemotherapy or surgery. (author)

  12. Implementation of TMA and digitalization in routine diagnostics of breast pathology

    DEFF Research Database (Denmark)

    Rossing, Henrik Holm; Talman, Maj-Lis; Laenkholm, Anne-Vibeke

    2012-01-01

    To ensure optimal treatment of breast cancer patients, breast tumours are classified based on clinico-pathological features. As part of this process, routine diagnostics of breast tumours includes histological typing and grading, as well as profiling by use of an immunohistochemistry panel...... of antibodies, probes and in situ hybridization. This will, as a minimum, include assessment of oestrogen receptor (OR) and HER2. The individual preparation and staining of many breast tumours in a large laboratory with this standard panel is thus time consuming and costly. Herein, we show that in breast cancer...... routine diagnostics the use of the tissue microarray technique in combination with digitalization of the stained multi-slides is not only economical, with a considerable cost reduction, but it also enhances standardization of tumour profiling. We demonstrate that 2 mm breast tumour cores correlate...

  13. Reproductive hormones in breast cancer bone metastasis: The role of inhibins

    Directory of Open Access Journals (Sweden)

    Caroline Wilson

    2016-09-01

    Full Text Available The spread of breast cancer cells to bone and survival in this new metastatic environment is influenced not only by the genetic signature of the cells, but also multiple host cells and soluble factors produced locally (paracrine or from distant sites (endocrine. Disrupting this metastatic process has been evaluated in clinical trials of the bone targeted agents bisphosphonates and denosumab and have shown that these agents reduce the recurrence of breast cancer in postmenopausal women only, suggesting the efficacy of the drugs are influenced by levels of reproductive endocrine hormones. The molecular mechanism driving this differential effect has not been definitively identified, however, there is evidence that both reproductive hormones and bisphosphonates can affect similar paracrine factors and cellular components of the bone metastatic niche. This review focuses on how the ovarian endocrine hormone, inhibin, interacts with the paracrine factors activin and follistatin, abundant in the primary tumour and bone microenvironment, with subsequent effects on tumour cell survival. Inhibin also affects the cellular components of the bone microenvironment primarily the osteoblastic niche. Recent evidence has shown that bisphosphonates also alter this niche, which may represent a common mechanism by which inhibin and bisphosphonates interact to influence disease outcomes in early breast cancer. Further research is needed to fully elucidate these molecular mechanisms to enable understanding and future development of alternative bone targeted treatments with anti-tumour efficacy in premenopausal women.

  14. In vivo bio-distribution and homing of endothelial outgrowth cells in a tumour model

    International Nuclear Information System (INIS)

    Bertelsen, Lotte B.; Hagensen, Mette; Busk, Morten; Zhang, Rui; Knudsen, Anne S.; Nielsen, Nathalie; Falborg, Lise; Møller, Bjarne K.; Horsman, Michael R.; Stødkilde-Jørgensen, Hans

    2014-01-01

    Introduction: Endothelial progenitor cells (EPCs) has been reported to have the potential for advancing revascularization of ischemic tissue. However, the heterogeneous nature of these cells calls for specification of the angiogenic potential of each subtype. The purpose of this study was to gain additional insight on the homing capacity of the EPC subtype, endothelial outgrowth cells (EOCs) in tumours using a well-established tumour model. Methods: 111 Indium ( 111 In) – and 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) labelled EOCs derived from human umbilical cord blood were injected into mice with a C3H mammary carcinoma foot tumour. The subsequent capture of the EOCs was traced by estimation of activity in individual organs, autoradiography and fluorescence microscopy. Results: 111 In activity was found in tumour and other organs. However, varying parts of the activity originated from free 111 In lost from EOCs. Autoradiography demonstrated accumulation of 111 In activity in the tumour rim. Microscopy proved that a least part of this radioactivity originated from the presence of human derived EOCs and that those EOCs were not located in the endothelial lining of vessels, in the tumour. Conclusion: The results demonstrated the presence of xenotransplanted EOCs in the rim of a C3H mammary carcinoma. They were, however, not located in the endothelial lining of the vessels, thus indicating that their effect in vasculogenesis might be mediated via paracrine mechanisms rather than differentiating into endothelial cells (ECs) in tumour vessels

  15. Tumour Cell Membrane Poration and Ablation by Pulsed Low-Intensity Electric Field with Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Lijun Wang

    2015-03-01

    Full Text Available Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell poration/ablation system was built for exploring these effects of CNTs in which two-electrode sets were constructed and two perpendicular electric fields could be generated sequentially. By applying this system to breast cancer cells in the presence of multi-walled CNTs (MWCNTs, the effective pulse amplitude was reduced to 50 V/cm (main field/15 V/cm (alignment field at the optimized pulse frequency (5 Hz of 500 pulses. Under these conditions instant cell membrane permeabilization was increased to 38.62%, 2.77-fold higher than that without CNTs. Moreover, we also observed irreversible electroporation occurred under these conditions, such that only 39.23% of the cells were viable 24 h post treatment, in contrast to 87.01% cell viability without presence of CNTs. These results indicate that CNT-enhanced electroporation has the potential for tumour cell ablation by significantly lower electric fields than that in conventional electroporation therapy thus avoiding potential risks associated with the use of high intensity electric pulses.

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

    LENUS (Irish Health Repository)

    Caiazza, F

    2012-02-01

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

  17. Growth of breast cancer recurrences assessed by consecutive MRI

    International Nuclear Information System (INIS)

    Millet, Ingrid; Bouic-Pages, Emmanuelle; Hoa, Denis; Azria, David; Taourel, Patrice

    2011-01-01

    Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI). Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer. Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10 -3 days -1 ] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics. These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events

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

    International Nuclear Information System (INIS)

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

    1977-01-01

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

  19. Development of an innovative 3D cell culture system to study tumour--stroma interactions in non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Arno Amann

    Full Text Available INTRODUCTION: We describe a novel 3D co-culture model using non-small cell lung cancer (NSCLC cell lines in combination with lung fibroblasts. This model allows the investigation of tumour-stroma interactions and addresses the importance of having a more in vivo like cell culture model. METHODS: Automation-compatible multi-well hanging drop microtiter plates were used for the production of 3D mono- and co-cultures. In these hanging drops the two NSCLC cell lines A549 and Colo699 were cultivated either alone or co-cultured with lung fibroblasts. The viability of tumour spheroids was confirmed after five and ten days by using Annexin V/Propidium Iodide staining for flow-cytometry. Tumour fibroblast spheroid formation was characterized by scanning electron microscope (SEM, semi-thin sections, fluorescence microscope and immunohistochemistry (IHC. In addition to conventional histology, protein expression of E-Cadherin, vimentin, Ki67, fibronectin, cytokeratin 7 and α-smooth muscle actin (α-SMA was investigated by IHC. RESULTS: Lower viability was observed in A549 monocultures compared to co-cultures, whereas Colo699 monocultures showed better viability compared to co-cultures. Ki67 expression varied significantly between mono- and co-cultures in both tumour cell lines. An increase of vimentin and decreased E-Cadherin expression could be detected during the course of the cultivation suggesting a transition to a more mesenchymal phenotype. Furthermore, the fibroblast cell line showed an expression of α-SMA only in co-culture with the cancer cell line A549, thereby indicating a mesenchymal to mesenchymal shift to an even more myofibroblast phenotype. CONCLUSION: We demonstrate that our method is a promising tool for the generation of tumour spheroid co-cultures. Furthermore, these spheroids allow the investigation of tumour-stroma interactions and a better reflection of in vivo conditions of cancer cells in their microenvironment. Our method holds

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

    Science.gov (United States)

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

    2012-12-01

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

  1. A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

    Directory of Open Access Journals (Sweden)

    Feiler Heidi S

    2009-12-01

    Full Text Available Abstract Background Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity. Methods A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI50 (dose required for 50% relative growth inhibition were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity. Results The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI50 values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response. Conclusions A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signalling and differential inhibition of aspects of motility and epithelial to mesenchymal transition. See the related commentary by Benes and Settleman: http://www.biomedcentral.com/1741-7015/7/78

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

    Directory of Open Access Journals (Sweden)

    Cameron E Snell

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

  3. Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002

    International Nuclear Information System (INIS)

    Jong, Marion de; Kwekkeboom, Dik; Valkema, Roelf; Krenning, Eric P.

    2003-01-01

    On their plasma membranes, cells express receptor proteins with high affinity for regulatory peptides, such as somatostatin. Changes in the density of these receptors during disease, e.g. overexpression in many tumours, provide the basis for new imaging methods. The first peptide analogues successfully applied for visualisation of receptor-positive tumours were radiolabelled somatostatin analogues. The next step was to label these analogues with therapeutic radionuclides for peptide receptor radionuclide therapy (PRRT). Results from preclinical and clinical multicentre studies have already shown an effective therapeutic response when using radiolabelled somatostatin analogues to treat receptor-positive tumours. Infusion of positively charged amino acids reduces kidney uptake, enlarging the therapeutic window. For PRRT of CCK-B receptor-positive tumours, such as medullary thyroid carcinoma, radiolabelled minigastrin analogues are currently being successfully applied. The combination of different therapy modalities holds interest as a means of improving the clinical therapeutic effects of radiolabelled peptides. The combination of different radionuclides, such as 177 Lu- and 90 Y-labelled somatostatin analogues, to reach a wider tumour region of high curability, has been described. A variety of other peptide-based radioligands, such as bombesin and NPY(Y 1 ) analogues, receptors for which are expressed on common cancers such as prostate and breast cancer, are currently under development and in different phases of (pre)clinical investigation. Multi-receptor tumour targeting using the combination of bombesin and NPY(Y 1 ) analogues is promising for scintigraphy and PRRT of breast carcinomas and their lymph node metastases. (orig.)

  4. A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

    Science.gov (United States)

    Goebel, Katie; Merner, Nancy D

    2017-05-01

    Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

  5. Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study

    Science.gov (United States)

    Ali, H. Raza; Chlon, Leon; Pharoah, Paul D. P.; Caldas, Carlos

    2016-01-01

    Background Immune infiltration of breast tumours is associated with clinical outcome. However, past work has not accounted for the diversity of functionally distinct cell types that make up the immune response. The aim of this study was to determine whether differences in the cellular composition of the immune infiltrate in breast tumours influence survival and treatment response, and whether these effects differ by molecular subtype. Methods and Findings We applied an established computational approach (CIBERSORT) to bulk gene expression profiles of almost 11,000 tumours to infer the proportions of 22 subsets of immune cells. We investigated associations between each cell type and survival and response to chemotherapy, modelling cellular proportions as quartiles. We found that tumours with little or no immune infiltration were associated with different survival patterns according to oestrogen receptor (ER) status. In ER-negative disease, tumours lacking immune infiltration were associated with the poorest prognosis, whereas in ER-positive disease, they were associated with intermediate prognosis. Of the cell subsets investigated, T regulatory cells and M0 and M2 macrophages emerged as the most strongly associated with poor outcome, regardless of ER status. Among ER-negative tumours, CD8+ T cells (hazard ratio [HR] = 0.89, 95% CI 0.80–0.98; p = 0.02) and activated memory T cells (HR 0.88, 95% CI 0.80–0.97; p = 0.01) were associated with favourable outcome. T follicular helper cells (odds ratio [OR] = 1.34, 95% CI 1.14–1.57; p < 0.001) and memory B cells (OR = 1.18, 95% CI 1.0–1.39; p = 0.04) were associated with pathological complete response to neoadjuvant chemotherapy in ER-negative disease, suggesting a role for humoral immunity in mediating response to cytotoxic therapy. Unsupervised clustering analysis using immune cell proportions revealed eight subgroups of tumours, largely defined by the balance between M0, M1, and M2 macrophages, with distinct

  6. 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

  7. [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

  8. Radio metal (169Yb) uptake in normal and tumour cells in vitro. Influence of metabolic cell activity and complex structure

    International Nuclear Information System (INIS)

    Franke, W.G.; Kampf, G.

    1996-01-01

    Trivalent radio metal tracers have been used for tumour imaging and metastatic pain palliation. For better understanding their tumour accumulation, basic model studies of uptake of different 169 Yb complexes into cultured normal and tumour cells were performed. Whereas the uptake of 169 Yb citrate is strongly dependent on the metabolic activity and is not tumour-cell pacific, the uptake of 169 Yb complexed with amino carbonic acid (NTA, EDTA, DTPA) does not correlate to the metabolic activities. These complexes are taken up to a greater amount by the tumour cells (by a factor of about 2). Uptake of both complex types leads to a stable association to cellular compounds, 169 Yb is not releasable by the strong complexing agent DTPA. Protein binding of the 169 Yb complexes shows great influence on their cellular uptake. The bound proportion is no more available,for cellular uptake. The results indicate that i 0 uptake of 169 Yb citrate is an active cellular transport process which i not tumor-specific, ii) the 169 Yb amino carbonic acid complexes show a weak favouring by the tumour cells, iii) different from earlier acceptions the Yb complexes studied are not taken up by the cells in protein-bound form. The structure of the Yb complex is decisive for its protein binding and cellular uptake. (author). 13 refs., 6 figs

  9. Granular cell tumour of the urinary bladder

    Directory of Open Access Journals (Sweden)

    Christoph von Klot

    2012-04-01

    Full Text Available With only 16 cases reported in the literature, the mostly benign granular cell tumour of the urinary bladder is exceptionally rare. We present the case of a 68-year old patient with one of these lesions demonstrating our histological findings including several immunohistochemical stainings used to differentiate between other more common entities.

  10. Future use of mitocans against tumour-initiating cells?

    Czech Academy of Sciences Publication Activity Database

    Morrison, B.J.; Anděra, Ladislav; Reynolds, B.A.; Ralph, S.J.; Neužil, Jiří

    2009-01-01

    Roč. 53, č. 1 (2009), s. 147-153 ISSN 1613-4125 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : mitocans * tumour-initiating cells * metastasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.356, year: 2009

  11. Immunohistochemical localisation of keratin and luminal epithelial antigen in myoepithelial and luminal epithelial cells of human mammary and salivary gland tumours.

    Science.gov (United States)

    Nathrath, W B; Wilson, P D; Trejdosiewicz, L K

    1982-01-01

    Rabbit antisera to human 40-63 000 MW epidermal keratin, one batch with restricted distribution of reactivity from an initial (aK1) and one with "broad spectrum" distribution of reactivity from a late bleeding (aK), and to "luminal epithelial antigen" (aLEA) were applied to formalin fixed paraffin embedded sections of human normal and neoplastic mammary and salivary glands using an indirect immunoperoxidase method. aK1 reacted with myoepithelial cells, aLEA with luminal epithelial cells and aK with both cell types in normal mammary and salivary gland. In breast carcinomas the majority of intraluminal and infiltrating carcinoma cells reacted with aLEA but not with aK1 which reacted only with surrounding myoepithelial cells. aK reacted with both myoepithelial cells and with intraluminal and infiltrating tumour cells. In the salivary gland adenomas the majority of cells reacted with aK, and those cells arranged in a tubular fashion reacted with aLEA.

  12. Radionuclide Tc-99m MDP Imaging for diagnosis of bone tumour at Korle-Bu Teaching Hospital (Ghana): an illustrative review

    International Nuclear Information System (INIS)

    Hasford, F.; Sosu, E.K.; Nani, K.; Sackey, T.A.; Boadu, M.; Wilson, I.K.; Addison, E.C.K.; Amuasi, J.H.

    2010-01-01

    Radioisotopes are used in diagnosing primary and metastatic bone tumours because of the high sensitivity. Diagnosing bone tumours using technetium methylene diphosphonate (Tc-99m MDP) on 9 randomly selected whole-body bone scans have been demonstrated by clinical studies of patients for illustrative review. Upon satisfactory testing of the e.cam (R) Single Photon Emission Computed Tomography at the Nuclear Medicine Department (Korle-Bu Teaching Hospital), scans of patients provided essential physiologic information about the sites of bone lesions and prognosis as shown by sequential changes in tracer uptake. The bone scintigrams were classified either as normal or pathologic. Of the 197 patients (91 males and 106 females) who underwent radioactive whole-body scans in the year 2006, the peak age at bone tumour detection was between 51 and 60 years. From qualitative analyses of the reported cases, 144 patients were diagnosed with bone tumours, but ∼ 17 % were found to be primary, while ∼ 83 % were metastatic in nature. The observation confirmed other published data that bone tumours with origin in the cells of bone are not prevalent compared to tumours that metastasize from other parts of the body, such as breast, cervix and prostate. Breast, prostate and cervical cancers contributed respectively to 34 %, 19 % and 18 % of the bone tumour cases, but only 3 % were diagnosed with osteoporosis (a relatively rare type of bone disease). (au)

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

    NARCIS (Netherlands)

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

    2014-01-01

    Recently protocols have been devised for the culturing of cell lines from fresh tumours under serum-free conditions in defined neural stem cell medium. These cells, frequently called tumour initiating cells (TICs) closely retained characteristics of the tumours of origin. We report the isolation of

  14. The tumour border on contrast-enhanced spectral mammography and its relation to histological characteristics of invasive breast cancer.

    Science.gov (United States)

    Ambicka, Aleksandra; Luczynska, Elzbieta; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Sas-Korczynska, Beata; Niemiec, Joanna

    Contrast-enhanced spectral mammography (CESM) is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: (1) their diagnostic usefulness, and (2) the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular). Therefore, we studied the relationship between the tumour margin assessed on CESM and (1) tumour borders defined on the basis of macroscopic and microscopic examination, (2) pT, (3) pN, and (4) tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1) macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004), (2) pT (p = 0.016), and (3) pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045). Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM), both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.

  15. Total hip arthroplasty for giant cell tumour.

    Directory of Open Access Journals (Sweden)

    Kulkarni S

    1996-07-01

    Full Text Available A 32 month follow up of an uncommon case of a Giant Cell Tumour affecting the proximal end of femur is presented. Following a wide excision, the hip was reconstructed using Charnley type of low friction total hip arthroplasty. At a 32 month review, there was no recurrence and the function was good.

  16. Normal and pathological breast, the histological basis

    Energy Technology Data Exchange (ETDEWEB)

    Guinebretiere, J.M. [Department of Pathology, Centre Rene-Huguenin, 35 rue Dailly, 92210 Saint Cloud (France)]. E-mail: jm.guinebretiere@stcloud-huguenin.org; Menet, E. [Department of Pathology, Centre Rene-Huguenin, 35 rue Dailly, 92210 Saint Cloud (France); Tardivon, A. [Department of Radiology, Institut Curie, 26 rue d' Ulm, 75248 Paris Cedex 5 (France); Cherel, P. [Department of Radiology, Centre Rene-Huguenin, 35 rue Dailly, 92210 Saint Cloud (France); Vanel, D. [Department of Diagnostic Radiology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France)

    2005-04-01

    Breast tissue is heterogeneous, associating connective and glandular structures, which grow and change cyclically under hormonal regulation. Hormones are also thought to be the main determinant of the major benign and malignant pathologies encountered in the breast. Benign lesions are more frequent and fibrocystic changes are by far the most common among them. They usually associate different entities (adenosis, fibrosis, cysts and hyperplasia) but vary in intensity and extension. Thus, their clinical and radiographic presentation is extremely different from one patient to another. Adenofibroma is the most frequent tumour. It also undergoes modifications according to hormonal conditions. About 90% of malignant tumours are primary carcinoma. The incidence of intra-ductal carcinoma has risen dramatically since the development of screening because of its ability to induce calcification. Two mechanisms could be involved in the formation of calcification: one active (tumour cell secretion of vesicles), the other passive (necrotic cell fragments are released). Invasive carcinoma comprises numerous histological types. Stromal reactions essentially determines their shape: a fibrous reaction commonly found in ductal carcinoma creates a stellate lesion while other stroma, inflammatory (medullary carcinoma), vascular (papillary carcinoma) or mucinous determine nodular lesions whose borders push the surrounding tissue. The histological features which give rise to the radiographic pattern will be emphasised.

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

    Directory of Open Access Journals (Sweden)

    Sander A. A. Kooijmans

    2016-03-01

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

  18. [Small cell neuroendocrine tumour of the bladder: with reference to a case and bibliographical revision].

    Science.gov (United States)

    Lahoz Tornos, A; Marrón Penón, Maria C; Pardo López, Maria L; Nogueras Gimeno, M A; Pujol Obis, E; Del Villar Sordo, V

    2006-09-01

    The small cell neuroendocrine tumour is an infrecuent neoplasia, with inmunohistochemistry being the key to diagnosis. We present a new case making reference to treatment and its evolution there after. The clinic, diagnosis and treatment of this tumour is described. Bibliographical revision follours. The neuroendocrine tumour of small cell is an infrecuent neoplasia, in which the inmunohistochemistry study is key in the diagnosis. The differential diagnosis includes the high degree diferentiation transitionals cells carcinoma and primary and secondary linfoma. The standard treatment is based on chemotherapy plus surgery.

  19. Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?

    Directory of Open Access Journals (Sweden)

    Roger von Moos

    2013-08-01

    Full Text Available Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in three phase 3 trials. Preclinical studies suggest that the RANKL pathway also plays a role in breast cancer tumourigenesis and migration to bone. In a subgroup analysis of the negative Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE trial, the bisphosphonate zoledronic acid showed potential for improving survival in patients who were postmenopausal; however, a prospective study in this patient population is required to validate this observation. Ongoing trials are examining whether adjuvant blockade of the RANKL pathway using denosumab can prevent disease recurrence in patients with high-risk breast cancer. These are building on analogous studies that have shown that denosumab improves bone metastasis-free survival in prostate cancer and suggested that it confers an overall survival benefit in non-small-cell lung cancer.

  20. Breast cancer recurrence after reoperation for surgical bleeding

    DEFF Research Database (Denmark)

    Pedersen, Rikke Nørgaard; Bhaskaran, K; Heide-Jørgensen, U

    2017-01-01

    BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group...... database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from.......i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence....

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  4. Cytotoxic effects of radiation and docetaxel in human tumour cells

    International Nuclear Information System (INIS)

    Dunne, A.L.

    2000-12-01

    Data from both single institutions and from randomised multicentre trials have demonstrated that the combination of chemotherapy with radiotherapy can increase the survival of cancer patients. Treatment regimens consisting of taxanes (paclitaxel and docetaxel), a potent class of new chemotherapeutic agents, combined with radiotherapy have recently undergone preclincal investigation. Overall, these studies show that taxanes can enhance the radiation sensitivity of tumour cells. However, data on docetaxel is very limited and the mechanism of radiosensitisation by docetaxel remains largely unknown. The chief purpose of this thesis was to investigate the ability of docetaxel to radiosensitise human tumour cells and investigate potential mechanisms for radiosensitisation. The results reported here for docetaxel indicate that for the cell fines examined this drug does have a synergistic effect and is thus a radiosensitising agent. The degree of radiosensitisation seen seems to be largely dependent on drug concentration. A mechanism involving docetaxel potentiation of radiation-induced apoptosis is also suggested. The second purpose of this thesis is to investigate the potential usefulness of an apoptosis assay and the comet assay as biological indicators for cellular radiosensitivity. Many scientists and clinicans have highlighted the need for development of new rapid, predictive assays of radiation responses. If the radiosensitivity of tumours could be predicted, it may eventually allow the individualisation of patient treatment by radiotherapy. In summary, initial DNA damage measured using the comet assay was successful in predicting the radiosensitivity of colorectal tumour cells. The results suggest that the comet assay appears more suitable than the detection of apoptosis for the prediction of radiosensitivity. We conclude that the results obtained from this thesis will contribute to the current attempts to improve the radiotherapeutic management of cancer. (author)

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

    Science.gov (United States)

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

    1992-06-01

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

  6. Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Mundy, Daniel W [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States); Harb, Wael [Horizon Oncology, The Care Group, Unity Medical Center, Lafayette, IN 47901 (United States); Jevremovic, Tatjana [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States)

    2006-03-21

    A novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin (registered) ). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available

  7. 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)

  8. 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

  9. Phosphorylation of a splice variant of collapsin response mediator protein 2 in the nucleus of tumour cells links cyclin dependent kinase-5 to oncogenesis.

    Science.gov (United States)

    Grant, Nicola J; Coates, Philip J; Woods, Yvonne L; Bray, Susan E; Morrice, Nicholas A; Hastie, C James; Lamont, Douglas J; Carey, Francis A; Sutherland, Calum

    2015-11-10

    Cyclin-dependent protein kinase-5 (CDK5) is an unusual member of the CDK family as it is not cell cycle regulated. However many of its substrates have roles in cell growth and oncogenesis, raising the possibility that CDK5 modulation could have therapeutic benefit. In order to establish whether changes in CDK5 activity are associated with oncogenesis one could quantify phosphorylation of CDK5 targets in disease tissue in comparison to appropriate controls. However the identity of physiological and pathophysiological CDK5 substrates remains the subject of debate, making the choice of CDK5 activity biomarkers difficult. Here we use in vitro and in cell phosphorylation assays to identify novel features of CDK5 target sequence determinants that confer enhanced CDK5 selectivity, providing means to select substrate biomarkers of CDK5 activity with more confidence. We then characterize tools for the best CDK5 substrate we identified to monitor its phosphorylation in human tissue and use these to interrogate human tumour arrays. The close proximity of Arg/Lys amino acids and a proline two residues N-terminal to the phosphorylated residue both improve recognition of the substrate by CDK5. In contrast the presence of a proline two residues C-terminal to the target residue dramatically reduces phosphorylation rate. Serine-522 of Collapsin Response Mediator-2 (CRMP2) is a validated CDK5 substrate with many of these structural criteria. We generate and characterise phosphospecific antibodies to Ser522 and show that phosphorylation appears in human tumours (lung, breast, and lymphoma) in stark contrast to surrounding non-neoplastic tissue. In lung cancer the anti-phospho-Ser522 signal is positive in squamous cell carcinoma more frequently than adenocarcinoma. Finally we demonstrate that it is a specific and unusual splice variant of CRMP2 (CRMP2A) that is phosphorylated in tumour cells. For the first time this data associates altered CDK5 substrate phosphorylation with

  10. 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)

  11. Tight correlation between expression of the Forkhead transcription factor FOXM1 and HER2 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Hartmann Arndt

    2008-02-01

    Full Text Available Abstract Background FOXM1 regulates expression of cell cycle related genes that are essential for progression into DNA replication and mitosis. Consistent with its role in proliferation, elevated expression of FOXM1 has been reported in a variety of human tumour entities. FOXM1 is a gene of interest because recently chemical inhibitors of FOXM1 were described to limit proliferation and induce apoptosis in cancer cells in vitro, indicating that FOXM1 inhibitors could represent useful anticancer therapeutics. Methods Using immunohistochemistry (IHC we systematically analysed FOXM1 expression in human invasive breast carcinomas (n = 204 and normal breast tissues (n = 46 on a tissue microarray. Additionally, using semiquantitative realtime PCR, a collection of paraffin embedded normal (n = 12 and cancerous (n = 25 breast tissue specimens as well as benign (n = 3 and malignant mammary cell lines (n = 8 were investigated for FOXM1 expression. SPSS version 14.0 was used for statistical analysis. Results FOXM1 was found to be overexpressed in breast cancer in comparison to normal breast tissue both on the RNA and protein level (e.g. 8.7 fold as measured by realtime PCR. We found a significant correlation between FOXM1 expression and the HER2 status determined by HER2 immunohistochemistry (P P = 0.110. Conclusion FOXM1 may represent a novel breast tumour marker with prognostic significance that could be included into multi-marker panels for breast cancer. Interestingly, we found a positive correlation between FOXM1 expression and HER2 status, pointing to a potential role of FOXM1 as a new drug target in HER2 resistant breast tumour, as FOXM1 inhibitors for cancer treatment were described recently. Further studies are underway to analyse the potential interaction between FOXM1 and HER2, especially whether FOXM1 directly activates the HER2 promoter.

  12. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

    Science.gov (United States)

    Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

    2015-07-10

    Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  13. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Brockton, Nigel T.; Gill, Stephanie J.; Laborge, Stephanie L.; Paterson, Alexander H. G.; Cook, Linda S.; Vogel, Hans J.; Shemanko, Carrie S.; Hanley, David A.; Magliocco, Anthony M.; Friedenreich, Christine M.

    2015-01-01

    Bone is the most common site of breast cancer distant metastasis, affecting 50–70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

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

    Science.gov (United States)

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

    2012-01-01

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

  15. The natural history of Leydig cell testicular tumours: an analysis of the National Cancer Registry.

    Science.gov (United States)

    Nason, G J; Redmond, E J; Considine, S W; Omer, S I; Power, D; Sweeney, P

    2018-05-01

    Leydig cell tumour (LCT) of the testis is a rare histological subtype of stromal tumours, accounting for 1 to 3% of testicular neoplasms. The natural history of LCT is poorly understood. The aim of this study was to assess the incidence and natural history of Leydig cell tumours (LCT) of the testes. A search of the National Cancer Registry of Ireland database was performed regarding Leydig cell testicular tumours. Recurrence free survival (RFS) and disease-specific survival (DSS) were analysed. Between 1994 and 2013, 2755 new cases of testicular cancer were diagnosed in Ireland. Of these, 22 (0.79%) were Leydig cell tumours. Nineteen were invasive (stage T1) and three were in situ (stage Tis). One patient developed a local recurrence following an organ preserving procedure and underwent a completion orchidectomy 107 days after initial diagnosis. No further treatment was required. There have been no disease-specific deaths. The 1-, 3- and 5-year overall survival (OS) rates were 95.5, 88.2 and 73.3%, respectively. The 5-year disease-specific survival (DSS) was 100% and the 5-year recurrence free survival (RFS) was 93.3%. From the National Cancer Registry, LCT has been shown to be a rare subtype of testicular tumour. Due to the relatively favourable natural history, it may be possible to tailor less aggressive surveillance regimens in these patients.

  16. The tumour border on contrast-enhanced spectral mammography and its relation to histological characteristics of invasive breast cancer

    Directory of Open Access Journals (Sweden)

    Aleksandra Ambicka

    2016-11-01

    Full Text Available Contrast-enhanced spectral mammography (CESM is one of the new diagnostic modalities implemented in clinical practice. In the case of these techniques, there are two major issues to be addressed: (1 their diagnostic usefulness, and (2 the relation between parameters assessed using these techniques and well-known diagnostic/prognostic/predictive markers (histological, clinical, and molecular. Therefore, we studied the relationship between the tumour margin assessed on CESM and (1 tumour borders defined on the basis of macroscopic and microscopic examination, (2 pT, (3 pN, and (4 tumour grade in a group of 82 breast cancer patients. Based on CESM, the tumour border was defined as sharp, indistinct or spiculated, whereas in the case of lesions showing weak or medium enhancement on CESM the borders were classified as unspecified. We found a statistically significant relationship between tumour margin on CESM and (1 macroscopic border (a spiculated margin on CESM was found only in carcinomas with an invasive border on histological examination; p = 0.004, (2 pT (p = 0.016, and (3 pN (nodal involvement was observed most frequently in carcinomas with a spiculated or indistinct margin on CESM; p = 0.045. Moreover, in cases with an undefined margin on CESM (cases showing weak or medium enhancement on CESM, both invasive and pushing borders were found on histological examination. The results of our preliminary study suggest that it is possible to assess macroscopic borders of examined lesions on the basis of CESM imaging. This might be useful in planning the extent of surgical excision. On the other hand, the assessment of the tumour margin on CESM might not be precise in cases showing weak enhancement.

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

    Science.gov (United States)

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

    2014-02-01

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

  18. The Genetic Landscape of Breast Carcinomas with Neuroendocrine Differentiation

    Science.gov (United States)

    Marchiò, Caterina; Geyer, Felipe C; Ng, Charlotte KY; Piscuoglio, Salvatore; De Filippo, Maria R; Cupo, Marco; Schultheis, Anne M; Lim, Raymond S; Burke, Kathleen A; Guerini-Rocco, Elena; Papotti, Mauro; Norton, Larry; Sapino, Anna; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Neuroendocrine breast carcinomas (NBCs) account for 2–5% of all invasive breast cancers and are histologically similar to neuroendocrine tumours from other sites. They typically express oestrogen receptor (ER), are HER2-negative and of luminal 'intrinsic' subtype. Here we sought to define the mutational profile of NBCs, and to investigate whether NBCs and common forms of luminal (ER+/HER2-) breast cancer display distinct repertoires of somatic mutations. Eighteen ER+/HER2- NBCs, defined as harbouring >50% of tumour cells expressing chromogranin A and/or synaptophysin, and matched normal tissue were microdissected and subjected to massively parallel sequencing targeting all exons of 254 genes most frequently mutated in breast cancer and/or related to DNA repair. Their mutational repertoire was compared to that of ER+/HER2- (n=240), PAM50-defined luminal breast cancers (n=209 luminal A; n=111 luminal B) and invasive lobular carcinomas (n=127) from The Cancer Genome Atlas. NBCs were found to harbour a median of 4.5 (range 1-11) somatic mutations, similar to that of luminal B breast cancers (median=3, range 0-17) but significantly higher than that of luminal A breast cancers (median=3, range 0-18, p=0.02). The most frequently mutated genes were GATA3, FOXA1, TBX3, ARID1A (3/18, 17%), and PIK3CA, AKT1, CDH1 (2/18, 11%). NBCs less frequently harboured PIK3CA mutations than common forms of ER+/HER2, luminal A and invasive lobular carcinomas (pcancers. No TP53 somatic mutations were detected in NBCs. Compared to common forms of luminal breast cancers, NBCs display a distinctive repertoire of somatic mutations featuring lower frequency of TP53 and PIK3CA mutations, and enrichment for FOXA1, TBX3 mutations, and akin to neuroendocrine tumours from other sites, ARID1A mutations. PMID:27925203

  19. EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

    International Nuclear Information System (INIS)

    Krause, Mechthild; Prager, Jenny; Zhou Xuanjing; Yaromina, Ala; Doerfler, Annegret; Eicheler, Wolfgang; Baumann, Michael

    2007-01-01

    Background and purpose: Waiting times before radiotherapy may reduce tumour control probability due to proliferation of tumour cells. The aim of the experiment was to test whether the growth inhibiting effect of epidermal growth factor receptor (EGFR)-inhibitors after surgery or tumour transplantation results in a lower tumour mass at time of irradiation and can thereby improve local tumour control. Materials and methods: The EGFR-tyrosine kinase inhibitor BIBX1382BS was applied over 14 days starting from microscopically non-in-sano-resection of FaDu tumours or from tumour transplantation, followed by irradiation (5f/5d). Endpoint was local tumour control. In addition, vital tumour areas, pimonidazole hypoxic fraction, BrdU labelling index, and colony forming ability in vitro were tested in control tumours and after BIBX1382BS treatment (starting from transplantation). Results: The tumour volume at start of irradiation was significantly lower in the BIBX1382BS treated tumours as compared to the control groups by factors of 11 (post-surgery setting) and 2.7 (transplantation setting). However, the reduced volume did not translate into improved local control after irradiation. The TCD 50 values after surgery were 25.4 Gy [95% CI 18; 33 Gy] in the control group and 30.5 Gy [24; 37] in the BIBX1382BS group (p = 0.25). Treatment after transplantation resulted in TCD 50 values of 41.1 Gy [35; 47] in the control group and 41.1 Gy [33; 49] in the BIBX1382BS group (p = 1). While the proportion of S-phase cells decreased after BIBX1382BS treatment, no differences were observed between the pimonidazole hypoxic fractions and in vitro colony forming ability. Conclusions: EGFR-TK inhibition with BIBX1382BS over 14 days between macroscopically complete tumour resection or tumour transplantation and start of radiotherapy significantly reduced tumour volume but did not improve local tumour control. One possible explanation is that the EGFR-TK inhibitor has a higher activity in

  20. Effects of glucocorticoid hormones on cell proliferation in dimethylhydrazine-induced tumours in rat colon.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1981-01-01

    Adrenocortical hormones have previously been shown to influence cell proliferation in many tissues. In this report, their influence on cell proliferation in the colonic crypt epithelium and in colonic adenocarcinomata is compared. Colonic tumour cell proliferation was found to be retarded following adrenalectomy and this retardation was reversible by administration of hydrocortisone, or by administration of synthetic steroids with predominantly glucocorticoid activity. Tumour cell proliferation in adrenalectomized rats was not promoted by the mineralocorticoid hormone aldosterone. Neither adrenalectomy, nor adrenocortical hormone treatment, significantly influenced colonic crypt cell proliferation.

  1. HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations.

    Science.gov (United States)

    Cuello-Carrión, F Darío; Shortrede, Jorge E; Alvarez-Olmedo, Daiana; Cayado-Gutiérrez, Niubys; Castro, Gisela N; Zoppino, Felipe C M; Guerrero, Martín; Martinis, Estefania; Wuilloud, Rodolfo; Gómez, Nidia N; Biaggio, Verónica; Orozco, Javier; Gago, Francisco E; Ciocca, Leonardo A; Fanelli, Mariel A; Ciocca, Daniel R

    2015-02-01

    In human breast cancer, β-catenin localization has been related with disease prognosis. Since HER2-positive patients are an important subgroup, and that in breast cancer cells a direct interaction of β-catenin/HER2 has been reported, in the present study we have explored whether β-catenin location is related with the disease survival. The study was performed in a tumor bank from patients (n = 140) that did not receive specific anti-HER2 therapy. The proteins were detected by immunohistochemistry in serial sections, 47 (33.5%) patients were HER2-positive with a long follow-up. HER2-positive patients that displayed β-catenin at the plasma membrane (completely surrounding the tumour cells) showed a significant better disease-free survival and overall survival than the patients showing the protein on other locations. Then we explored the dynamics of the co-expression of β-catenin and HER2 in human MCF-7 and SKBR3 cells exposed to different stressful situations. In untreated conditions MCF-7 and SKBR3 cells showed very different β-catenin localization. In MCF-7 cells, cadmium administration caused a striking change in β-catenin localization driving it from plasma membrane to cytoplasmic and perinuclear areas and HER2 showed a similar localization patterns. The changes induced by cadmium were compared with heat shock, H2O2 and tamoxifen treatments. In conclusion, this study shows the dynamical associations of HER2 and β-catenin and their changes in subcellular localizations driven by stressful situations. In addition, we report for the first time the correlation between plasma membrane associated β-catenin in HER2-positive breast cancer and survival outcome, and the importance of the protein localization in breast cancer samples.

  2. Content of DNA in cancerous tumours of the breast before and after large-fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shiukashvili, N N

    1976-07-01

    The article presents the results of microspectrophotometric investigation of DNA in different cancerous tumors of the breast gland before and after large-fractionated irradiation. The study of quantitative content of DNA in the non-irradiated tumors of the breast of different histological structure showed that parenchymatous cells are characterized by a definite variety in the DNA content with a different level of their polyploidy. This points to the fact that different histological forms of the breast cancer are distinguished by the character of the components differentiation. The comparative assessment of the ploidity of the cancerous cells of irradiated and non-irradiated tumors revealed that under the changed conditions of co-existence in all histological forms of cancer new modal classes of the cells develop and general quantity of the DNA content decreases. This testifies to the fact that the histological forms of the breast cancer are not equal sensitive tumors. A microspectrophotometric study of the breast tumors makes it possible to reveal the injury of the malignant tumor cells in the initial period of irradiation, when it is difficult to discover clear-cut dystrophical changes during histological investigation.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  4. Breast metastases from rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  5. Cytotoxicity Enhancement in Breast Cancer Cells with Carbonate Apatite-Facilitated Intracellular Delivery of Anti-Cancer Drugs

    Science.gov (United States)

    Fatemian, Tahereh; Chowdhury, Ezharul Hoque

    2018-01-01

    Pharmacotherapy as the mainstay in the management of breast cancer has demonstrated various drawbacks, including non-targeted bio distribution and narrow therapeutic and safety windows. Thus, enhancements in pharmacodynamic and pharmacokinetic profiles of the classical anti-cancer drugs could lead to improved efficacy against cancer cells. Therefore, inorganic pH-dependent carbonate apatite (CA) nanoparticles were utilized to efficiently deliver various drugs into cancer cells. Following characterization and various modifications in the structure of CA complexes with different drugs, lifted outcomes were achieved. Markedly, complexing paclitaxel with CA resulted in 20.71 ± 4.34% loading efficiency together with 24.14 ± 2.21% enhancement in cytotoxicity on MCF-7 cells plus superior in vivo anti-tumour efficacy compared to free paclitaxel. PMID:29401738

  6. Cytotoxicity Enhancement in Breast Cancer Cells with Carbonate Apatite-Facilitated Intracellular Delivery of Anti-Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Tahereh Fatemian

    2018-02-01

    Full Text Available Pharmacotherapy as the mainstay in the management of breast cancer has demonstrated various drawbacks, including non-targeted bio distribution and narrow therapeutic and safety windows. Thus, enhancements in pharmacodynamic and pharmacokinetic profiles of the classical anti-cancer drugs could lead to improved efficacy against cancer cells. Therefore, inorganic pH-dependent carbonate apatite (CA nanoparticles were utilized to efficiently deliver various drugs into cancer cells. Following characterization and various modifications in the structure of CA complexes with different drugs, lifted outcomes were achieved. Markedly, complexing paclitaxel with CA resulted in 20.71 ± 4.34% loading efficiency together with 24.14 ± 2.21% enhancement in cytotoxicity on MCF-7 cells plus superior in vivo anti-tumour efficacy compared to free paclitaxel.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  8. Mechanisms of Bone Metastasis from Breast Cancer Using a Clinically Relevant Model

    National Research Council Canada - National Science Library

    Anderson, Robin

    2001-01-01

    .... We have developed a murine model of breast cancer that actively mimics the human disease. After implantation of tumor cells into the mammary gland, a primary tumour develops and subsequently metastasises to the lymph nodes, lung and bone...

  9. Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and technetium-99m methoxyisobutylisonitrile scintimammography in the detection of breast tumours

    Energy Technology Data Exchange (ETDEWEB)

    Palmedo, H.; Bender, H.; Gruenwald, F.; Zamora, P.; Biersack, H.J. [Department of Nuclear Medicine, University of Bonn (Germany); Mallmann, P.; Krebs, D. [Department of Gynecology and Obstetrics, University of Bonn (Germany)

    1997-09-01

    The aim of this study was to compare, in breast cancer patients, the diagnostic accuracy of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) and scintimammography (SMM) using technetium-99m methoxyisobutylisonitrile (MIBI). A total of 20 patients (40 breasts with 22 lesions) were evaluated serially with MIBI and, on the following day, with FDG. For SMM, planar and single-photon emission tomography imaging in the prone position was performed starting at 10 min following the injection of MIBI (740 MBq). For PET, scans were acquired 45-60 min after the injection of FDG (370 MBq) and attentuation correction was performed following transmission scans. Results from SMM and PET were subsequently compared with the histopathology results. True-positive results were obtained in 12/13 primary breast cancers (mean diameter=29 mm, range 8-53 mm) with both FDG and MIBI. False-negative results were obtained in two local recurrences (diameter <9 mm) with both FDG and MIBI. In benign disease, FDG and MIBI did not localize three fibrocystic lesions, two fibroadenomas and one inflammatory lesion (true-negative), but both localized one fibroadenoma (false-positive). Collectively, the results demonstrate a sensitivity of 92%, and a specificity of 86%, for primary breast cancer regardless of whether FDG or MIBI was used. In contrast to MIBI scintigraphy, FDG PET scored the axillae correctly as either positive (metastatic disease) or negative (no axillary disease) in all 12 patients. The tumour/non-tumour ratio for MIBI was 1.97 (range 1.43-3.1). The mean standard uptake value (SUV) for FDG uptake was 2.57 (range 0.3-6.2). The diagnostic accuracy of SMM was equivalent to that of FDG PET for the detection of primary breast cancer. For the detection of in situ lymph node metastases of the axilla, FDG seems to be more sensitive than {sup 99m}Tc-MIBI. (orig.). With 4 figs., 2 tabs.

  10. Merkel cell tumour of the face successfully treated with radical radiotherapy

    International Nuclear Information System (INIS)

    Pople, I.K.

    1988-01-01

    A case of Merkel cell tumour of the face and its dramatic response to a course of radical radiotherapy is presented below. The patient has been free of recurrence for 18 months and has suffered minimal side-effects from the treatment. This suggests that radical radiotherapy, as opposed to the standard wide excision, may be preferred first-line treatment for at least some of these rare, but highly malignant tumours. (author)

  11. Polystyrene nanoparticles facilitate the internalization of impermeable biomolecules in non-tumour and tumour cells from colon epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Cabeza, Laura [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Cano-Cortés, Victoria; Rodríguez, María J. [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Vélez, Celia; Melguizo, Consolación, E-mail: melguizo@ugr.es [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain); Sánchez-Martín, Rosario M., E-mail: rmsanchez@ugr.es [University of Granada, Department of Pharmaceutical and Organic Chemistry (Spain); Prados, Jose [University of Granada, Department of Human Anatomy and Embryology, Institute of Biopathology and Regenerative Medicine (IBIMER) (Spain)

    2015-01-15

    Advanced colon cancer has a poor prognosis due to the limited effectiveness of current chemotherapies. Treatment failures may be avoided by the utilization of nanoparticles, which can enhance the effects of antitumor drugs, reduce their side effects and increase their directionality. Polystyrene nanoparticles have shown high biocompatibility and appropriate physicochemical properties and may represent a novel and more effective approach against colon cancer. In the present study, polystyrene nanoparticles were synthesized and fluorescently labelled, analyzing their cell internalization, intracellular localization and capacity to release transported molecules in tumour and non-tumour human colon cell lines (T84 and CCD-18). Flow cytometry and fluorescence microscopy studies demonstrated that polystyrene nanoparticles are an effective vehicle for the intracellular delivery of small molecules into colon epithelium cells. The percentage cell