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Sample records for cancer cells harbouring

  1. Potential influence of interleukin-6 on the therapeutic effect of gefitinib in patients with advanced non-small cell lung cancer harbouring EGFR mutations.

    Science.gov (United States)

    Tamura, Tomoki; Kato, Yuka; Ohashi, Kadoaki; Ninomiya, Kiichiro; Makimoto, Go; Gotoda, Hiroko; Kubo, Toshio; Ichihara, Eiki; Tanaka, Takehiro; Ichimura, Koichi; Maeda, Yoshinobu; Hotta, Katsuyuki; Kiura, Katsuyuki

    2018-01-01

    Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are a key therapy used for patients with EGFR-mutant non-small cell lung cancer (NSCLC), some of whom do not respond well to its therapy. Cytokine including IL-6 secreted by tumour cells is postulated as a potential mechanism for the primary resistance or low sensitivity to EGFR-TKIs. Fifty-two patients with advanced EGFR-mutant NSCLC who had received gefitinib were assessed retrospectively. The protein expression of IL-6 in the tumour cells was assessed by immunostaining and judged as positive if ≥ 50 of 100 tumour cells stained positively. Of the 52 patients, 24 (46%) and 28 (54%) were defined as IL-6-postitive (group P) and IL-6-negative (group N), respectively. Group P had worse progression-free survival (PFS) than that of group N, which was retained in the multivariate analysis (hazard ratio: 2.39; 95 %CI: 1.00-5.68; p < 0.05). By contrast, the PFS after platinum-based chemotherapy did not differ between groups P and N (p = 0.47). In cell line-based model, the impact of IL-6 on the effect of EGFR-TKIs was assessed. The combination of EGFR-TKI and anti-IL-6 antibody moderately improved the sensitivity of EGFR-TKI in lung cancer cell with EGFR mutation. Interestingly, suppression of EGFR with EGFR-TKI accelerated the activation of STAT3 induced by IL-6. Taken together, tumour IL-6 levels might indicate a subpopulation of EGFR-mutant NSCLC that benefits less from gefitinib monotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Spatial Cognition: Grid Cells Harbour Three Complementary Positional Codes.

    Science.gov (United States)

    Stemmler, Martin; Herz, Andreas V M

    2017-08-07

    The firing fields of mammalian grid cells, which map an animal's environment, lie on hexagonal lattices. Three new studies report significant field-to-field differences in the firing rates, a finding with far-reaching consequences for how grid fields form and encode spatial information. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Toxic effects of tributyltin and its metabolites on harbour seal (Phoca vitulina) immune cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Frouin, Heloise [Institut National de la Recherche Scientifique - Institut Armand-Frappier, Laval, Quebec H7V 1B7 (Canada); Fisheries and Oceans Canada, Maurice Lamontagne Institute, Mont-Joli, Quebec G5H 3Z4 (Canada)], E-mail: heloise.frouin@iaf.inrs.ca; Lebeuf, Michel [Fisheries and Oceans Canada, Maurice Lamontagne Institute, Mont-Joli, Quebec G5H 3Z4 (Canada); Saint-Louis, Richard [Institut des Sciences de la Mer de Rimouski (ISMER), Universite du Quebec a Rimouski, Rimouski, Quebec G5L 3A1 (Canada); Hammill, Mike [Fisheries and Oceans Canada, Maurice Lamontagne Institute, Mont-Joli, Quebec G5H 3Z4 (Canada); Pelletier, Emilien [Institut des Sciences de la Mer de Rimouski (ISMER), Universite du Quebec a Rimouski, Rimouski, Quebec G5L 3A1 (Canada); Fournier, Michel [Institut National de la Recherche Scientifique - Institut Armand-Frappier, Laval, Quebec H7V 1B7 (Canada)

    2008-11-21

    The widespread environmental contamination, bioaccumulation and endocrine disruptor effects of butyltins (BTs) to wildlife are well documented. Although suspected, potential effects of BTs exposure on the immune system of marine mammals have been little investigated. In this study, we assessed the effects of tributyltin (TBT) and its dealkylated metabolites dibutyltin (DBT) and monobutyltin (MBT) on the immune responses of harbour seals. Peripheral blood mononuclear cells isolated from pup and adult harbour seals were exposed in vitro to varying concentrations of BTs. DBT resulted in a significant decrease at 100 and 200 nM of phagocytotic activity and reduced significantly phagocytic efficiency at 200 nM in adult seals. There was no effect in phagocytosis with TBT and MBT. In pups, the highest concentration (200 nM) of DBT inhibited phagocytic efficiency. A reduction of tumor-killing capacity of adult natural killer (NK) cells occurred when leukocytes were incubated in vitro with 50 nM DBT and 200 nM TBT for 24 h. In adult seals, T-lymphocyte proliferation was significantly suppressed when the cells were exposed to 200 nM TBT and 100 nM DBT. In pups, the proliferative response increased after an exposure to 100 nM TBT and 50 nM DBT, but decreased with 200 nM TBT and 100 nM DBT. The immune functions were more affected by BTs exposure in adults than in pups, suggesting that other unsuspected mechanisms could trigger immune parameters in pups. The toxic potential of BTs followed the order of DBT > TBT > MBT. BT concentrations of harbour seal pups from the St. Lawrence Estuary (Bic National Park) ranged between 0.1-0.4 ng Sn/g wet weight (ww) and 1.2-13.4 ng Sn/g ww in blood and blubber, respectively. For these animals, DBT concentrations were consistently below the quantification limit of 0.04 ng Sn/g ww in blood and 0.2 ng Sn/g ww in blubber. Results suggest that concentrations measured in pups are considered too low to induce toxic effects to their immune system

  4. Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma.

    Science.gov (United States)

    Zeng, A-L; Yan, W; Liu, Y-W; Wang, Z; Hu, Q; Nie, E; Zhou, X; Li, R; Wang, X-F; Jiang, T; You, Y-P

    2017-09-21

    Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma (GBM) progression, and many fusion genes are strong driver mutations in neoplasia and are involved in tumorigenesis. However, the ability of fusion genes to be transduced by exosomes is unknown. We characterized exosomes from GBM cells harbouring and not harbouring PTPRZ1-MET fusion (ZM fusion). We also determined the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic secretions and showed that ZM exosomes are internalized by the recipient cells. In addition, we studied the effect of ZM exosome-mediated intercellular communication in the GBM microenvironment. MET proto-oncogene expression was higher in ZM exosomes. Moreover, phosphorylated MET was detected only in ZM exosomes and not in exosomes released by non-ZM fusion GBM cells. ZM exosomes transferred to non-ZM fusion GBM cells and normal human astrocytes altered gene expression and induced epithelial-mesenchymal transition. The uptake of ZM exosomes also induced an exosome-dependent phenotype defined by GBM cell migration and invasion, neurosphere growth and angiogenesis. In addition, ZM exosomes conferred temozolomide resistance to the GBM cells, and exosome-derived ZM fusion network proteins targeted multiple pro-oncogenic effectors in recipient cells within the GBM microenvironment. Our findings show that exosomes mediate the aggressive character of GBM and demonstrate the role of ZM fusion in the exacerbation of this effect. These findings have possible implications for the foundation of gene fusion-based therapy for managing GBM.

  5. Effects of carbonic anhydrase-related protein VIII on human cells harbouring an A8344G mitochondrial DNA mutation.

    Science.gov (United States)

    Wang, Tze-Kai; Cheng, Che-Kun; Chi, Tang-Hao; Ma, Yi-Shing; Wu, Shi-Bei; Wei, Yau-Huei; Hsieh, Mingli

    2014-04-01

    MERRF (myoclonus epilepsy associated with ragged-red fibres) is a maternally inherited mitochondrial encephalomyopathy with various syndromes involving both muscular and nervous systems. The most common mutation in MERRF syndrome, the A8344G mutation in mtDNA, has been associated with severe defects in the respiratory function of mitochondria. In the present study, we show that there is a significant decrease in CA8 (carbonic anhydrase-related protein VIII) in cybrids harbouring the MERRF A8344G mutation. CA8 deficiency and mutations were found to be associated with a distinctive lifelong gait disorder in wdl (Waddles) mice and novel syndromes characterized by cerebellar ataxia and mental retardation in humans. The results of the present study showed that overexpression of CA8 in MERRF cybrids significantly decreased cell death induced by STS (staurosporine) treatment, suggesting a protective function of CA8 in cells harbouring the A8344G mutation of mtDNA. Interestingly, an increase in the formation of LC3-II (microtubule-associated protein 1 light chain 3-II) was found in the cybrids with down-regulated CA8 expression, suggesting that reduced expression of CA8 leads to autophagy activation. Furthermore, cybrids exhibiting down-regulated CA8 showed increased cytosolic Ca2+ signals and reduced levels of phospho-Akt compared with those in the cybrids with overexpressed CA8, indicating that phospho-Akt is involved in the protection of cells by CA8. Our findings suggest that CA8 is involved in the autophagic pathway and may have a protective role in cultured cells from patients with MERRF. Targeting CA8 and the downstream autophagic pathway might help develop therapeutic agents for treatment of MERRF syndrome in the future.

  6. Hambantota Fishery Harbour

    NARCIS (Netherlands)

    Everts, P.S.; Julianus, E.J.B.; Marijnissen, M.; Voorend, S.J.M.

    2014-01-01

    At the southern coast of Sri Lanka a small fishery harbour is located in Hambantota. Soon after construction of the harbour in 2006 the harbour started silting up at various places. From that point onwards the harbour’s basin has been dredged multiple times, but the problem turned out to be

  7. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST mimicking hereditary GIST syndromes

    Directory of Open Access Journals (Sweden)

    Mafalda Costa Neves

    2015-01-01

    Conclusion: We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder.

  8. Beta2 toxin is not involved in in vitro cell cytotoxicity caused by human and porcine cpb2-harbouring Clostridium perfringens.

    Science.gov (United States)

    Allaart, Janneke G; van Asten, Alphons J A M; Vernooij, Johannes C M; Gröne, Andrea

    2014-06-25

    Clostridium perfringens is a common cause of intestinal disease in animals and humans. Its pathogenicity is attributed to the toxins it can produce, including the beta2 toxin. The presence of cpb2, the gene encoding the beta2 toxin, has been associated with diarrhoea in neonatal piglets and humans. However, the exact role of the beta2 toxin in the development of diarrhoea is still unknown. In this study we investigated the level of cytotoxicity to porcine IPI-21 and human Caco-2 cell-lines caused by porcine and human cpb2-harbouring C. perfringens and the significance of the beta2 toxin for the induction of cell cytotoxicity. Supernatants of porcine cpb2-harbouring C. perfringens strains were cytotoxic to both cell lines. Cell cytotoxicity caused by supernatant of human cpb2-harbouring C. perfringens strains was variable among strains. However, removal of the beta2 toxin by anti-beta2 toxin antibodies or degradation of the beta2 toxin by trypsin did not reduce the cytotoxic effect of any of the supernatants. These data suggest that beta2 toxin does not play a role in the development of cell cytotoxicity in in vitro experiments. In vivo studies are necessary to definitely define the role of beta2 toxin in the development of cell cytotoxicity and subsequent diarrhoea. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Oncolytic vaccine virus harbouring the IL-24 gene suppresses the growth of lung cancer by inducing apoptosis.

    Science.gov (United States)

    Lv, Chunwei; Su, Qunshu; Liang, Yupei; Hu, Jinqing; Yuan, Sujing

    2016-07-15

    Lung cancer has an especially high incidence rate worldwide, and its resistance to cell death and chemotherapeutic drugs increases its intractability. The vaccinia virus has been shown to destroy neoplasm within a short time and disseminate rapidly and extensively as an enveloped virion throughout the circulatory system, and this virus has also demonstrated a strong ability to overexpress exogenous genes. Interleukin-24 (IL-24/mda-7) is an important cytokine that belongs to the activating caspase family and facilitates the inhibition of STAT3 when a cell enters the apoptosis pathway. In this study, we constructed a cancer-targeted vaccinia virus carrying the IL-24 gene knocked in the region of the viral thymidine kinase (TK) gene (VV-IL-24). Our results showed that VV-IL-24 efficiently infected and destroyed lung cancer cells via caspase-dependent apoptosis and decreased the expression of STAT3. In vivo, VV-IL-24 expressed IL-24 at a high level in the transplanted tumour, reduced STAT3 activity, and eventually led to apoptosis. In conclusion, we demonstrated that vv-IL-24 has the potential for use as a new human lung cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations

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    Gentilcore Giusy

    2013-01-01

    Full Text Available Abstract Background Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436, has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations. Methods Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib. Results Our experiments demonstrated an effective action of Dabrafenib (GSK2118436 and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. Conclusion These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.

  11. Subpopulations of stem-like cells in side population cells from the human bladder transitional cell cancer cell line T24.

    Science.gov (United States)

    Ning, Z-F; Huang, Y-J; Lin, T-X; Zhou, Y-X; Jiang, C; Xu, K-W; Huang, H; Yin, X-B; Huang, J

    2009-01-01

    Cancer stem cells can be isolated from human tumours using specific cell surface markers. Bladder cancer cells, however, lack specific cell surface markers, making this approach impracticable. In this study an alternative method was used, involving isolation of side population cells to explore the stem cell characteristics of bladder cancer. Side population cells were isolated from the bladder transitional cell cancer cell line T24 and examined for potential stem cell characteristics related to proliferation, cell cycle distribution, self-renewal and differentiation. It was observed that T24 side population cells have stronger proliferative and colony formation abilities than non-side population cells. Side population cells were also more resistant to chemotherapy and radiotherapy, which may be due to expression of the ATP-binding cassette half-transporter, sub-family G, member 2 protein. Overall, the results suggest that side population cells from the human bladder transitional cell cancer cell line T24 harbour stem-like cells.

  12. Lung cancer - small cell

    Science.gov (United States)

    ... carcinoma Small cell carcinoma Squamous cell carcinoma Secondhand smoke and lung cancer Normal lungs and alveoli Respiratory system Smoking hazards Bronchoscope References Horn L, Eisenberg R, ...

  13. Cell phones and cancer

    Science.gov (United States)

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of exposure ...

  14. Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity

    NARCIS (Netherlands)

    Doorenspleet, M.E.; Klarenbeek, P.L.; de Hair, M.J.H.; van Schaik, B.D.C.; Esveldt, R.E.E.; van Kampen, A.H.C.; Gerlag, D.M.; Musters, A.; Baas, F.; Tak, P.P.; de Vries, N.

    2014-01-01

    OBJECTIVE: To identify potential autoreactive B-cell and plasma-cell clones by quantitatively analysing the complete human B-cell receptor (BCR) repertoire in synovium and peripheral blood in early and established rheumatoid arthritis (RA). METHODS: The BCR repertoire was screened in synovium and

  15. Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity

    NARCIS (Netherlands)

    Doorenspleet, M. E.; Klarenbeek, P. L.; de Hair, M. J. H.; van Schaik, B. D. C.; Esveldt, R. E. E.; van Kampen, A. H. C.; Gerlag, D. M.; Musters, A. [=Anne; Baas, F.; Tak, P. P.; de Vries, N. [=Niek

    2014-01-01

    To identify potential autoreactive B-cell and plasma-cell clones by quantitatively analysing the complete human B-cell receptor (BCR) repertoire in synovium and peripheral blood in early and established rheumatoid arthritis (RA). The BCR repertoire was screened in synovium and blood of six patients

  16. Liver Cancer Stem Cells

    OpenAIRE

    Sameh Mikhail; Aiwu Ruth He

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers fo...

  17. Cancer stem cell metabolism

    National Research Council Canada - National Science Library

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    .... Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes...

  18. Gene co-expression analyses differentiate networks associated with diverse cancers harbouring TP53 missense or null mutations

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    Kathleen Oros Klein

    2016-08-01

    Full Text Available In a variety of solid cancers, missense mutations in the well-established TP53 tumour suppressor gene may lead to presence of a partially-functioning protein molecule, whereas mutations affecting the protein encoding reading frame, often referred to as null mutations, result in the absence of p53 protein. Both types of mutations have been observed in the same cancer type. As the resulting tumour biology may be quite different between these two groups, we used RNA-sequencing data from The Cancer Genome Atlas (TCGA from four different cancers with poor prognosis, namely ovarian, breast, lung and skin cancers, to compare the patterns of co-expression of genes in tumours grouped according to their TP53 missense or null mutation status. We used Weighted Gene Coexpression Network analysis (WGCNA and a new test statistic built on differences between groups in the measures of gene connectivity. For each cancer, our analysis identified a set of genes showing differential coexpression patterns between the TP53 missense- and null mutation-carrying groups that was robust to the choice of the tuning parameter in WGCNA. After comparing these sets of genes across the four cancers, one gene (KIR3DL2 consistently showed differential coexpression patterns between the null and missense groups. KIR3DL2 is known to play an important role in regulating the immune response, which is consistent with our observation that this gene’s strongly-correlated partners implicated many immune-related pathways. Examining mutation-type-related changes in correlations between sets of genes may provide new insight into tumour biology.

  19. Basal cell cancer (image)

    Science.gov (United States)

    ... biopsy is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure ... is required to watch for new sites of basal cell cancer.

  20. Prostate cancer stem cells.

    Science.gov (United States)

    Tu, Shi-Ming; Lin, Sue-Hwa

    2012-06-01

    Stem cells have long been implicated in prostate gland formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative androgen receptor-negative (AR(-)) status of prostate stem cells renders them inherently insensitive to androgen blockade therapy. The androgen-regulated gene fusion TMPRSS2-ERG could be used to clarify both the cells of origin and the evolution of prostate cancer cells. In this review, we show that the hypothesis that distinct subtypes of cancer result from abnormalities within specific cell types-the stem cell theory of cancer-may instigate a major paradigm shift in cancer research and therapy. Ultimately, the stem cell theory of cancers will affect how we practice clinical oncology: our diagnosis, monitoring, and therapy of prostate and other cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  2. Turning tumour cells into antigen presenting cells: The next step to improve cancer immunotherapy?

    Science.gov (United States)

    de Charette, Marie; Marabelle, Aurélien; Houot, Roch

    2016-11-01

    Downregulation/loss of the antigen presentation is a major immune escape mechanism in cancer. It allows tumour cells to become 'invisible' and avoid immune attack by antitumour T cells. In tumour harbouring properties of professional antigen presenting cells (i.e. tumour B cells in lymphoma), downregulation/loss of the antigen presentation may also prevent direct priming of naïve T cells by tumour cells. Here, we review treatments that may induce/restore antigen presentation by the tumour cells. These treatments may increase the generation of antitumour T cells and/or their capacity to recognise and eliminate tumour cells. By forcing tumour cells to present their antigens, these treatments may sensitise patients to T cell-based immunotherapies, including checkpoint inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Hurthle Cell Cancer

    Science.gov (United States)

    ... breath Hurthle cell cancer Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  4. Basal cell skin cancer

    Science.gov (United States)

    Basal cell skin cancer almost never spreads. If it is left untreated, it may spread into surrounding areas and nearby tissues and bone. In these cases, treatment can injure the appearance of the skin.

  5. Hereditary leiomyomatosis and renal cell cancer syndrome: a family affair.

    Science.gov (United States)

    Teh, Jiasian; Kinnear, Ned; Douglass-Molloy, Hannah; Hennessey, Derek Barrry

    2017-01-25

    A 49-year-old woman with cutaneous and uterine leiomyomas, flank pain and a family history of hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome sought genetic testing. She was found to harbour a fumarate hydratase (FH) genetic mutation and a previously undetected renal tumour. The patient underwent radical nephrectomy, and remains well at follow-up. HLRCC syndrome is a rare autosomal dominant disease, with patients at increased risk for cutaneous leiomyomas, early-onset uterine leiomyomas and aggressive renal carcinoma. Although the syndrome may manifest life-threatening complications, outcomes may be improved by preventative family screening and surveillance, compelling early diagnosis. 2017 BMJ Publishing Group Ltd.

  6. Incidence of Child cancers in the Finistere and around the Brest harbour between 1991 and 2005; Incidence des cancers de l'enfant dans le Finistere et autour de la rade de Brest entre 1991 et 2005

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    The objective of the study was to describe the temporal variations of child cancers incidence in the Finistere department and around the Brest harbour between 1991 and 2005 looking for any excess. In case of identification of an aggregate of cases, the secondary objective was to describe the aggregate by seeking common risk factors for cases in particular in relation to the activities of 'Ile Longue'. A leukemia excess was highlighted in Brest on the period 200-2005 and more particularly in 200-2001. This peak of incidence seems isolated in time, that is not in favour of a persistent environmental cause but should be the object of a follow-up in the future. Besides, no argument in favour of an occupational exposure of the parents of suffering children was highlighted. (N.C.)

  7. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans

    2017-01-01

    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  8. Inflammation and cancer stem cells.

    Science.gov (United States)

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Exosomes in the nose induce immune cell trafficking and harbour an altered protein cargo in chronic airway inflammation.

    Science.gov (United States)

    Lässer, Cecilia; O'Neil, Serena E; Shelke, Ganesh V; Sihlbom, Carina; Hansson, Sara F; Gho, Yong Song; Lundbäck, Bo; Lötvall, Jan

    2016-06-20

    Exosomes are nano-sized extracellular vesicles participating in cell-to-cell communication both in health and disease. However, the knowledge about the functions and molecular composition of exosomes in the upper airways is limited. The aim of the current study was therefore to determine whether nasal exosomes can influence inflammatory cells and to establish the proteome of nasal lavage fluid-derived exosomes in healthy subjects, as well as its alterations in individuals with chronic airway inflammatory diseases [asthma and chronic rhinosinusitis (CRS)]. Nasal lavage fluid was collected from 14 healthy subjects, 15 subjects with asthma and 13 subjects with asthma/CRS. Exosomes were isolated with differential centrifugation and the proteome was analysed by LC-MS/MS with the application of two exclusion lists as well as using quantitative proteomics. Ingenuity Pathways Analysis and GO Term finder was used to predict the functions associated with the exosomal proteome and a migration assay was used to analyse the effect on immune cells by nasal exosomes. Firstly, we demonstrate that nasal exosomes can induce migration of several immune cells, such as monocytes, neutrophils and NK cells in vitro. Secondly, a mass spectrometry approach, with the application of exclusion lists, was utilised to generate a comprehensive protein inventory of the exosomes from healthy subjects. The use of exclusion lists resulted in the identification of ~15 % additional proteins, and increased the confidence in ~20 % of identified proteins. In total, 604 proteins were identified in nasal exosomes and the nasal exosomal proteome showed strong associations with immune-related functions, such as immune cell trafficking. Thirdly, a quantitative proteomics approach was used to determine alterations in the exosome proteome as a result of airway inflammatory disease. Serum-associated proteins and mucins were more abundant in the exosomes from subjects with respiratory diseases compared to

  10. Squamous cell skin cancer

    Science.gov (United States)

    ... squamous cell cancer include: Having light-colored skin, blue or green eyes, or blond or red hair Long-term, daily sun exposure (such as in people who work outside) Many severe sunburns early in life Older age Having had many x-rays Chemical exposure A weakened immune system, especially in ...

  11. Alcohol and Cancer Stem Cells

    OpenAIRE

    Mei Xu; Jia Luo

    2017-01-01

    Heavy alcohol consumption has been associated with increased risk of several cancers, including cancer of the colon, rectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. Cancer stem cells (CSC), a subpopulation of cancer cells with self-renewal and ...

  12. Kinetic Algorithms for Harbour Management

    Science.gov (United States)

    Gold, C. M.; Goralski, R. I.

    2012-07-01

    Modern harbour management for a busy port needs to resolve a variety of simultaneous problems. Harbour traffic may be busy and the waterways congested, both by the major shipping and by the attendant harbour tugs. The harbour channel may be narrow and tortuous, and rapidly changing tides may require frequent course adjustments. Navigation aids must be clearly specified and immediately identifiable, in order to permit safe passage for the vessels. This requires a GIS with attributes not easily available with traditional products. The GeoVS system is a kinetic GIS with full three-dimensional visualisation, so that ships, bathymetry and landscape may be viewed in a form that is immediately understandable to both harbour pilots and the harbour authority. The system is kinetic because the data structures used to preserve the topological relationships between ships, seafloor and coastline are able to be maintained on a real-time basis, taking account of ship movement recorded on the compulsory AIS (Automatic Information System) beacons. Maintenance of this real-time topology allows for easy detection of potential collisions, as well as real-time bathymetric estimations, necessary to prevent ship grounding in highly tidal environments. The system, based on previous research into kinetic Voronoi diagrams, as well as development of a completely new graphical engine, is now in commercial production, where its advantages over simpler twodimensional models without automatic collision and grounding detection are becoming evident. Other applications are readily envisaged, and will be addressed in the near future.

  13. KINETIC ALGORITHMS FOR HARBOUR MANAGEMENT

    Directory of Open Access Journals (Sweden)

    C. M. Gold

    2012-07-01

    Full Text Available Modern harbour management for a busy port needs to resolve a variety of simultaneous problems. Harbour traffic may be busy and the waterways congested, both by the major shipping and by the attendant harbour tugs. The harbour channel may be narrow and tortuous, and rapidly changing tides may require frequent course adjustments. Navigation aids must be clearly specified and immediately identifiable, in order to permit safe passage for the vessels. This requires a GIS with attributes not easily available with traditional products. The GeoVS system is a kinetic GIS with full three-dimensional visualisation, so that ships, bathymetry and landscape may be viewed in a form that is immediately understandable to both harbour pilots and the harbour authority. The system is kinetic because the data structures used to preserve the topological relationships between ships, seafloor and coastline are able to be maintained on a real-time basis, taking account of ship movement recorded on the compulsory AIS (Automatic Information System beacons. Maintenance of this real-time topology allows for easy detection of potential collisions, as well as real-time bathymetric estimations, necessary to prevent ship grounding in highly tidal environments. The system, based on previous research into kinetic Voronoi diagrams, as well as development of a completely new graphical engine, is now in commercial production, where its advantages over simpler twodimensional models without automatic collision and grounding detection are becoming evident. Other applications are readily envisaged, and will be addressed in the near future.

  14. Muddy waters and the Wadden Sea harbours

    NARCIS (Netherlands)

    Eekelen, van E.; Baptist, M.J.; Dankers, P.; Grasmeijer, B.T.; Kessel, van T.; Maren, van D.S.

    2016-01-01

    Several harbours along the Dutch Wadden Sea deal with large siltation rates and limited possibilities for developments. However, development of new harbour activities is needed for these harbours to be able to survive in the long run. As these harbours lie in or close to areas with a protected

  15. Cancer Stem Cells and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sheetal Dyall

    2010-01-01

    Full Text Available The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs, or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

  16. Cancer treatments transform residual cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    Harless William W

    2011-01-01

    Full Text Available Abstract Background Physiologic wound repair and tissue regeneration are associated with distinct cellular behaviors triggered by tissue damage. Normally quiescent stem cells proliferate to regenerate damaged tissue, while relatively immobile epithelial cells can transform into a motile, tissue invasive phenotype through a partial epithelial-mesenchymal transition. These distinct cellular behaviors may have particular relevance to how cancer cells can be predicted to behave after treatments damaging a tumor. Presentation of the hypothesis Surgery, chemotherapy, and radiation therapy trigger highly conserved wound healing pathways that: (1 facilitate the phenotypic transformation of surviving cancer cells into a highly mobile, metastatic phenotype through an EMT or epithelial-mesenchymal transition and (2 induce residual cancer stem cell proliferation. Testing the hypothesis Tissue damage caused by cancer treatments will trigger the release of distinct cytokines with established roles in physiologic wound healing, EMT induction, and stem cell activation. They will be released rapidly after treatment and detectable in the patient's blood. Careful histologic evaluation of cancerous tissue before and after treatment will reveal cellular changes suggestive of EMT induction (down regulation of cytokeratin expression and cancer stem cell enrichment (stem cell markers upregulated. Implications of the hypothesis Cancer cells surviving treatment will be more capable of metastasis and resistant to conventional therapies than the pre-treatment population of cancer cells. These changes will develop rapidly after treatment and, in distinct contrast to selection pressures fostering such changes, be triggered by highly conserved wound repair signals released after tissue damage. This pattern of tissue (tumor repair may be amenable to treatment intervention at the time it is upregulated.

  17. Stem cells and solid cancers.

    Science.gov (United States)

    McDonald, Stuart A C; Graham, Trevor A; Schier, Stefanie; Wright, Nicholas A; Alison, Malcolm R

    2009-07-01

    Recently, there have been significant advances in our knowledge of stem cells found in tissues that can develop solid tumours. In particular, novel stem cell markers have been identified for the first time identifying multipotential cells: a required characteristic of a stem cell. The scarcity of cancer stem cells has been questioned. Current dogma states that they are rare, but novel research has suggested that this may not be the case. Here, we review the latest literature on stem cells, particularly cancer stem cells within solid tumours. We discuss current thinking on how stem cells develop into cancer stem cells and how they protect themselves from doing so and do they express unique markers that can be used to detect stem cells. We attempt to put into perspective these latest advances in stem cell biology and their potential for cancer therapy.

  18. Cancer stem cells and personalized cancer nanomedicine.

    Science.gov (United States)

    Gener, Petra; Rafael, Diana Fernandes de Sousa; Fernández, Yolanda; Ortega, Joan Sayós; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

    2016-02-01

    Despite the progress in cancer treatment over the past years advanced cancer is still an incurable disease. Special attention is pointed toward cancer stem cell (CSC)-targeted therapies, because this minor cell population is responsible for the treatment resistance, metastatic growth and tumor recurrence. The recently described CSC dynamic phenotype and interconversion model of cancer growth hamper even more the possible success of current cancer treatments in advanced cancer stages. Accordingly, CSCs can be generated through dedifferentiation processes from non-CSCs, in particular, when CSC populations are depleted after treatment. In this context, the use of targeted CSC nanomedicines should be considered as a promising tool to increase CSC sensitivity and efficacy of specific anti-CSC therapies.

  19. SECURITY SYSTEMS FOR MARITIME HARBOUR

    Directory of Open Access Journals (Sweden)

    Georgică SLĂMNOIU

    2010-11-01

    Full Text Available Infrastructure protection objectives are at the top of the agenda of those responsible in the European Union. Currently Romania is one of the countries on its eastern border of the Union and this has special implications in terms of security measures that are required to be implemented. Ships and harbours are important current conflict stage. An integrated system of protection of harbours must be prepared in advance in order to continuously provide information that will increase the overall performance of the intervention forces.

  20. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. No mutations of FGFR3 in normal urothelium in the vicinity of urothelial carcinoma of the bladder harbouring activating FGFR3 mutations in patients with bladder cancer.

    Science.gov (United States)

    Otto, Wolfgang; Denzinger, Stefan; Bertz, Simone; Gaumann, Andreas; Wild, Peter J; Hartmann, Arndt; Stoehr, Robert

    2009-11-01

    Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene causing constitutive oncogenic protein activation have been shown to be frequent in papillary noninvasive bladder tumours and are associated with a low risk of progression and a favourable outcome. FGFR3 alterations have also been found in benign urothelial papilloma and flat urothelial hyperplasia suggesting FGFR3 alterations as an early event in bladder tumorigenesis. To date there is no data available on FGFR3 mutations in normal urothelium from patients with bladder cancer. We therefore analysed 64 samples of histopathological unsuspicious normal urothelium from 38 patients with FGFR3 mutated bladder tumours and 15 samples of urothelium from patients (n = 15) without any urothelial malignancy as a control group. Urothelial cells were microdissected from formalin-fixed, paraffin-embedded material. After DNA isolation whole genome amplification was done by I-PEP-PCR. FGFR3 mutations were detected using SNaPshot analysis. All samples could successfully be investigated. FGFR3 analyses did not reveal any mutation in the urothelium from neither the control group nor the bladder cancer group. All urothelial samples showed a wildtype sequence for FGFR3. These data suggest that mutations in the FGFR3 gene are not the earliest genetic alterations in bladder carcinogenesis and are associated with a hyperproliferative (hyperplastic) phenotype in the urothelium. Chromosomal alterations like deletions on chromosome 9q or aberrant promoter hypermethylation could play more important roles in early urothelial transformation than mutational FGFR3 activation. (c) 2009 UICC.

  2. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer

    Science.gov (United States)

    Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

    2012-01-01

    According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research. PMID:22507219

  3. Epigenetics in cancer stem cells.

    Science.gov (United States)

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  4. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ...

  5. Mechanotransduction in cancer stem cells.

    Science.gov (United States)

    Hao, Jin; Zhang, Yueling; Ye, Rui; Zheng, Yingcheng; Zhao, Zhihe; Li, Juan

    2013-09-01

    The cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self-renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt. © 2013 International Federation for Cell Biology.

  6. Use of Human Cancer Cell Lines Mitochondria to Explore the Mechanisms of BH3 Peptides and ABT-737-Induced Mitochondrial Membrane Permeabilization

    OpenAIRE

    Nelly Buron; Mathieu Porceddu; Magali Brabant; Diana Desgué; Cindy Racoeur; Myriam Lassalle; Christine Péchoux; Pierre Rustin; Etienne Jacotot; Annie Borgne-Sanchez

    2010-01-01

    Current limitations of chemotherapy include toxicity on healthy tissues and multidrug resistance of malignant cells. A number of recent anti-cancer strategies aim at targeting the mitochondrial apoptotic machinery to induce tumor cell death. In this study, we set up protocols to purify functional mitochondria from various human cell lines to analyze the effect of peptidic and xenobiotic compounds described to harbour either Bcl-2 inhibition properties or toxic effects related to mitochondria....

  7. Nanotechniques Inactivate Cancer Stem Cells

    Science.gov (United States)

    Goltsev, Anatoliy N.; Babenko, Natalya N.; Gaevskaya, Yulia A.; Bondarovich, Nikolay A.; Dubrava, Tatiana G.; Ostankov, Maksim V.; Chelombitko, Olga V.; Malyukin, Yuriy V.; Klochkov, Vladimir K.; Kavok, Nataliya S.

    2017-06-01

    One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44- subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44- cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24-, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.

  8. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

    Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues...

  9. Multifaceted Interpretation of Colon Cancer Stem Cells

    OpenAIRE

    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

    2017-01-01

    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but...

  10. Characterising Castrate Tolerant Prostate Cancer Cells

    OpenAIRE

    ASHLEE KATE CLARK

    2017-01-01

    Prostate cancer is a prevalent disease in aging males. This thesis explores prostate cancer cells that escape current therapy and give rise to end-stage disease. Using sophisticated experimental approaches, this important cancer cell population was identified and characterised in human prostate cancer tissues.  Our discoveries will eventually lead to improved cancer treatments for men with prostate cancer.

  11. Transfer pricing and safe harbours

    Directory of Open Access Journals (Sweden)

    Veronika Solilová

    2013-01-01

    Full Text Available Transfer prices are significant for both taxpayers and tax administrations because they determine in large part taxable profits of associated enterprises in different tax jurisdictions. Moreover, in the context of taxation, transfer prices must be complied with the arm’s length principle. However, Multinational Enterprises have been faced daily by conflicting rules and approaches to applying the arm’s length principle, burdensome documentation requirements, inconsistent audit standards and unpredictable competent authority outcomes. Therefore, the Committee on Fiscal Affairs launched another project on the administrative aspects of transfer pricing in 2010. On 16 May 2013 as a partial solution of this project was approved by the OECD Council the Revised Section E on Safe Harbours in Chapter IV of the Transfer Pricing Guidelines for Multinational Enterprises and Tax Authorities. The paper is focused on significant changes of newly approved chapter IV of the Transfer Pricing Guidelines for Multinational Enterprises and Tax Authorities, further on analysis of practice in this area, on advantages and disadvantages of safe harbours for taxpayers and competent authorities with aim to suggest recommendations on use of safe harbours in the Czech Republic.

  12. Differential Effects of Variations at Codon 106 on Sprouty2 Functions in Lung Cancer-Derived Cells.

    Science.gov (United States)

    Kral, Rosana; Doriguzzi, Angelina; Mayer, Christoph-Erik; Krenbek, Dagmar; Setinek, Ulrike; Sutterlüty-Fall, Hedwig

    2016-08-01

    Sprouty2 is a modulator of receptor tyrosine kinase-mediated signalling with an important role during lung carcinogenesis. Here, we characterize a Sprouty2 variant harbouring a substitution of proline 106 with serine. Serine substitution fails to influence expression, but accumulation of slower migrating phosphatase-sensitive forms indicates that its presence facilitates phosphorylation. In normal lung cells the serine variant is slightly more potent in inhibiting proliferation and migration. Additionally non-malignant cells expressing the major Sprouty2 variant attach more effective to fibronectin, while the serine variant only weakly stimulates cell adhesion. Mechanistically, the serine variant interferes less effectively with mitogen-activated protein kinase induction in response to serum. Concerning the positive Sprouty2 effect on epidermal growth factor receptor activation the serine variant is more potent. In all lung cancer-derived cell lines proliferation is more effectively inhibited if the Sprouty2 protein harbours the serine. In contrast, an increased interference of the serine Sprouty2 variant is only observed in cells with unaltered K-Ras. In cells harbouring a K-Ras mutation the serine conversion weakens the reduction of migration velocity indicating that dependent on the status of K-Ras the serine influences Sprouty2 functions differently. Accordingly, cell adhesion in cells with unaffected K-Ras is only stimulated by a Sprouty2 protein harbouring proline, while a serine conversion improves the attachment of the cells with constitutive active Ras. In summary our studies demonstrate that substitution of proline by serine at position 106 has biological significance and that the observed effects of this conversion depend on the activation status of endogenous K-Ras. J. Cell. Biochem. 117: 1822-1832, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Single cancer cell analysis on a chip

    NARCIS (Netherlands)

    Yang, Yoon Sun

    2016-01-01

    Cancer cells in blood may represent “a real time liquid biopsy” through the interrogation of single cancer cells thereby determining the outspread of their heterogeneity and guiding therapy. In this thesis, we focused on single cancer cell analysis downstream of the isolation of cancer cells from

  14. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, Milind; Meijer, Coby; de Bock, Geertruida H.; Boersma-van Ek, Wytske; Terstappen, Leon W. M. M.; Groen, Harry J. M.; Timens, Wim; Kruyt, Frank A. E.; Hiltermann, T. Jeroen N.

    2016-01-01

    The prognostic value of markers of cancer stem cells and epithelial to mesenchymal transition in small cell lung cancer is not known. We retrospectively studied these markers in the biopsy tissue of patients with small cell lung cancer and correlated them with overall survival and the strongest

  15. Ocean disposal of dredged materials from Atlantic Canadian harbours ll. small craft harbours, Gulf Region

    National Research Council Canada - National Science Library

    1984-01-01

    The objective of this report is to provide a compilation of all data related to dredging/ocean disposal of dredged materials from harbours maintained by the Small Craft Harbours Branch of Fisheries...

  16. Melatonin sensitizes H1975 non-small-cell lung cancer cells harboring a T790M-targeted epidermal growth factor receptor mutation to the tyrosine kinase inhibitor gefitinib.

    Science.gov (United States)

    Yun, Miyong; Kim, Eun-Ok; Lee, Duckgue; Kim, Ji-Hyun; Kim, Jaekwang; Lee, Hyemin; Lee, Jihyun; Kim, Sung-Hoon

    2014-01-01

    The use of tyrosine kinase inhibitors (TKIs) to target active epidermal growth factor receptor (EGFR)-harbouring mutations has been effective in patients with advanced non-small-cell lung cancer (NSCLC). However, the use of TKIs in NSCLS patients with somatic EGFR mutations, particularly T790M, causes drug resistance. Thus, in the present study, we investigated overcoming resistance against the TKI gefitinib by combination treatment with melatonin in H1975 NSCLC cells harbouring the T790M somatic mutation. H1975 and HCC827 cells were treated with melatonin in combination with gefitinib, and cell viability, cell cycle progression, apoptosis, and EGFR, AKT, p38, Bcl-2, Bcl-xL, caspase 3 and Bad protein levels were examined. Treatment with melatonin dose-dependently decreased the viability of H1975 cells harbouring the T790M somatic mutation compared to HCC827 cells with an EGFR active mutation. Melatonin-mediated cell death resulted in decreased phosphorylation of EGFR and Akt, leading to attenuated expression of survival proteins, such as Bcl-2, Bcl-xL and survivin, and activated caspase 3 in H1975 cells, but not in HCC827 cells. However, we did not observe a significant change in expression of cell cycle proteins, such as cyclin D, cyclin A, p21 and CDK4 in H1975 cells. Surprisingly, co-treatment of gefitinib with melatonin effectively decreased the viability of H1975 cells, but not HCC827 cells. Moreover, co-treatment of H1975 cells caused consistent down-regulation of EGFR phosphorylation and induced apoptosis compared to treatment with gefitinib or melatonin alone. Our findings demonstrate that melatonin acts as a potent chemotherapeutic agent by sensitising to gefitinib TKI-resistant H1975 cells that harbour a EGFR T790M mutation. © 2014 S. Karger AG, Basel.

  17. Melatonin Sensitizes H1975 Non-Small-Cell Lung Cancer Cells Harboring a T790M-Targeted Epidermal Growth Factor Receptor Mutation to the Tyrosine Kinase Inhibitor Gefitinib

    Directory of Open Access Journals (Sweden)

    Miyong Yun

    2014-08-01

    Full Text Available Background/Aims: The use of tyrosine kinase inhibitors (TKIs to target active epidermal growth factor receptor (EGFR-harbouring mutations has been effective in patients with advanced non-small-cell lung cancer (NSCLC. However, the use of TKIs in NSCLS patients with somatic EGFR mutations, particularly T790M, causes drug resistance. Thus, in the present study, we investigated overcoming resistance against the TKI gefitinib by combination treatment with melatonin in H1975 NSCLC cells harbouring the T790M somatic mutation. Methods: H1975 and HCC827 cells were treated with melatonin in combination with gefitinib, and cell viability, cell cycle progression, apoptosis, and EGFR, AKT, p38, Bcl-2, Bcl-xL, caspase 3 and Bad protein levels were examined. Results: Treatment with melatonin dose-dependently decreased the viability of H1975 cells harbouring the T790M somatic mutation compared to HCC827 cells with an EGFR active mutation. Melatonin-mediated cell death resulted in decreased phosphorylation of EGFR and Akt, leading to attenuated expression of survival proteins, such as Bcl-2, Bcl-xL and survivin, and activated caspase 3 in H1975 cells, but not in HCC827 cells. However, we did not observe a significant change in expression of cell cycle proteins, such as cyclin D, cyclin A, p21 and CDK4 in H1975 cells. Surprisingly, co-treatment of gefitinib with melatonin effectively decreased the viability of H1975 cells, but not HCC827 cells. Moreover, co-treatment of H1975 cells caused consistent down-regulation of EGFR phosphorylation and induced apoptosis compared to treatment with gefitinib or melatonin alone. Conclusions: Our findings demonstrate that melatonin acts as a potent chemotherapeutic agent by sensitising to gefitinib TKI-resistant H1975 cells that harbour a EGFR T790M mutation.

  18. Do Cell Phones Cause Cancer?

    CERN Document Server

    Leikind, Bernard

    2010-01-01

    Do cell phones, household electrical power wiring or appliance, or high voltage power lines cause cancer? Fuggedaboudit! No way! When pigs fly! When I'm the Pope! Don't text while you're driving, however, or eat your cell phone. All organisms absorb microwave radiation directly as thermal energy. In living organisms, the organisms' thermal control systems, including the blood flow, and various cooling mechanisms, such as sweating in humans, that work to maintain a stable body temperature rapidly transfer the absorbed energy to the environment. Any temperature rise is small or even unobserved. Any proposed mechanism by which cell phone radiation might cause cancer must begin with this fact. But the amount of radiation absorbed from a cell phone is less than that produced by normal metabolic processes, and much less than that produced by, for example, exercise. None of these normal metabolic processes cause cancer. Therefore, the much smaller amounts of energy from cell phones doesn't cause cancer either. All f...

  19. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  20. Breast cancer circulating tumor cells

    Directory of Open Access Journals (Sweden)

    Maria Joao Carvalho

    2011-12-01

    Full Text Available Metastasization of breast cancer involves various mechanisms responsible for progression from invasive lesion to dissemination in distant organs. Regional lymph node metastasization was considered an initial step in this process, but it is now recognized that hematogenous dissemination is a deviation from lymphatic circulation. The detection of circulating tumor cells (CTC is an aim in several oncology areas. For this purpose, several techniques have been used to detect CTC, including the use of antibodies and techniques with nucleic acids. This study reviews the published studies considering the detection of breast cancer CTC. There are focused the difficulties in identifying a CTC in a heterogeneous population, the handling of the sample, criteria of positivity, analytical techniques, and specific markers. There are systematized various specific markers of breast cancer cells also the problems with false positive results. Finally, we hypothesize clinical applications either as a prognostic marker or as a therapeutic response monitor.

  1. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, Veronica [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Gaggianesi, Miriam [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Spina, Valentina; Iovino, Flora [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Dieli, Francesco [Departement of Biopathology and Medicine Biotechnologies, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Stassi, Giorgio, E-mail: giorgio.stassi@unipa.it [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Todaro, Matilde [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy)

    2011-04-11

    Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem–like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool.

  2. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  3. Stem cells in prostate cancer.

    Science.gov (United States)

    Mateo, Francesca; Fernandez, Pedro L; Thomson, Timothy M

    2013-06-01

    Tumors constitute complex ecosystems with multiple interactions among neoplastic cells displaying various phenotypes and functions and where the tumoral niche is built with an active participation of the host environment that also impacts the malignant progression of the tumor cells. Irrespective of the cell of origin of prostate adenocarcinoma, mounting evidences support the existence of a hierarchy within neoplastic prostate cells that contributes to the heterogeneity of these tumors. At the origin of this hierarchy are small populations of tumor cells with high self-renewal potential and also capable of generating progeny tumor cells that lose self-renewal properties as they acquire more differentiated phenotypes. These cancer stem cells (CSC) depend on active gene networks that confer them with their self-renewal capacity through symmetrical divisions whereas they can also undergo asymmetrical division and differentiation either as stochastic events or in response to environmental cues. Although new experimental evidences indicate that this is can be a reversible process, thus blurring the distinction between CSCs and non-CSCs, the former are considered as the drivers of tumor growth and evolution, and thus a prime target for therapeutic intervention. Of particular importance in prostate cancer, CSCs may constitute the repository population of androgen-insensitive and chemotherapy-resistant tumor cells responsible for castration-resistant and chemotherapy-insensitive tumors, thus their identification and quantification in primary and metastatic neoplasms could play important roles in the management of this disease.

  4. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, M.M.; Meijer, C.; de Bock, G.H.; Boersma-van Ek, W.; Terstappen, Leonardus Wendelinus Mathias Marie; Groen, H.J.M.; Timens, W.; Kruyt, F.A.E.; Hiltermann, T.N.J.

    2016-01-01

    Background Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and

  5. Glutathione in Cancer Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Angel L. [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain); Mena, Salvador [Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia (Spain); Estrela, Jose M., E-mail: jose.m.estrela@uv.es [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)

    2011-03-11

    Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.

  6. [Dendritic cells in cancer immunotherapy].

    Science.gov (United States)

    Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities.

  7. Proteasome expression and activity in cancer and cancer stem cells.

    Science.gov (United States)

    Voutsadakis, Ioannis A

    2017-03-01

    Proteasome is a multi-protein organelle that participates in cellular proteostasis by destroying damaged or short-lived proteins in an organized manner guided by the ubiquitination signal. By being in a central place in the cellular protein complement homeostasis, proteasome is involved in virtually all cell processes including decisions on cell survival or death, cell cycle, and differentiation. These processes are important also in cancer, and thus, the proteasome is an important regulator of carcinogenesis. Cancers include a variety of cells which, according to the cancer stem cell theory, descend from a small percentage of cancer stem cells, alternatively termed tumor-initiating cells. These cells constitute the subsets that have the ability to propagate the whole variety of cancer and repopulate tumors after cytostatic therapies. Proteasome plays a role in cellular processes in cancer stem cells, but it has been found to have a decreased function in them compared to the rest of cancer cells. This article will discuss the transcriptional regulation of proteasome sub-unit proteins in cancer and in particular cancer stem cells and the relationship of the proteasome with the pluripotency that is the defining characteristic of stem cells. Therapeutic opportunities that present from the understanding of the proteasome role will also be discussed.

  8. Prostate Cancer Stem Cells: Research Advances

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2015-11-01

    Full Text Available Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  9. Cancer Stem Cells and the Ontogeny of Lung Cancer

    OpenAIRE

    Peacock, Craig D.; Watkins, D. Neil

    2008-01-01

    Lung cancer is the leading cause of cancer death in the world today and is poised to claim approximately 1 billion lives during the 21st century. A major challenge in treating this and other cancers is the intrinsic resistance to conventional therapies demonstrated by the stem/progenitor cell that is responsible for the sustained growth, survival, and invasion of the tumor. Identifying these stem cells in lung cancer and defining the biologic processes necessary for their existence is paramou...

  10. Reprogramming cancer cells: overview & current progress.

    Science.gov (United States)

    Lim, Kian Lam; Teoh, Hoon Koon; Choong, Pei Feng; Teh, Hui Xin; Cheong, Soon Keng; Kamarul, Tunku

    2016-07-01

    Cancer is a disease with genetic and epigenetic origins, and the possible effects of reprogramming cancer cells using the defined sets of transcription factors remain largely uninvestigated. In the handful of publications available so far, findings have shown that reprogramming cancer cells changed the characteristics of the cells to differ from the parental cancer cells. These findings indicated the possibility of utilizing reprogramming technology to create a disease model in the laboratory to be used in studying the molecular pathogenesis or for drug screening of a particular cancer model. Despite numerous methods employed in generating induced pluripotent stem cells (iPSCs) from cancer cells only a few studies have successfully reprogrammed malignant human cells. In this review we will provide an overview on i) methods to reprogram cancer cells, ii) characterization of the reprogrammed cancer cells, and iii) the differential effects of reprogramming on malignancy, epigenetics and response of the cancer cells to chemotherapeutic agents. Continued technical progress in cancer cell reprogramming technology will be instrumental for more refined in vitro disease models and ultimately for the development of directed and personalized therapy for cancer patients in the future.

  11. Mercury in Thana creek, Bombay harbour

    Digital Repository Service at National Institute of Oceanography (India)

    Zingde, M.D.; Desai, B.N.

    weight) with marked increased from harbour to the creek region suggests substantial mercury input in the head region. Chemical extraction by hydrogen peroxide indicated that more than 70% of mercury was leachable and probably organically bound...

  12. Cancer stem cells: the theory and perspectives in cancer therapy.

    Science.gov (United States)

    Gil, Justyna; Stembalska, Agnieszka; Pesz, Karolina A; Sasiadek, Maria M

    2008-01-01

    The cancer stem cell theory elucidates not only the issue of tumour initiation and development, tumour's ability to metastasise and reoccur, but also the ineffectiveness of conventional cancer therapy. This review examines stem cell properties, such as self-renewal, heterogeneity, and resistance to apoptosis. The 'niche' hypothesis is presented, and mechanisms of division, differentiation, self-renewal and signalling pathway regulation are explained. Epigenetic alterations and mutations of genes responsible for signal transmission may promote the formation of cancer stem cells. We also present the history of development of the cancer stem cell theory and discuss the experiments that led to the discovery and confirmation of the existence of cancer stem cells. Potential clinical applications are also considered, including therapeutic models aimed at selective elimination of cancer stem cells or induction of their proper differentiation.

  13. A POX on Renal Cancer Cells | Center for Cancer Research

    Science.gov (United States)

    Proline oxidase, or POX, is an enzyme responsible for metabolizing the amino acid proline. POX contributes to the regulation of cell death that occurs when cellular systems malfunction, a process called apoptosis. Previous studies have determined that levels of POX are reduced in several types of human cancer. Likewise, many cancer cells become resistant to apoptosis, suggesting a link between POX and cancer cell survival.

  14. Intersex in Littorina littorea and DNA damage in Mytilus edulis as indicators of harbour polllution

    DEFF Research Database (Denmark)

    Rank, Jette

    2009-01-01

    Intersex in snails (Littorina littorea) and DNA damage in blue mussels (Mytilus edulis) were analysed to assess how these bio-indicators reflected the level of chemical contamination at two sites in a highly contaminated harbour in Denmark. The comet assay using mussel gill cells was an indicator...... effects were found to reflect the levels of the chemicals, and it was concluded that intersex in L. littorea and DNA damage in M. edulis can be used as bio-indicators of harbour pollution...

  15. Syndecan-1 (CD138) contributes to prostate cancer progression by stabilizing tumour-initiating cells.

    Science.gov (United States)

    Shimada, Keiji; Anai, Satoshi; Fujii, Tomomi; Tanaka, Nobumichi; Fujimoto, Kiyohide; Konishi, Noboru

    2013-12-01

    Increasing evidence suggests that tumour-initiating cells (TICs) contribute to the development of prostate cancer. Here, we identified syndecan-1 as a key molecule maintaining the stability of prostate cancer TICs. Holoclones harbouring the biological properties of stemness were derived from single-cell cultures of the PC3 human prostate cancer cell line. These holoclones over-expressed syndecan-1, but showed reduced expression of NADPH oxidase (NOX) and synthesis of hydrogen peroxide and oxygen radicals. Stable RNA-mediated silencing of syndecan-1 gene expression up-regulated NOX-dependent generation of reactive oxygen species and reduced the survival of holoclones in vitro. Syndecan-1 down-regulation also strongly reduced the number of CD133(+)/CD44(+) primitive cancer cells and tumour growth in vivo. Interestingly, syndecan-1 gene knockdown significantly enhanced the tumour-suppressive effects of docetaxel by inhibiting the docetaxel-induced increase in CD133(+)/CD44(+) cells in vivo. In the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model of prostate cancer, early intervention with a syndecan-1 inhibitor (OGT2115) or syndecan-1 RNAi reduced the incidence of adenocarcinoma and the number of c-kit(+)/CD44(+) cells in cancer foci. Finally, we found that syndecan-1 immunopositivity in prostate cancer cells was significantly associated with biochemical recurrence after radical prostatectomy. Taken together, our results show that syndecan-1 contributes to prostatic carcinogenesis by maintaining TICs and may be a target molecule for therapy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Colon Cancer Cell Separation by Dielectrophoresis

    Science.gov (United States)

    Yang, Fang; Yang, Xiaoming; Jiang, H.; Wood, P.; Hrushesky, W.; Wang, Guiren

    2009-11-01

    Separation of cancer cells from the other biological cells can be useful for clinical cancer diagnosis and cancer treatment. In this presentation, conventional dielectrophoresis (c-DEP) is used in a microfluidic chip to manipulate and collect colorectal cancer HCT116 cell, which is doped with Human Embryonic Kidney 293 cells (HEK 293). It is noticed that, the HCT116 cell are deflected to a side channel from a main channel clearly by apply electric field at particular AC frequency band. This motion caused by negative DEP can be used to separate the cancer cell from others. In this manuscript, chip design, flow condition, the DEP spectrum of the cancer cell are reported respectively, and the separation and collection efficiency are investigated as well. The sorter is microfabricated using plastic laminate technology. -/abstract- This work has been financially supported by the NSF RII funding (EP

  17. Prostate Cancer Stem-Like Cells | Center for Cancer Research

    Science.gov (United States)

    Prostate cancer is the third leading cause of cancer-related death among men, killing an estimated 27,000 men each year in the United States. Men with advanced prostate cancer often become resistant to conventional therapies. Many researchers speculate that the emergence of resistance is due to the presence of cancer stem cells, which are believed to be a small subpopulation of tumor cells that can self-renew and give rise to more differentiated tumor cells. It is thought that these stem cells survive initial therapies (such as chemotherapy and hormone therapy) and then generate new tumor cells that are resistant to these standard treatments. If prostate cancer stem cells could be identified and characterized, it might be possible to design treatments that prevent resistance.

  18. Cancer Cell Fusion: Mechanisms Slowly Unravel

    Directory of Open Access Journals (Sweden)

    Felicite K. Noubissi

    2016-09-01

    Full Text Available Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion was a mechanism of cancer metastasis. This hypothesis gained some support over the years, and recently became the focus of many studies that revealed increasing evidence pointing to the possibility that cancer cell fusion probably gives rise to the metastatic phenotype by generating widespread genetic and epigenetic diversity, leading to the emergence of critical populations needed to evolve resistance to the treatment and development of metastasis. In this review, we will discuss the clinical relevance of cancer cell fusion, describe emerging mechanisms of cancer cell fusion, address why inhibiting cancer cell fusion could represent a critical line of attack to limit drug resistance and to prevent metastasis, and suggest one new modality for doing so.

  19. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

    OpenAIRE

    Yuan, Zhi-xiang; Mo, Jingxin; Zhao, Guixian; Shu, Gang; Fu, Hua-Lin; Wei ZHAO

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...

  20. Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer.

    Directory of Open Access Journals (Sweden)

    Jingxian Ding

    Full Text Available Breast cancer is one of the most frequently diagnosed cancers among women, and metastasis makes it lethal. Tumor-associated macrophages (TAMs that acquire an alternatively activated macrophage (M2 phenotype may promote metastasis. However, the underlying mechanisms are still elusive. Here, we examined how TAMs interact with breast cancer cells to promote metastasis. Immunohistochemistry was used to examine the expression of the M2-specific antigen CD163 in paraffin-embedded mammary carcinoma blocks to explore fusion events in breast cancer patients. U937 cells were used as a substitute for human monocytes, and these cells differentiated into M2 macrophages following phorbol 12-myristate 13-acetate (PMA and M-CSF stimulation. M2 macrophages and the breast cancer cell lines MCF-7 and MDA-MB-231 fused in the presence of 50% polyethylene glycol. Hybrids were isolated by fluorescence-activated cell sorting, and the relevant cell biological properties were compared with their parental counterparts. Breast cancer stem cell (BCSC-related markers were quantified by immunofluorescence staining, RT-PCR, quantitative RT-PCR and/or western blotting. The tumor-initiating and metastatic capacities of the hybrids and their parental counterparts were assessed in NOD/SCID mice. We found that the CD163 expression rate in breast cancer tissues varied significantly and correlated with estrogen receptor status (p0.05. Characterization of the fusion hybrids revealed a more aggressive phenotype, including increased migration, invasion and tumorigenicity, but reduced proliferative ability, compared with the parental lines. The hybrids also gained a CD44(+CD24(-/low phenotype and over-expressed epithelial-mesenchymal transition-associated genes. These results indicate that TAMs may promote breast cancer metastasis through cell fusion, and the hybrids may gain a BCSC phenotype.

  1. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  2. Ovarian Cancer Stem Cells: A New Target for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Qinglei Zhan

    2013-01-01

    Full Text Available Ovarian cancer is a highly lethal disease among all gynecologic malignancies and is the fifth leading cause of cancer-related death in women. Although the standard combination of surgery and chemotherapy was initially effective in patients with ovarian cancer, disease relapse commonly occurred due to the generation of chemoresistance. It has been reported that cancer stem cells (CSCs are involved in drug resistance and cancer recurrence. Over the past decades, increasing studies have been done to identify CSCs from human ovarian cancer cells. The present paper will summarize different investigations on ovarian CSCs, including isolation, mechanisms of chemoresistance, and therapeutic approaches. Although there are still numerous challenges to translate basic research to clinical applications, understanding the molecular details of CSCs is essential for developing effective strategies to prevent ovarian cancer and its recurrence.

  3. Cancer stem cell targeted therapy: progress amid controversies

    Science.gov (United States)

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  4. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  5. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  6. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  7. Source of Aegean Sea harbour porpoises

    DEFF Research Database (Denmark)

    Lockyer, Christina; Rosel, P. E.; Frantzis, A.

    2003-01-01

    Documented sightings of harbour porpoises in the Mediterranean are rare, although the species is common in the neighbouring North Atlantic and Black Sea. However, in the past 2 decades, 4 harbour porpoises Phocoena phocoena have been recorded in the northern Aegean Sea in the eastern Mediterranean...... Basin. Samples were taken from 2 of these. Both have a genetic signature indicative of the Black Sea and their age and small size further suggest they originated from the Black Sea rather than the Atlantic population. These results are the first to indicate probable movement of porpoises out...... of the Black Sea and into the Mediterranean Sea....

  8. Cancer stem cells of the digestive system.

    Science.gov (United States)

    Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Molecular Biology of Liver Cancer Stem Cells

    National Research Council Canada - National Science Library

    Oishi, Naoki; Yamashita, Taro; Kaneko, Shuichi

    2014-01-01

    .... The concept of cancer stem cells (CSCs) is based primarily on the clinical and experimental observations that indicate the existence of a subpopulation of cells with the capacity to self-renew and differentiate as well as show increased...

  10. Cancer Stem Cells: Repair Gone Awry?

    Directory of Open Access Journals (Sweden)

    Fatima Rangwala

    2011-01-01

    Full Text Available Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on this process, and thus may unmask defective regulation of pathways, such as Hedgehog (Hh, that modulate progenitor cell fate. Hh pathway dysregulation has been demonstrated in many types of cancer, including pancreatic and liver cancers, in which defective Hh signaling has been linked to outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements. Hence, the Hh pathway might be a therapeutic target in such tumors.

  11. NK Cells and Virus-Related Cancers

    OpenAIRE

    Mishra, Rabinarayan; Welsh, Raymond M.; Szomolanyi-Tsuda, Eva

    2014-01-01

    Natural killer (NK) cells become activated during viral infections and can play roles in such infections by attacking virus-infected cells or by regulating adaptive immune responses. Experimental models suggest that NK cells may also have the capacity to restrain virus-induced cancers. Here, we discuss the seven viruses linked to human cancers and the evidence of NK cell involvement in these systems.

  12. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics ......, help us both in the identification and characterization of cancer stem cells and in the further development of therapeutic strategies including tissue engineering...

  13. Targeting the osteosarcoma cancer stem cell

    Directory of Open Access Journals (Sweden)

    Qin Ling

    2010-10-01

    Full Text Available Abstract Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.

  14. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  15. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2015-07-01

    dominant role over some oncogene function.In addition, we recently reported that cancer stem cells (CSCs)- stem cell like cells in tumors that have stem ... cell properties and tumor initiating ability- retain epigenetic memories of their cells of origin (Chow et al., 2014). We showed that CSCs derived from

  16. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  17. Betulinic Acid Kills Colon Cancer Stem Cells

    NARCIS (Netherlands)

    Potze, Lisette; Di Franco, Simone; Kessler, Jan H.; Stassi, Giorgio; Medema, Jan Paul

    2016-01-01

    Cancer stem cells (CSCs) are considered to be the origin of cancer and it is suggested that they are resistant to chemotherapy. Current therapies fail to eradicate CSCs and therefore selecting a resistant cell subset that is able to facilitate tumor recurrences. Betulinic acid (BetA) is a broad

  18. A cancer cell-specific fluorescent probe for imaging Cu2 + in living cancer cells

    Science.gov (United States)

    Wang, Chao; Dong, Baoli; Kong, Xiuqi; Song, Xuezhen; Zhang, Nan; Lin, Weiying

    2017-07-01

    Monitoring copper level in cancer cells is important for the further understanding of its roles in the cell proliferation, and also could afford novel copper-based strategy for the cancer therapy. Herein, we have developed a novel cancer cell-specific fluorescent probe for the detecting Cu2 + in living cancer cells. The probe employed biotin as the cancer cell-specific group. Before the treatment of Cu2 +, the probe showed nearly no fluorescence. However, the probe can display strong fluorescence at 581 nm in response to Cu2 +. The probe exhibited excellent sensitivity and high selectivity for Cu2 + over the other relative species. Under the guidance of biotin group, could be successfully used for detecting Cu2 + in living cancer cells. We expect that this design strategy could be further applied for detection of the other important biomolecules in living cancer cells.

  19. Are cancer cells really softer than normal cells?

    Science.gov (United States)

    Alibert, Charlotte; Goud, Bruno; Manneville, Jean-Baptiste

    2017-05-01

    Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  20. Of germ cells, trophoblasts, and cancer stem cells.

    Science.gov (United States)

    Burleigh, Angela R

    2008-12-01

    The trophoblastic theory of cancer, proposed in the early 1900s by Dr John Beard, may not initially seem relevant to current cancer models and treatments. However, the underpinnings of this theory are remarkably similar to those of the cancer stem cell (CSC) theory. Beard noticed that a significant fraction of germ cells never reach their final destination as they migrate during embryonic development from the hindgut to the germinal ridge. In certain situations, upon aberrant stimulation, these vagrant germ cells are able to generate tumors. Simplistically, the CSC theory surmises that a small population of tumorigenic cells exists, which initiate and maintain tumors, and these cells have a likely origin in normal stem cells. Both these theories are based on the potential of a single primitive cell to form a tumor. This has a major implication for cancer therapy, in that only a small percentage of cells need to be targeted to ablate a tumor.

  1. Single Cell Characterization of Prostate Cancer Circulating Tumor Cells

    Science.gov (United States)

    2011-08-01

    CTCs from patient blood, a single T24 bladder and LNCaP prostate cancer cells, a pool of 8 prostate CTCs, and one leukocyte isolated from the blood...amplify 66% of mRNA pool from a single cell. Clustering analysis does differentiate CTCs from LNCaP and T24 bladder cell lines (Figure 4). At present we...profiles could distinguish a CTC from prostate cancer cell line LNCaP and T24 bladder cancer cell line.  There was intra and inter patient heterogeneity

  2. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  3. Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

    Directory of Open Access Journals (Sweden)

    Hyemi Lee

    Full Text Available Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5-10 mM metformin for 48 h caused significant clonogenic cell death. Culturing breast cancer cells with 30 µM metformin, clinically relevant plasma concentration of metformin, significantly reduced the survival of cancer cells. Importantly, metformin was preferentially cytotoxic to CD44(high/CD24(low cells of MCF-7 cells and, CD44(high/CD24(high cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs of MCF-7 cells and MIA PaCa-2 cells, respectively. Heating at 42°C for 1 h was slightly toxic to both cancer cells and CSCs, and it markedly enhanced the efficacy of metformin to kill cancer cells and CSCs. Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. For the first time, we show that hyperthermia activates AMPK and inactivates mTOR and its downstream effector S6K. Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. It is conclude that the effects of metformin against cancer cells including CSCs can be markedly enhanced by hyperthermia.

  4. Cancer stem cells in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Trapasso S

    2012-11-01

    Full Text Available Eugenia Allegra, Serena TrapassoOtolaryngology – Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, ItalyAbstract: Cancer stem cells (CSCs, also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal, giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division. A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on

  5. Subsurface geology of the Bombay Harbour

    Digital Repository Service at National Institute of Oceanography (India)

    Almeida, F.; Ramana, M.V.; Vora, K.H.; Bhattacharya, G.C.; Subrahmanyam, V.

    As part of engineering pre-design investigations, high resolution geophysical surveys were carried out in and around Bombay harbour, India. The depth in the area varies from dries over the mudflats to about 14m towards the offshore end. The seabed...

  6. Seabed surveys of Victoria harbour, Mahe, Seychelles

    Digital Repository Service at National Institute of Oceanography (India)

    Hashimi, N.H.; Wagle, B.G.

    The seabed surveys in the Victoria Harbour, Mahe, Seychelles shows that the prominent feature is the navigational channel aligned in the northeast-southwest direction with a width varying from 300 to 450m. The depth in the channel ranges from 14...

  7. Earlier pupping in harbour seals, Phoca vitulina

    NARCIS (Netherlands)

    Reijnders, P.J.H.; Brasseur, S.M.J.M.; Meesters, H.W.G.

    2010-01-01

    The annual reproductive cycle of most seal species is characterized by a tight synchrony of births. Typically, timing of birth shows little inter-annual variation. Here, however we show that harbour seals Phoca vitulina from the Wadden Sea (southeast North Sea) have shortened their yearly cycle,

  8. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    Directory of Open Access Journals (Sweden)

    Thomas W.J. Lennard

    2011-04-01

    Full Text Available In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP, have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC, combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis.

  9. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Kelly M. [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); Kirby, John A. [Institute of Cellular Medicine, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Lennard, Thomas W.J. [Faculty of Medical Sciences, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Meeson, Annette P., E-mail: annette.meeson@ncl.ac.uk [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); North East England Stem Cell Institute, Bioscience Centre, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom)

    2011-04-19

    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis.

  10. Impact investigations of access channel modifications of Cochin harbour, India

    Digital Repository Service at National Institute of Oceanography (India)

    DineshKumar, P.K.

    Though the modernization projects over the decades for harbour development also brought about several severe environmental modifications in Cochin harbour, along the west coast of India, so far, the physical processes involved are seldom...

  11. Pollution characteristics and water quality in the Visakhapatnam harbour

    Digital Repository Service at National Institute of Oceanography (India)

    Sarma, V.V.; Raju, G.R.K.; Babu, T.B.

    The impact of organic pollution on the quality of waters in the Visakhapatnam harbour has been studied over a year at 8 stations. The enrichment of nutrients in these waters enhances the eutrophication. The construction of outer harbour retards...

  12. Cisplatin induces differentiation of breast cancer cells.

    Science.gov (United States)

    Prabhakaran, Praseetha; Hassiotou, Foteini; Blancafort, Pilar; Filgueira, Luis

    2013-01-01

    Breast tumors are heterogeneous including cells with stem cell properties and more differentiated cells. This heterogeneity is reflected into the molecular breast cancer subtypes. Breast cancer stem cells are resistant to chemotherapy, thus recent efforts are focusing on identifying treatments that shift them toward a more differentiated phenotype, making them more susceptible to chemotherapy. We examined whether the drug cisplatin induces differentiation in breast cancer cell lines that represent different breast cancer subtypes. We used three cell lines representing triple-negative breast cancers, BT-549 and MDA-MB-231 (claudin-low), and MDA-MB-468 (basal-like), along with estrogen and progesterone receptor positive MCF-7 cells (luminal). Cisplatin was applied at 2.5, 5, 10, and 20 μM, and cell viability and proliferation were measured using MTS and BrdU assays, respectively. The effect of cisplatin on the cellular hierarchy was examined by flow cytometry, immunofluorescence and qRT-PCR. Cisplatin treatment of 10 and 20 μM reduced cell viability by 36-51% and proliferation capacity by 36-67%. Treatment with cisplatin resulted in 12-67% down-regulation of stem cell markers (CD49f, SSEA4) and 10-130% up-regulation of differentiation markers (CK18, SMA, β-tubulin). At the mRNA level, CD49f was down-regulated whilst β-tubulin was up-regulated in the claudin-low cell lines. SSEA4 protein expression decreased upon cisplatin treatment, but SSEA4 mRNA expression increased indicating a differential regulation of cisplatin at the post-transcriptional level. It is concluded that cisplatin reduces breast cancer cell survival and induces differentiation of stem/progenitor cell subpopulations within breast cancer cell lines. These effects indicate the potential of this drug to target specific chemotherapy-resistant cells within a tumor.

  13. Cancer-associated fibroblasts promote proliferation of endometrial cancer cells.

    Directory of Open Access Journals (Sweden)

    Kavita S Subramaniam

    Full Text Available Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin and hormonal (estrogen and progesterone receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175% when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51% (P<0.0001. These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001, suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR, also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP-1, interleukin (IL-6, IL-8, RANTES and vascular

  14. Syncytin is involved in breast cancer-endothelial cell fusions

    DEFF Research Database (Denmark)

    Bjerregaard, B; Holck, Susanne; Christensen, Ib Jarle

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  15. Targetless T cells in cancer immunotherapy

    DEFF Research Database (Denmark)

    thor Straten, Eivind Per; Garrido, Federico

    2016-01-01

    Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell...... transfer (ACT) using expanded tumor infiltrating lymphocytes (TIL) or genetically modified cytotoxic T cells. However, despite clear clinical responses, only a fraction of patients respond to treatment and there is an urgent call for characterization of predictive biomarkers. CD8 positive T cells can...... infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However...

  16. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, Shin [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Hamada, Hirofumi [Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji (Japan); Kobune, Masayoshi [Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo (Japan); Satoh, Kennichi [Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  17. Analysis of the performance of swash in harbour domains

    NARCIS (Netherlands)

    Alabart, J.; Sanchez-Arcilla, A.; Van Vledder, G.P.

    2014-01-01

    Wave penetration inside harbours has been one the main issues that port planners and engineers have had to deal with in recent years. Wave conditions inside harbours trigger vessel movements, create dynamic loads on port structures and condition harbour exploitation and safety. For this reason in

  18. The zooplankton community of Richards Bay Harbour and adjacent ...

    African Journals Online (AJOL)

    During construction of the current Richards Bay Harbour in the early 1970s, the original shallow Mhlathuze Estuary was divided into two separate systems: a new estuary and a deep-water harbour. This study compares the zooplankton communities of the current systems with reference to that of the original, before harbour ...

  19. Targeting Cancer Stem Cells with Natural Killer Cell Immunotherapy.

    Science.gov (United States)

    Luna, Jesus I; Grossenbacher, Steven K; Murphy, William J; Canter, Robert J

    2017-03-01

    Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with 'stem-cell' like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered: Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. The authors review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert opinion: Unlike cytotoxic cancer treatments, NK cells can target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells.

  20. Ocean disposal of dredged materials from Atlantic Canadian harbours. 1. Small craft harbours, Scotia-Fundy Region

    National Research Council Canada - National Science Library

    1985-01-01

    The objective of this report is to provide a compilation of all data related to dredging/ocean disposal of dredged materials from harbours maintained by the Small Craft Harbours Branch of Fisheries...

  1. Lipid degradation promotes prostate cancer cell survival

    Science.gov (United States)

    Itkonen, Harri M; Brown, Michael; Urbanucci, Alfonso; Tredwell, Gregory; Lau, Chung Ho; Barfeld, Stefan; Hart, Claire; Guldvik, Ingrid J.; Takhar, Mandeep; Heemers, Hannelore V.; Erho, Nicholas; Bloch, Katarzyna; Davicioni, Elai; Derua, Rita; Waelkens, Etienne; Mohler, James L.; Clarke, Noel; Swinnen, Johan V.; Keun, Hector C.; Rekvig, Ole P.; Mills, Ian G.

    2017-01-01

    Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. PMID:28415728

  2. Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45.

    Science.gov (United States)

    Zhang, Hai-hong; Cai, Ai-zhen; Wei, Xue-ming; Ding, Li; Li, Feng-zhi; Zheng, Ai-ming; Dai, Da-jiang; Huang, Rong-rong; Cao, Hou-jun; Zhou, Hai-yang; Wang, Jian-mei; Wang, Xue-jing; Shi, Wei; Zhu, Heng; Yuan, Xiao-ying; Chen, Lin

    2013-03-01

    Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissues have demonstrated the presence of SP cells, including several gastric cancer cell lines. This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45. We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells. This study found that the SP cells had higher clone formation efficiency than major population (MP) cells. Five stemness-related gene expression profiles, including OCT-4, SOX-2, NANOG, CD44, and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2, were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Western blot was used to show the difference of protein expression between SP and MP cells. Both results show that there was significantly higher protein expression in SP cells than in MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells show higher tumorigenesis tendency than MP cells. These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

  3. Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Germana Castelli

    2017-09-01

    Full Text Available Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC and intrahepatic cholangiocarcinoma (iCCA. Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV infection (frequent in Asia and Africa, hepatitis C virus (HCV, chronic alcohol abuse, or metabolic syndrome (frequent in Western countries. In cirrhosis, hepatocarcinogenesis is a multi-step process where pre-cancerous dysplastic macronodules transform progressively into HCC. The patterns of genomic alterations observed in these tumors were recently identified and were instrumental for the identification of potential targeted therapies that could improve patient care. Liver cancer stem cells are a small subset of undifferentiated liver tumor cells, responsible for cancer initiation, metastasis, relapse and chemoresistance, enriched and isolated according to immunophenotypic and functional properties: cell surface proteins (CD133, CD90, CD44, EpCAM, OV-6, CD13, CD24, DLK1, α2δ1, ICAM-1 and CD47; the functional markers corresponding to side population, high aldehyde dehydrogenase (ALDH activity and autofluorescence. The identification and definition of liver cancer stem cells requires both immunophenotypic and functional properties.

  4. Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression.

    Science.gov (United States)

    Lopes-Coelho, Filipa; Gouveia-Fernandes, Sofia; Serpa, Jacinta

    2018-02-01

    The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

  5. c-Myc-Dependent Cell Competition in Human Cancer Cells.

    Science.gov (United States)

    Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

    2017-07-01

    Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

    Science.gov (United States)

    Rahman, Ruman; Heath, Rachel; Grundy, Richard

    2009-04-01

    Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

  7. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  8. The Ancient Harbours of the Piraeus, Volume I.1

    DEFF Research Database (Denmark)

    Lovén, Bjørn

    of Athenian power. This first volume in the peer-reviewed Ancient Harbours of the Piraeus series is the culmination of the first phase of archaeological investigations conducted by the Zea Harbour Project, 2001-2006. The study focuses on Zea Harbour, where two previously unidentified building phases were...... and measurement of the relative changes in sea level since antiquity - a key piece of the puzzle, and one that has led to a broader understanding of the topography of the ancient harbours of the Piraeus. The naval installations built in Zea Harbour in the 4th century BC were amongst the largest building complexes...

  9. Estimation of Wave Disturbance in Harbours

    DEFF Research Database (Denmark)

    Helm-Petersen, Jacob

    been presented for the analysis of reflected wave fields in 2D and 3D. The Bayesian Directional Wave Spectrum Estimation Method has been applied throughout the study. Reflection characteristics have been investigated by use of physical models for three types of coastal structures with vertical fronts......The motivation for the present study has been to improve the reliability in using numerical wave propagation models as a tool for estimating wave disturbance in harbours. Attention has been directed towards the importance of the modelling of reflection in the applied mild-slope model. Methods have....... The analyses include mainly directional waves. Analysis of field measurements has also taken place. Simulations with a mild-slope model have been carried out with individual structures and a complete harbour. The analyses clarify to a wide extent the behaviour of the sponge layers applied in the model...

  10. Spindle Cell Metaplastic Breast Cancer: Case Report

    Directory of Open Access Journals (Sweden)

    Dursun Ozgur Karakas

    2013-08-01

    Conclusion: Spindle cell metaplastic breast cancer must be considered in differential diagnosis of breast cancers, and preoperative immunohistochemical examination, including cytokeratin and vimentin, must be added to pathological examination in intervening cases. [Arch Clin Exp Surg 2013; 2(4.000: 259-262

  11. Stem Cells and Cancer; Celulas madre y cancer

    Energy Technology Data Exchange (ETDEWEB)

    Segrelles, C.; Paraminio, J. M.; Lorz, C.

    2014-04-01

    Stem cell research has thrived over the last years due to their therapeutic and regenerative potential. Scientific breakthroughs in the field are immediately translated from the scientific journals to the mass media, which is not surprising as the characterisation of the molecular mechanisms that regulate the biology of stem cells is crucial for the treatment of degenerative and cardiovascular diseases, as well as cancer. In the Molecular Oncology Unit at Ciemat we work to unravel the role of cancer stem cells in tumour development, and to find new antitumor therapies. (Author)

  12. Epigenetic control of the basal-like gene expression profile via Interleukin-6 in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Mitrugno Valentina

    2010-11-01

    Full Text Available Abstract Background Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6, a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells. Results Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions. Conclusion We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.

  13. Alterations of calcium homeostasis in cancer cells.

    Science.gov (United States)

    Marchi, Saverio; Pinton, Paolo

    2016-08-01

    Typical hallmarks of cancer include programmed cell death evasion, uncontrolled cell growth, invasion, and metastasis. Changes in intracellular Ca(2+) levels can modulate signaling pathways that control a broad range of cellular events, including those important to tumorigenesis and cancer progression. Here we discuss how known molecular mediators of cellular Ca(2+) homeostasis impact tumor dynamics and how deregulation of major oncogenes and tumor suppressors is tightly associated with Ca(2+) signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Lgr5-Positive Cells are Cancer-Stem-Cell-Like Cells in Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Zhongli Wang

    2015-07-01

    Full Text Available Background/Aims: Effective treatment of gastric cancer (GC requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs in GC appears to be a critical question. Methods: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV that carries diphtheria toxin fragment A (DTA under the control of Lgr5 promoter (AAV-pLgr5-DTA to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. Results: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. Conclusion: Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome.

  15. Study characterizes how DNA-damaging anti-cancer drugs kill cancer cells | Center for Cancer Research

    Science.gov (United States)

    Patients whose cancer cells express the SLFN11 protein are more likely to respond to DNA-damaging anti-cancer drugs than those whose cancer cells don’t express SLFN11. In a new study, Center for Cancer Research investigators show how these drugs recruit SLFN11 to block replication and kill cancer cells. Read more…

  16. Epigenetics of solid cancer stem cells.

    Science.gov (United States)

    Mishra, Alok; Verma, Mukesh

    2012-01-01

    Epigenetics is an emerging science that can help to explain carcinogenesis. The possibility that carcinogenesis may originate in a stem cell process was proposed recently. Stem cells are generated and contribute to tumor formation during the process of tumor development. This chapter focuses on the role of epigenetics and genetics in stem cell formation, different theories about the origin of cancer stem cells (CSCs), and epigenetic mechanisms that occur in solid CSCs. Potential applications of knowledge gained through this field and future prospects for cancer treatment also are discussed.

  17. Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics

    Directory of Open Access Journals (Sweden)

    Halliday A Idikio

    2011-01-01

    Full Text Available Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture the known attributes of cancer stem cells and their potential contribution to treatment response, and metastases. The integrated model of cancer classification presented here incorporates all morphology, cancer stem cell contributions, genetic, and functional attributes of cancer. Integrated cancer classification models could eliminate the unclassifiable cancers as used in current classifications. Future cancer treatment may be advanced by using an integrated model of cancer classification.

  18. Cell-of-Origin of Cancer versus Cancer Stem Cells: Assays and Interpretations.

    Science.gov (United States)

    Rycaj, Kiera; Tang, Dean G

    2015-10-01

    A tumor originates from a normal cell that has undergone tumorigenic transformation as a result of genetic mutations. This transformed cell is the cell-of-origin for the tumor. In contrast, an established clinical tumor is sustained by subpopulations of self-renewing cancer cells operationally called cancer stem cells (CSC) that can generate, intraclonally, both tumorigenic and nontumorigenic cells. Identifying and characterizing tumor cell-of-origin and CSCs should help elucidate tumor cell heterogeneity, which, in turn, should help understand tumor cell responses to clinical treatments, drug resistance, tumor relapse, and metastatic spread. Both tumor transplantation and lineage-tracing assays have been helpful in characterizing these cancer cell populations, although each system has its strengths and caveats. In this article, we briefly review and summarize advantages and limitations of both assays in support of a combinatorial approach to accurately define the roles of both cancer-initiating and cancer-propagating cells. As an aside, we also wish to clarify the definitions of cancer cell-of-origin and CSCs, which are often interchangeably used by mistake. ©2015 American Association for Cancer Research.

  19. Fatty acids and breast cancer cell proliferation.

    Science.gov (United States)

    Hardy, R W; Wickramasinghe, N S; Ke, S C; Wells, A

    1997-01-01

    We and others have shown that fatty acids are important regulators of breast cancer cell proliferation. In particular individual fatty acids specifically alter EGF-induced cell proliferation in very different ways. This regulation is mediated by an EGFR/G-protein signaling pathway. Understanding the molecular mechanisms of how this signaling pathway functions and how fatty acids regulate it will provide important information on the cellular and molecular basis for the association of dietary fat and cancer. Furthermore these in vitro studies may explain data previously obtained from in vivo animal studies and identify "good" as well as "bad" fatty acids with respect to the development of cancer.

  20. Expression of periostin in breast cancer cells.

    Science.gov (United States)

    Ratajczak-Wielgomas, Katarzyna; Grzegrzolka, Jedrzej; Piotrowska, Aleksandra; Matkowski, Rafal; Wojnar, Andrzej; Rys, Janusz; Ugorski, Maciej; Dziegiel, Piotr

    2017-10-01

    Periostin (POSTN) is a protein involved in multiple processes important for cancer development, both at the stage of cancer initiation and progression, as well as metastasis. The aim of this study was to determine the expression of POSTN in the cells of non-invasive ductal breast carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to correlate it with clinicopathological data. Immunohistochemical studies (IHC) were conducted on 21 cases of fibrocystic breast change (FC), 44 cases of DCIS and 92 cases of IDC. POSTN expression at mRNA (real-time PCR) and protein level (western blot analysis) was also confirmed in selected breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2). Statistically significant higher level of POSTN expression in IDC and DCIS cancer cells compared to FC was noted. Also, the level of POSTN expression in the cytoplasm of IDC cells was shown to increase with the increasing degree of tumour malignancy (G) and significantly higher expression of POSTN was observed in each degree of tumour malignancy (G) relative to FC. Statistically significant higher POSTN expression was observed in tumours with estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) phenotypes in comparison to estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) cases, as well as significant negative correlation between POSTN expression in cancer cells and expression of ER and PR (p<0.05). Additionally, statistically significant differences in POSTN expression were shown between particular breast cancer cell lines, both at mRNA and protein level. Observed POSTN expression was the lowest in the case of MCF-7, and the highest in MDA-MB-231 and BO2 of the most aggressive potential clinically corresponding to G3 tumours. POSTN expression in the cytoplasm of IDC cancer cells may play an important role in cancer transformation mechanism.

  1. Exercise regulates breast cancer cell viability

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Lillelund, Christian; Midtgaard, Julie

    2016-01-01

    Purpose: Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses......, in breast cancer survivors could regulate breast cancer cell viability in vitro. Methods: Blood samples were collected from breast cancer survivors, partaking in either a 6-month training intervention or across a 2 h acute exercise session. Changes in training parameters and systemic factors were evaluated...... and pre/post exercise-conditioned sera from both studies were used to stimulate breast cancer cell lines (MCF-7, MDA-MB-231) in vitro. Results: Six months of training increased VO2peak (16.4 %, p

  2. Cancer stem cells, the ultimate targets in cancer therapy

    OpenAIRE

    Shabbir A; Esfandyari T; Farassati F

    2018-01-01

    Ahmed Shabbir,1 Tuba Esfandyari,2 Faris Farassati1,3,4 1Midwest Biomedical Research Foundation, Kansas City Veterans Affairs Medical Center, 2Department of Medicine, School of Medicine, The University of Kansas, 3Saint Luke’s Cancer Institute, 4Saint Luke’s Marion Bloch Neuroscience Institute, Saint Luke’s Health System, Kansas City, MO, USAThe concept of cancer stem cells (CSCs) is currently of significant interest due to its important implications in our under...

  3. Cancer stem cells, the ultimate targets in cancer therapy

    OpenAIRE

    Shabbir A; Esfandyari T; Farassati F

    2018-01-01

    Ahmed Shabbir,1 Tuba Esfandyari,2 Faris Farassati1,3,4 1Midwest Biomedical Research Foundation, Kansas City Veterans Affairs Medical Center, 2Department of Medicine, School of Medicine, The University of Kansas, 3Saint Luke’s Cancer Institute, 4Saint Luke’s Marion Bloch Neuroscience Institute, Saint Luke’s Health System, Kansas City, MO, USAThe concept of cancer stem cells (CSCs) is currently of significant interest due to its important implications in our understanding of ...

  4. Overcoming Multidrug Resistance in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Karobi Moitra

    2015-01-01

    Full Text Available The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed.

  5. Identification of cancer stem-like side population cells in ovarian cancer cell line OVCAR-3.

    Science.gov (United States)

    Gao, Quanli; Geng, Li; Kvalheim, Gunnar; Gaudernack, Gustav; Suo, Zhenhe

    2009-01-01

    Side population (SP) cells may enrich stem-like cells in many normal and malignant tissues. However, SP method application has drawn special attention to the field of stem cell research, and the existence of SP cells in cell culture is being debated, most probably because different cell lines require different technical modifications, especially when cell staining is considered. In this study, the authors aimed to disclose whether the hoechst33342 staining required extensive optimization for identifying SP cells in the human ovarian cancer cell line OVCAR-3. After systematic evaluations, it was found that only 2.5 microg/mL hoechst33342 staining of the cells for 60 min could get an ideal SP population, which accounted for 0.9% of the whole cell population. The sorted SP cells showed significantly higher colony formation efficiency than the non-side population (NSP) cells, and only the SP cells could form holoclones. Real-time PCR disclosed that SP cells expressed higher levels of "stemness" gene Oct3/4 than the NSP cells did, indicating that the SP cells might harbor cancer stem cells in this cell line. The results highlight the necessity of SP method optimization in cell studies, and the SP cells in this cell line merit further studies when cancer stem cell identification and isolation are considered.

  6. Cancer stem cells and their implication in breast cancer.

    Science.gov (United States)

    Carrasco, E; Alvarez, Pablo J; Prados, José; Melguizo, Consolación; Rama, Ana R; Aránega, Antonia; Rodríguez-Serrano, Fernando

    2014-07-01

    The cancer stem cell (CSC) hypothesis on the origin of cancer has recently gained considerable support. CSCs are tumour cells with the capacity for self-renewal and differentiation that direct the origin and progression of the disease and may be responsible for relapse, metastasis and treatment failures. This article reviews breast CSCs (BCSCs) phenotyping, clinical implications and clinical trials focused on BCSCs in breast cancer. Relevant studies were found through PubMed and Clinicaltrials.gov databases. Cancer stem cells are identified and isolated using membrane and cell activity markers; in the case of BCSCs, these are CD44(+) /CD24(low/-) and show aldehyde dehydrogenase activity, alongside their capacity to grow and form mammospheres. The presence of stem cell properties is associated with a worse outcome. Hence, these cells have important clinical implications, and elucidation of the mechanisms underlying their activity will allow the development of novel effective therapies and diagnostic instruments, improving the prognosis of these patients. Standard treatments are directed against the tumour mass and do not eliminate CSCs. There is therefore a need for specific anti-CSC therapies, and numerous authors are investigating new targets to this end, as reported in this review. It is also necessary for clinical trials to be undertaken to allow this new knowledge to be applied in the clinical setting. However, there have been few trials on anti-BCSCs therapies to date. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  7. Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics

    OpenAIRE

    Halliday A Idikio

    2011-01-01

    Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture...

  8. Cell Phones and Cancer Risk

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... interagency program headquartered at the National Institute of Environmental Health Sciences (NIEHS), which is part of the ...

  9. Induction of cancer stem cell properties in colon cancer cells by defined factors.

    Directory of Open Access Journals (Sweden)

    Nobu Oshima

    Full Text Available Cancer stem cells (CSCs are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4 into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs. Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.

  10. The therapeutic promise of the cancer stem cell concept

    National Research Council Canada - National Science Library

    Frank, Natasha Y; Schatton, Tobias; Frank, Markus H

    2010-01-01

    Cancer stem cells (CSCs) are a subpopulation of tumor cells that selectively possess tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of nontumorigenic cancer cell progeny through differentiation...

  11. Penile/anal condylomas and squamous cell cancer. A HPV DNA hybridization study.

    Science.gov (United States)

    Löning, T; Riviere, A; Henke, R P; von Preyss, S; Dörner, A

    1988-01-01

    Acuminate condylomas from the penis (n = 17) and anus (six cases), three anal/penile giant condylomas, anal Bowen's disease (four cases), and intraanal squamous cell carcinomas with associated condylomatous changes (10 cases) including two verrucous carcinoma were studied for human papillomavirus (HPV) infections with nick translated, biotinylated cDNA probes for HPV 6, 11, 16 and 18. In addition, six cases of flat white penile lesions designated as lichen sclerosus et atrophicus were examined. Reannealed complementary DNA strands were detected in situ with either immunoenzyme or immunogold protocols. The in situ hybridizations resulted in 1/6 positive penile lichenoid lesions, 12/17 positive penile acuminate condylomas, 6/6 positive anal acuminate condylomas (including two condylomas with cellular atypias), 2/3 positive giant condylomas, 1/4 positive anal bowenoid lesions, and 4/10 positive keratinized squamous cell carcinomas, two of them being verrucous carcinomas. All penile/anal condylomas and two giant condylomas harboured HPV 6 and/or 11 DNA. The five positive carcinomas (carcinoma in situ/invasive cancer) contained HPV 6 and/or 11 in two cases (including the verrucous carcinomas), and HPV 16 and/or 18 in three cases (one carcinoma in situ, two invasive carcinomas). Recurrent malignancies were seen in one case to harbour the same HPV type as the primary lesions (HPV 16). In one particular patient, a double infection with HPV 16 and HPV 18 was demonstrated in distantly located malignant tumours. Our study confirms the restrictions and the value of non-isotopic hybridization methods applied to archival tissues, and extends the knowledge on the presence and distribution of HPV infections at anogenital sites.

  12. The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines.

    Science.gov (United States)

    Joseph, Immanual; Tressler, Robert; Bassett, Ekaterina; Harley, Calvin; Buseman, Christen M; Pattamatta, Preeti; Wright, Woodring E; Shay, Jerry W; Go, Ning F

    2010-11-15

    Cancer stem cells (CSC) are rare drug-resistant cancer cell subsets proposed to be responsible for the maintenance and recurrence of cancer and metastasis. Telomerase is constitutively active in both bulk tumor cell and CSC populations but has only limited expression in normal tissues. Thus, inhibition of telomerase has been shown to be a viable approach in controlling cancer growth in nonclinical studies and is currently in phase II clinical trials. In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited. Additionally, imetelstat treatment reduced the CSC fractions present in the breast and pancreatic cell lines. In vitro treatment with imetelstat, but not control oligonucleotides, also reduced the proliferation and self-renewal potential of MCF7 mammospheres and resulted in cell death after telomerase activity expression levels or telomere length of CSCs and bulk tumor cells in these cell lines did not correlate with the increased sensitivity of CSCs to imetelstat, suggesting a mechanism of action independent of telomere shortening for the effects of imetelstat on the CSC subpopulations. Our results suggest that imetelstat-mediated depletion of CSCs may offer an alternative mechanism by which telomerase inhibition may be exploited for cancer therapy. Copyright © 2010 AACR.

  13. Liver cancer stem cells as an important target in liver cancer therapies.

    Science.gov (United States)

    Zou, Gang-Ming

    2010-02-01

    Hepatic cancer is one of most common cause of cancer-related death. Hepato-epithelial cancers are believed to originate from the malignant transformation of liver-resident stem/progenitor cells. Liver cancer stem cells have been characterized recently and the phenotype of liver cancer stem cells has been defined as CD133+ CD44+ cancer cells. Recently, it has been also demonstrated about the relevance of targeting liver cancer stem cells, due to cancer stem cells are related to cancer metastasis. These advances no doubt to bring the new strategy in liver cancer treatment and control in this disease. This review describes the current status and progress about cancer stem cell research in liver and discuss of the implications of these studies in new liver cancer treatment strategies.

  14. Cells as delivery vehicles for cancer therapeutics.

    Science.gov (United States)

    Basel, Matthew T; Shrestha, Tej B; Bossmann, Stefan H; Troyer, Deryl L

    2014-05-01

    Cell-based therapeutics have advanced significantly over the past decade and are poised to become a major pillar of modern medicine. Three cell types in particular have been studied in detail for their ability to home to tumors and to deliver a variety of different payloads. Neural stem cells, mesenchymal stem cells and monocytes have each been shown to have great potential as future delivery systems for cancer therapy. A variety of other cell types have also been studied. These results demonstrate that the field of cell-based therapeutics will only continue to grow.

  15. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh

    2010-06-01

    Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

  16. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  17. IL-4-mediated drug resistance in colon cancer stem cells

    NARCIS (Netherlands)

    Todaro, Matilde; Perez Alea, Mileidys; Scopelliti, Alessandro; Medema, Jan Paul; Stassi, Giorgio

    2008-01-01

    Cancer stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Cancer stem cells are thus likely to be responsible for maintaining or spreading a cancer, and may be the most relevant targets for cancer therapy. The CD133 glycoprotein was recently

  18. Stem Cell Transplants in Cancer Treatment

    Science.gov (United States)

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  19. Harnessing the apoptotic programs in cancer stem-like cells.

    Science.gov (United States)

    Wang, Ying-Hua; Scadden, David T

    2015-09-01

    Elimination of malignant cells is an unmet challenge for most human cancer types even with therapies targeting specific driver mutations. Therefore, a multi-pronged strategy to alter cancer cell biology on multiple levels is increasingly recognized as essential for cancer cure. One such aspect of cancer cell biology is the relative apoptosis resistance of tumor-initiating cells. Here, we provide an overview of the mechanisms affecting the apoptotic process in tumor cells emphasizing the differences in the tumor-initiating or stem-like cells of cancer. Further, we summarize efforts to exploit these differences to design therapies targeting that important cancer cell population. © 2015 The Authors.

  20. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  1. T cell recognition of breast cancer antigens

    DEFF Research Database (Denmark)

    Petersen, Nadia Viborg; Andersen, Sofie Ramskov; Andersen, Rikke Sick

    Recent studies are encouraging research of breast cancer immunogenicity to evaluate the applicability ofimmunotherapy as a treatment strategy. The epitope landscape in breast cancer is minimally described, thus it is necessary to identify T cell targets to develop immune mediated therapies.......This project investigates four proteins commonly upregulated in breast cancer and thus probable tumor associated antigens (TAAs). Aromatase, prolactin, NEK3, and PIAS3 contribute to increase growth, survival, and motility of malignant cells. Aspiring to uncover novel epitopes for cytotoxic T cells, a reverse...... immunology approach is applied. Via in silico screening of the protein sequences, 415 peptides were predicted as HLA-A*0201 and HLA-B*0702 binders. Subsequent in vitro binding analysis in a MHC ELISA platform confirmed binding for 147 of the 415 predicted binders. The 147 peptides were evaluated for T cell...

  2. Dual ligand insertion in gB and in gD of oncolytic HSVs for the retargeting to a producer Vero cell line and to cancer cells.

    Science.gov (United States)

    Petrovic, Biljana; Leoni, Valerio; Gatta, Valentina; Zaghini, Anna; Vannini, Andrea; Campadelli-Fiume, Gabriella

    2017-12-20

    Oncolytic viruses gain cancer specificity in several ways. Like the majority of viruses, they grow better in cancer cells which are defective in mounting the host response to viruses. Often they are attenuated by deletion or mutation of virulence genes which counteract the host response, or are naturally occurring oncolytic mutants. In contrast, retargeted viruses are not attenuated or deleted; their cancer-specificity rests on a modified, specific tropism for cancer receptors. For herpes simplex virus (HSV)-based oncolytics, the detargeting-retargeting strategies employed so far were based on genetic modifications of gD. Recently, we showed that even gH or gB can serve as retargeting tools. To enable the growth of retargeted HSVs in cells that can be used for clinical grade virus production, a double retargeting strategy has been developed. Here we show that several sites in the N-terminus of gB are suitable to harbour the 20 aa long GCN4 peptide, which readdresses HSV tropism to Vero cells expressing the artificial GCN4 receptor, and thus enables virus cultivation in the producer non-cancer Vero-GCN4R cell line. The gB modifications can be combined with a minimal detargeting modification in gD, consisting in the deletion of two residues, aa 30 and 38, and replacement of aa 38 with the scFv to HER2, for retargeting to the cancer receptor. The panel of recombinants was analysed comparatively in terms of virus growth, cell-to-cell spread, cytotoxicity, in vivo anti-tumor efficacy to define the best double retargeting strategy. IMPORTANCE There is increasing interest in oncolytic viruses, following FDA and EMA approval of HSV Oncovex GM-CSF , and, mainly, because they greatly boost the immune response to the tumor and can be combined with immunotherapeutic agents, particularly checkpoint inhibitors. A strategy to gain cancer specificity and avoid virus attenuation is to retarget the virus tropism to cancer-specific receptors of choice. Cultivation of fully retargeted

  3. Phenotypic Heterogeneity of Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Aurelio Lorico

    2011-01-01

    Full Text Available Many types of tumors are organized in a hierarchy of heterogeneous cell populations, with only a small proportion of cancer stem cells (CSCs capable of sustaining tumor formation and growth, giving rise to differentiated cells, which form the bulk of the tumor. Proof of the existence of CSC comes from clinical experience with germ-cell cancers, where the elimination of a subset of undifferentiated cells can cure patients (Horwich et al., 2006, and from the study of leukemic cells (Bonnet and Dick, 1997; Lapidot et al., 1994; and Yilmaz et al., 2006. The discovery of CSC in leukemias as well as in many solid malignancies, including breast carcinoma (Al-Hajj et al. 2003; Fang et al., 2005; Hemmati et al., 2003; Kim et al., 2005; Lawson et al., 2007; Li et al., 2007; Ricci-Vitiani et al., 2007; Singh et al., 2003; and Xin et al., 2005, has suggested a unifying CSC theory of cancer development. The reported general insensitivity of CSC to chemotherapy and radiation treatment (Bao et al., 2006 has suggested that current anticancer drugs, which inhibit bulk replicating cancer cells, may not effectively inhibit CSC. The clinical relevance of targeting CSC-associated genes is supported by several recent studies, including CD44 targeting for treatment of acute myeloid leukemia (Jin et al., 2006, CD24 targeting for treatment of colon and pancreatic cancer (Sagiv et al., 2008, and CD133 targeting for hepatocellular and gastric cancer (Smith et al., 2008. One promising approach is to target CSC survival signaling pathways, where leukemia stem cell research has already made some progress (Mikkola et al., 2010.

  4. Post-Harbour Areas - New Urban Space

    Directory of Open Access Journals (Sweden)

    Nowacka-Rejzner Urszula

    2015-12-01

    Full Text Available In the article on selected examples one illustrated the different solutions for shaping post-harbour areas. One highlighted the complexity and longevity of activities conducted in these areas, which include both: the modernization of building structures, shaping of new functional and spatial interactions, reproduction of natural resources, protection and sharing of preserved buildings and complexes of cultural heritage, but also well balanced management of transformed area. The basis for conducted deliberations constitute studies and field studies concerning the development of urban structures, conducted for many years by the author.

  5. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L

    2012-01-31

    Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

  6. Cancer stem cells in the development of liver cancer

    Science.gov (United States)

    Yamashita, Taro; Wang, Xin Wei

    2013-01-01

    Liver cancer is an aggressive disease with a poor outcome. Several hepatic stem/progenitor markers are useful for isolating a subset of liver cells with stem cell features, known as cancer stem cells (CSCs). These cells are responsible for tumor relapse, metastasis, and chemoresistance. Liver CSCs dictate a hierarchical organization that is shared in both organogenesis and tumorigenesis. An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies. This Review highlights recent advances in understanding the pathogenesis of liver CSCs and discusses unanswered questions about the concept of liver CSCs. PMID:23635789

  7. Sunitinib for advanced renal cell cancer

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2008-03-01

    Full Text Available Chris CoppinBC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Renal cell cancer has been refractory to drug therapy in the large majority of patients. Targeted agents including sunitinib have been intensively evaluated in renal cell cancer over the past 5 years. Sunitinib is an oral small molecule inhibitor of several targets including multiple tyrosine kinase receptors of the angiogenesis pathway. This review surveys the rationale, development, validation, and clinical use of sunitinib that received conditional approval for use in North America and Europe in 2006. In patients with the clear-cell subtype of renal cell cancer and metastatic disease with good or moderate prognostic factors for survival, sunitinib 50 mg for 4 weeks of a 6-week cycle provides superior surrogate and patient-reported outcomes when compared with interferon-alfa, the previous commonly used first-line drug. Overall survival has not yet shown improvement over interferon and is problematic because of patient crossover from the control arm to sunitinib at disease progression. Toxicity is significant but manageable with experienced monitoring. Sunitinib therapy is an important step forward for this condition. High cost and limited efficacy support the ongoing search for further improved therapy.Keywords: renal cell cancer, targeted therapy, sunitinib

  8. with esophageal squamous cell cancer

    Directory of Open Access Journals (Sweden)

    Tao Li

    2017-02-01

    Full Text Available Purpose: The aim of this study was to retrospectively observe and analyze the long-term treatment outcomes of 191 elderly patients with esophageal squamous cell cancer (ESCC who were treated with californium-252 (252Cf neutron brachytherapy (NBT in combination with external beam radiotherapy (EBRT. Material and methods : From January 2002 to November 2012, 191 patients with ESCC underwent NBT in combination with EBRT. The total radiation dose to the reference point via NBT was 8-25 Gy-eq in two to five fractions with one fraction per week. The total dose via EBRT was 50-60 Gy, which was delivered over a period of 5 to 6 weeks with normal fractionation. Results : The median survival time for the 191 patients was 23.6 months, and the 5-year rates for overall survival (OS and local-regional control (LRC were 28.7% and 54.2%, respectively. The patients’ age was a factor that was significantly associated with OS (p = 0.010, according to univariate analysis. The 5-year OS (LRC was 37.3% (58.6% for patients aged 70-74 years and 14.5% (47.9% for patients aged > 74 years (p = 0.010 and p = 0.038. In multivariate analysis, age and clinical N stage were associated with OS and LRC (p = 0.011 [0.041] and p = 0.005 [0.005]. From the time of treatment completion to the development of local-regional recurrence or death, 5 (2.6% patients experienced fistula and 15 (7.9% experienced massive bleeding. The incidence of severe late complications was related to older age (p = 0.027, higher NBT dose/fraction (20-25 Gy/5 fractions, and higher total dose (> 66 Gy. Conclusions : The clinical data indicated that NBT in combination with EBRT produced favorable local control and long-term survival rates for elderly patients with ESCC, and that the side effects were tolerable. Patient’s age, clinical stage N status, and radiation dose could be used to select the appropriate treatment for elderly patients.

  9. Gastric cancer stem cells: A novel therapeutic target

    Science.gov (United States)

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  10. Altered calcium signaling in cancer cells.

    Science.gov (United States)

    Stewart, Teneale A; Yapa, Kunsala T D S; Monteith, Gregory R

    2015-10-01

    It is the nature of the calcium signal, as determined by the coordinated activity of a suite of calcium channels, pumps, exchangers and binding proteins that ultimately guides a cell's fate. Deregulation of the calcium signal is often deleterious and has been linked to each of the 'cancer hallmarks'. Despite this, we do not yet have a full understanding of the remodeling of the calcium signal associated with cancer. Such an understanding could aid in guiding the development of therapies specifically targeting altered calcium signaling in cancer cells during tumorigenic progression. Findings from some of the studies that have assessed the remodeling of the calcium signal associated with tumorigenesis and/or processes important in invasion and metastasis are presented in this review. The potential of new methodologies is also discussed. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Cellular radiosensitivity of small-cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Krarup, M; Poulsen, H S; Spang-Thomsen, M

    1997-01-01

    PURPOSE: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based...

  12. Dendritic cell immunotherapy in uterine cancer.

    Science.gov (United States)

    Coosemans, An; Tuyaerts, Sandra; Vanderstraeten, Anke; Vergote, Ignace; Amant, Frédéric; Van Gool, Stefaan W

    2014-01-01

    Uterine cancer is the most common pelvic gynecological malignancy. Uterine sarcomas and relapsed uterine carcinomas have limited treatment options. The search for new therapies is urgent. Dendritic cell (DC) immunotherapy holds much promise, though has been poorly explored in uterine cancer. This commentary gives an insight in existing DC immunotherapy studies in uterine cancer and summarizes the possibilities and the importance of the loading of tumor antigens onto DC and their subsequent maturation. However, the sole application of DC immunotherapy to target uterine cancer will be insufficient because of tumor-induced immunosuppression, which will hamper the establishment of an effective anti-tumor immune response. The authors give an overview on the limited existing immunosuppressive data and propose a novel approach on DC immunotherapy in uterine cancer.

  13. Dormancy activation mechanism of oral cavity cancer stem cells.

    Science.gov (United States)

    Chen, Xiang; Li, Xin; Zhao, Baohong; Shang, Dehao; Zhong, Ming; Deng, Chunfu; Jia, Xinshan

    2015-07-01

    Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

  14. Cells of Origin of Epithelial Ovarian Cancers

    Science.gov (United States)

    2015-09-01

    lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only after the cancer has metastasized into the...Epithelial ovarian cancer (EOC) is the most lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only...experience in ovary research (ovarian physiology , oogonial stem cells) to work on this project. We also ! 5! obtained approval of our animal

  15. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Felthaus, O. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Ettl, T.; Gosau, M.; Driemel, O. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Brockhoff, G. [Department of Gynecology and Obstetrics, University of Regensburg (Germany); Reck, A. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Zeitler, K. [Institute of Pathology, University of Regensburg (Germany); Hautmann, M. [Department of Radiotherapy, University of Regensburg (Germany); Reichert, T.E. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Schmalz, G. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Morsczeck, C., E-mail: christian.morsczeck@klinik.uni-regensburg.de [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany)

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  16. The evolving cancer stem cell paradigm: implications in veterinary oncology.

    Science.gov (United States)

    Pang, Lisa Y; Argyle, David J

    2015-08-01

    The existence of subpopulations of cells in cancer with increased tumour-initiating ability, self-renewal potential, and intrinsic resistance to conventional therapeutics formed the basis of the cancer stem cell model. Some tumours have since been viewed as aberrant tissues with a unidirectional hierarchical structure consisting of cancer stem cells at the apex, driving tumour growth, metastasis and relapse after therapy. Here, recent developments in cancer stem cell research are reviewed with a focus on tumour heterogeneity, cellular plasticity and cancer stem cell reprogramming. The impact of these findings on the cancer stem cell model is discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Side population cells isolated from KATO III human gastric cancer cell line have cancer stem cell-like characteristics.

    Science.gov (United States)

    She, Jun-Jun; Zhang, Peng-Ge; Wang, Xuan; Che, Xiang-Ming; Wang, Zi-Ming

    2012-09-07

    To investigate whether the side population (SP) cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer. We analyzed the presence of SP cells in different human gastric carcinoma cell lines, and then isolated and identified the SP cells from the KATO III human gastric cancer cell line by flow cytometry. The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays. The related genes were determined by reverse transcription polymerase chain reaction. To compare tumorigenic ability, SP and non-side population (NSP) cells from the KATO III human gastric cancer cell line were subcutaneously injected into nude mice. SP cells from the total population accounted for 0.57% in KATO III, 1.04% in Hs-746T, and 0.02% in AGS (CRL-1739). SP cells could grow clonally and have self-renewal capability in conditioned media. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was different between SP and NSP cells. However, there was no apparent difference between SP and NSP cells when they were injected into nude mice. SP cells have some cancer stem cell-like characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.

  18. Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells.

    Science.gov (United States)

    Debeb, Bisrat G; Zhang, Xiaomei; Krishnamurthy, Savitri; Gao, Hui; Cohen, Evan; Li, Li; Rodriguez, Angel A; Landis, Melissa D; Lucci, Anthony; Ueno, Naoto T; Robertson, Fredika; Xu, Wei; Lacerda, Lara; Buchholz, Thomas A; Cristofanilli, Massimo; Reuben, James M; Lewis, Michael T; Woodward, Wendy A

    2010-07-08

    Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells. 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including beta-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres. 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.

  19. Stemness is Derived from Thyroid Cancer Cells

    Science.gov (United States)

    Ma, Risheng; Bonnefond, Simon; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2014-01-01

    Background: One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs). Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT) from malignant cells since EMT is known to confer stem-like characteristics. Furthermore, EMT is a critical process for epithelial tumor progression, local invasion, and metastasis formation. In addition, stemness provides cells with therapeutic resistance and is the likely cause of tumor recurrence. However, the relevance of EMT and stemness in thyroid cancer progression has not been extensively studied. Methods: To examine the status of stemness in thyroid papillary cancer, we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E)/TPO-Cre). This construct is only activated at the time of thyroid peroxidase (TPO) expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells, which do not express TPO. Results: There was decreased expression of thyroid-specific genes such as Tg and NIS and increased expression of stemness markers, such as Oct4, Rex1, CD15, and Sox2 in the thyroid carcinoma tissue from 6-week-old BRAFV600E mice indicating the dedifferentiated status of the cells and the fact that stemness was derived in this model from differentiated thyroid cells. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-β1 and TGF-β3, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a cancer thyroid cell line (named Marca cells) derived from one of the murine tumors. In this cell line, we also found that overexpression of Snail caused up-regulation of

  20. Getting to the heart of the matter in cancer: Novel approaches to targeting cancer stem cells.

    Science.gov (United States)

    Colvin, Hugh; Mori, Masaki

    2017-01-01

    Cancer is one of the leading causes of deaths worldwide. While cancers may initially show good response to chemotherapy or radiotherapy, it is not uncommon for them to recur at a later date. This phenomenon may be explained by the existence of a small population of cancer stem cells, which are inherently resistant to anti-cancer treatment as well as being capable of self-renewal. Therefore, while most of the tumour bulk consisting of cells that are not cancer stem cells respond to treatment, the cancer stem cells remain, leading to disease recurrence. Following this logic, the effective targeting of cancer stem cells holds promise for providing long-term cure in individuals with cancer. Cancer stem cells, like normal stem cells are endowed with mechanisms to protect themselves against a wide range of insults including anti-cancer treatments, such as the enhancement of the DNA damage response and the ability to extrude drugs. It is therefore important to develop new strategies if cancer stem cells are to be eradicated. In this review, we describe the strategies that we have developed to target cancer stem cells. These strategies include the targeting of the histone demethylase jumonji, AT rich interactive domain 1B (JARID1B), which we found to be functionally significant in the maintenance of cancer stem cells. Other strategies being pursued include reprogramming of cancer stem cells and the targeting of a functional cell surface marker of liver cancer stem cells, the aminopeptidase CD13.

  1. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness.

    Science.gov (United States)

    Xue, Jianguo; Zhu, Yuan; Sun, Zixuan; Ji, Runbi; Zhang, Xu; Xu, Wenrong; Yuan, Xiao; Zhang, Bin; Yan, Yongmin; Yin, Lei; Xu, Huijuan; Zhang, Leilei; Zhu, Wei; Qian, Hui

    2015-10-24

    Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial- mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer.

  2. Cancer stem cells and field cancerization of oral squamous cell carcinoma.

    Science.gov (United States)

    Simple, M; Suresh, Amritha; Das, Debashish; Kuriakose, Moni A

    2015-07-01

    Oral squamous cell carcinoma (OSCC) has a high propensity for local failure, which is attributed to recurrence at the primary site or the development of second primary tumors (SPT). Field cancerization that refers to the existence of transformed cells in areas adjacent to the primary tumor, has been attributed to be one of the probable reasons underlying disease relapse. The carcinogenic process necessitates multiple molecular events for the transformation of a normal cell into a cancer cell. This implies that only the long-time residents of the epithelium, such as the stem cells, might be the candidates capable of accumulating these genetic hits. These transformed stem cells- the 'Cancer stem cells' (CSCs), are further known to be equipped with the properties of tumor initiation and migration, both of which are essential for orchestrating field cancerization. The concept that the CSCs might be responsible for field cancerization in OSCC has not been explored extensively. If the role of CSCs as the primary units of field cancerization process is established, their presence in the mucosa adjacent to the tumor may be an indicator for local recurrence and/or development of second primary tumors. In this review, we examine the available evidence in literature exploring the possibilities of CSCs driving the process of field cancerization and thereby being the underlying mechanism for disease recurrence and development of SPT. Published by Elsevier Ltd.

  3. Targeting Lung Cancer Stem Cells: Research and Clinical Impacts

    Directory of Open Access Journals (Sweden)

    Norashikin Zakaria

    2017-05-01

    Full Text Available Lung cancer is the most common cancer worldwide, accounting for 1.8 million new cases and 1.6 million deaths in 2012. Non-small cell lung cancer (NSCLC, which is one of two types of lung cancer, accounts for 85–90% of all lung cancers. Despite advances in therapy, lung cancer still remains a leading cause of death. Cancer relapse and dissemination after treatment indicates the existence of a niche of cancer cells that are not fully eradicated by current therapies. These chemoresistant populations of cancer cells are called cancer stem cells (CSCs because they possess the self-renewal and differentiation capabilities similar to those of normal stem cells. Targeting the niche of CSCs in combination with chemotherapy might provide a promising strategy to eradicate these cells. Thus, understanding the characteristics of CSCs has become a focus of studies of NSCLC therapies.

  4. Cancer Cell Colonisation in the Bone Microenvironment

    Directory of Open Access Journals (Sweden)

    Casina Kan

    2016-10-01

    Full Text Available Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow.

  5. Single cell sequencing reveals heterogeneity within ovarian cancer epithelium and cancer associated stromal cells.

    Science.gov (United States)

    Winterhoff, Boris J; Maile, Makayla; Mitra, Amit Kumar; Sebe, Attila; Bazzaro, Martina; Geller, Melissa A; Abrahante, Juan E; Klein, Molly; Hellweg, Raffaele; Mullany, Sally A; Beckman, Kenneth; Daniel, Jerry; Starr, Timothy K

    2017-03-01

    The purpose of this study was to determine the level of heterogeneity in high grade serous ovarian cancer (HGSOC) by analyzing RNA expression in single epithelial and cancer associated stromal cells. In addition, we explored the possibility of identifying subgroups based on pathway activation and pre-defined signatures from cancer stem cells and chemo-resistant cells. A fresh, HGSOC tumor specimen derived from ovary was enzymatically digested and depleted of immune infiltrating cells. RNA sequencing was performed on 92 single cells and 66 of these single cell datasets passed quality control checks. Sequences were analyzed using multiple bioinformatics tools, including clustering, principle components analysis, and geneset enrichment analysis to identify subgroups and activated pathways. Immunohistochemistry for ovarian cancer, stem cell and stromal markers was performed on adjacent tumor sections. Analysis of the gene expression patterns identified two major subsets of cells characterized by epithelial and stromal gene expression patterns. The epithelial group was characterized by proliferative genes including genes associated with oxidative phosphorylation and MYC activity, while the stromal group was characterized by increased expression of extracellular matrix (ECM) genes and genes associated with epithelial-to-mesenchymal transition (EMT). Neither group expressed a signature correlating with published chemo-resistant gene signatures, but many cells, predominantly in the stromal subgroup, expressed markers associated with cancer stem cells. Single cell sequencing provides a means of identifying subpopulations of cancer cells within a single patient. Single cell sequence analysis may prove to be critical for understanding the etiology, progression and drug resistance in ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Innate immune cells in inflammation and cancer.

    Science.gov (United States)

    Nowarski, Roni; Gagliani, Nicola; Huber, Samuel; Flavell, Richard A

    2013-08-01

    The innate immune system has evolved in multicellular organisms to detect and respond to situations that compromise tissue homeostasis. It comprises a set of tissue-resident and circulating leukocytes primarily designed to sense pathogens and tissue damage through hardwired receptors and eliminate noxious sources by mediating inflammatory processes. While indispensable to immunity, the inflammatory mediators produced in situ by activated innate cells during injury or infection are also associated with increased cancer risk and tumorigenesis. Here, we outline basic principles of innate immune cell functions in inflammation and discuss how these functions converge upon cancer development. ©2013 AACR.

  7. Cancer stem cells: a minor cancer subpopulation that redefines global cancer features

    Directory of Open Access Journals (Sweden)

    Heiko eEnderling

    2013-04-01

    Full Text Available In recent years cancer stem cells (CSCs have been hypothesized to comprise only a minor subpopulation in solid tumors that drives tumor initiation, development and metastasis; the so-called cancer stem cell hypothesis. While a seemingly trivial statement about numbers, much is put at stake. If true, the conclusions of many studies of cancer cell populations could be challenged, as the bulk assay methods upon which they depend have, by and large, taken for granted the notion that a ‘typical’ cell of the population possesses the attributes of a cell capable of perpetuating the cancer, i.e., a CSC. In support of the CSC hypothesis, populations enriched for so-called ‘tumor-initiating’ cells have demonstrated a corresponding increase in tumorigenicity as measured by dilution assay, although estimates have varied widely as to what the fractional contribution of tumor-initiating cells is in any given population. Some have taken this variability to suggest the CSC fraction may be nearly 100% after all, countering the CSC hypothesis, and that there are simply assay-dependent error rates in our ability to ‘reconfirm’ CSC status at the cell level. To explore this controversy more quantitatively, we developed a simple theoretical model of cancer stem cell-driven tumor growth dynamics. Assuming CSC and non-stem cancer cell subpopulations coexist to some degree, we evaluated the impact of an environmentally-dependent cancer stem cell symmetric division probability and a non-stem cancer cell proliferation capacity on tumor progression and morphology. Our model predicts, as expected, that the frequency of CSC divisions that are symmetric highly influences the frequency of CSCs in the population, but goes on to predict the two frequencies can be widely divergent, and that spatial constraints will tend to increase the CSC fraction over time.

  8. Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

    Science.gov (United States)

    Pelosi, Elvira; Castelli, Germana

    2017-01-01

    Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-driven genetically-engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer have clarified the mechanisms through which various mutated genes act in neoplasia induction and progression and have led to identifying the possible cellular origin of these neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for the development of personalized medicine strategies. The studies of the purification and characterization of pancreatic cancer stem cells have suggested that a minority cell population is responsible for initiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contribute to the identification and clinical development of more efficacious drug treatments. PMID:29156578

  9. Sphingosine 1-Phosphate and Cancer: Lessons from Thyroid Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kid Törnquist

    2013-05-01

    Full Text Available Sphingomyelin is found in the cell membrane of all eukaryotic cells, and was for a long time considered merely as a structural component. However, during the last two decades, metabolites of sphingomyelin, especially sphingosine 1-phosphate (S1P, have proven to be physiologically significant regulators of cell function. Through its five different G protein-coupled receptors, S1P regulates a wide array of cellular processes, ranging from stimulating cellular proliferation and migration, to the inhibition of apoptosis and induction of angiogenesis and modulation of cellular calcium homeostasis. Many of the processes regulated by S1P are important for normal cell physiology, but may also induce severe pathological conditions, especially in malignancies like cancer. Thus, understanding S1P signaling mechanisms has been the aim of a multitude of investigations. Great interest has also been shown in understanding the action of sphingosine kinase (SphK, i.e., the kinase phosphorylating sphingosine to S1P, and the interactions between S1P and growth factor signaling. In the present review, we will discuss recent findings regarding the possible importance of S1P and SphK in the etiology of thyroid cancer. Although clinical data is still scarce, our in vitro findings suggest that S1P may function as a “double-edged sword”, as the receptor profile of thyroid cancer cells largely determines whether S1P stimulates or blocks cellular migration. We will also discuss the interactions between S1P- and VEGF-evoked signaling, and the importance of a S1P1-VEGF receptor 2 complex in thyroid cancer cells.

  10. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  11. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  12. Population genetics of cancer cell clones: possible implications of cancer stem cells

    Directory of Open Access Journals (Sweden)

    Naugler Christopher T

    2010-11-01

    Full Text Available Abstract Background The population dynamics of the various clones of cancer cells existing within a tumour is complex and still poorly understood. Cancer cell clones can be conceptualized as sympatric asexual species, and as such, the application of theoretical population genetics as it pertains to asexual species may provide additional insights. Results The number of generations of tumour cells within a cancer has been estimated at a minimum of 40, but high cancer cell mortality rates suggest that the number of cell generations may actually be in the hundreds. Such a large number of generations would easily allow natural selection to drive clonal evolution assuming that selective advantages of individual clones are within the range reported for free-living animal species. Tumour cell clonal evolution could also be driven by variation in the intrinsic rates of increase of different clones or by genetic drift. In every scenario examined, the presence of cancer stem cells would require lower selection pressure or less variation in intrinsic rates of increase. Conclusions The presence of cancer stem cells may result in more rapid clonal evolution. Specific predictions from theoretical population genetics may lead to a greater understanding of this process.

  13. Eutrophication problems in the Western Harbour of Alexandria, Egypt

    Directory of Open Access Journals (Sweden)

    Mohamed A. Okbah

    2004-03-01

    Full Text Available Eutrophication-related problems in the Western Harbour of Alexandria were studied monthly from April 1999 to March 2000. Variation in salinity appeared to be the key to all changes in water quality and plankton abundance in the harbour. Both at the surface and near the bottom the salinity was lower (annual average: 35.1 and 38.3 PSU respectively than in the open sea (39 PSU. Dissolved oxygen levels indicated poor aeration conditions along the water column (2.3-3.98 mg l-1. Average pH values were approximately similar in the two layers (8.1 and 8 respectively but exhibited different ranges of variations. Nutrient salts varied widely, often occurring in high concentrations, with ranges of 0.12-5.7 and 0.06-2.6 µM at the surface and the bottom respectively for phosphate, 0.21-20.46 and 0.25-18.12 µM for nitrate, 0.29-3.3 and 0.23-1.66 µM for nitrite, 0.56-57.46 and 2.32-43.73 µM for ammonia and 0.3-36.3 and 0.48-38.4 µM for silicate. As a result of nutrient enrichment, phytoplankton growth was very intensive, reflected by an abnormally high concentration of chlorophyll a (annual average: 33.82 µg l-1. At the same time the death of large numbers of phytoplankton cells could be inferred from the relatively large amount of phaeopigment (annual average: 10.39 µg l-1. The high levels of nutrient salts and phytoplankton biomass together serve as a good indicator of high eutrophication levels in the Western Harbour throughout the year. These conditions clearly affected the zooplankton stock, which varied between 5.8-93.6 × 103 indiv. m-3, although for most of the time values remained at a low level (annual average: 26 728 indiv. m-3.

  14. Distinct metabolic responses of an ovarian cancer stem cell line.

    Science.gov (United States)

    Vermeersch, Kathleen A; Wang, Lijuan; McDonald, John F; Styczynski, Mark P

    2014-12-18

    Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues. Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations. The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to

  15. Draft genome sequence of an O25:H4-ST131 Escherichia coli harbouring blaNDM-1 on an IncHI3 plasmid: A first report.

    Science.gov (United States)

    Subramanian, Gopalakrishnan Kaushik; Palani, Gnanasoundari; Vijayakumar, Ramanathan; Krishnan, Padma

    2017-03-01

    Carbapenem resistance conferred by New Delhi metallo-β-lactamases is mediated by plasmids of diverse incompatibility types harboured by different lineages of Enterobacteriaceae. In this study, we report the draft genome sequence of a ST131 Escherichia coli harbouring the blaNDM gene on an IncHI3 plasmid. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  16. Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish

    OpenAIRE

    Kanada, Masamitsu; Zhang, Jinyan; Libo YAN; Sakurai, Takashi; Terakawa, Susumu

    2014-01-01

    The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility re...

  17. Diet, Stem Cells, and Breast Cancer Prevention

    Science.gov (United States)

    2011-01-01

    abrogated by small interfering RNA to PTEN, indicating PTEN-dependence. Using FACS analysis , we showed that GEN induced cell cycle arrest at G0-G1 phase...isolated from WT (PND 100) and Tg (PND75) mice. The percentage of mammary SCs was quantified by Fluorescence activated cell sorting analysis of...fruits and vegetables in breast cancer prevention due to their phytochemical components, yet mechanisms underlying their presumed anti-tumor activities

  18. Circulating Tumor Cells in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Brian Hu

    2013-12-01

    Full Text Available Circulating tumor cells (CTCs can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  19. Results of Optical Detection Trials in Harbour Environment

    NARCIS (Netherlands)

    Lange, D.J.J. de; Dijk, J.; Schwering, P.B.W.; Kemp, R.A.W.; Groot, J.F. de; Broek, S.P. van den

    2008-01-01

    In harbour environments operators should perform tasks as detection and classification. Present-day threats of smallobjects, as jet skis etc, should be detected, classified and recognized. Furthermore threat intention should be analysed. As harbour environments contain several hiding spaces, due to

  20. Reuse of harbour sediments in the Greenlandic construction industry

    DEFF Research Database (Denmark)

    Belmonte, Louise Josefine; Kirkelund, Gunvor Marie; Ottosen, Lisbeth M.

    2010-01-01

    The purpose of this study is to investigate possibilities of using harbour sediments from the Greenlandic harbours as substitutes in the Greenlandic construction industry, mainly for concrete production and road construction. Materials for use in the Greenlandic construction industry are shipped...

  1. Sediment dynamics in Lagos Harbour reconnaissance on effects of dredging

    NARCIS (Netherlands)

    Vijverberg, T.; Reneerkens, M.J.J.; Winterwerp, J.C.; Scholl, O.; Haruna, Y.

    2012-01-01

    Due to economic growth, Lagos Harbour is expanding. Capital dredging is needed to allow larger vessels to call the port. As harbour siltation is already a problem, increase of maintenance dredging is a worry. In the past no data was available to understand the hydraulics and sediment transport to

  2. Lead intoxication in Sydney Harbour Bridge workers.

    Science.gov (United States)

    Pollock, C A; Ibels, L S

    1988-02-01

    Thirty-eight Sydney Harbour Bridge workers were assessed for possible lead intoxication. Forty-seven per cent were found to have significant lead intoxication as assessed by calcium disodium edetate chelation (Ca EDTA) testing and were subsequently effectively and safely treated with Ca EDTA. The prevalence of neurological, constitutional, gastrointestinal and musculoskeletal symptoms was significantly greater in those with, than those without, lead toxicity. Although blood lead levels and, to a lesser extent, hematological parameters were of some use in diagnosis, they were not sufficiently sensitive and thus should not be used in screening workers at risk of lead intoxication. Ca EDTA testing remains the diagnostic method of choice. Patients exposed to lead dust and fumes, in whom symptoms of lead intoxication are present, should undergo such testing and if a positive result is obtained, then EDTA chelation therapy should be instituted.

  3. Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and. L929). Methods: A. sieberi was extracted with methanol and further purification was carried out using liquid-.

  4. Germ cell cancer and disorders of spermatogenesis

    DEFF Research Database (Denmark)

    Skakkebaek, N E; Rajpert-De Meyts, E; Jørgensen, N

    1998-01-01

    Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads...

  5. Cancer stem cells: the challenges ahead

    NARCIS (Netherlands)

    Medema, Jan Paul

    2013-01-01

    Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. Recently, the identification of CSCs in endogenously developing mouse tumours has provided further support for this

  6. Current therapy of small cell lung cancer

    DEFF Research Database (Denmark)

    Sorensen, M; Lassen, U; Hansen, H H

    1998-01-01

    This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated...

  7. DNA repair of cancer stem cells

    National Research Council Canada - National Science Library

    Mathews, Lesley A; Cabarcas, Stephanie M; Hurt, Elaine M

    2013-01-01

    ... leukemia by John E. Dick from the University of Toronto. The heterogeneity of human leukemia and the presence of stem cells in cancer was further translated into solid tumors by Al-Hajj et al. when they published a provocative paper in Proceedings of the National Academy of Sciences discussing the ability to distinguish tumorigenic (tumor-initi...

  8. Optical imaging of cancer and cell death

    NARCIS (Netherlands)

    Xie, Bangwen

    2013-01-01

    The aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and cell death. In this thesis, we mainly focus on optical imaging and its application, both at microscopic

  9. Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism.

    Science.gov (United States)

    Phiboonchaiyanan, Preeyaporn Plaimee; Kiratipaiboon, Chayanin; Chanvorachote, Pithi

    2016-04-25

    Cancer stem cells (CSCs), a subpopulation of cancer cells with high aggressive behaviors, have been identified in many types of cancer including lung cancer as one of the key mediators driving cancer progression and metastasis. Here, we have reported for the first time that ciprofloxacin (CIP), a widely used anti-microbial drug, has a potentiating effect on CSC-like features in human non-small cell lung cancer (NSCLC) cells. CIP treatment promoted CSC-like phenotypes, including enhanced anchorage-independent growth and spheroid formation. The known lung CSC markers: CD133, CD44, ABCG2 and ALDH1A1 were found to be significantly increased, while the factors involving in epithelial to mesenchymal transition (EMT): Slug and Snail, were depleted. Also, self-renewal transcription factors Oct-4 and Nanog were found to be up-regulated in CIP-treated cells. The treatment of CIP on CSC-rich populations obtained from secondary spheroids resulted in the further increase of CSC markers. In addition, we have proven that the mechanistic insight of the CIP induced stemness is through Caveolin-1 (Cav-1)-dependent mechanism. The specific suppression of Cav-1 by stably transfected Cav-1 shRNA plasmid dramatically reduced the effect of CIP on CSC markers as well as the CIP-induced spheroid formation ability. Cav-1 was shown to activate protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways in CSC-rich population; however, such an effect was rarely found in the main lung cancer cells population. These findings reveal a novel effect of CIP in positively regulating CSCs in lung cancer cells via the activation of Cav-1, Akt and ERK, and may provoke the awareness of appropriate therapeutic strategy in cancer patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Stemness is derived from thyroid cancer cells

    Directory of Open Access Journals (Sweden)

    Risheng eMa

    2014-07-01

    Full Text Available Background: One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs. Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT from malignant cells since EMT is known to confer stem-like characteristics. Methods: To examine the status of stemness in thyroid papillary cancer we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E/TPO-Cre. This construct is only activated at the time of thyroid peroxidase (TPO expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells which do not express TPO.Results: There was decreased expression of thyroid specific genes such as Tg and NIS and increased expression of stemness markers such as Oct4, Rex1, CD15 and Sox2 in the thyroid carcinoma tissue from 6 week old BRAFV600E mice. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-β1 and TGF-β3, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a derived cancer thyroid cell line in which overexpression of Snail caused up-regulation of vimentin expression and up regulation of stemness markers Oct4, Rex1, CD15 with enhanced migration ability of the cells. Conclusions: Our findings support our earlier hypothesis that stemness in thyroid cancer is derived via EMT rather than from resident thyroid stem cells. In mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E/TPO-Cre the neoplastic changes were dependent on thyroid cell differentiation and the onset of stemness must have been derived from differentiated thyroid epithelial cells.

  11. Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Narumol Bhummaphan

    2015-01-01

    Full Text Available As cancer stem cells (CSCs contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

  12. Anti-EGFR and antiangiogenic monoclonal antibodies in metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Losanno, Tania; Rossi, Antonio; Maione, Paolo; Napolitano, Alba; Gridelli, Cesare

    2016-06-01

    In recent years, several clinical trials have evaluated the efficacy and safety of biological therapies in lung cancer. Epidermal growth factor receptor (EGFR) and the axis vascular endothelial growth factor receptor (VEGF/VEGFR) are targeted by small molecules and monoclonal antibodies (mAbs), especially in non-squamous non-small-cell lung cancer (NSCLC). The current state of the art of anti-EGFR and antiangiogenic monoclonal antibodies in metastatic NSCLC is reviewed and discussed. Bevacizumab and cetuximab are the most studied mAbs in NSCLC, but only bevacizumab is in clinical practice in the first-line setting. Necitumumab is a new anti-EGFR monoclonal antibody that improves survival when combined to cisplatin/gemcitabine chemotherapy and has been approved in first-line advanced NSCLC. Ramucirumab, an antiangiogenic drug binding with high affinity to VEGFR-2, improves the results of chemotherapy alone when administered with docetaxel and has been approved in second-line setting. Moreover, the novel combination of bevacizumab and erlotinib is very promising for the treatment of patients with NSCLC harbouring EGFR mutations. The association of antiangiogenic mAbs and immunotherapy is under investigation too.

  13. No serological evidence that harbour porpoises are additional hosts of influenza B viruses.

    Directory of Open Access Journals (Sweden)

    Rogier Bodewes

    Full Text Available Influenza A and B viruses circulate among humans causing epidemics almost annually. While various hosts for influenza A viruses exist, influenza B viruses have been detected only in humans and seals. However, recurrent infections of seals in Dutch coastal waters with influenza B viruses that are antigenetically distinct from influenza B viruses circulating among humans suggest that influenza B viruses have been introduced into this seal population by another, non-human, host. Harbour porpoises (Phocoena phocoena are sympatric with seals in these waters and are also occasionally in close contact with humans after stranding and subsequent rehabilitation. In addition, virus attachment studies demonstrated that influenza B viruses can bind to cells of the respiratory tract of these animals. Therefore, we hypothesized that harbour porpoises might be a reservoir of influenza B viruses. In the present study, an unique set of serum samples from 79 harbour porpoises, stranded alive on the Dutch coast between 2003 and 2013, was tested for the presence of antibodies against influenza B viruses by use of the hemagglutination inhibition test and for antibodies against influenza A viruses by use of a competitive influenza A nucleoprotein ELISA. No antibodies were detected against either virus, suggesting that influenza A and B virus infections of harbour porpoises in Dutch coastal waters are not common, which was supported by statistical analysis of the dataset.

  14. The origin of stroma surrounding epithelial ovarian cancer cells.

    Science.gov (United States)

    Akahane, Tomoko; Hirasawa, Akira; Tsuda, Hiroshi; Kataoka, Fumio; Nishimura, Sadako; Tanaka, Hideo; Tominaga, Eiichiro; Nomura, Hiroyuki; Chiyoda, Tatsuyuki; Iguchi, Yoko; Yamagami, Wataru; Susumu, Nobuyuki; Aoki, Daisuke

    2013-01-01

    Cancer stroma is thought to play an important role in tumor behavior, including invasion or metastasis and response to therapy. Cancer stroma is generally thought either to be non-neoplastic cells, including tissue-marrow or bone-marrow-derived fibroblasts, or to originate in epithelial mesenchymal transition of cancer cells. In this study, we evaluated the status of the p53 gene in both the cancer cells and the cancer stroma in epithelial ovarian cancer (EOC) to elucidate the origin of the stroma. Samples from 16 EOC patients were included in this study. Tumor cells and adjacent nontumor stromal cells were microdissected and DNA was extracted separately. We analyzed p53 sequences (exons 5-8) of both cancer and stromal tissues in all cases. Furthermore, we examined p53 protein expression in all cases. Mutations in p53 were detected in 9 of the 16 EOCs: in 8 of these cases, the mutations were detected only in cancer cells. In 1 case, the same mutation (R248Q) was detected in both cancer and stromal tissues, and p53 protein expression was detected in both the cancer cells and the cancer stroma. Most cancer stroma in EOC is thought to originate from non-neoplastic cells, but some parts of the cancer stroma might originate from cancer cells.

  15. Groundwater vulnerability assessment of the Cork Harbour area, SW Ireland

    Science.gov (United States)

    Allen, A. R.; Milenic, D.

    2007-11-01

    In the Cork Harbour area of SW Ireland, high yield karst and intergranular gravel aquifers are extremely vulnerable to pollution from a variety of sources, mainly due to the limited protection afforded by the thin cover of low permeability glacial and alluvial overburden. The main potential sources of pollution are due to rapid urbanisation of the Cork city area and its attendant infrastructure, and increased industrialisation in the area, with numerous new industries, particularly pharmaceutical and chemical industries, located around Cork Harbour. Other potential sources of pollution are a number of landfills in the area and an oil refinery near the mouth of Cork Harbour. Traditional agricultural sources of pollution also exist, due to increased use of chemical fertilisers. Finally, the susceptibility to saline intrusion of the karst and gravel aquifers around Cork Harbour is high due to the long coastline of the harbour and the low-lying nature of the karst synclines with their superimposed buried valleys.

  16. Harbour of Ravenna: The contribution of harbour traffic to air quality

    Science.gov (United States)

    Lucialli, Patrizia; Ugolini, Pamela; Pollini, Elisa

    Ravenna is one of the main Italian ports and has assumed a leadership position in Italy for some products and markets. The commercial harbour and the adjacent industrial area are very important for the economic system of Ravenna but, at the same time, they are highly critical areas. In particular, on average 8000 ships per year pass through the harbour of Ravenna, influencing air quality in harbour environment. The paper originates from a study about the contribution of different sources of air pollution in Ravenna and its aim is to evaluate the maritime traffic contribution to the air quality in the port area and to determine the suitability of an urban air quality model to support the air quality management in Ravenna. NO x and PM are selected as modelled pollutants. The study is made up of two parts. The first deals with the evaluation of annual emission of PM 10 and NO x coming from ships through a standard European methodology while in the second we simulated the diffusion of these pollutants in the whole area. In order to evaluate the capability of the model to treat maritime traffic emissions, we compared hour-by-hour simulated concentrations with data collected by a fixed monitoring station located near the Candiano Canal. NO x concentrations obtained by short- and long-term simulations show a good match with the values measured by the fixed monitoring station, located in the centre of harbour area, and these results are also supported by FA2 performance index. Instead the omission of the secondary particulate and the contribution of other sources of particulate matter in the port area are probably the most important causes of the PM 10 underestimation. The worse results obtained according to the performance indexes indicate the need to consider the formation and transport of secondary particulate matter in order to obtain more reliable predictions.

  17. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Science.gov (United States)

    Choi, Yun-Jung; Park, Jung-Hyun; Han, Jae Woong; Kim, Eunsu; Jae-Wook, Oh; Lee, Seung Yoon; Kim, Jin-Hoi; Gurunathan, Sangiliyandi

    2016-01-01

    The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells. PMID:27973444

  18. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  19. Levobuipivacaine-Induced Dissemination of A549 Lung Cancer Cells.

    Science.gov (United States)

    Chan, Shun-Ming; Lin, Bo-Feng; Wong, Chih-Shung; Chuang, Wen-Ting; Chou, Yu-Ting; Wu, Zhi-Fu

    2017-08-17

    While anaesthetics are frequently used on cancer patients during surgical procedures, their consequence on cancer progression remains to be elucidated. In this study, we sought to investigate the influence of local anesthetics on lung cancer cell dissemination in vitro and in vivo. A549 human non-small lung cancer cells were treated with various local anaesthetics including ropivacaine, lidocaine, levobupivacaine and bupivacaine. Cell barrier property was assessed using an electric cell-substrate impedance sensing (ECIS) system. The epithelial-to-mesenchymal transition (EMT) of treated cells was studied by immunofluorescence staining. In vitro and in vivo cancer cell dissemination were investigated.Gene expression microarray and quantitative real-time PCR (qrt-PCR) assays were used to identify the genes responsible for levobupivacaine-mediated cancer cell dissemination.The results illustrated that only levobupivacaine induced EMT in the treated cells and also caused the dissemination of cancer cells in vitro. In addition, after intravenous injection, levobupivacaine encouraged cancer cell dissemination in vivo. Gene expression microarray, qrt-PCR and immunoblotting revealed that after levobupivacaine treatment, the hypoxia-inducible factor (HIF)- 2α gene was upregulated in cancer cells. Our findings suggest that levobupivacaine may induce A549 lung cancer cell dissemination both in vitro and in vivo. More specifically, HIF-2α signaling possibly contributes to levobupivacaine-mediated A549 lung cancer cell dissemination.

  20. Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

    Science.gov (United States)

    Hereditary kidney cancer (renal cell cancer) syndromes include von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Learn about the genetics, clinical manifestations, and management of these hereditary cancer syndromes in this expert-reviewed summary.

  1. Probiotics, dendritic cells and bladder cancer.

    Science.gov (United States)

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  2. Dendritic Cells in the Cancer Microenvironment

    Directory of Open Access Journals (Sweden)

    Yang Ma, Galina V. Shurin, Zhu Peiyuan, Michael R. Shurin

    2013-01-01

    Full Text Available The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

  3. Are All Highly Malignant Cancer Cells Identical?

    Science.gov (United States)

    1979-01-01

    ADA3665 ARE AL HIGHL MAGNANTCANCER CELLS DENOIALU) PENNSYLVANIA HOSPITAL PHILADELPHIA DEPT OF MOLECULAR BIOLOGY G NIGET AL 199 N00014-ACA026 UNCLASFE...embryo cells or even the original fertilized ovum . If this speculation has validity, the carcinogenesis and differentiation have the same destinies but...F/G /5 N 1111 2Z111117 1 125iiI 1 1. 1111_L6. -11 O=M 1 MrCROCOP RErSOLUTICN TEST CHART N, APoP SN A’ ,- ARE ALL HIGHLY MALIGNANT CANCER CELLS

  4. Gastrin releasing peptide GRP(14-27) in human breast cancer cells and in small cell lung cancer

    DEFF Research Database (Denmark)

    Vangsted, A J; Andersen, E V; Nedergaard, L

    1991-01-01

    Immunoreactivity related to the gastrin-releasing peptide (GRP) precursor was detected in four different human breast cancer cell lines. The amounts and the characteristics in extracts from different breast carcinoma cells were compared with cell extracts from small cell lung cancer (SCLC) cells...

  5. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

    Science.gov (United States)

    2013-03-25

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  6. Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells.

    Directory of Open Access Journals (Sweden)

    Shuping Yin

    Full Text Available Women with triple negative breast cancer (TNBC have poor prognosis compared to other breast cancer subtypes. There were several reports indicating racial disparity in breast cancer outcomes between African American (AA and European American (EA women. For example, the mortality rates of AA breast cancer patients were three times higher than of EA patients, even though, the incidence is lower in AA women. Our in vitro studies indicate that cancer stem-like cells (CSCs derived from AA TNBC cell lines have significantly higher self-renewal potential (mammosphere formation than CSCs derived from EA cell lines. TNBC tumors express high levels of Myc compared to luminal A or HER2 expressing breast cancers. We studied the effects of c-Myc overexpression on CSCs and chemotherapy in AA, and EA derived TNBC cell line(s. Overexpression of c-Myc in AA derived MDA-MB-468 (Myc/MDA-468 cells resulted in a significant increase in CSCs and with minimal changes in epithelial-to-mesenchymal transition (EMT compared to the control group. In contrast, overexpression of c-Myc in EA derived MDA-MB-231(Myc/MDA-231 cells led to increased epithelial-to-mesenchymal transition (EMT, with a minimal increase in CSCs compared to the control group. Myc/MDA-468 cells were resistant to standard chemotherapeutic treatments such as iniparib (PARP inhibitor plus cisplatin, / iniparib, cisplatin, paclitaxel and docetaxel. However, Myc/MDA-231 cells, which showed EMT changes responded to iniparib with cisplatin, but were resistant to other drugs, such as iniparib, cisplatin, paclitaxel and docetaxel. Collectively, our results indicate that intrinsic differences in the tumor biology may contribute to the breast cancer disparities.

  7. Guidelines on renal cell cancer

    NARCIS (Netherlands)

    Mickisch, G; Carballido, J; Hellsten, S; Schuize, H; Mensink, H

    Objectives., On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and. Follow Up of Renal. Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. Method: A

  8. Decreased Iron in Cancer Cells and Their Microenvironment Improves Cytolysis of Breast Cancer Cells by Natural Killer Cells.

    Science.gov (United States)

    Jiang, Xian-Peng; Elliott, Robert L

    2017-05-01

    The association of iron with anticancer immunity is unclear. In order to determine the role of iron in anticancer immunity, we manipulated intracellular iron levels of the human MCF-7 and MDA-MB-231 breast cancer cell lines, and measured cytolysis of breast cancer cells by the natural killer cell line NK-92MI, nitric oxide (NO) production, tumor necrosis factor alpha (TNFα) production and gene expression of ferritin heavy chain (FTH1). We found that NK-92MI increased synthesis and release of NO and TNFα into the medium during co-culturing of NK-92MI cells with MCF-7 or MDA-MB-231 cells. Addition of iron inhibited the cytolysis of the breast cancer cell lines. The iron chelator deferoxamine (DFOM) increased NK-92MI cytolysis to MCF-7 or MDA-MB-231 cells. Iron reversed cytotoxicity to breast cancer cells induced by NO, released from S-nitroso-N-acetyl-penicillamine (NO donor). Real time quantitative polymerase chain reaction showed that iron up-regulated the expression of FTH1 and iron chelator DFOM reduced FTH1 expression of MCF-7 and MDA-MB-231 cells. In conclusion, increased iron in cancer cells and their microenvironment protects cancer cells from natural killer cell cytolysis by antagonizing NO- and TNFα-associated cytotoxicity and by up-regulation of ferritin expression in breast cancer cells. Conversely, a decrease in iron concentration caused by DFOM improves natural killer cytolysis of tumor cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    Science.gov (United States)

    2017-09-14

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer

  10. Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming hypothesis of cancer?

    Science.gov (United States)

    Trosko, James E

    2014-01-01

    This article as designed to examine whether the "stoichiometric" or "elite models" of the origin of the "induced pluripotent stem" (iPS) cells fits some experiment facts from the developmental biology of adult stem cells and from the field of cancer research. In brief, since the evidence presented to support the stoichiometric model failed to recognize the factual existence of adult organ specific stem cells, the model has not been rigorously tested. In addition, the demonstration of a subset of cells (MUSE cells) in normal primary in vitro cultures of human fibroblasts (the usual source of iPS cells) seems to be the origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem cell" versus "de-differentiation" or "reprogramming" hypotheses were examined. Again, using the role of glycolysis, known to be associated with the Warburg effect in cancer cells, a list of experiments showing that (a) normal stem cells, which have few mitochondria, metabolize via glycolysis; (b) the stem cells are targets for "initiation" or "immortalization" or the blockage of differentiation and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate dehydrogenase A (LDHA), when expressed, is associated with glycolysis and therefore, must be expressed in normal adult stem cells, as well as in cancer cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen, is associated with the reduction of mitochondrial function and mass and is associated with the Warburg effect. Together, these observations from the iPS and "cancer stem cell" fields support the idea that both iPS cells and cancer stem cell are derived from adult organ-specific stem cells that do not restore or switch their metabolism of glucose from oxidative metabolism to glycolysis but, rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is prevented from differentiation or from metabolizing by oxidative phosphorylation. Copyright © 2013 Wiley Periodicals

  11. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Ahmed Abdal Dayem

    2016-09-01

    Full Text Available The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer.

  12. Calcium wave signaling in cancer cells

    Science.gov (United States)

    PARKASH, JAI; ASOTRA, KAMLESH

    2010-01-01

    Ca2+ functions as an important signaling messenger right from beginning of the life to final moment of the end of the life. Ca2+ is needed at several steps of the cell cycle such as early G1, at the G1/S, and G2/M transitions. The Ca2+ signals in the form of time-dependent changes in intracellular Ca2+ concentrations, [Ca2+]i, are presented as brief spikes organized into regenerative Ca2+ waves. Ca2+-mediated signaling pathways have also been shown to play important roles in carcinogenesis such as transformation of normal cells to cancerous cells, tumor formation and growth, invasion, angiogenesis and metastasis. Since the global Ca2+ oscillations arise from Ca2+ waves initiated locally, it results in stochastic oscillations because although each cell has many IP3Rs and Ca2+ ions, the law of large numbers does not apply to the initiating event which is restricted to very few IP3Rs due to steep Ca2+ concentration gradients. The specific Ca2+ signaling information is likely to be encoded in a calcium code as the amplitude, duration, frequency, waveform or timing of Ca2+ oscillations and decoded again at a later stage. Since Ca2+ channels or pumps involved in regulating Ca2+ signaling pathways show altered expression in cancer, one can target these Ca2+ channels and pumps as therapeutic options to decrease proliferation of cancer cells and to promote their apoptosis. These studies can provide novel insights into alterations in Ca2+ wave patterns in carcinogenesis and lead to development of newer technologies based on Ca2+ waves for the diagnosis and therapy of cancer. PMID:20875431

  13. Magnetic imaging of a submerged Roman harbour, Caesarea Maritima, Israel

    Science.gov (United States)

    Boyce, J. I.; Reinhardt, E. G.; Raban, A.; Pozza, M. R.

    2003-04-01

    The harbour built by King Herod's engineers at Caesarea represented a major advance in Roman harbour construction that incorporated the use of large (390 m^3), form-filled hydraulic concrete blocks to build an extensive foundation for the harbour moles and breakwater barriers. Marine geophysical surveys were recently conducted across the submerged harbour in an attempt to map the configuration of the buried concrete foundation. A total of 107 line km of high-resolution marine magnetic surveys (nominal 15 m line separations) and bathymetry data were acquired over a 1 km^2 area of the submerged harbour using an Overhauser marine magnetometer, integrated DGPS and single-beam (200 KHz) echosounder. The feasibility of magnetic detection of the concrete was established before the survey by magnetic susceptibility testing of concrete core samples. All concrete samples contained appreciable amounts of fe-oxide-rich volcanic ash ('pozzolana') and showed uniformly high susceptibility values (k > 10^-^4 cgs) when compared to harbour bottom sediments and building stones (k construction of the harbour moles and quays.

  14. Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

    Directory of Open Access Journals (Sweden)

    Lisa Y. Pang

    2016-01-01

    Full Text Available Cyclooxygenase-2 (COX-2 is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2, a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2 release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

  15. Advances in Lung Stem Cells and Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Huijing YIN

    2015-10-01

    Full Text Available Cancer stem cells (CSCs are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs, including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH and ATP-binding cassette sub-family G member 2 (ABCG2. Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR, signal transducer and activator of transcription 3 (STAT3 and phosphatidylinositol 3 kinase (PI3K pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  16. Heat induces gene amplification in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Bin, E-mail: yanbin@mercyhealth.com [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401 (United States); Ouyang, Ruoyun [Department of Respiratory Medicine, The Second Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410011 (China); Huang, Chenghui [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013 (China); Liu, Franklin [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Neill, Daniel [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Li, Chuanyuan [Dermatology, Duke University Medical Center, Durham, NC 27710 (United States); Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Sign C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and

  17. Induction of artificial cancer stem cells from tongue cancer cells by defined reprogramming factors.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Cui, Dan; Kuramitsu, Yasuhiro; Matsumoto, Takuya; Ikeda, Eiji; Okano, Hideyuki; Ueyama, Yoshiya

    2016-07-27

    The cancer stem cells (CSCs), a small subpopulation of cells in tumor are responsible for the tumor initiation, growth, recurrence and metastasis of cancer, as well as resistance of cancers to drugs or radiotherapy. CSCs are an important target for the development of novel strategies in cancer treatment. However, CSCs-targeted new anti-cancer drug discovery is currently hindered by the lack of easy and reliable methods for isolating, collecting and maintaining sufficient number of CSCs. Here, we examined whether introduction of defined reprogramming factors (Oct4, shp53, Sox2, Klf4, l-Myc and Lin28) into HSC2 tongue cancer cells could transform the HSC2 into HSC2 with CSCs properties. We introduced the defined reprogramming factors into HSC2 tongue cancer cells via episomal vectors by electroporation method to generate transfectant cells. We investigated the malignant properties of the transfectant cells by cell proliferation assay, migration assay, wound healing assay, sphere formation assay, chemosensitivity and radiosensitivity assay in vitro; and also examined the tumorigenic potential of the transfectants in vivo. The transfectant cells (HSC2/hOCT3/4-shp53-F, HSC2/hSK, HSC2/hUL, HSC2/hOCT3/4-shp53-F + hSK, HSC2/hOCT3/4-shp53-F + hUL, HSC2/hSK + hUL, HSC2/hOCT3/4-shp53-F + hSK + hUL) displayed a malignant phenotype in culture and form tumors on the back of nude mice more efficiently than parental HSC2 and control HSC2/EGFP transfectant cells. They exhibited increased resistance to chemotherapeutic agents; 5-fluorouracil, cisplatin, docetaxel, trifluorothymidine, zoledronic acid, cetuximab, bortezomib and radiation when compared with HSC2 and HSC2/EGFP. Among all the transfected cells, HSC2/hOCT3/4-shp53-F + hSK + hUL cell containing all of the reprogramming factors showed the most aggressive and malignant properties and presented the highest number of spheres in the culture medium containing human recombinant fibroblast Growth Factor

  18. Transcription profiles of non-immortalized breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Holland James F

    2006-04-01

    Full Text Available Abstract Background Searches for differentially expressed genes in tumours have made extensive use of array technology. Most samples have been obtained from tumour biopsies or from established tumour-derived cell lines. Here we compare cultures of non-immortalized breast cancer cells, normal non-immortalized breast cells and immortalized normal and breast cancer cells to identify which elements of a defined set of well-known cancer-related genes are differentially expressed. Methods Cultures of cells from pleural effusions or ascitic fluids from breast cancer patients (MSSMs were used in addition to commercially-available normal breast epithelial cells (HMECs, established breast cancer cell lines (T-est and established normal breast cells (N-est. The Atlas Human Cancer 1.2 cDNA expression array was employed. The data obtained were analysed using widely-available statistical and clustering software and further validated through real-time PCR. Results According to Significance Analysis of Microarray (SAM and AtlasImage software, 48 genes differed at least 2-fold in adjusted intensities between HMECs and MSSMs (p Conclusion The expression profiles of 1176 genes were determined in finite life-span cultures of metastatic breast cancer cells and of normal breast cells. Significant differences were detected between the finite life-span breast cancer cell cultures and the established breast cancer cell lines. These data suggest caution in extrapolating information from established lines for application to clinical cancer research.

  19. Natural killer cells enhance the immune surveillance of cancer

    African Journals Online (AJOL)

    Faisal Nouroz

    2015-09-11

    Sep 11, 2015 ... All the cells of the immune sys- tem cooperatively work against infectious agents and cancerous cells but Natural killer (NK) cells ..... Cancer stem cells (CSCs) retain the growth of tumor and resist chemotherapy [25]. ... radiation therapy and mushroom beta glucans showed only 1 nodule. The experiments ...

  20. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  1. Hazard function for cancer patients and cancer cell dynamics.

    Science.gov (United States)

    Horová, Ivana; Pospísil, Zdenek; Zelinka, Jirí

    2009-06-07

    The aim of the paper is to develop a procedure for an estimate of an analytical form of a hazard function for cancer patients. Although a deterministic approach based on cancer cell population dynamics yields the analytical expression, it depends on several parameters which should be estimated. On the other hand, a kernel estimate is an effective nonparametric method for estimating hazard functions. This method provides the pointwise estimate of the hazard function. Our procedure consists of two steps: in the first step we find the kernel estimate of the hazard function and in the second step the parameters in the deterministic model are obtained by the least squares method. A simulation study with different types of censorship is carried out and the developed procedure is applied to real data.

  2. A stochastic model for cancer stem cell origin in metastatic colon cancer.

    Science.gov (United States)

    Odoux, Christine; Fohrer, Helene; Hoppo, Toshitaka; Guzik, Lynda; Stolz, Donna Beer; Lewis, Dale W; Gollin, Susanne M; Gamblin, T Clark; Geller, David A; Lagasse, Eric

    2008-09-01

    Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.

  3. Surgery for nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Loïc Lang-Lazdunski

    2013-09-01

    Full Text Available Surgery remains the best curative option in patients with early stage lung cancer (stage I and II. Developments in minimally invasive techniques now allow surgeons to perform lung resections on elderly patients, patients with poor pulmonary function or significant cardiopulmonary comorbidities. New techniques, such as stereotactic radiotherapy and ablative procedures, are being evaluated in early-stage lung cancer and may represent an alternative to surgery in patients unfit for lung resection. Perioperative mortality rates have dropped significantly at most institutions in the past two decades and complications are managed more efficiently. Progress in imaging and staging techniques have helped cut futile thoracotomy rates and offer patients the most adequate treatment options. Large randomised trials have helped clarify the role of neoadjuvant, induction and adjuvant chemotherapy, as well as radiotherapy. Surgery remains an essential step in the multimodality therapy of selected patients with advanced-stage lung cancer (stage III and IV. Interventional and endoscopic techniques have reduced the role of surgery in the diagnosis and staging of nonsmall cell lung cancer, but surgery remains an important tool in the palliation of advanced-stage lung cancer. Large national/international surgical databases have been developed and predictive risk-models for surgical mortality/morbidity published by learned surgical societies. Nonetheless, lung cancer overall survival rates remain deceptively low and it is hoped that early detection/screening, better understanding of tumour biology and development of biomarkers, and development of efficient targeted therapies will help improve the prognosis of lung cancer patients in the next decade.

  4. Uptake of DNA by cancer cells without a transfection reagent.

    Science.gov (United States)

    Kong, Yanping; Zhang, Xianbo; Zhao, Yongliang; Xue, Yanfang; Zhang, Ye

    2017-01-21

    Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis. Their uptake of DNAs might be different from normal cells; they may take in DNAs directly from the environment. In this report, we studied the uptake of DNAs in cancer cells without a transfection reagent. A group of DNA fragments were prepared with PCR and labeled with isotope phosphorous-32 to test their uptake by Huh 7 (liver cancer) and THLE3 (normal liver cells) after incubation overnight by counting radioactivity of the cells' genomic DNA. Multiple cell lines including breast cancer and lung cancer were tested with the same method. DNA molecules were also labeled with fluorescence to test the location in the cells using a kit of "label it fluorescence in situ hybridization (FISH)" from Mirus (USA). The data demonstrated that hepatocellular carcinoma cells possess the ability to take in large DNA fragments directly without a transfection reagent whereas normal liver cells cannot. Huh7 and MDA-MB231 cells displayed a significantly higher Rhodamine density in the cytoplasmic phagosomes and this suggests that the mechanism of uptake of large DNA by cancer cells is likely endocytosis. The efficacy of uptake is related to the DNA's size. Some cell lines of lung cancer and breast cancer also showed similar uptake of DNA. In the present study, we have revealed the evidence that some cancer cells, but not nontumorigenic cells, can take DNA fragments directly from the environment without the aid of the transfecting

  5. Calcium, cancer and killing: the role of calcium in killing cancer cells by cytotoxic T lymphocytes and natural killer cells.

    Science.gov (United States)

    Schwarz, Eva C; Qu, Bin; Hoth, Markus

    2013-07-01

    Killing cancer cells by cytotoxic T lymphocytes (CTL) and by natural killer (NK) cells is of vital importance. Cancer cell proliferation and apoptosis depend on the intracellular Ca(2+) concentration, and the expression of numerous ion channels with the ability to control intracellular Ca(2+) concentrations has been correlated with cancer. A rise of intracellular Ca(2+) concentrations is also required for efficient CTL and NK cell function and thus for killing their targets, in this case cancer cells. Here, we review the data on Ca(2+)-dependent killing of cancer cells by CTL and NK cells. In addition, we discuss emerging ideas and present a model how Ca(2+) may be used by CTL and NK cells to optimize their cancer cell killing efficiency. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  7. Optical imaging of cancer and cell death

    OpenAIRE

    Xie, Bangwen

    2013-01-01

    The aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and cell death. In this thesis, we mainly focus on optical imaging and its application, both at microscopic and macroscopic level. Because we believe optical imaging in particular represents a technology that has unique potential to exploit further our knowledge in preclinical research. First, we imaged...

  8. Mesenchymal Stem Cell Based Therapy for Prostate Cancer

    Science.gov (United States)

    2015-11-01

    14 4 1. Introduction Prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer- related deaths in American men...internalization by MSCs (red (DiI) - MPs, green ( cholera toxin) - cell membrane, blue (Hoechst) - cell nucleus). (d) To assess drug release from G114 MP-loaded

  9. Therapeutic Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells.

    Science.gov (United States)

    Oh, Jisun; Hlatky, Lynn; Jeong, Yong-Seob; Kim, Dohoon

    2016-06-30

    Understanding how to target cancer stem cells (CSCs) may provide helpful insights for the development of therapeutic or preventive strategies against cancers. Dietary phytochemicals with anticancer properties are promising candidates and have selective impact on CSCs. This review summarizes the influence of phytochemicals on heterogeneous cancer cell populations as well as on specific targeting of CSCs.

  10. Novel regulators of prostate cancer stem cells and tumor aggressiveness

    NARCIS (Netherlands)

    Zoni, E.

    2016-01-01

    In the past decade it became increasingly clear that tumor heterogeneity represents one of the major problems for cancer treatment, also in prostate cancer. The identification of the molecular properties of highly aggressive cells (Cancer Stem Cells, CSCs) dispersed within the tumor represents a

  11. Differentiation of Prostate Cancer Cells by Using Flexible Fluorescent Polymers

    Science.gov (United States)

    Scott, Michael D.; Dutta, Rinku; Haldar, Manas K.; Guo, Bin; Friesner, Daniel L.; Mallik, Sanku

    2011-01-01

    Using water soluble, fluorescent, flexible polymers, we have devised a novel methodology for identification and differentiation of prostate cancer cells. By using a step-wise linear discriminant analysis we demonstrate that the differential modulations of the polymer emission intensities in the presence of conditioned cell culture media can be used to distinguish between prostate cancer subtypes and between cancerous and non-cancer cells. The differences in the compositions of the conditioned cell culture media are likely contributing to different fluorescence spectral patterns of the polymers. This in vitro approach may provide a novel platform for the development of an alternative prostate cancer diagnostic and subtyping technique. PMID:22148518

  12. Breast Cancer Stem Cells and Tumor Suppressor Genes

    Directory of Open Access Journals (Sweden)

    Wendy W. Hwang-Verslues

    2008-10-01

    Full Text Available Studies of breast cancer stem cells are in their infancy and many fundamental questions have yet to be fully addressed. The molecular distinction between normal and cancerous breast stem cells is not clear. While there have been recent breakthroughs in mouse mammary stem cells and lineage determination in mammary glands, little has been determined in human cells. Microarray analyses have provided molecular categorization of breast cancer. However, the cellular origin of different types of breast cancer is largely unknown. In addition, the relationship between breast cancer stem cells and mammary progenitor cells has yet to be clarified. One of the key questions is how a normal mammary stem cell becomes a breast cancer stem cell. Importantly, the existence of different types of human breast cancers with distinct pathologic and molecular signatures suggests the possibility that different types of breast cancer stem cells may exist. Here, we aim to review the current evidence for the existence of different subtypes of breast cancer stem cells and provide further insight into how tumor suppressors might be involved in the initiation of breast cancer stem cells.

  13. Telmisartan inhibits human urological cancer cell growth through early apoptosis

    Science.gov (United States)

    MATSUYAMA, MASAHIDE; FUNAO, KIYOAKI; KURATSUKURI, KATSUYUKI; TANAKA, TOMOAKI; KAWAHITO, YUTAKA; SANO, HAJIME; CHARGUI, JAMEL; TOURAINE, JEAN-LOUIS; YOSHIMURA, NORIO; YOSHIMURA, RIKIO

    2010-01-01

    Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. In addition, studies have provided evidence that ARBs have the potential to inhibit the growth of several types of cancer cells. It was reported that telmisartan (a type of ARB) has peroxisome proliferator-activated receptor (PPAR)-γ activation activity. We previously reported that the PPAR-γ ligand induces growth arrest in human urological cancer cells through apoptosis. In this study, we evaluated the effects of telmisartan and other ARBs on cell proliferation in renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines. The inhibitory effects of telmisartan and other ARBs (candesartan, valsartan, irbesartan and losartan) on the growth of the RCC, BC, PC and TC cell lines was investigated using an MTT assay. Flow cytometry and Hoechst staining were used to determine whether the ARBs induced apoptosis. Telmisartan caused marked growth inhibition in the urological cancer cells in a dose- and time-dependent manner. Urological cancer cells treated with 100 μM telmisartan underwent early apoptosis and DNA fragmentation. However, the other ARBs had no effect on cell proliferation in any of the urological cancer cell lines. Telmisartan may mediate potent anti-proliferative effects in urological cancer cells through PPAR-γ. Thus, telmisartan is a potent target for the prevention and treatment of human urological cancer. PMID:22993542

  14. Generation of induced pluripotent stem cell (iPSC) line from a patient with triple negative breast cancer with hereditary exon 17 deletion of BRCA1 gene.

    Science.gov (United States)

    Griscelli, Frank; Oudrhiri, Noufissa; Feraud, Olivier; Divers, Dominique; Portier, Lucie; Turhan, Ali G; Bennaceur Griscelli, Annelise

    2017-10-01

    BRCA1 germline mutation confers hereditary predisposition for breast and ovarian cancer. To understand the physiopathology of mammary and ovarian epithelial cancer transformation, and to identify early driver molecular events, we have generated an iPSC line from a patient carrying a germline exon 17 deletion in BRCA1 gene (BRAC1Ex17 iPSC) in a high-risk family context. Blood cells were reprogrammed used non-integrative virus of Sendaï. The BRCA1-deleted iPSC had normal karyotype, harboured a deletion in the exon 17 of the BRCA1 gene, expressed pluripotent hallmarks and had the differentiation capacity into the three germ layers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Generation of induced pluripotent stem cell (iPSC line from a patient with triple negative breast cancer with hereditary exon 17 deletion of BRCA1 gene

    Directory of Open Access Journals (Sweden)

    Frank Griscelli

    2017-10-01

    Full Text Available BRCA1 germline mutation confers hereditary predisposition for breast and ovarian cancer. To understand the physiopathology of mammary and ovarian epithelial cancer transformation, and to identify early driver molecular events, we have generated an iPSC line from a patient carrying a germline exon 17 deletion in BRCA1 gene (BRAC1Ex17 iPSC in a high-risk family context. Blood cells were reprogrammed used non-integrative virus of Sendaï. The BRCA1-deleted iPSC had normal karyotype, harboured a deletion in the exon 17 of the BRCA1 gene, expressed pluripotent hallmarks and had the differentiation capacity into the three germ layers.

  16. Cell-ECM Interactions During Cancer Invasion

    Science.gov (United States)

    Jiang, Yi

    The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

  17. CGGBP1 regulates cell cycle in cancer cells

    Directory of Open Access Journals (Sweden)

    Uhrbom Lene

    2011-07-01

    Full Text Available Abstract Background CGGBP1 is a CGG-triplet repeat binding protein, which affects transcription from CGG-triplet-rich promoters such as the FMR1 gene and the ribosomal RNA gene clusters. Earlier, we reported some previously unknown functions of CGGBP1 in gene expression during heat shock stress response. Recently we had found CGGBP1 to be a cell cycle regulatory midbody protein required for normal cytokinetic abscission in normal human fibroblasts, which have all the cell cycle regulatory mechanisms intact. Results In this study we explored the role of CGGBP1 in the cell cycle in various cancer cell lines. CGGBP1 depletion by RNA interference in tumor-derived cells caused an increase in the cell population at G0/G1 phase and reduced the number of cells in the S phase. CGGBP1 depletion also increased the expression of cell cycle regulatory genes CDKN1A and GAS1, associated with reductions in histone H3 lysine 9 trimethylation in their promoters. By combining RNA interference and genetic mutations, we found that the role of CGGBP1 in cell cycle involves multiple mechanisms, as single deficiencies of CDKN1A, GAS1 as well as TP53, INK4A or ARF failed to rescue the G0/G1 arrest caused by CGGBP1 depletion. Conclusions Our results show that CGGBP1 expression is important for cell cycle progression through multiple parallel mechanisms including the regulation of CDKN1A and GAS1 levels.

  18. Breast cancer stem cells, cytokine networks, and the tumor microenvironment

    National Research Council Canada - National Science Library

    Korkaya, Hasan; Liu, Suling; Wicha, Max S

    2011-01-01

    .... These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment - including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune...

  19. Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment.

    Science.gov (United States)

    Aponte, Pedro M; Caicedo, Andrés

    2017-01-01

    Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

  20. Preimplantation death of xenomitochondrial mouse embryo harbouring bovine mitochondria

    Science.gov (United States)

    Kawahara, Manabu; Koyama, Shiori; Iimura, Satomi; Yamazaki, Wataru; Tanaka, Aiko; Kohri, Nanami; Sasaki, Keisuke; Takahashi, Masashi

    2015-01-01

    Mitochondria, cellular organelles playing essential roles in eukaryotic cell metabolism, are thought to have evolved from bacteria. The organization of mtDNA is remarkably uniform across species, reflecting its vital and conserved role in oxidative phosphorylation (OXPHOS). Our objectives were to evaluate the compatibility of xenogeneic mitochondria in the development of preimplantation embryos in mammals. Mouse embryos harbouring bovine mitochondria (mtB-M embryos) were prepared by the cell-fusion technique employing the haemagglutinating virus of Japan (HVJ). The mtB-M embryos showed developmental delay at embryonic days (E) 3.5 after insemination. Furthermore, none of the mtB-M embryos could implant into the maternal uterus after embryo transfer, whereas control mouse embryos into which mitochondria from another mouse had been transferred developed as well as did non-manipulated embryos. When we performed quantitative PCR (qPCR) of mouse and bovine ND5, we found that the mtB-M embryos contained 8.3% of bovine mitochondria at the blastocyst stage. Thus, contamination with mitochondria from another species induces embryonic lethality prior to implantation into the maternal uterus. The heteroplasmic state of these xenogeneic mitochondria could have detrimental effects on preimplantation development, leading to preservation of species-specific mitochondrial integrity in mammals. PMID:26416548

  1. Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  2. Esophageal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  3. Stages of Gallbladder Cancer

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  4. NCI Designated Cancer Centers

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  5. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  6. Esophageal Cancer Prevention

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  7. Stages of Vulvar Cancer

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  8. Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Teodoro Anderson

    2012-08-01

    Full Text Available Abstract Background Lycopene, a major carotenoid component of tomato, has a potential anticancer activity in many types of cancer. Epidemiological and clinical trials rarely provide evidence for mechanisms of the compound’s action, and studies on its effect on cancer of different cell origins are now being done. The aim of the present study was to determine the effect of lycopene on cell cycle and cell viability in eight human cancer cell lines. Methods Human cell lines were treated with lycopene (1–5 μM for 48 and 96 h. Cell viability was monitored using the method of MTT. The cell cycle was analyzed by flow cytometry, and apoptotic cells were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling (TUNEL and by DAPI. Results Our data showed a significant decrease in the number of viable cells in three cancer cells lines (HT-29, T84 and MCF-7 after 48 h treatment with lycopene, and changes in the fraction of cells retained in different cell cycle phases. Lycopene promoted also cell cycle arrest followed by decreased cell viability in majority of cell lines after 96 h, as compared to controls. Furthermore, an increase in apoptosis was observed in four cell lines (T-84, HT-29, MCF-7 and DU145 when cells were treated with lycopene. Conclusions Our findings show the capacity of lycopene to inhibit cell proliferation, arrest cell cycle in different phases and increase apoptosis, mainly in breast, colon and prostate lines after 96 h. These observations suggest that lycopene may alter cell cycle regulatory proteins depending on the type of cancer and the dose of lycopene administration. Taken together, these data indicated that the antiproliferative effect of lycopene was cellular type, time and dose-dependent.

  9. Reprogramming of human cancer cells to pluripotency for models of cancer progression

    Science.gov (United States)

    Kim, Jungsun; Zaret, Kenneth S

    2015-01-01

    The ability to study live cells as they progress through the stages of cancer provides the opportunity to discover dynamic networks underlying pathology, markers of early stages, and ways to assess therapeutics. Genetically engineered animal models of cancer, where it is possible to study the consequences of temporal-specific induction of oncogenes or deletion of tumor suppressors, have yielded major insights into cancer progression. Yet differences exist between animal and human cancers, such as in markers of progression and response to therapeutics. Thus, there is a need for human cell models of cancer progression. Most human cell models of cancer are based on tumor cell lines and xenografts of primary tumor cells that resemble the advanced tumor state, from which the cells were derived, and thus do not recapitulate disease progression. Yet a subset of cancer types have been reprogrammed to pluripotency or near-pluripotency by blastocyst injection, by somatic cell nuclear transfer and by induced pluripotent stem cell (iPS) technology. The reprogrammed cancer cells show that pluripotency can transiently dominate over the cancer phenotype. Diverse studies show that reprogrammed cancer cells can, in some cases, exhibit early-stage phenotypes reflective of only partial expression of the cancer genome. In one case, reprogrammed human pancreatic cancer cells have been shown to recapitulate stages of cancer progression, from early to late stages, thus providing a model for studying pancreatic cancer development in human cells where previously such could only be discerned from mouse models. We discuss these findings, the challenges in developing such models and their current limitations, and ways that iPS reprogramming may be enhanced to develop human cell models of cancer progression. PMID:25712212

  10. Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties.

    Science.gov (United States)

    Liu, Jianming; Ma, Lilin; Xu, Junfei; Liu, Chun; Zhang, Jianguo; Liu, Jie; Chen, Ruixin; Zhou, Youlang

    2013-02-01

    The cancer stem cell theory hypothesizes that cancer stem cells (CSCs), which possess self-renewal and other stem cell properties, are regarded as the cause of tumor formation, recurrence and metastasis. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs. In this study, we enriched gastric cancer stem cells through spheroid body formation by cultivating the human gastric cancer cell line MKN-45 in defined serum-free medium. The stemness characteristics of spheroid body-forming cells, including self-renewal, proliferation, chemoresistance, tumorigenicity of the MKN-45 spheroid body-forming cells were evaluated, and the expression levels of stemness genes and related proteins in the MKN-45 spheroid body-forming cells were assessed. Furthermore, immunofluorescence staining for the stem cell markers on spheroid body-forming cells was examined to evaluate the association between stemness factors (Oct4, Sox2, Nanog) and the proposed CSC marker CD44. Our data demonstrated that non-adherent spheroid body-forming cells from the gastric cancer cell line MKN-45 cultured in stem cell-conditioned medium possessed gastric CSC properties, such as persistent self-renewal, extensive proliferation, drug resistance, high tumorigenic capacity and overexpression of CSC-related genes and proteins (Oct4, Sox2, Nanog and CD44), compared with the parental cells. More importantly, CD44-positive cells co-expressing the pluripotency genes Oct4, Sox2 and Nanog may represent gastric CSCs. Further experiments using more refined selection criteria such as a combination of two or multiple markers would be useful to specifically identify and purify CSCs.

  11. Pollution studies on harbours and jetties in Nigeria | Agbagwa ...

    African Journals Online (AJOL)

    40%) were Vibrio parahaemolyticus, four isolates were also identified as Salmonella species. The high distribution of the bacteria which is of public health importance in the harbours/jetties, indicates pollution. Physiochemical parameters such ...

  12. Results of optical detection trials in harbour environment

    Science.gov (United States)

    Kemp, Rob A. W.; de Groot, Johannes F.; van den Broek, Sebastiaan P.; de Lange, Dirk-Jan J.; Dijk, Judith; Schwering, Piet B. W.

    2008-04-01

    In harbour environments operators should perform tasks as detection and classification. Present-day threats of small objects, as jet skis etc, should be detected, classified and recognized. Furthermore threat intention should be analysed. As harbour environments contain several hiding spaces, due to fixed and floating neutral objects, correct assessment of the threats is complicated when detection tracks are intermittently known. For this purpose we have analysed the capability of our image enhancement and detection technology to assess the performance of the algorithms in a harbour environment. Data were recorded in a warm harbour location. During these trials several small surfaces targets were used, that were equipped with ground truth equipment. In these environments short-range detection is mandatory, followed by immediate classification. Results of image enhancement and detection are shown. An analysis was made into the performance assessment of the detection algorithms.

  13. Cancer stem cell-like side population cells in clear cell renal cell carcinoma cell line 769P.

    Science.gov (United States)

    Huang, Bin; Huang, Yi Jun; Yao, Zhi Jun; Chen, Xu; Guo, Sheng Jie; Mao, Xiao Peng; Wang, Dao Hu; Chen, Jun Xing; Qiu, Shao Peng

    2013-01-01

    Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells as compared with other four cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.

  14. Nonequilibrium population dynamics of phenotype conversion of cancer cells.

    Directory of Open Access Journals (Sweden)

    Joseph Xu Zhou

    Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

  15. Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells.

    Science.gov (United States)

    Pizato, Nathalia; Luzete, Beatriz Christina; Kiffer, Larissa Fernanda Melo Vasconcelos; Corrêa, Luís Henrique; de Oliveira Santos, Igor; Assumpção, José Antônio Fagundes; Ito, Marina Kiyomi; Magalhães, Kelly Grace

    2018-01-31

    The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation. Omega-3 fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. Pyroptosis is an inflammation related cell death and so far, the function of docosahexaenoic acid (DHA) in pyroptosis cell death has not been described. This study investigated the role of DHA in triggering pyroptosis activation in breast cancer cells. MDA-MB-231 breast cancer cells were supplemented with DHA and inflammation cell death was analyzed. DHA-treated breast cancer cells triggered increased caspase-1and gasdermin D activation, enhanced IL-1β secretion, translocated HMGB1 towards the cytoplasm, and membrane pore formation when compared to untreated cells, suggesting DHA induces pyroptosis programmed cell death in breast cancer cells. Moreover, caspase-1 inhibitor (YVAD) could protect breast cancer cells from DHA-induced pyroptotic cell death. In addition, membrane pore formation showed to be a lysosomal damage and ROS formation-depended event in breast cancer cells. DHA triggered pyroptosis cell death in MDA-MB-231by activating several pyroptosis markers in these cells. This is the first study that shows the effect of DHA triggering pyroptosis programmed cell death in breast cancer cells and it could improve the understanding of the omega-3 supplementation during breast cancer treatment.

  16. Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Tae Hun Kim

    2014-01-01

    Full Text Available Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.

  17. Renal cell cancer among African Americans: an epidemiologic review

    National Research Council Canada - National Science Library

    Lipworth, Loren; Tarone, Robert E; McLaughlin, Joseph K

    2011-01-01

    Incidence rates for renal cell cancer, which accounts for 85% of kidney cancers, have been rising more rapidly among blacks than whites, almost entirely accounted for by an excess of localized disease...

  18. Integrins in mammary-stem-cell biology and breast-cancer progression – a role in cancer stem cells?

    Science.gov (United States)

    Pontier, Stephanie M.; Muller, William J.

    2009-01-01

    Summary Cancer cells with stem cell-like properties (cancer stem cells) are believed to drive cancer and are associated with poor prognosis. Data from mouse models have demonstrated that integrins, the major cellular receptors for extracellular-matrix components, have essential roles both during cancer initiation and progression, and during cell differentiation in normal development. By presenting an overview of the role of integrins in stem-cell biology and in cancer progression, this Commentary aims to present evidence for a role of integrins in the biology of cancer stem cells. Given the recent interest in the role of integrins in breast-cancer initiation and progression, we focus on the role of the members of the integrin family and their coupled signaling pathways in mammary-gland development and tumorigenesis. PMID:19118213

  19. Integrins in mammary-stem-cell biology and breast-cancer progression--a role in cancer stem cells?

    Science.gov (United States)

    Pontier, Stephanie M; Muller, William J

    2009-01-15

    Cancer cells with stem cell-like properties (cancer stem cells) are believed to drive cancer and are associated with poor prognosis. Data from mouse models have demonstrated that integrins, the major cellular receptors for extracellular-matrix components, have essential roles both during cancer initiation and progression, and during cell differentiation in normal development. By presenting an overview of the role of integrins in stem-cell biology and in cancer progression, this Commentary aims to present evidence for a role of integrins in the biology of cancer stem cells. Given the recent interest in the role of integrins in breast-cancer initiation and progression, we focus on the role of the members of the integrin family and their coupled signaling pathways in mammary-gland development and tumorigenesis.

  20. Ecology, tourism and management of harbour seals (Phoca vitulina)

    OpenAIRE

    Granquist, Sandra M.

    2016-01-01

    In cases where human and wildlife are co-using the same geographical areas and resources, management issues often get complex and stakeholder conflicts are common. The Icelandic harbour seal (Phoca vitulina) population is rapidly decreasing, but direct culling of seals still occurs. At the same time seals are becoming an important resource due to increased interest in wildlife watching. Despite the complicated management situation, the Icelandic harbour seal population is one of the least stu...

  1. Immuno Nanoparticles Integrated Electrical Control of Targeted Cancer Cell Development Using Whole Cell Bioelectronic Device

    Science.gov (United States)

    Hondroulis, Evangelia; Zhang, Rui; Zhang, Chengxiao; Chen, Chunying; Ino, Kosuke; Matsue, Tomokazu; Li, Chen-Zhong

    2014-01-01

    Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (electrotherapy for clinical and drug delivery applications. PMID:25057316

  2. Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1′-S-1′-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors

    OpenAIRE

    Arshad, Norhafiza M.; In, Lionel L.A.; Soh, Tchen Lin; Azmi, Mohamad Nurul; Ibrahim, Halijah; Awang, Khalijah; Dudich, Elena; Tatulov, Eduard; Nagoor, Noor Hasima

    2015-01-01

    Purpose Previous in vitro and in vivo studies have reported that 1′-S-1′-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tum...

  3. Marine debris in harbour porpoises and seals from German waters.

    Science.gov (United States)

    Unger, B; Herr, H; Benke, H; Böhmert, M; Burkhardt-Holm, P; Dähne, M; Hillmann, M; Wolff-Schmidt, K; Wohlsein, P; Siebert, U

    2017-09-01

    Records of marine debris in and attached to stranded harbour porpoises (Phocoena phocoena), harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) were studied comprising information on 6587 carcasses collected along the German coast between 1990 and 2014, the decomposition state allowed for necropsy in 1622 cases. Marine debris items were recorded in 31 carcasses including 14 entanglements (5 harbour porpoises, 6 harbour seals, 3 grey seals) and 17 cases of ingestion (4 harbour porpoises, 10 harbour seals, 3 grey seals). Objects comprised general debris (35.1%) and fishing related debris (64.9%). Injuries associated with marine debris included lesions, suppurative ulcerative dermatitis, perforation of the digestive tract, abscessation, suppurative peritonitis and septicaemia. This study is the first investigation of marine debris findings in all three marine mammal species from German waters. It demonstrates the health impacts marine debris can have, including severe suffering and death. The results provide needed information on debris burdens in the North and Baltic Seas for implementing management directives, such as the Marine Strategy Framework Directive (MSFD). Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Inner harbour wave agitation using boussinesq wave model

    Directory of Open Access Journals (Sweden)

    Panigrahi Jitendra K.

    2015-01-01

    Full Text Available Short crested waves play an important role for planning and design of harbours. In this context a numerical simulation is carried out to evaluate wave tranquility inside a real harbour located in east coast of India. The annual offshore wave climate proximity- to harbour site is established using Wave Model (WAM hindcast wave data. The deep water waves are transformed to harbour front using a Near Shore spectral Wave model (NSW. A directional analysis is carried out to determine the probable incident wave directions towards the harbour. Most critical threshold wave height and wave period is chosen for normal operating conditions using exceedence probability analysis. Irregular random waves from various directions are generated confirming to Pierson Moskowitz spectrum at 20m water depth. Wave incident into inner harbor through harbor entrance is performed using Boussinesq Wave model (BW. Wave disturbance experienced inside the harbour and at various berths are analysed. The paper discusses the progresses took place in short wave modeling and it demonstrates application of wave climate for the evaluation of harbor tranquility using various types of wave models.

  5. Inner harbour wave agitation using boussinesq wave model

    Directory of Open Access Journals (Sweden)

    Jitendra K. Panigrahi

    2015-01-01

    Full Text Available Short crested waves play an important role for planning and design of harbours. In this context a numerical simulation is carried out to evaluate wave tranquility inside a real harbour located in east coast of India. The annual offshore wave climate proximity to harbour site is established using Wave Model (WAM hindcast wave data. The deep water waves are transformed to harbour front using a Near Shore spectral Wave model (NSW. A directional analysis is carried out to determine the probable incident wave directions towards the harbour. Most critical threshold wave height and wave period is chosen for normal operating conditions using exceedence probability analysis. Irregular random waves from various directions are generated confirming to Pierson Moskowitz spectrum at 20 m water depth. Wave incident into inner harbor through harbor entrance is performed using Boussinesq Wave model (BW. Wave disturbance experienced inside the harbour and at various berths are analysed. The paper discusses the progresses took place in short wave modeling and it demonstrates application of wave climate for the evaluation of harbor tranquility using various types of wave models.

  6. Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Alvero, Ayesha B; Yang, Yingkui

    2011-01-01

    Epithelial ovarian cancer stem cells (EOC stem cells) have been associated with recurrence and chemoresistance. CD44 and CK18 are highly expressed in cancer stem cells and function as tools for their identification and characterization. We investigated the association between the number of CD44......+ EOC stem cells in ovarian cancer tumors and progression-free survival. EOC stem cells exist as clusters located close to the stroma forming the cancer stem cell "niche". 17.1% of the samples reveled high number of CD44+ EOC stem cells (>20% positive cells). In addition, the number of CD44+ EOC stem...... cells was significantly higher in patients with early-stage ovarian cancer (FIGO I/II), and it was associated with shorter progression-free survival (P = 0.026). This study suggests that quantification of the number of EOC stem cells in the tumor can be used as a predictor of disease and could...

  7. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E

    2007-01-01

    with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment....... for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells...

  8. Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment.

    Science.gov (United States)

    Islam, Farhadul; Gopalan, Vinod; Smith, Robert A; Lam, Alfred K-Y

    2015-07-01

    Cancer stem cells (CSCs) are a subpopulation of cancer cells with many clinical implications in most cancer types. One important clinical implication of CSCs is their role in cancer metastases, as reflected by their ability to initiate and drive micro and macro-metastases. The other important contributing factor for CSCs in cancer management is their function in causing treatment resistance and recurrence in cancer via their activation of different signalling pathways such as Notch, Wnt/β-catenin, TGF-β, Hedgehog, PI3K/Akt/mTOR and JAK/STAT pathways. Thus, many different therapeutic approaches are being tested for prevention and treatment of cancer recurrence. These may include treatment strategies targeting altered genetic signalling pathways by blocking specific cell surface molecules, altering the cancer microenvironments that nurture cancer stem cells, inducing differentiation of CSCs, immunotherapy based on CSCs associated antigens, exploiting metabolites to kill CSCs, and designing small interfering RNA/DNA molecules that especially target CSCs. Because of the huge potential of these approaches to improve cancer management, it is important to identify and isolate cancer stem cells for precise study and application of prior the research on their role in cancer. Commonly used methodologies for detection and isolation of CSCs include functional, image-based, molecular, cytological sorting and filtration approaches, the use of different surface markers and xenotransplantation. Overall, given their significance in cancer biology, refining the isolation and targeting of CSCs will play an important role in future management of cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. [Case of heterochronous triple urogenital cancer (renal cell carcinoma, bladder cancer, prostatic cancer)].

    Science.gov (United States)

    Okumura, Akiou; Tsuritani, Shinji; Takagawa, Kiyoshi; Fuse, Hideki

    2013-11-01

    We report a case of a 73-year-old male with heterochronous triple urogenital cancer. The patient was referred to our hospital because serum PSA was elevated (7.0 ng/ml) in 1998. Prostatic needle biopsy revealed prostatic cancer in the right lobe, and total prostatectomy was performed. The histopathological diagnosis was moderately differentiated adenocarcinoma (TlcNOMO). Non-muscle invasive bladder cancer (NMIBC) was detected during an examination for microhematuria in 2002. Transurethral resection of the bladder tumor (TURBT) procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). A right renal mass was detected incidentally on follow-up CT for bladder cancer in 2008. Renal enucleation was performed in 2009. The histopathological diagnosis was grade 2 clear cell renal cell carcinoma (pTlaNXMO). NMIBC was detected on follow-up urethrocystoscopy in 2011. The TURBT procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). On follow-up for urogenital cancer patients, it is important to investigate recurrence of the primary cancer and also heterochronous canceration of other urogenital organs.

  10. The spatial distribution of LGR5+ cells correlates with gastric cancer progression.

    Directory of Open Access Journals (Sweden)

    Eva Simon

    Full Text Available In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction and translational level (immunohistochemistry in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e. oesophagus, stomach, liver, pancreas, colon and rectum. The clinico-pathological significance of LGR5 expression was studied in 100 patients with gastric carcinoma (GC. Non-neoplastic tissue usually harboured only very few scattered LGR5(+ cells. The corresponding carcinomas of the oesophagus, stomach, liver, pancreas, colon and rectum showed significantly more LGR5(+ cells as well as significantly higher levels of LGR5-mRNA compared with the corresponding non-neoplastic tissue. Double staining experiments revealed a coexpression of LGR5 with the putative stem cell markers CD44, Musashi-1 and ADAM17. Next we tested the hypothesis that the sequential changes of gastric carcinogenesis, i.e. chronic atrophic gastritis, intestinal metaplasia and invasive carcinoma, are associated with a reallocation of the LGR5(+ cells. Interestingly, the spatial distribution of LGR5 changed: in non-neoplastic stomach mucosa, LGR5(+ cells were found predominantly in the mucous neck region; in intestinal metaplasia LGR5(+ cells were localized at the crypt base, and in GC LGR5(+ cells were present at the luminal surface, the tumour centre and the invasion front. The expression of LGR5 in the tumour centre and invasion front of GC correlated significantly with the local tumour growth (T-category and the nodal spread (N-category. Furthermore, patients with LGR5(+ GCs had a shorter median survival (28.0±8.6 months than patients with LGR5(- GCs (54.5±6.3 months. Our results show that LGR5 is

  11. From gametogenesis and stem cells to cancer: common metabolic themes.

    Science.gov (United States)

    Pereira, Sandro L; Rodrigues, Ana Sofia; Sousa, Maria Inês; Correia, Marcelo; Perestrelo, Tânia; Ramalho-Santos, João

    2014-01-01

    Both pluripotent stem cells (PSCs) and cancer cells have been described as having similar metabolic pathways, most notably a penchant for favoring glycolysis even under aerobiosis, suggesting common themes that might be explored for both stem cell differentiation and anti-oncogenic purposes. A search of the scientific literature available in the PubMed/Medline was conducted for studies on metabolism and mitochondrial function related to gametogenesis, early development, stem cells and cancers in the reproductive system, notably breast, prostate, ovarian and testicular cancers. Both PSCs and some types of cancer cells, particularly reproductive cancers, were found to obtain energy mostly by glycolysis, often reducing mitochondrial activity and oxidative phosphorylation. This strategy links proliferating cells, allowing for the biosynthesis reactions necessary for cell division. Interventions that affect metabolic pathways, and force cells to change their preferences, can lead to shifts in cell status, increasing either pluripotency or differentiation of stem cells, and causing cancer cells to become more or less aggressive. Interestingly metabolic changes in many cases seemed to lead to cell transformation, not necessarily follow it, suggesting a direct role of metabolic choices in influencing the (epi)genetic program of different cell types. There are uncanny similarities between PSCs and cancer cells at the metabolic level. Furthermore, metabolism may also play a direct role in cell status and targeting metabolic pathways could therefore be a promising strategy for both the control of cancer cell proliferation and the regulation of stem cell physiology, in terms of manipulating stem cells toward relevant phenotypes that may be important for tissue engineering, or making cancer cells become less tumorigenic. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For

  12. Measuring density and compressibility of white blood cells and prostate cancer cells by microchannel acoustophoresis

    DEFF Research Database (Denmark)

    Barnkob, Rune; Augustsson, Per; Magnusson, Cecilia

    2011-01-01

    to determine the density and compressibility of individual cells enables the prediction and alteration of the separation outcome for a given cell mixture. We apply the method on white blood cells (WBCs) and DU145 prostate cancer cells (DUCs) aiming to improve isolation of circulating tumor cells from blood......, an emerging tool in the monitoring and characterizing of metastatic cancer....

  13. Oct-4 expression maintained stem cell properties in prostate cancer ...

    African Journals Online (AJOL)

    The purpose of the present study is to isolate cancerous stem-like cells from normal healthy volunteers and prostate cancer patients (CD133+) which also express MDR1 and to ascertain the influence of Oct-4 on 'stem-ness' and differentiation of these CD133+ cells towards epithelium. Methods: CD133+ cells were isolated ...

  14. Cytotoxicity of Sambucus ebulus on cancer cell lines and protective ...

    African Journals Online (AJOL)

    Cytotoxicity of Sambucus ebulus on cancer cell lines and protective effects of vitamins C and E against its cytotoxicity on normal cell lines. ... Cytotoxicity of SEE on cancer (HepG2 and CT26) and normal (CHO and rat fibroblast) cell lines was evaluated by MTT assay. IC50 of SEE on ... African Journal of Biotechnology Vol.

  15. Targeting Apoptotic Activity Against Prostate Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2017-07-01

    Full Text Available Numerous data suggest that an increase of cancer stem cells (CSCs in tumor mass can be the reason for failure of conventional therapies because of their resistance. CD44+/CD24− cells are a putative cancer stem cells subpopulation in prostate cancer. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand is an activator of apoptosis in tumor cells. However, some tumors are TRAIL-resistant. Cancer cells can be re-sensitized to TRAIL induced apoptosis by a combination of TRAIL and taxanes. The aim of this work was to analyze the enhancement of the anticancer effect of TRAIL by paclitaxel, cabazitaxel and docetaxel in the whole population of PC3 and DU145 prostate cancer cells, but also in CD44+/CD24− prostate cancer stem cells. We examined the apoptotic effect of TRAIL and taxanes using flow cytometry and Annexin-V-PE staining. The co-treatment with taxanes and TRAIL enhanced significantly the apoptosis in CD44+/CD24− cells only in PC3 cell line but not in DU145 cells. We discovered also that taxanes can increase the expression of death receptor TRAIL-R2 in PC3 prostate cancer cells. The results of our study show that treatment with paclitaxel, cabazitaxel and docetaxel is able to enhance the apoptosis induced by TRAIL even in prostate cancer stem cells.

  16. Milk stimulates growth of prostate cancer cells in culture.

    Science.gov (United States)

    Tate, Patricia L; Bibb, Robert; Larcom, Lyndon L

    2011-11-01

    Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.

  17. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail: arlhee@cim.sld.cu; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)

    2011-08-15

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC.

  18. Advanced Merkel cell cancer and the elderly.

    LENUS (Irish Health Repository)

    Bird, B R

    2012-02-03

    BACKGROUND: Merkel cell cancer (MCC) is an uncommon neuroendocrine skin cancer occurring predominantly in elderly Caucasians. It tends to metastasize to regional lymph nodes and viscera and is sensitive to chemotherapy but recurs rapidly. AIM: To report one such case, its response to chemotherapy and briefly review the literature. METHODS: A 73-year-old male with a fungating primary lesion on his left knee and ulcerated inguinal lymph nodes was diagnosed with MCC and treated with chemotherapy. The two largest case series and reviews of case reports were summarised. RESULTS: His ulcer healed after two cycles of carboplatin and etoposide with improvement in quality of life. Overall response rates of nearly 60% to chemotherapy are reported but median survival is only nine months with metastatic disease. CONCLUSIONS: Chemotherapy should be considered for fit elderly patients with MCC who have recurrent or advanced disease.

  19. Icotinib is an active treatment of non-small-cell lung cancer: a retrospective study.

    Directory of Open Access Journals (Sweden)

    Xiaofeng Chen

    Full Text Available Icotinib hydrochloride is a novel epidermal growth factor receptor (EGFR tyrosine kinase inhibitor (TKI with preclinical and clinical activity in non-small cell lung cancer (NSCLC. This retrospective analysis was performed to assess the efficacy of icotinib on patients with non-small-cell lung cancer (NSCLC.82 consecutive patients treated with icotinib as first (n = 24 or second/third line (n = 58 treatment at three hospitals in Nanjing were enrolled into our retrospective research. The Response Evaluation Criteria in Solid Tumors (RECIST was used to evaluate the tumor responses and the progression-free survival (PFS and overall survival (OS was evaluated by the Kaplan-Meier method.Median PFS was 4.0 months (95% CI 2.311-5.689. Median OS was 11.0 months (95% CI 8.537-13.463 in this cohort. Median PFS for first and second/third line were 7.0 months (95% CI 2.151-11.8 and 3.0 months (95% CI 1.042-4.958, respectively. Median OS for first and second/third line were 13.0 months (95% CI 10.305-15.695 and 10.0 months (95% CI 7.295-12.70, respectively. In patients with EGFR mutation (n = 19, icotinib significantly reduced the risk of progression (HR 0.36, 95% CI 0.18-0.70, p = 0.003 and death (HR 0.10, 95% CI 0.02-0.42, p = 0.002 compared with those EGFR status unknown (n = 63. The most common adverse events were acne-like rash (39.0% and diarrhea (20.7%.Icotinib is active in the treatment of patients with NSCLC both in first or second/third line, especially in those patients harbouring EGFR mutations, with an acceptable adverse event profile.

  20. Comparison of 2-compartment, 3-compartment and stack designs for electrodialytic removal of heavy metals from harbour sediments

    DEFF Research Database (Denmark)

    Pedersen, Kristine B.; Ottosen, Lisbeth M.; Jensen, Pernille Erland

    2015-01-01

    Comparisons of cell and stack designs for the electrodialytic removal of heavy metals from two harbour sediments, were made. Multivariate modelling showed that sediment properties and experimental set-ups had the highest influence on the heavy metal removal indicating that they should be modelled...

  1. Amygdalin Influences Bladder Cancer Cell Adhesion and Invasion In Vitro

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Igor Tsaur; Karen Nelson; Jesco Pfitzenmaier; Axel Haferkamp; Blaheta, Roman A

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as...

  2. Spheroid Cultures of Primary Urothelial Cancer Cells: Cancer Tissue-Originated Spheroid (CTOS) Method.

    Science.gov (United States)

    Yoshida, Takahiro; Okuyama, Hiroaki; Endo, Hiroko; Inoue, Masahiro

    2018-01-01

    Increasingly, it has been recognized that studying cancer samples from individual patients is important for the development of effective therapeutic strategies and in endeavors to overcome therapy resistance. Primary cultures of cancer cells acutely dissected from individual patients can provide a platform that enables the study and characterization of individual tumors. To that end, we have developed a method for preparing cancer cells in the form of multi-cellular spheroids. The cells can be derived from patient tumors (primary cells), from patient-derived xenografts, or from genetically- or chemically induced animal tumors. This method of culturing spheroids composed of cells derived from cancer tissues can be applied to various types of cancer, including urothelial cancer. The method is based on the principle of retaining cell-cell contact throughout cancer cell preparation and culturing. The first step is a partial digestion of the tumor specimen into small fragments; these fragments spontaneously form spheroidal shapes within several hours. The spheroid is referred to as a cancer tissue-originated spheroid (CTOS). The advantage of the CTOS method is that it allows one to prepare pure cancer cells at high yield. CTOSs can be stably cultured in serum-free conditions. The CTOS method can be applied to drug sensitivity assays, drug screening, and analyses of intracellular signaling. Moreover, the CTOS method provides a platform for studying the nature of cancer cell clusters.

  3. Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer.

    Science.gov (United States)

    Zhang, Le; Xu, Liang; Zhang, Fengchun; Vlashi, Erina

    2017-04-18

    Experimental evidence suggest that breast tumors originate from breast cancer stem cells (BCSCs), and that mitochondrial biogenesis is essential for the anchorage-independent clonal expansion and survival of CSCs, thus rendering mitochondria a significant target for novel treatment approaches. One of the recognized side effects of the FDA-approved drug, doxycycline is the inhibition of mitochondrial biogenesis. Here we investigate the mechanism by which doxycycline exerts its inhibitory effects on the properties of breast cancer cells and BCSCs, such as mammosphere forming efficiency, invasion, migration, apoptosis, the expression of stem cell markers and epithelial-to-mesenchymal transition (EMT) related markers of breast cancer cells. In addition, we explored whether autophagy plays a role in the inhibitory effect of doxycycline on breast cancer cells. We find that doxycyline can inhibit the viability and proliferation of breast cancer cells and BCSCs, decrease mammosphere forming efficiency, migration and invasion, and EMT of breast cancer cells. Expression of stem cell factors Oct4, Sox2, Nanog and CD44 were also significantly downregulated after doxycycline treatment. Moreover, doxycycline could down-regulate the expression of the autophagy marker LC-3BI and LC-3BII, suggesting that inhibiting autophagy may be responsible in part for the observed effects on proliferation, EMT and stem cell markers. The potent inhibition of EMT and cancer stem-like characteristics in breast cancer cells by doxycycline treatment suggests that this drug can be repurposed as an anti-cancer drug in the treatment of breast cancer patients in the clinic.

  4. Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds

    Science.gov (United States)

    Li, Yanyan; Wicha, Max S.; Schwartz, Steven J.; Sun, Duxin

    2011-01-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anti-cancer drugs targeting cancer stem cells. Naturally-occurring dietary compounds have received increasing attention in cancer chemoprevention. The anti-cancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog, and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine, and vitamin D3, are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. PMID:21295962

  5. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells

    Science.gov (United States)

    Lawson, Devon A.; Bhakta, Nirav R.; Kessenbrock, Kai; Prummel, Karin D.; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-01-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality1. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours2–5. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown2. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are

  6. Risk of spilling cancer cells during total laparoscopic hysterectomy in low-risk endometrial cancer

    Directory of Open Access Journals (Sweden)

    Satoshi Shinohara

    2017-08-01

    Conclusion: We conclude that fallopian tubal cauterization is sufficient to provide protection from the dissemination of cancer cells into the peritoneal cavity at the time of TLH for endometrial cancers in early stages.

  7. Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Eunice Yuen-Ting Lau

    2017-01-01

    Full Text Available Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance. With a better understanding of how CSC interacts with its niche, we are able to identify potential therapeutic targets for the development of more effective treatments against cancer.

  8. Differentiation of prostate cancer cells using flexible fluorescent polymers.

    Science.gov (United States)

    Scott, Michael D; Dutta, Rinku; Haldar, Manas K; Guo, Bin; Friesner, Daniel L; Mallik, Sanku

    2012-01-03

    Using water-soluble, fluorescent, flexible polymers, we have devised a novel methodology for identification and differentiation of prostate cancer cells. Using a stepwise linear discriminant analysis, we demonstrate that the differential modulations of the polymer emission intensities in the presence of conditioned cell culture media can be used to distinguish between prostate cancer subtypes and between cancerous and noncancer cells. The differences in the compositions of the conditioned cell culture media are likely contributing to different fluorescence spectral patterns of the polymers. This in vitro approach may provide a novel platform for the development of an alternative prostate cancer diagnostic and subtyping technique. © 2011 American Chemical Society

  9. Cancer stem cell: fundamental experimental pathological concepts and updates.

    Science.gov (United States)

    Islam, Farhadul; Qiao, Bin; Smith, Robert A; Gopalan, Vinod; Lam, Alfred K-Y

    2015-04-01

    Cancer stem cells (CSCs) are a subset of cancer cells which play a key role in predicting the biological aggressiveness of cancer due to its ability of self-renewal and multi-lineage differentiation (stemness). The CSC model is a dynamic one with a functional subpopulation of cancer cells rather than a stable cell population responsible for tumour regeneration. Hypotheses regarding the origins of CSCs include (1) malignant transformation of normal stem cells; (2) mature cancer cell de-differentiation with epithelial-mesenchymal transition and (3) induced pluripotent cancer cells. Surprisingly, the cancer stem cell hypothesis originated in the late nineteenth century and the existence of haematopoietic stem cells was demonstrated a century later, demonstrating that the concept was possible. In the last decade, CSCs have been identified and isolated in different cancers. The hallmark traits of CSCs include their heterogeneity, interaction with microenvironments and plasticity. Understanding these basic concepts of CSCs is important for translational applications using CSCs in the management of patients with cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The ratio of cancer cells to stroma after induction therapy in the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Goto, Masaki; Naito, Masahito; Saruwatari, Koichi; Hisakane, Kakeru; Kojima, Motohiro; Fujii, Satoshi; Kuwata, Takeshi; Ochiai, Atsushi; Nomura, Shogo; Aokage, Keiju; Hishida, Tomoyuki; Yoshida, Junji; Yokoi, Kohei; Tsuboi, Masahiro; Ishii, Genichiro

    2017-02-01

    Induction therapy induces degenerative changes of various degrees in both cancerous and non-cancerous cells of non-small cell lung cancer (NSCLC). The effect of induction therapy on histological characteristics, in particular the ratio of residual cancer cells to non-cancerous components, is unknown. Seventy-four NSCLC patients treated with induction therapy followed by surgery were enrolled. Residual cancer cells were identified using anti-pan-cytokeratin antibody (AE1/AE3). We analyzed and quantified the following three factors via digital image analysis; (1) the tumor area containing cancer cells and non-cancerous components (TA), (2) the total area of AE1/AE3 positive cancer cells (TACC), (3) the percentage of TACC to TA (%TACC). These factors were also analyzed in a matched control group (surgery alone, n = 80). The median TACC of the induction therapy group was significantly lower than that of the control group (p induction therapy group (5.9 %) was significantly lower than that of the control group (58.6 %) (p induction therapy group. Conversely, TACC had a strong positive correlation with %TACC in the induction therapy group (r = 0.95), but not in the control group. Unlike the control group, the smaller the total area of residual cancer cells, the higher residual tumor contained non-cancerous components in the induction group, which may be the characteristic histological feature of NSCLC after induction therapy.

  11. Application of single-cell technology in cancer research.

    Science.gov (United States)

    Liang, Shao-Bo; Fu, Li-Wu

    2017-07-01

    In this review, we have outlined the application of single-cell technology in cancer research. Single-cell technology has made encouraging progress in recent years and now provides the means to detect rare cancer cells such as circulating tumor cells and cancer stem cells. We reveal how this technology has advanced the analysis of intratumor heterogeneity and tumor epigenetics, and guided individualized treatment strategies. The future prospects now are to bring single-cell technology into the clinical arena. We believe that the clinical application of single-cell technology will be beneficial in cancer diagnostics and treatment, and ultimately improve survival in cancer patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. The cancer-germline antigen SSX2 causes cell cycle arrest and DNA damage in cancer cells

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green

    2011-01-01

    , we show that SSX2 is involved in regulation of cancer cell growth. We found that ectopic expression of SSX2 in melanoma and colon cancer cells strongly reduced cell growth and induced apoptosis in vitro. Importantly, in a xenograft mouse model, the growth of tumors derived from SSX2 overexpressing...... dependent. The growth reduction was similar in isogenic colon cancer cells with and without p53, indicating that SSX2 is able to inhibit the growth of cancer cells, even in absence of functional p53. Our results show that SSX2 acts as an inhibitor of cancer cell proliferation, possibly through replicative...... stress, and therefore have important implications for the use of SSX2 as a target for cancer therapy....

  13. MEMBRANE LEc EXPRESSION IN BREAST CANCER CELLS

    Directory of Open Access Journals (Sweden)

    Ya. A. Udalova

    2009-01-01

    Full Text Available Affine chromatography was used to isolate Lec antibodies from the sera of a healthy female donor with the high titers of these anti- bodies, which were labeled with biotin. The study enrolled 51 patients with primary breast cancer (BC. Antigen expression was found by immunohistochemistry and flow cytometry. With these two techniques being used, the detection rate of Lec expression in BC cells was 65% (33/51; the antigen was most frequently found by flow cytometry as compared with immunohistochemistry: 72 and 58% of cases, respectively.

  14. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  15. Verrucous Squamous Cell Cancer in the Esophagus

    DEFF Research Database (Denmark)

    Egeland, C; Achiam, M P; Federspiel, B

    2016-01-01

    Verrucous carcinoma is a rare, slow-growing type of squamous cell cancer. Fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide. In 2014, two male patients were diagnosed with verrucous carcinoma in the distal part of the esophagus. The endoscopic examinat...... with dysphagia, weight loss, and an endoscopically malignant tumor, but surgery was not performed until after 9 and 10 months, respectively, and then in order to get a diagnosis. At the last follow-up, both patients were without any recurrence of the disease....

  16. Inhibitory Effect of Baicalin and Baicalein on Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Gary O. Rankin

    2013-03-01

    Full Text Available Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70 cell lines and a normal ovarian cell line (IOSE-364 were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD50 values in the range of 45–55 µM for baicalin and 25–40 µM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD50 values of 177 µM for baicalin and 68 µM for baicalein. Baicalin decreased expression of VEGF (20 µM, cMyc (80 µM, and NFkB (20 µM; baicalein decreased expression of VEGF (10 µM, HIF-1α (20 µM, cMyc (20 µM, and NFkB (40 µM. Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers.

  17. Identification of genes involved in breast cancer and breast cancer stem cells

    OpenAIRE

    Apostolou P; Toloudi M; Papasotiriou I

    2015-01-01

    Panagiotis Apostolou, Maria Toloudi, Ioannis Papasotiriou Research and Development Department, Research Genetic Cancer Centre Ltd, Florina, Greece Abstract: Breast cancer is the most frequent type of cancer in women. Great progress has been made in its treatment but relapse is common. One hypothesis to account for the high recurrence rates is the presence of cancer stem cells (CSCs), which have the ability to self-renew and differentiate into multiple malignant cell types. This study aimed t...

  18. Activated leukocyte cell adhesion molecule regulates the interaction between pancreatic cancer cells and stellate cells.

    Science.gov (United States)

    Zhang, Wei-Wei; Zhan, Shu-Hui; Geng, Chang-Xin; Sun, Xin; Erkan, Mert; Kleeff, Jörg; Xie, Xiang-Jun

    2016-10-01

    Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a transmembrane glycoprotein that is involved in tumor progression and metastasis. In the present study, the expression and functional role of ALCAM in pancreatic cancer cells and pancreatic stellate cells (PSCs) was investigated. Tissue specimens were obtained from patients with pancreatic ductal adenocarcinoma (n=56) or chronic pancreatitis (CP; n=10), who underwent pancreatic resection, and from normal pancreatic tissue samples (n=10). Immunohistochemistry was used to analyze the localization and expression of ALCAM in pancreatic tissues. Subsequently, reverse transcription‑quantitative polymerase chain reaction and immunoblotting were applied to assess the expression of ALCAM in pancreatic cancer Panc‑1 and T3M4 cells, as well as in PSCs. An enzyme‑linked immunosorbent assay was used to measure ALCAM levels in cell culture medium stimulated by hypoxia, tumor necrosis factor (TNF)‑α and transforming growth factor‑β. Silencing of ALCAM was performed using ALCAM small interfering (si)RNA and immunocytochemistry was used to analyze the inhibition efficiency. An invasion assay and a cell interaction assay were performed to assess the invasive ability and co‑cultured adhesive potential of Panc‑1 and T3M4 cells, as well as PSCs. Histologically, ALCAM expression was generally weak or absent in pancreatic cancer cells, but was markedly upregulated in PSCs in pancreatic cancer tissues. ALCAM was highly expressed in PSCs from CP tissues and PSCs surrounding pancreatic intraepithelial neoplasias, as well as in pancreatic cancer cells. ALCAM mRNA was highly expressed in PSCs, with a low to moderate expression in T3M4 and Panc‑1 cells. Similar to the mRNA expression, immunoblotting demonstrated that ALCAM protein levels were high in PSCs and T3M4 cells, but low in Panc‑1 cells. The expression of TNF‑α increased, while hypoxia decreased the secretion of ALCAM in pancreatic cancer Panc

  19. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2017-09-01

    chose to make new medulloblastoma models with oncogenic PIK3CA (PIK3CAH1047R). However, this change caused major delay in our progress since we have not...these tumors. 15. SUBJECT TERMS cancer stem cells, medulloblastoma, targeted therapy, therapy resistance , pediatric cancer, brain tumor, Notch1...Keywords……………………………………………………………. 4 3. Accomplishments………..………………………………………….. 4 4. Impact…………………………...…………………………………… 8 5. Changes /Problems

  20. Squamous Cell Lung Cancer: From Tumor Genomics to Cancer Therapeutics

    Science.gov (United States)

    Gandara, David R.; Hammerman, Peter S.; Sos, Martin L.; Lara, Primo N.; Hirsch, Fred R.

    2016-01-01

    Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the last several years, therapeutic progress in SCC has lagged behind the now more common NSCLC histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC. PMID:25979930

  1. Chromosomal aberrations in thyroid follicular-cell neoplasia: in the search of novel oncogenes and tumour suppressor genes

    OpenAIRE

    Zitzelsberger, Horst; Thomas, Gerry; Unger, Kristian

    2010-01-01

    Abstract Thyroid cancer derived from the follicular cell is characterised by specific gene alterations that are closely linked to the various pathological types comprising papillary, follicular and anaplastic thyroid cancer. However, the correlation between molecular biology and pathology is not absolute, since about 30% of cases do not harbour the typical gene alterations. This situation, coupled with the demonstration of genetic heterogeneity in thyroid cancer, is a strong motiva...

  2. Tracking the Evolution of Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Jamal-Hanjani, Mariam; Wilson, Gareth A.; McGranahan, Nicholas

    2017-01-01

    Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine...... as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .)....

  3. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

    Science.gov (United States)

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate tha...

  4. Treatment Options by Stage (Small Cell Lung Cancer)

    Science.gov (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  5. New insights into Wellington Harbours' tectonic settings from marine geophysical and sedimentological data

    Science.gov (United States)

    Woelz, Susi; Nodder, Scott; Barnes, Philip; Orpin, Alan

    2015-04-01

    After the experience of several damaging coastal earthquakes in New Zealand in the last three years, the importance of locating and characterising the earthquake potential of active faults close to urban areas has become more obvious, especially when cities lie in complex tectonic settings as it is the case for Wellington. To assess the earthquake and tsunami potential and the associated hazard posed by such faults, it is necessary to characterise fault geometry, slip rate, earthquake history and earthquake potential. In the marine environment, we have the advantage that faults can be assessed cross-sectionally through the application of high-resolution geophysical data without having to excavate trenches across the active fault trace. We present new marine data from Wellington Harbour that helps to characterise three faults; the Wellington Fault at Kaiwharawhara, the Evans Bay Fault, and a newly discovered fault off Oriental Bay, informally referred to as the Mount Victoria Fault. New marine geophysical data has better delineated the location and characteristics of these faults. High-resolution multi-beam bathymetric data (50 cm grid-cell size), covering the entire Wellington Harbour, were also used to determine the occurrence of seafloor scarps associated with surface ruptures on the faults. Sediment cores from either side of the Wellington Fault off Kaiwharawhara Stream, in about 17.5 m water depth, provide insight into the late Quaternary-Holocene stratigraphy and age of sediments that have been deformed by activity on the faults delineated in Wellington Harbour. The stratigraphy reveals details of the post-glacial marine flooding of the harbour that occurred about 10,000 years ago.

  6. [Expression of a new lung cancer drug resistance-related gene in lung cancer tissues and lung cancer cell strains].

    Science.gov (United States)

    Liu, Ling-Zhi; Qian, Gui-Sheng; Zhou, Xiang-Dong

    2003-02-01

    A new drug resistance-related gene fragment which was 494 bp long was found using suppression subtractive hybridization (SSH) and its full-length cDNA fragment was cloned by the authors. This study was designed to determine the expression of this lung cancer drug resistance-related gene (LCDRG) in lung cancer tissues, juxtacancerous tissues, and five lung cancer cell strains. The expression of LCDRG was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method in 38 lung cancer tissues,12 juxtacancerous tissues, and 5 lung cancer cell strains. The expression of LCDRG in cancer tissues was significantly higher than that in juxtacancerous tissue (Pcancer cell strains, the expression levels of LCDRG in adenocarcinoma cell strains SPC-A-1 and A549, big cell lung cancer cell strain H460, small cell lung cancer cell strains H446 and SH77 were decreased gradually. LCDRG is closely related to lung cancer and may be involved in the pathogenesis of lung cancer.

  7. Ganoderma lucidum (Reishi) Inhibits Cancer Cell Growth and Expression of Key Molecules in Inflammatory Breast Cancer

    OpenAIRE

    Martínez-Montemayor, Michelle M; Acevedo, Raysa Rosario; Otero-Franqui, Elisa; Cubano, Luis A.; Dharmawardhane, Suranganie F.

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell–cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy...

  8. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4

    NARCIS (Netherlands)

    Todaro, Matilde; Alea, Mileidys Perez; Di Stefano, Anna B.; Cammareri, Patrizia; Vermeulen, Louis; Iovino, Flora; Tripodo, Claudio; Russo, Antonio; Gulotta, Gaspare; Medema, Jan Paul; Stassi, Giorgio

    2007-01-01

    A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor. Here, we describe the identification and characterization of such cells from colon carcinomas using the stem cell marker CD133 that accounts around 2% of the cells in human colon cancer. The

  9. Role of the Microenvironment in Ovarian Cancer Stem Cell Maintenance

    Directory of Open Access Journals (Sweden)

    Jennifer Pasquier

    2013-01-01

    Full Text Available Despite recent progresses in cancer therapy and increased knowledge in cancer biology, ovarian cancer remains a challenging condition. Among the latest concepts developed in cancer biology, cancer stem cells and the role of microenvironment in tumor progression seem to be related. Indeed, cancer stem cells have been described in several solid tumors including ovarian cancers. These particular cells have the ability to self-renew and reconstitute a heterogeneous tumor. They are characterized by specific surface markers and display resistance to therapeutic regimens. During development, specific molecular cues from the tumor microenvironment can play a role in maintaining and expanding stemness of cancer cells. The tumor stroma contains several compartments: cellular component, cytokine network, and extracellular matrix. These different compartments interact to form a permissive niche for the cancer stem cells. Understanding the molecular cues underlying this crosstalk will allow the design of new therapeutic regimens targeting the niche. In this paper, we will discuss the mechanisms implicated in the interaction between ovarian cancer stem cells and their microenvironment.

  10. Turning ecology and evolution against cancer.

    Science.gov (United States)

    Korolev, Kirill S; Xavier, Joao B; Gore, Jeff

    2014-05-01

    The fight against cancer has drawn researchers from a wide variety of disciplines, ranging from molecular biology to physics, but the perspective of an ecological theorist has been mostly overlooked. By thinking about the cells that make up a tumour as an endangered species, cancer vulnerabilities become more apparent. Studies in conservation biology and microbial experiments indicate that extinction is a complex phenomenon, which is often driven by the interaction of ecological and evolutionary processes. Recent advances in cancer research have shown that tumours, like species striving for survival, harbour intricate population dynamics, which suggests the possibility to exploit the ecology of tumours for treatment.

  11. Quantum cascade laser infrared spectroscopy of single cancer cells

    KAUST Repository

    Patel, Imran

    2017-03-27

    Quantum cascade laser infrared spectroscopy is a next generation novel imaging technique allowing high resolution spectral imaging of cells. We show after spectral pre-processing, identification of different cancer cell populations within minutes.

  12. Protective mechanism against cancer found in progeria patient cells

    Science.gov (United States)

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  13. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin

    1979-01-01

    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  14. Engineering chemically modified viruses for prostate cancer cell recognition.

    Science.gov (United States)

    Mohan, K; Weiss, G A

    2015-12-01

    Specific detection of circulating tumor cells and characterization of their aggressiveness could improve cancer diagnostics and treatment. Metastasis results from such tumor cells, and causes the majority of cancer deaths. Chemically modified viruses could provide an inexpensive and efficient approach to detect tumor cells and quantitate their cell surface biomarkers. However, non-specific adhesion between the cell surface receptors and the virus surface presents a challenge. This report describes wrapping the virus surface with different PEG architectures, including as fusions to oligolysine, linkers, spacers and scaffolded ligands. The reported PEG wrappers can reduce by >75% the non-specific adhesion of phage to cell surfaces. Dynamic light scattering verified the non-covalent attachment by the reported wrappers as increased sizes of the virus particles. Further modifications resulted in specific detection of prostate cancer cells expressing PSMA, a key prostate cancer biomarker. The approach allowed quantification of PSMA levels on the cell surface, and could distinguish more aggressive forms of the disease.

  15. The complexity of the complicity of mast cells in cancer.

    Science.gov (United States)

    Nechushtan, Hovav

    2010-05-01

    Mast cells are evolutionarly ancient cells of the immune cells which can secrete a variety of effector molecules. Animal and pathologic studies suggest that mast cells may promote tumor growth in some cancer types but may act in an opposite manner in others. In several mouse models a critical role of mast cells for tumor promotion was demonstrated. In humans mast cells are dependent upon the tyrosine kinase receptor c-Kit. This receptor is inhibited by many of the new anti-cancer tyrosine kinase inhibitors including Pazopanib, Imatinib and Masitinib. These drugs probably ablate some tumor mast cells, in addition to their other known antitumor effects. Understanding the complex roles of mast cells in cancer should aid in understanding mechanisms of current tyrosine kinase inhibitors, and the development of innovative anti-cancer therapies. 2009 Elsevier Ltd. All rights reserved.

  16. Targeting therapy-resistant cancer stem cells by hyperthermia

    DEFF Research Database (Denmark)

    Oei, A L; Vriend, L E M; Krawczyk, P M

    2017-01-01

    Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

  17. Cancer metabolism: the volatile signature of glycolysis-in vitro model in lung cancer cells.

    Science.gov (United States)

    Feinberg, Tali; Herbig, Jens; Kohl, Ingrid; Las, Guy; Cancilla, John C; Torrecilla, Jose S; Ilouze, Maya; Haick, Hossam; Peled, Nir

    2017-01-09

    Discovering the volatile signature of cancer cells is an emerging approach in cancer research, as it may contribute to a fast and simple diagnosis of tumors in vivo and in vitro. One of the main contributors to such a volatile signature is hyperglycolysis, which characterizes the cancerous cell. The metabolic perturbation in cancer cells is known as the Warburg effect; glycolysis is preferred over oxidative phosphorylation (OXPHOS), even in the presence of oxygen. The precise mitochondrial alterations that underlie the increased dependence of cancer cells on aerobic glycolysis for energy generation have remained a mystery. We aimed to profile the volatile signature of the glycolysis activity in lung cancer cells. For that an in vitro model, using lung cancer cell line cultures (A549, H2030, H358, H322), was developed. The volatile signature was measured by proton transfer reaction mass spectrometry under normal conditions and glycolysis inhibition. Glycolysis inhibition and mitochondrial activity were also assessed by mitochondrial respiration capacity measurements. Cells were divided into two groups upon their glycolytic profile (PET positive and PET negative). Glycolysis blockade had a unique characteristic that was shared by all cells. Furthermore, each group had a characteristic volatile signature that enabled us to discriminate between those sub-groups of cells. In conclusion, lung cancer cells may have different subpopulations of cells upon low and high mitochondrial capacity. In both groups, glycolysis blockade induced a unique volatile signature.

  18. Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds.

    Science.gov (United States)

    Li, Yanyan; Wicha, Max S; Schwartz, Steven J; Sun, Duxin

    2011-09-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Lincan [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Shen, Hongmei [Cancer Center of Integrative Medicine, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhao, Guangqiang [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Yang, Runxiang [Cancer Chemotherapy Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Cai, Xinyi [Colorectal Cancer Center, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Zhang, Lijuan [Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Jin, Congguo [Cancer Institute, The Third Affiliated Hospital of Kunming Medical University, Kunming (China); Huang, Yunchao, E-mail: daliduanlincan@163.com [Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming (China)

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  20. Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Donatella D’Eliseo

    2016-01-01

    Full Text Available Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy.

  1. Cytokines in immunogenic cell death: Applications for cancer immunotherapy.

    Science.gov (United States)

    Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R

    2017-09-01

    Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.

  2. Evolution and phenotypic selection of cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Jan Poleszczuk

    2015-03-01

    Full Text Available Cells of different organs at different ages have an intrinsic set of kinetics that dictates their behavior. Transformation into cancer cells will inherit these kinetics that determine initial cell and tumor population progression dynamics. Subject to genetic mutation and epigenetic alterations, cancer cell kinetics can change, and favorable alterations that increase cellular fitness will manifest themselves and accelerate tumor progression. We set out to investigate the emerging intratumoral heterogeneity and to determine the evolutionary trajectories of the combination of cell-intrinsic kinetics that yield aggressive tumor growth. We develop a cellular automaton model that tracks the temporal evolution of the malignant subpopulation of so-called cancer stem cells(CSC, as these cells are exclusively able to initiate and sustain tumors. We explore orthogonal cell traits, including cell migration to facilitate invasion, spontaneous cell death due to genetic drift after accumulation of irreversible deleterious mutations, symmetric cancer stem cell division that increases the cancer stem cell pool, and telomere length and erosion as a mitotic counter for inherited non-stem cancer cell proliferation potential. Our study suggests that cell proliferation potential is the strongest modulator of tumor growth. Early increase in proliferation potential yields larger populations of non-stem cancer cells(CC that compete with CSC and thus inhibit CSC division while a reduction in proliferation potential loosens such inhibition and facilitates frequent CSC division. The sub-population of cancer stem cells in itself becomes highly heterogeneous dictating population level dynamics that vary from long-term dormancy to aggressive progression. Our study suggests that the clonal diversity that is captured in single tumor biopsy samples represents only a small proportion of the total number of phenotypes.

  3. Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chun Yin

    2015-02-01

    Full Text Available Background/Aims: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. Methods: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. Results: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. Conclusions: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

  4. Oncogene-directed alterations in cancer cell metabolism.

    Science.gov (United States)

    Nagarajan, Arvindhan; Malvi, Parmanand; Wajapeyee, Narendra

    2016-07-01

    Oncogenes are key drivers of tumor growth. Although several cancer-driving mechanisms have been identified, the role of oncogenes in shaping metabolic patterns in cancer cells is only beginning to be appreciated. Recent studies show that oncogenes directly regulate critical metabolic enzymes and metabolic signaling pathways. Here, we present evidence for oncogene-directed cancer metabolic regulation and discuss the importance of identifying underlying mechanisms that can be targeted for developing precision cancer therapies.

  5. Prognostic Value of Homotypic Cell Internalization by Nonprofessional Phagocytic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Manuela Schwegler

    2015-01-01

    Full Text Available Background. In this study, we investigated the prognostic role of homotypic tumor cell cannibalism in different cancer types. Methods. The phenomenon of one cell being internalized into another, which we refer to as “cell-in-cell event,” was assessed in 416 cases from five head and neck cancer cohorts, as well as one anal and one rectal cancer cohort. The samples were processed into tissue microarrays and immunohistochemically stained for E-cadherin and cleaved caspase-3 to visualize cell membranes and apoptotic cell death. Results. Cell-in-cell events were found in all of the cohorts. The frequency ranged from 0.7 to 17.3 cell-in-cell events per mm2. Hardly any apoptotic cells were found within the cell-in-cell structures, although apoptotic cell rates were about 1.6 to two times as high as cell-in-cell rates of the same tissue sample. High numbers of cell-in-cell events showed adverse effects on patients’ survival in the head and neck and in the rectal cancer cohorts. In multivariate analysis, high frequency was an adverse prognostic factor for overall survival in patients with head and neck cancer (p=0.008. Conclusion. Cell-in-cell events were found to predict patient outcomes in various types of cancer better than apoptosis and proliferation and might therefore be used to guide treatment strategies.

  6. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Clinical Trials Information A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about ... Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to ...

  7. Modeling selective elimination of quiescent cancer cells from bone marrow.

    Science.gov (United States)

    Cavnar, Stephen P; Rickelmann, Andrew D; Meguiar, Kaille F; Xiao, Annie; Dosch, Joseph; Leung, Brendan M; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E; Takayama, Shuichi; Luker, Gary D

    2015-08-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Cytotoxic effect of TDZ on human cervical cancer cells.

    Science.gov (United States)

    Enkhtaivan, Gansukh; Kim, Doo Hwan; Pandurangan, Muthuraman

    2017-08-01

    The present study investigates the anticancer activity of Thidiazuron (TDZ). Anticancer activity of TDZ was evaluated in cervical carcinoma cells (HeLa cells). Sulforhodamine-B (SRB) assay indicates that TDZ was about 100 times more toxic to the cancer cell than normal cells. TUNEL assay showed TDZ induced DNA damage in tumor cells. The loss of mitochondrial membrane potential (MMP) in cancer cells was observed following TDZ treatment. The Bax and bcl-2 gene expression ratio are highly responsible for the regulation of MMP balance, and these ratio was significantly altered following TDZ treatment. The p53 and caspase-3 expressions were increased in cancer cells following treatment. Caspase-3 activation is the key factor for apoptosis. Cytotoxicity of TDZ on HeLa cells was 100 times higher than normal kidney cell (MDCK cells). Moreover, the anticancer activity of TDZ was tested by DNA damage, mitochondrial dysfunction, some gene expression and caspase-3 inhibition in silico. TDZ detected has higher ability on early apoptosis of cancer cell through DNA damage. Additionally, cancer cellular MMP was significantly reduced under inoculation of TDZ. In silico assay confirmed that TDZ was able to bind with the active site of the capase-3 protein. Therefore, taking all these data together it is suggested that the TDZ may be a potential agent to act against cervical cancer cells. Copyright © 2017. Published by Elsevier B.V.

  9. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    user

    2011-02-18

    Feb 18, 2011 ... To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells. (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No.

  10. Sensitizing Cancer Cells: Is It Really All about U?

    OpenAIRE

    Stover, Patrick J.; Weiss, Robert S.

    2012-01-01

    In this issue of Cancer Cell, Hu et al. report that TMPK and RNR, two key enzymes in deoxyribonucleotide biosynthesis, co-localize to damaged DNA and produce nucleotides necessary for DNA repair while suppressing uracil incorporation. TMPK inhibition disrupts this balance and selectively sensitizes cancer cells to low-dose chemotherapy.

  11. Dendritic cell-based immunotherapy in ovarian cancer.

    Science.gov (United States)

    Coosemans, An; Vergote, Ignace; Van Gool, Stefaan W

    2013-12-01

    Worldwide, 80% of patients with ovarian cancer die of the disease. New treatments for this aggressive disease are therefore being intensively searched. Although dendritic cell-based vaccines against gynecological malignancies are in their infancy, this immunotherapeutic approach holds much promise. Here, we present our view on an optimal dendritic cell-based immunotherapeutic strategy against ovarian cancer.

  12. Intravital characterization of tumor cell migration in pancreatic cancer

    NARCIS (Netherlands)

    Beerling, Evelyne; Oosterom, Ilse; Voest, Emile E; Lolkema, Martijn P; van Rheenen, Jacco

    2016-01-01

    Curing pancreatic cancer is difficult as metastases often determine the poor clinical outcome. To gain more insight into the metastatic behavior of pancreatic cancer cells, we characterized migratory cells in primary pancreatic tumors using intravital microscopy. We visualized the migratory behavior

  13. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No severe toxicity ...

  14. GLUT 5 is not over-expressed in breast cancer cells and patient breast cancer tissues.

    Directory of Open Access Journals (Sweden)

    Gayatri Gowrishankar

    Full Text Available F18 2-Fluoro 2-deoxyglucose (FDG has been the gold standard in positron emission tomography (PET oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues.

  15. Cell proliferation and apoptosis in gastric cancer and intestinal metaplasia

    OpenAIRE

    Nora Manoukian Forones; Ana Paula Souza Carvalho; Oswaldo Giannotti-Filho; Laércio Gomes Lourenço; Celina Tizuko Fujiyama Oshima

    2005-01-01

    BACKGROUND: Higher proliferation is commonly observed in cancer cells. Apoptosis can be a useful measure of a tumor cell kinetic. Alteration of the balance between proliferation and apoptosis is associated with cancer. AIM: To study proliferation and apoptosis on gastric cancer and in intestinal metaplasia. METHODOLOGY: Twenty-two samples from gastric adenocarcinomas and 22 biopsies from intestinal metaplasia were studied. The apoptotic bodies in hematoxylin-eosin slides and the expression of...

  16. Renal cell cancer among African Americans: an epidemiologic review

    Science.gov (United States)

    2011-01-01

    Incidence rates for renal cell cancer, which accounts for 85% of kidney cancers, have been rising more rapidly among blacks than whites, almost entirely accounted for by an excess of localized disease. This excess dates back to the 1970s, despite less access among blacks to imaging procedures in the past. In contrast, mortality rates for this cancer have been virtually identical among blacks and whites since the early 1990s, despite the fact that nephrectomy rates, regardless of stage, are lower among blacks than among whites. These observations suggest that renal cell cancer may be a less aggressive tumor in blacks. We have reviewed the epidemiology of renal cell cancer, with emphasis on factors which may potentially play a role in the observed differences in incidence and mortality patterns of renal cell cancer among blacks and whites. To date, the factors most consistently, albeit modestly, associated with increased renal cell cancer risk in epidemiologic studies among whites - obesity, hypertension, cigarette smoking - likely account for less than half of these cancers, and there is virtually no epidemiologic evidence in the literature pertaining to their association with renal cell cancer among blacks. There is a long overdue need for detailed etiologic cohort and case-control studies of renal cell cancer among blacks, as they now represent the population at highest risk in the United States. In particular, investigation of the influence on renal cell cancer development of hypertension and chronic kidney disease, both of which occur substantially more frequently among blacks, is warranted, as well as investigations into the biology and natural history of this cancer among blacks. PMID:21486465

  17. Fouling Bryozoa from some Alexandria harbours, EGYPT. (I Erect species

    Directory of Open Access Journals (Sweden)

    KH.M. ABDEL-SALAM

    2008-05-01

    Full Text Available The fouling erect Bryozoa settled on polystyrene test panels immersed half a meter deep in the water of Abu Qir Harbour, the Eastern Harbour and El-Dekheila Harbour were studied. The present study yields 5 species of erect bryozoa. These areAmathia pruvoti, Zoobotryon verticillatum, Bowerbankia gracilis,Bugula neritina and Bugula stolonifera. The first three ones pertain to 3 genera of the family Vesiculariidae belonging to suborder the Stolonifera; while the other two species affiliate to the genus Bugula belonging to the family Bugulidae of suborder Anasca. The present record of Amathia pruvoti is the first from the Egyptian Mediterranean waters. A re-description, supplied with full structural illustrations of the recorded species is given. Moreover, the temporal and spatial distributions of the species recorded are encountered.

  18. An overview of concepts for cancer stem cells.

    Science.gov (United States)

    Chen, Shih-Yin; Huang, Yu-Chuen; Liu, Shih-Ping; Tsai, Fuu-Jen; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2011-01-01

    For many years, cancer research has focused on the adult stem cells present in malignant tumors. It is believed that current cancer treatments sometimes fail because they do not target these cells. According to classic models of carcinogenesis, these events can occur in any cell. In contrast, the cancer stem cell (CSC) hypothesis states that the preferential targets of oncogenic transformation are tissue stem cells or early progenitor cells that have acquired the potential for self-renewal. These tumor-initiating cells, or CSCs, in turn, are characterized by their ability to undergo self-renewal, a process that drives tumorigenesis and differentiation, which contributes to the cellular heterogeneity of tumors. Herein, we discuss the definitions and properties of CSCs in the major human cancers.

  19. Endothelial cells activate the cancer stem cell-associated NANOGP8 pathway in colorectal cancer cells in a paracrine fashion.

    Science.gov (United States)

    Wang, Rui; Bhattacharya, Rajat; Ye, Xiangcang; Fan, Fan; Boulbes, Delphine R; Xia, Ling; Ellis, Lee M

    2017-08-01

    In colorectal cancer (CRC), cancer stem cells (CSCs) have been hypothesized to mediate cell survival and chemoresistance. Previous studies from our laboratory described a role for liver parenchymal endothelial cells (LPECs) in mediating the CSC phenotype in CRC cells in a paracrine/angiocrine fashion. The objectives of this study were to determine whether endothelial cells (ECs) from different organs can induce the CSC phenotype in CRC cells and to elucidate the signaling pathways involved. We treated a newly developed CRC cell line (HCP-1) and established CRC cell lines (HT29 and SW480) with conditioned medium (CM) from primary ECs isolated from nonmalignant liver, lung, colon mucosa, and kidney. Our results showed that CM from ECs from all organs increased the number of CSCs, as determined by sphere formation, and protein levels of NANOG and OCT4 in CRC cells. With the focus of further elucidating the role of the liver vascular network in mediating the CSC phenotype, we demonstrated that CM from LPECs increased resistance to 5-fluorouracil in CRC cells. Moreover, we showed that LPEC CM specifically induced NANOGP8 expression in CRC cells by specific enzyme digestion and a luciferase reporter assay using a vector containing the NANOGP8 promoter. Lastly, we found that LPEC CM-induced NANOGP8 expression and sphere formation were mediated by AKT activation. Our studies demonstrated a paracrine role for ECs in regulating the CSC phenotype and chemoresistance in CRC cells by AKT-mediated induction of NANOGP8. These studies suggest a more specific approach to target CSCs by blocking the expression of NANOGP8 in cancer cells. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  20. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  1. Cancer stem cells: constantly evolving and functionally heterogeneous therapeutic targets.

    Science.gov (United States)

    Yang, Tao; Rycaj, Kiera; Liu, Zhong-Min; Tang, Dean G

    2014-06-01

    Elucidating the origin of and dynamic interrelationship between intratumoral cell subpopulations has clear clinical significance in helping to understand the cellular basis of treatment response, therapeutic resistance, and tumor relapse. Cancer stem cells (CSC), together with clonal evolution driven by genetic alterations, generate cancer cell heterogeneity commonly observed in clinical samples. The 2013 Shanghai International Symposium on Cancer Stem Cells brought together leaders in the field to highlight the most recent progress in phenotyping, characterizing, and targeting CSCs and in elucidating the relationship between the cell-of-origin of cancer and CSCs. Discussions from the symposium emphasize the urgent need in developing novel therapeutics to target the constantly evolving CSCs. ©2014 American Association for Cancer Research.

  2. Stromal cells in tumor microenvironment and breast cancer.

    Science.gov (United States)

    Mao, Yan; Keller, Evan T; Garfield, David H; Shen, Kunwei; Wang, Jianhua

    2013-06-01

    Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion, and metastasis. In breast cancer, CAFs not only promote tumor progression but also induce therapeutic resistance. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistance. This review summarizes the current understandings of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. In addition, the effects of other stromal components such as endothelial cells, macrophages, and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment.

  3. Stroma Cells in Tumor Microenvironment and Breast Cancer

    Science.gov (United States)

    Mao, Yan; Keller, Evan T.; Garfield, David H.; Shen, Kunwei; Wang, Jianhua

    2015-01-01

    Cancer is a systemic disease, encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion and metastasis. In breast cancer, CAFs not only promote tumor progression, but also induce therapeutic resistances. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistances. This review summarizes the current understanding of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. The effects of other stromal components such as endothelial cells, macrophages and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to sort patients into a specific and confirmed subtype for personalized treatment. PMID:23114846

  4. Calorimetric signatures of human cancer cells and their nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Todinova, S. [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria); Stoyanova, E. [Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Tzarigradsko shose Blvd. 73, Sofia 1113 (Bulgaria); Krumova, S., E-mail: sakrumo@gmail.com [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria); Iliev, I. [Institute of Experimental Morphology, Pathology and Anthropology with Museum, Acad. G. Bonchev Str., Bl. 25, Sofia 1113 (Bulgaria); Taneva, S.G. [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, Sofia 1113 (Bulgaria)

    2016-01-10

    Graphical abstract: - Highlights: • Two temperature ranges are distinguished in the thermograms of cells/nuclei. • Different thermodynamic properties of cancer and normal human cells/nuclei. • Dramatic reduction of the enthalpy of the low-temperature range in cancer cells. • Oxaliplatin and 5-FU affect the nuclear matrix proteins and the DNA stability. - Abstract: The human cancer cell lines HeLa, JEG-3, Hep G2, SSC-9, PC-3, HT-29, MCF7 and their isolated nuclei were characterized by differential scanning calorimetry. The calorimetric profiles differed from normal human fibroblast (BJ) cells in the two well distinguished temperature ranges—the high-temperature range (H{sub T}, due to DNA-containing structures) and the low-temperature range (L{sub T}, assigned to the nuclear matrix and cellular proteins). The enthalpy of the L{sub T} range, and, respectively the ratio of the enthalpies of the L{sub T}- vs. H{sub T}-range, ΔH{sub L}/ΔH{sub H}, is strongly reduced for all cancer cells compared to normal fibroblasts. On the contrary, for most of the cancer nuclei this ratio is higher compared to normal nuclei. The HT-29 human colorectal cancer cells/nuclei differed most drastically from normal human fibroblast cells/nuclei. Our data also reveal that the treatment of HT-29 cancer cells with cytostatic drugs affects not only the DNA replication but also the cellular proteome.

  5. DNA Methylation and Apoptosis Resistance in Cancer Cells

    Science.gov (United States)

    Hervouet, Eric; Cheray, Mathilde; Vallette, François Marie; Cartron, Pierre-François

    2013-01-01

    Apoptosis is a cell death programme primordial to cellular homeostasis efficiency. This normal cell suicide program is the result of the activation of a cascade of events in response to death stimuli. Apoptosis occurs in normal cells to maintain a balance between cell proliferation and cell death. A deregulation of this balance due to modifications in the apoptosic pathway leads to different human diseases including cancers. Apoptosis resistance is one of the most important hallmarks of cancer and some new therapeutical strategies focus on inducing cell death in cancer cells. Nevertheless, cancer cells are resistant to treatment inducing cell death because of different mechanisms, such as DNA mutations in gene coding for pro-apoptotic proteins, increased expression of anti-apoptotic proteins and/or pro-survival signals, or pro-apoptic gene silencing mediated by DNA hypermethylation. In this context, aberrant DNA methylation patterns, hypermethylation and hypomethylation of gene coding for proteins implicated in apoptotic pathways are possible causes of cancer cell resistance. This review highlights the role of DNA methylation of apoptosis-related genes in cancer cell resistance. PMID:24709797

  6. LATTARA: the ancient and Medieval harbour of Lattes

    OpenAIRE

    Marriner, Nick

    2009-01-01

    The LATTARA series, named after the ancient town, publishes work on the archaeological site of Latte and its harbour environment. Subjects discussed range from past research to recent multidisciplinary excavations. Over three decades ago, Arnal et al. (1974) published «Le port de Lattara (Lattes, Hérault)» a work which summarised the discoveries made in and around Latte. The term «harbour» was taken in the largest sense of the word, that is to say a maritime city with strong links to the sea....

  7. EZH2 depletion blocks the proliferation of colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Bettina Fussbroich

    Full Text Available The Enhancer of Zeste 2 (EZH2 protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer.

  8. Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

    Directory of Open Access Journals (Sweden)

    Seyed Jalal Hosseinimehr

    2014-01-01

    Full Text Available Background. In this study, the radiosensitizing effect of resveratrol as a natural product was investigated on cell toxicity induced by 131I in thyroid cancer cell. Methods. Human thyroid cancer cell and human nonmalignant fibroblast cell (HFFF2 were treated with 131I and/or resveratrol at different concentrations for 48 h. The cell proliferation was measured by determination of the percent of the survival cells using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results. Findings of this study show that resveratrol enhanced the cell death induced by 131I on thyroid cancer cell. Also, resveratrol exhibited a protective effect on normal cells against 131I toxicity. Conclusion. This result indicates a promising effect of resveratrol on improvement of cellular toxicity during iodine therapy.

  9. Investigation of the selenium metabolism in cancer cell lines

    DEFF Research Database (Denmark)

    Lunøe, Kristoffer; Gabel-Jensen, Charlotte; Stürup, Stefan

    2011-01-01

    The aim of this work was to compare different selenium species for their ability to induce cell death in different cancer cell lines, while investigating the underlying chemistry by speciation analysis. A prostate cancer cell line (PC-3), a colon cancer cell line (HT-29) and a leukaemia cell line...... (Jurkat E6-1) were incubated with five selenium compounds representing inorganic as well as organic Se compounds in different oxidation states. Selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), methylseleninic acid (MeSeA), selenite and selenate in the concentration range 5-100 mu M were...... incubated with cells for 24 h and the induction of cell death was measured using flow cytometry. The amounts of total selenium in cell medium, cell lysate and the insoluble fractions was determined by ICP-MS. Speciation analysis of cellular fractions was performed by reversed phase, anion exchange and size...

  10. Risks of Esophageal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  11. Stages of Small Intestine Cancer

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  12. Treatment Options for Gallbladder Cancer

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  13. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  14. Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update

    Directory of Open Access Journals (Sweden)

    Arif Malik

    2016-01-01

    Full Text Available Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

  15. Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update.

    Science.gov (United States)

    Malik, Arif; Sultana, Misbah; Qazi, Aamer; Qazi, Mahmood Husain; Parveen, Gulshan; Waquar, Sulayman; Ashraf, Abdul Basit; Rasool, Mahmood

    2016-01-01

    Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

  16. P27 in cell cycle control and cancer

    DEFF Research Database (Denmark)

    Møller, Michael Boe

    2000-01-01

    In order to survive, cells need tight control of cell cycle progression. The control mechanisms are often lost in human cancer cells. The cell cycle is driven forward by cyclin-dependent kinases (CDKs). The CDK inhibitors (CKIs) are important regulators of the CDKs. As the name implies, CKIs were...

  17. Bergenin suppresses the growth of colorectal cancer cells by ...

    African Journals Online (AJOL)

    Purpose: To investigate anticancer effects of bergenin on human colorectal cancer cell lines. Methods: Human colorectal adenocarcinoma cell line HCT116 was treated with various concentrations of bergenin for 24 and 48 h. Cell viability, apoptosis, cell cycle arrest and reactive oxygen species (ROS) level were analyzed ...

  18. Cancer Stem Cells and stress induced evolution - understanding the ...

    Indian Academy of Sciences (India)

    Dr S Bapat

    2015-11-08

    Nov 8, 2015 ... Most therapies fail to consider differential drug sensitivities of various cells in a tumor. (Tumor Cell Heterogeneity). • Drug refractory behaviour of tumor cells may arise due to either –. - Intrinsic drug resistance mechanisms (Molecular Heterogeneity). - Cell dormancy / reversible quiescence (Cancer stem ...

  19. Cell Surface and Secreted Protein Profiles of Human Thyroid Cancer Cell Lines Reveal Distinct Glycoprotein Patterns

    Science.gov (United States)

    Arcinas, Arthur; Yen, Ten-Yang; Kebebew, Electron; Macher, Bruce A.

    2009-01-01

    Cell surface proteins have been shown to be effective therapeutic targets. In addition, shed forms of these proteins and secreted proteins can serve as biomarkers for diseases, including cancer. Thus, identification of cell surface and secreted proteins has been a prime area of interest in the proteomics field. Most cell surface and secreted proteins are known to be glycosylated and therefore, a proteomics strategy targeting these proteins was applied to obtain proteomic profiles from various thyroid cancer cell lines that represent the range of thyroid cancers of follicular cell origin. In this study, we oxidized the carbohydrates of secreted proteins and those on the cell surface with periodate and isolated them via covalent coupling to hydrazide resin. The glycoproteins obtained were identified from tryptic peptides and N-linked glycopeptides released from the hydrazide resin using 2-dimensional liquid chromatography-tandem mass spectrometry in combination with the gas phase fractionation. Thyroid cancer cell lines derived from papillary thyroid cancer (TPC-1), follicular thyroid cancer (FTC-133), Hürthle cell carcinoma (XTC-1), and anaplastic thyroid cancer (ARO and DRO-1) were evaluated. An average of 150 glycoproteins were identified per cell line, of which more than 57 percent are known cell surface or secreted glycoproteins. The usefulness of the approach for identifying thyroid cancer associated biomarkers was validated by the identification of glycoproteins (e.g. CD44, galectin 3 and metalloproteinase inhibitor 1) that have been found to be useful markers for thyroid cancer. In addition to glycoproteins that are commonly expressed by all of the cell lines, we identified others that are only expressed in the more well-differentiated thyroid cancer cell lines (follicular, Hürthle cell and papillary), or by cell lines derived from undifferentiated tumors that are uniformly fatal forms of thyroid cancer (i.e. anaplastic). Based on the results obtained, a

  20. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xiaolan, E-mail: huxiaolan1998@yahoo.com.cn [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Zhang, Xianqi [The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou (China); Qiu, Shuifeng [Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou (China); Yu, Daihua; Lin, Shuxin [Fourth Military Medical University, Xi' an (China)

    2010-07-16

    Research highlights: {yields} Salidroside inhibits the growth of human breast cancer cells. {yields} Salidroside induces cell-cycle arrest of human breast cancer cells. {yields} Salidroside induces apoptosis of human breast cancer cell lines. -- Abstract: Recently, salidroside (p-hydroxyphenethyl-{beta}-D-glucoside) has been identified as one of the most potent compounds isolated from plants of the Rhodiola genus used widely in traditional Chinese medicine, but pharmacokinetic data on the compound are unavailable. We were the first to report the cytotoxic effects of salidroside on cancer cell lines derived from different tissues, and we found that human breast cancer MDA-MB-231 cells (estrogen receptor negative) were sensitive to the inhibitory action of low-concentration salidroside. To further investigate the cytotoxic effects of salidroside on breast cancer cells and reveal possible ER-related differences in response to salidroside, we used MDA-MB-231 cells and MCF-7 cells (estrogen receptor-positive) as models to study possible molecular mechanisms; we evaluated the effects of salidroside on cell growth characteristics, such as proliferation, cell cycle duration, and apoptosis, and on the expression of apoptosis-related molecules. Our results demonstrated for the first time that salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells and may be a promising candidate for breast cancer treatment.

  1. Amygdalin-mediated inhibition of non-small cell lung cancer cell invasion in vitro

    OpenAIRE

    Qian, Liyu; Xie, Bo; Wang, Yaguo; Qian, Jun

    2015-01-01

    Lung cancer is a common malignant tumor claiming the highest fatality worldwide for a long period of time. Unfortunately, most of the current treatment methods are still based on the characteristics of cancer cells in the primary lesion and the prognosis is often much poorer in patients with metastatic cancers. Amygdalin, a natural product of glycosides and lots of evidence shows that amygdalin can inhibit the proliferation of some kinds of cancer cells. In this study, we first obtained the h...

  2. Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer cells

    OpenAIRE

    Tang, Yuzhe; Chen, Ruibao; Huang, Yan; Li, Guodong; Huang, Yiling; Chen, Jiepeng; Duan, Lili; Zhu, Bao-Ting; Thrasher,J. Brantley; Zhang, Xu; Li, Benyi

    2014-01-01

    Prostate cancers at the late stage of castration resistance are not responding well to most of current therapies available in clinic, reflecting a desperate need of novel treatment for this life-threatening disease. In this study, we evaluated the anti-cancer effect of a recently isolated natural compound Alternol in multiple prostate cancer cell lines with the properties of advanced prostate cancers in comparison to prostate-derived non-malignant cells. As assessed by trypan blue exclusion a...

  3. MET and Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gelsomino, Francesco, E-mail: francesco.gelsomino@istitutotumori.mi.it [Medical Oncology Unit 1, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano (Italy); Rossi, Giulio [Operative Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Via del Pozzo 71, 41124 Modena (Italy); Tiseo, Marcello [Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Viale A. Gramsci 14, 43126 Parma (Italy)

    2014-10-13

    Small-cell lung cancer (SCLC) is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  4. MET and Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Francesco Gelsomino

    2014-10-01

    Full Text Available Small-cell lung cancer (SCLC is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

  5. Differential roles of leptin in regulating cell migration in thyroid cancer cells.

    Science.gov (United States)

    Cheng, Shih-Ping; Yin, Pen-Hui; Chang, Yuan-Ching; Lee, Chen-Hsen; Huang, Shih-Yuan; Chi, Chin-Wen

    2010-06-01

    Excess body weight is associated with a moderately increased risk of thyroid cancer. Adipocyte-derived hormone, leptin, has been shown to enhance cell growth and migration in many cancer types. Limited evidence suggests that leptin has direct actions on the thyroid gland, but there are no data available on the effect of leptin on thyroid cancer cells. We evaluated the action of leptin on gene expression, cell growth, cell cycle, and cell migration in anaplastic (ARO), follicular (WRO) and papillary (CGTH-W3) thyroid carcinoma cell lines. Expression of long-form leptin receptors was observed in all thyroid cancer cell lines. Leptin stimulation did not alter the expression levels of leptin, leptin receptor and sodium-iodide symporter. Cell growth and cell cycle were not changed after leptin treatment. However, leptin was able to promote cell migration of papillary thyroid cancer cells, but inhibited migration of anaplastic and follicular cancer cells. In summary, our study suggests that leptin modulates cell migration of thyroid cancer cells in a cell type-specific manner.

  6. Current advances in T-cell-based cancer immunotherapy

    Science.gov (United States)

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

    2015-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

  7. Characteristics of liver cancer stem cells and clinical correlations.

    Science.gov (United States)

    Cheng, Zhuo; Li, Xiaofeng; Ding, Jin

    2016-09-01

    Liver cancer is an aggressive malignant disease with a poor prognosis. Patients with liver cancer are usually diagnosed at an advanced stage and thus miss the opportunity for surgical resection. Chemotherapy and radiofrequency ablation, which target tumor bulk, have exhibited limited therapeutic efficacy to date. Liver cancer stem cells (CSCs) are a small subset of undifferentiated cells existed in liver cancer, which are considered to be responsible for liver cancer initiation, metastasis, relapse and chemoresistance. Elucidating liver CSC characteristics and disclosing their regulatory mechanism might not only deepen our understanding of the pathogenesis of liver cancer but also facilitate the development of diagnostic, prognostic and therapeutic approaches to improve the clinical management of liver cancer. In this review, we will summarize the recent advances in liver CSC research in terms of the origin, identification, regulation and clinical correlation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. The role of proteasome inhibition in nonsmall cell lung cancer.

    Science.gov (United States)

    Escobar, Mauricio; Velez, Michel; Belalcazar, Astrid; Santos, Edgardo S; Raez, Luis E

    2011-01-01

    Lung cancer therapy with current available chemotherapeutic agents is mainly palliative. For these and other reasons there is now a great interest to find targeted therapies that can be effective not only palliating lung cancer or decreasing treatment-related toxicity, but also giving hope to cure these patients. It is already well known that the ubiquitin-proteasome system like other cellular pathways is critical for the proliferation and survival of cancer cells; thus, proteosome inhibition has become a very attractive anticancer therapy. There are several phase I and phase II clinical trials now in non-small cell lung cancer and small cell lung cancer using this potential target. Most of the trials use bortezomib in combination with chemotherapeutic agents. This paper tends to make a state-of-the-art review based on the available literature regarding the use of bortezomib as a single agent or in combination with chemotherapy in patients with lung cancer.

  9. The Role of Proteasome Inhibition in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Mauricio Escobar

    2011-01-01

    Full Text Available Lung cancer therapy with current available chemotherapeutic agents is mainly palliative. For these and other reasons there is now a great interest to find targeted therapies that can be effective not only palliating lung cancer or decreasing treatment-related toxicity, but also giving hope to cure these patients. It is already well known that the ubiquitin-proteasome system like other cellular pathways is critical for the proliferation and survival of cancer cells; thus, proteosome inhibition has become a very attractive anticancer therapy. There are several phase I and phase II clinical trials now in non-small cell lung cancer and small cell lung cancer using this potential target. Most of the trials use bortezomib in combination with chemotherapeutic agents. This paper tends to make a state-of-the-art review based on the available literature regarding the use of bortezomib as a single agent or in combination with chemotherapy in patients with lung cancer.

  10. Nanomedicine-mediated cancer stem cell therapy.

    Science.gov (United States)

    Shen, Song; Xia, Jin-Xing; Wang, Jun

    2016-01-01

    Circumstantial evidence suggests that most tumours are heterogeneous and contain a small population of cancer stem cells (CSCs) that exhibit distinctive self-renewal, proliferation and differentiation capabilities, which are believed to play a crucial role in tumour progression, drug resistance, recurrence and metastasis in multiple malignancies. Given that the existence of CSCs is a primary obstacle to cancer therapy, a tremendous amount of effort has been put into the development of anti-CSC strategies, and several potential approaches to kill therapeutically-resistant CSCs have been explored, including inhibiting ATP-binding cassette transporters, blocking essential signalling pathways involved in self-renewal and survival of CSCs, targeting CSCs surface markers and destroying the tumour microenvironment. Meanwhile, an increasing number of therapeutic agents (e.g. small molecule drugs, nucleic acids and antibodies) to selectively target CSCs have been screened or proposed in recent years. Drug delivery technology-based approaches hold great potential for tackling the limitations impeding clinical applications of CSC-specific agents, such as poor water solubility, short circulation time and inconsistent stability. Properly designed nanocarrier-based therapeutic agents (or nanomedicines) offer new possibilities of penetrating CSC niches and significantly increasing therapeutic drug accumulation in CSCs, which are difficult for free drug counterparts. In addition, intelligent nanomedicine holds great promise to overcome pump-mediated multidrug resistance which is driven by ATP and to decrease detrimental effects on normal somatic stem cells. In this review, we summarise the distinctive biological processes related to CSCs to highlight strategies against inherently drug-resistant CSCs. We then focus on some representative examples that give a glimpse into state-of-the-art nanomedicine approaches developed for CSCs elimination. A perspective on innovative therapeutic

  11. A basal stem cell signature identifies aggressive prostate cancer phenotypes

    Science.gov (United States)

    Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

    2015-01-01

    Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

  12. Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

    Directory of Open Access Journals (Sweden)

    Hiroshi Katoh

    2015-01-01

    Full Text Available Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs. Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

  13. Valproic acid enhances bosutinib cytotoxicity in colon cancer cells.

    Science.gov (United States)

    Mologni, Luca; Cleris, Loredana; Magistroni, Vera; Piazza, Rocco; Boschelli, Frank; Formelli, Franca; Gambacorti-Passerini, Carlo

    2009-04-15

    Unbalanced histone deacetylase (HDAC) hyperactivity is a common feature of tumor cells. Inhibition of HDAC activity is often associated with cancer cell growth impairment and death. Valproic acid (VPA) is a HDAC inhibitor used for the treatment of epilepsy. It has recently been recognized as a promising anticancer drug. We investigated the effects of VPA on growth and survival of colon cancer cells. VPA caused growth inhibition and programmed cell death that correlated with histone hyperacetylation. VPA modulated the expression of various factors involved in cell cycle control and apoptosis and induced caspase activation. Interestingly, VPA induced downregulation of c-Src and potentiated the cytotoxic effects of the c-Src inhibitor bosutinib, both in vitro and in vivo. The combination of sublethal doses of VPA and bosutinib led to massive apoptosis of colon cancer cells, irrespective of their genetic background. These results suggest that VPA may be employed as a positive modulator of bosutinib antitumor activity in colorectal cancer.

  14. Rhein Induces Apoptosis in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ching-Yao Chang

    2012-01-01

    Full Text Available Human breast cancers cells overexpressing HER2/neu are more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2 and control vector MCF-7 (MCF-7/VEC cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

  15. Oncotripsy: Targeting cancer cells selectively via resonant harmonic excitation

    CERN Document Server

    Heyden, Stefanie

    2015-01-01

    We investigate a method of selectively targeting cancer cells by means of ultrasound harmonic excitation at their resonance frequency, which we refer to as oncotripsy. The geometric model of the cells takes into account the cytoplasm, nucleus and nucleolus, as well as the plasma membrane and nuclear envelope. Material properties are varied within a pathophysiologically-relevant range. A first modal analysis reveals the existence of a spectral gap between the natural frequencies and, most importantly, resonant growth rates of healthy and cancerous cells. The results of the modal analysis are verified by simulating the fully-nonlinear transient response of healthy and cancerous cells at resonance. The fully nonlinear analysis confirms that cancerous cells can be selectively taken to lysis by the application of carefully tuned ultrasound harmonic excitation while simultaneously leaving healthy cells intact.

  16. Adoptive T cell therapy: Addressing challenges in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Yee Cassian

    2005-04-01

    Full Text Available Abstract Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.

  17. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer.

    Science.gov (United States)

    Martínez-Montemayor, Michelle M; Acevedo, Raysa Rosario; Otero-Franqui, Elisa; Cubano, Luis A; Dharmawardhane, Suranganie F

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells (SUM-149). Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E-cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase activity. These findings suggest that Reishi is an effective anti-IBC therapeutic.

  18. Duramycin-induced calcium release in cancer cells.

    Science.gov (United States)

    Broughton, Laura J; Crow, Chris; Maraveyas, Anthony; Madden, Leigh A

    2016-03-01

    Duramycin, through binding with phosphatidylethanolamine (PE), has shown potential to be an effective antitumour agent. However, its mode of action in relation to tumour cells is not fully understood. PE expression on the surface of a panel of cancer cell lines was analysed using duramycin and subsequent antibody labelling, and then analysed by flow cytometry. Cell viability was also assessed by flow cytometry using annexin V and propidium iodide. Calcium ion (Ca) release by tumour cells in response to duramycin was determined by spectrofluorometry following incubation with Fluo-3, AM. Confocal microscopy was performed on the cancer cell line AsPC-1 to assess real-time cell response to duramycin treatment. Duramycin could detect cell surface PE expression on all 15 cancer cell lines screened, which was shown to be duramycin concentration dependent. However, higher concentrations induced necrotic cell death. Duramycin induced calcium ion (Ca) release from the cancer cell lines also in a concentration-dependent and time-dependent manner. Confocal microscopy showed an influx of propidium iodide into the cells over time and induced morphological changes. Duramycin induces Ca release from cancer cell lines in a time-dependent and concentration-dependent manner.

  19. Elasticity measurement of breast cancer cells by atomic force microscopy

    Science.gov (United States)

    Xu, Chaoxian; Wang, Yuhua; Jiang, Ningcheng; Yang, Hongqin; Lin, Juqiang; Xie, Shusen

    2014-09-01

    Mechanical properties of living cells play an important role in understanding various cells' function and state. Therefore cell biomechanics is expected to become a useful tool for cancer diagnosis. In this study, atomic force microscopy (AFM) using a square pyramid probe was performed to investigate cancerous (MCF-7) and benign (MCF-10A) human breast epithelial cells. The new QITM mode was used to acquire high-resolution topographic images and elasticity of living cells. Furthermore, individual force curves were recorded at maximum loads of 0.2, 0.5 and 1 nN, and the dependence of cell's elasticity with loading force was discussed. It was showed that the cancerous cells exhibited smaller elasticity modulus in comparison to non-cancerous counterparts. The elasticity modulus increased as the loading force increased from 0.2 nN to 1 nN. This observation indicates that loading force affects the cell's apparent elasticity and it is important to choose the appropriate force applied to cells in order to distinguish normal and cancer cells. The results reveal that the mechanical properties of living cells measured by atomic force microscopy may be a useful indicator of cell type and disease.

  20. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kikuta, Kazuhiro [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Egawa, Shinichi; Unno, Michiaki [Department of Hepatobiliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2010-12-17

    Research highlights: {yields} Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. {yields} Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. {yields} PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. {yields} This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated {beta}-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered

  1. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    OpenAIRE

    Ewelina Szliszka; Zenon P. Czuba; Bogdan Mazur; Lukasz Sedek; Andrzej Paradysz; Wojciech Krol

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showe...

  2. Random matrix analysis for gene interaction networks in cancer cells

    CERN Document Server

    Kikkawa, Ayumi

    2016-01-01

    Motivation: The investigation of topological modifications of the gene interaction networks in cancer cells is essential for understanding the desease. We study gene interaction networks in various human cancer cells with the random matrix theory. This study is based on the Cancer Network Galaxy (TCNG) database which is the repository of huge gene interactions inferred by Bayesian network algorithms from 256 microarray experimental data downloaded from NCBI GEO. The original GEO data are provided by the high-throughput microarray expression experiments on various human cancer cells. We apply the random matrix theory to the computationally inferred gene interaction networks in TCNG in order to detect the universality in the topology of the gene interaction networks in cancer cells. Results: We found the universal behavior in almost one half of the 256 gene interaction networks in TCNG. The distribution of nearest neighbor level spacing of the gene interaction matrix becomes the Wigner distribution when the net...

  3. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

    2012-01-01

    Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...

  4. E. coli as a biological model for cancer cells

    Science.gov (United States)

    Liao, David; Lambert, Guillaume; Austin, Robert

    2010-03-01

    Uninhibited growth and invasion of healthy tissue characterize cancer. We co-cultured two strains of E. coli bacteria in a microfabricated environment to model cancer. During starvation, growth-advantage-in-stationary-phase, or GASP, cells grew to a higher population than wild-type cells. GASP cells also displaced wild-type cells from nutrient-rich chambers. When we repeated the experiment with medium depleted by wild-type cells, the peak GASP population density increased 54%, and the ``invasion,'' or displacement of wild-type cells from nutrient-rich chambers, occurred 5 hours earlier. We mathematically modeled both this increase in GASP population and this acceleration of spatial invasion by assuming that GASP cells consume detritus secreted by wild-type cells. Our experimental and model results corroborate recent caution against using tumor starvation as a cancer therapy.

  5. RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

    Science.gov (United States)

    Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

    2017-10-15

    Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRasG12D in mouse lung epithelial cells markedly impairs the progression of KRasG12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRasG12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

  6. Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou

    2013-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4 and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with WNT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT. Emerging evidence has demonstrated that cancer stem cells (CSCs, small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5 of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric and ampullary carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs and EMT-type cells in PDAC.

  7. MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Debin Ma

    2015-09-01

    Full Text Available MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy.

  8. Collective cell migration: Implications for wound healing and cancer invasion

    Directory of Open Access Journals (Sweden)

    Li Li

    2013-07-01

    Full Text Available During embryonic morphogenesis, wound repair and cancer invasion, cells often migrate collectively via tight cell-cell junctions, a process named collective migration. During such migration, cells move as coherent groups, large cell sheets, strands or tubes rather than individually. One unexpected finding regarding collective cell migration is that being a "multicellular structure" enables cells to better respond to chemical and physical cues, when compared with isolated cells. This is important because epithelial cells heal wounds via the migration of large sheets of cells with tight intercellular connections. Recent studies have gained some mechanistic insights that will benefit the clinical understanding of wound healing in general. In this review, we will briefly introduce the role of collective cell migration in wound healing, regeneration and cancer invasion and discuss its underlying mechanisms as well as implications for wound healing.

  9. Targeting cancer stem cells: emerging role of Nanog transcription factor

    Directory of Open Access Journals (Sweden)

    Wang ML

    2013-09-01

    Full Text Available Mong-Lien Wang,1 Shih-Hwa Chiou,2,3 Cheng-Wen Wu1,4–61Institute of Biochemistry and Molecular Biology, 2Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan; 3Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Microbiology and Immunology, 5Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; 6Institute of Biomedical Science, Academia Sinica, Taipei, TaiwanAbstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the

  10. Isolation and characterization of spheroid cells from the HT29 colon cancer cell line.

    Science.gov (United States)

    Fan, Xinlan; Ouyang, Nengyong; Teng, Hong; Yao, Herui

    2011-10-01

    Colorectal cancer stem cells (Cr-CSCs) are involved in the growth of colon cancer, but their specific role in tumor biology, including metastasis, is still unclear. Currently, methods for sorting Cr-CSCs are based on the expression of surface markers (e.g., CD133(+), CD44(+), and aldehyde dehydrogenase 1 (ALDH1(+))); however, the specificity of these markers for Cr-CSCs is uncertain. This study aimed to develop more effective ways of isolating and purifying Cr-CSCs. Suspension culture was used for isolation of Cr-CSCs. And spheroid cells were performed by side population technology, and the putative molecular marker analysis of colorectal cancer stem cell. Migration assay and chemoresistance experiment were conducted between the adherent cells and spheroid cells. HT29 colon cancer cells grew well in suspension culture. The percentage of CD44(+) cancer cell of spheroid cells was 68 times higher than that of adherent cells (89.5% vs. 1.3%), but there was no obvious difference in the percentage of CD133(+) cells (6.25% vs. 5.6%). Moreover, it is worth noting that the percent of CD133 (+)/CD44(+) cells remarkably rose (from 0.6% to 5.4%). The expression of ALDH1 was markedly increased (7.5% vs. 20.5%) for the spheroid cells than the adherent cells. The side population within the spheroid population dramatically increased from 0.2% to 6.3%. The resistance of spheroid cells to 5-FU was higher than that of adherent cells, as was their ability to migrate in the presence of SDF-1α. Suspension culture is an effective approach for enriching Cr-CSCs and can provide an inexhaustible supply of genetically stable colon cancer stem cells for targeted Cr-CSC studies. Spheroid cell models also enable the study of colon cancer chemoresistance and metastasis and may help to elucidate the role of cancer stem cells in colon cancer.

  11. Stem Cell Based Gene Therapy in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jae Heon Kim

    2014-01-01

    Full Text Available Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations.

  12. Single Cell “Glucose Nanosensor” Verifies Elevated Glucose Levels in Individual Cancer Cells

    OpenAIRE

    Nascimento, Raphael A. S.; Özel, Rıfat Emrah; Mak, Wai Han; Mulato, Marcelo; Singaram, Bakthan; Pourmand, Nader

    2016-01-01

    Because the transition from oxidative phosphorylation to anaerobic glycolytic metabolism is a hallmark of cancer progression, approaches to identify single living cancer cells by their unique glucose metabolic signature would be useful. Here, we present nanopipettes specifically developed to measure glucose levels in single cells with temporal and spatial resolution, and we use this technology to verify the hypothesis that individual cancer cells can indeed display higher intracellular glucos...

  13. New high-speed cell sorting methods for stem cell sorting and breast cancer cell purging

    Science.gov (United States)

    Leary, James F.; McLaughlin, Scott R.; Hokanson, James A.; Rosenblatt, Judah I.

    1998-04-01

    An important problem in clinical medicine is that of positively selecting hematopoietic stem cells or mobilized peripheral blood stem cells for autologous bone marrow transplantation while purging it of contaminating tumor cells. Since both the stem cells to be positively selected and the tumor cells to be purged are relatively rare cells, this poses special problems for their isolation in terms of purity and yield of stem cells, with a high penalty of misclassification for contaminating tumor cells. A model system of tumor cells spiked into bone marrow or blood cells was used to validate the system. Multiparameter data mixtures of human MCF-7 breast cancer cells and human peripheral blood or bone marrow cells were first analyzed by discriminant function analysis. Mathematical methods were developed to assess the relative probabilities of misclassification. Cell identification tags, implemented as additional correlated listmode parameters not used for these analyses, were used to uniquely identify each cell type and to compare classifier results. The performance of classifier systems was also assessed using ROC (`receiver operating characteristics') analysis. Then the classification system was implemented using lookup tables allowing for real-time (in this system approximately 625 microseconds) rapid separation of these cell types. Isolated cell types, purities and yields were assessed by single-cell PCR molecular characterizations.

  14. Water quality effects of harbour activities assessed with integrated ...

    African Journals Online (AJOL)

    moes2

    such as the intensity of the crafts traffic, the nature of the transported materials, as well as those materials used ... set of bio-chemical parameters were studied in Cochin harbour region so as to find out their reliability and ..... water, washing water, lubricant oil and other residues in machinery space comes under this category.

  15. Shoreline stability in the vicinity of Cochin Harbour

    Digital Repository Service at National Institute of Oceanography (India)

    PrasannaKumar, S.; Vethamony, P.

    A small stretch of barrier beach on either side of Cochin harbour along the west coast of India has been investigated for its stability through systematic surveys. The observed erosion of the beaches during the southwest monsoon is due to an order...

  16. Water quality effects of harbour activities assessed with integrated ...

    African Journals Online (AJOL)

    Ecological tools were developed to study the water quality in Cochin harbour, a complex aquatic ecosystems, through the integration of microbiological monitoring (faecal coliforms and Pseudomonas species) and heavy metal contamination (lead, cadmium and mercury). One way ANOVA indicates statistically significant ...

  17. Plastic ingestion by harbour seal (Phoca vitulina) in the Netherlands

    NARCIS (Netherlands)

    Bravo Rebolledo, E.; Franeker, van J.A.; Jansen, O.E.; Brasseur, S.M.J.M.

    2013-01-01

    Abundance of ingested debris by seals has been mentioned as a potential indicator of marine litter in the European Marine Strategy Framework Directive (MSFD). A sample of 107 stomachs, 100 intestines and 125 scats of harbour seals from the Netherlands was analysed for the presence of plastics.

  18. Aspects of Water Quality of Freshwater Systems Harbouring Snail ...

    African Journals Online (AJOL)

    A study of some aspects of water quality of freshwater systems harbouring snail vectors of schistosome parasites was conducted in Jos, Nigeria. Calcium ion concentration of the water bodies was a mean value of 31 mg.l-1. The range of temperature was 15 - 30OC. The occurrence of Biomphalaria pferifferi was attributed to ...

  19. Status of harbour seals (Phoca vitulina in Atlantic Canada

    Directory of Open Access Journals (Sweden)

    Mike O Hammill

    2010-09-01

    Full Text Available Harbour seals are associated with small islets, reefs and rocks exposed at low tide and estuarine habitats throughout eastern Canada. Evidence of harvesting by indigenous people has been found in pre-European contact archaeological excavations. A bounty harvest as well as subsistence and commercial hunting probably lead to a decline in the population from 1949 to the early 1970s. The bounty was removed in 1976, and harbour seals, in the southern parts of their range have been protected since then. There is little information available on total abundance and current population trend. Mitochondrial and microsatellite DNA research has shown separation between Northeast and Northwest Atlantic harbour seals. Within Canada, the subspecies Phoca vitulina concolor shows some population sub-structure with three distinct units that could be separated into Hudson Bay, Gulf of St. Lawrence and Sable Island. Urban development resulting in habitat degradation is probably the most important factor affecting harbour seal populations in AtlanticCanada, although other factors such as incidental catches in commercial fisheries and competition with grey seals may also be important.

  20. Predicting recurrent PDV epizootics in European harbour seals (Phoca vitulina

    Directory of Open Access Journals (Sweden)

    Tero Härkönen

    2010-09-01

    Full Text Available Phocine Distemper Virus (PDV caused mass mortality in European harbour seals (Phoca vitulina in 1988 and in 2002. Both epizootics likely originated from refugia in Arctic seals, where data indicate PDV hops among populations and species. The metapopulation structure of host populations is suggested to be the reason why PDV is preserved among Arctic seals, since the high rate of spread of PDV would require much larger panmictic populations to maintain an infection. The pattern of sudden outbreaks of PDVis also seen in grey seals (Halichoerus grypus, the only to date identified species that could act as a vector between Arctic and North Sea seal populations. Harbour seal populations along mainland Europe were below critical herd immunity levels by 3-5 years after the events, and thus vulnerable for new outbreaks, but historical data and the 14 years between the 2 epizootics suggest that harbour seals in the North Sea area are only rarely exposed to the infective agent. The risk for new outbreaks of the seal plague in North Sea harbour seals is likely linked to the dynamics of the disease in Arctic seal species as well asvector species.

  1. Epizootics in harbour seals (Phoca vitulina: clinical aspects

    Directory of Open Access Journals (Sweden)

    Ursula Siebert

    2010-09-01

    Full Text Available Epizootic diseases causing considerable mortality in harbour seal populations have mainly been reported from the waters of the United States and Europe. Such die-offs were largely attributable to viral infections. Several hundred individuals died from respiratory infections caused by Influenza A viruses at the coast of New England, USA, in 1979, 1980 and 1982. More than 53,000 harbour seals were killed in European waters by Phocine Distemper Virus (PDV, a morbillivirus,in two outbreaks in 1988 and 2002. For several other epizootics of smaller scale in the waters of the Atlantic and Pacific coast of the USA and, most recently, in Danish and Swedish waters in 2007 the causes remain unclear, although characteristic respiratory symptoms and interstitial pneumonia suspicious of viral etiology were detected as well as occasionally bacterial infections caused by Erysipelothrix rhusiopathiae and Pseudomonas aeruginosa. Mass mortalities caused by biotoxins, direct human interactions or changes in oceanographic conditions have so far not been described for harbour seals. However, high organochlorine loads detected in European harbour seal populations and suspected to impede immune functions, were considered an aggravating factor in the 1988 morbillivirus epizootic. Establishing supranational stranding networks is a key prerequisite for the detection of future unusual die-offs in marine mammals. Detailed post-mortem investigations of all organ systems are essential for targeted etiological studies towards the causes of mass mortalities in seals.

  2. The status of the harbour seal (Phoca vitulina in Ireland

    Directory of Open Access Journals (Sweden)

    Michelle A Cronin

    2010-09-01

    Full Text Available The status of Ireland’s harbour seal population and its relationship with that of Britain and Western Europe are poorly understood. Prior to 2003, limited research efforts and poor co-ordination of survey methods fell short at providing an accurate assessment of overall distribution and population size on a regional or national scale. However, in August 2003, the Republic of Ireland’s harbour seal population was assessed by means of a geographically extensive survey conducted during the annual moult, providing an up-to-date minimum population estimate and a reliable baseline for future surveys. Trends on a national scale could not be assessed due to absence of a reliable historic population estimate; however there is some evidence of local decreases and increases in harbour seal numbers in Northern Ireland and southwest Ireland respectively. Research effort to date on aspects of the ecology of the harbour seal in the Republic of Ireland is reviewed and current research and management priorities highlighted.

  3. Declines of seagrasses in a tropical harbour, North Queensland ...

    Indian Academy of Sciences (India)

    A recent paper inferred that all seagrass in Cairns Harbour, tropical north-eastern Australia, had undergone 'complete and catastrophic loss' as a result of tropical cyclone Yasi in 2011. While we agree with the concern expressed, we would like to correct the suggestion that the declines were the result of a single climatic ...

  4. Pollution studies on harbours and jetties in Nigeria

    African Journals Online (AJOL)

    user

    2011-03-14

    Mar 14, 2011 ... of the bacteria which is of public health importance in the harbours/jetties, indicates pollution. ... people live along side serious pollution sources and not ..... beach-clean and survey report. Marine Conservation. Society, Rosson-Wye. Mombershora C, Ajauyi SO, Osibainjo O (1981). Pollution studies on.

  5. of Sediment Deposition into the Dar es Salaam Harbour

    African Journals Online (AJOL)

    Sediment traps, a wave-gauge and a current-meter were deployed in the entrance channel during .... rivers namely Yombo, Mbagala and Mzinga drain into the ..... Harbour Transportation, Fishing Ports, Sediment. Transport, Geomorphology, Inlets, and Dredging. Gulf Publishing Company, Book Division,. Houston, Texas.

  6. Seabed surveys of Mormugao Harbour, Central west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Wagle, B.G.; Gujar, A.R.; Subrahmanyam, V.; Mislankar, P.G.

    with natural and man-made features. The depth in the area ranged from 2-16 m and in the navigational channel from 7-15 m. The seabed in the inner harbour and towards the offshore end was marked by even topography, whereas in the northern and northwestern part...

  7. Status of the harbour seal (Phoca vitulina in Southern Scandinavia

    Directory of Open Access Journals (Sweden)

    Morten Tange Olsen

    2013-09-01

    Full Text Available The harbour seal population in Southern Scandinavia has experienced repeated declines caused by hunting and epizootics. These events have shaped the current distribution and abundance of the population. This paper assesses the current status of the population. We estimate trends in abundance of harbour seals from long term survey data, compare these with historic trends inferred from previously published material, and discuss past and potential threats to the harbour seal population of Southern Scandinavia. It is evident that harbour seals have disappeared from haulout areas along the Danish shores of Kattegat and in the westernmost part of the Baltic Sea, where they were previously numerous. In the 1920-30s, when abundance was at its lowest, the population is estimated to have been only a fraction of its original size. Following 30 years of protection the population is currently approaching historic abundance and might have reached the carrying capacity in some areas. Further development depends largely on effects of future epizootics, anthropogenic disturbance, and availability of suitable haulout sites.

  8. Phytoplankton dynamic responses to oil spill in Mumbai Harbour

    Digital Repository Service at National Institute of Oceanography (India)

    JiyalalRam, M.J.; Ram, A; Rokade, M.A; Karangutkar, S.H.; Yengal, B.; Dalvi, S.; Acharya, D.; Sharma, S.; Gajbhiye, S.N.

    The oil spill caused by collision of MSC-Chitra with MV-Khalijia on August 7, 2010 in Mumbai Harbour and surrounding area contaminated the shore and resulted in augmented level of PHc (6692.4-16902.2 mew g/l), though it was seen in low concentration...

  9. Numerical simulation of ship motion in offshore and harbour areas

    DEFF Research Database (Denmark)

    Christensen, Erik Damgaard; Jensen, Bjarne; Mortensen, Simon Brandi

    2008-01-01

    A method for simulating the motions and mooring forces of a moored ship subject to wave forcing has been further developed and validated for both the open water case and inside harbour areas. The method was originally developed and reported in Bingham (2000). The simulation tool is named WAMSIM...

  10. Reprogramming to developmental plasticity in cancer stem cells.

    Science.gov (United States)

    O'Brien-Ball, Caitlin; Biddle, Adrian

    2017-10-15

    During development and throughout adult life, sub-populations of cells exist that exhibit phenotypic plasticity - the ability to differentiate into multiple lineages. This behaviour is important in embryogenesis, is exhibited in a more limited context by adult stem cells, and can be re-activated in cancer cells to drive important processes underlying tumour progression. A well-studied mechanism of phenotypic plasticity is the epithelial-to-mesenchymal transition (EMT), a process which has been observed in both normal and cancerous cells. The epigenetic and metabolic modifications necessary to facilitate phenotypic plasticity are first seen in development and can be re-activated both in normal regeneration and in cancer. In cancer, the re-activation of these mechanisms enables tumour cells to acquire a cancer stem cell (CSC) phenotype with enhanced ability to survive in hostile environments, resist therapeutic interventions, and undergo metastasis. However, recent research has suggested that plasticity may also expose weaknesses in cancer cells that could be exploited for future therapeutic development. More research is needed to identify developmental mechanisms that are active in cancer, so that these may be targeted to reduce tumour growth and metastasis and overcome therapeutic resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. GOLPH2 expression in renal cell cancer

    Directory of Open Access Journals (Sweden)

    Jung Klaus

    2008-11-01

    Full Text Available Abstract Background Renal cell carcinomas (RCC are among the most common and most lethal genitourinary malignancies. GOLPH2 (golgi phosphoprotein 2, GOLM1 has recently been proposed as a biomarker for hepatocellular and prostate cancer. In this study we analysed the expression patterns and the prognostic and diagnostic value of GOLPH2 in RCC. Methods GOLPH2 protein expression was analysed by immunohistochemistry in 104 clinically well characterized RCC cases in comparison with matched normal kidney tissue and in association with clinico-pathological parameters. Statistical analyses including Kaplan Meier analyses were performed with SPSS version 15.0. Results GOLPH2 was highly expressed in normal renal tubules and in almost half of RCC with a statistically significant predominance in the papillary and chromophobe histological subtypes. No other associations with clinico-pathological parameters were detectable. The Kaplan-Meier curves showed a weak trend for unfavourable prognosis of tumours with high GOLPH2 expression, but failed significance. Conclusion GOLPH2 protein is expressed in normal renal tissue (especially in distal tubular epithelia and is down-regulated in the majority of clear cell RCC. In papillary and chromophobe RCC GOLPH2 expression is consistently present. In contrast to its diagnostic value in hepatocellular and prostatic carcinomas, a prognostic or diagnostic value of GOLPH2 in RCC appears to be unlikely.

  12. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  13. Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

    OpenAIRE

    Castelli, Germana; Pelosi, Elvira; Testa, Ugo

    2017-01-01

    Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV) infection (frequent in Asia and Africa)...

  14. The thioredoxin system in breast cancer cell invasion and migration

    Directory of Open Access Journals (Sweden)

    Maneet Bhatia

    2016-08-01

    Full Text Available Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1 in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1 expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

  15. Isolation and identification of a distinct side population cancer cells in the human epidermal squamous cancer cell line A431.

    Science.gov (United States)

    Geng, Songmei; Wang, Qianqian; Wang, Jianli; Hu, Zhishang; Liu, Chunchun; Qiu, Junkang; Zeng, Weihui

    2011-04-01

    Side population (SP) cells have been suggested to be multipotent cancer stem cells. To address whether SP cells exist in epidermal squamous cancer cell line A431, A431 cells dyed with Hoechst 33342 were sorted through flow cytometry. The SP cells were then analyzed by colony-forming and cell proliferation assay. Further, tumorigenicity and microarray analysis were used to compare biological difference between SP and non-SP (NSP) cells. Our results showed that SP cells existed in the A431 cell line, showing higher proliferating and colony-forming ability than NSP cells. Tumors generated from SP cells were larger than those from the NSP cells in NOD/SCID mice. The mRNA microarray profiling revealed that five cancer marker gene expressions were up-regulated and one tumor suppressor gene expression was down-regulated. These findings suggest that SP cells in A431 could contribute to self-renewal, neoplastic transformation, and cancer metastasis of human epidermal squamous cell carcinoma.

  16. Forced Expression of ZNF143 Restrains Cancer Cell Growth

    OpenAIRE

    Kimitoshi Kohno; Noriaki Kitamura; Akihiro Kuma; Yoshihiro Yasuniwa; Takahiro Yamaguchi; Masaki Akiyama; Hiroto Izumi

    2011-01-01

    We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143) regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression in the cell cycle, we established two cells with forced expression of ZNF143 derived from PC3 prostate cancer cell lines. These cell lines overexpress genes associated with cell cycle and cell division, such as polo-li...

  17. Targeting autophagic cancer stem-cells to reverse chemoresistance in human triple negative breast cancer.

    Science.gov (United States)

    Bousquet, Guilhem; El Bouchtaoui, Morad; Sophie, Tan; Leboeuf, Christophe; de Bazelaire, Cédric; Ratajczak, Philippe; Giacchetti, Sylvie; de Roquancourt, Anne; Bertheau, Philippe; Verneuil, Laurence; Feugeas, Jean-Paul; Espié, Marc; Janin, Anne

    2017-05-23

    There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC).We found that chemoresistance was associated with large numbers of breast cancer stem-cells, and that these cancer stem-cells were neither proliferative nor apoptotic, but in an autophagic state related to hypoxia. Using relevant pharmacological models of patient-derived TNBC xenografts, we further investigated the role of autophagy in chemoresistance of breast cancer stem-cells. We demonstrated that hypoxia increased drug resistance of autophagic TNBC stem-cells, and showed that molecular or chemical inhibition of autophagic pathway was able to reverse chemoresistance.Our results support breast cancer stem-cell evaluation in pre-treatment biopsies of TNBC patients, and the need for further research on autophagy inhibition to reverse resistance to chemotherapy.

  18. Metabolic Plasticity in Cancer Cells: Reconnecting Mitochondrial Function to Cancer Control.

    Science.gov (United States)

    Ramanujan, V Krishnan

    2015-06-01

    Anomalous increase in glycolytic activity defines one of the key metabolic alterations in cancer cells. A realization of this feature has led to critical advancements in cancer detection techniques such as positron emission tomography (PET) as well as a number of therapeutic avenues targeting the key glycolytic steps within a cancer cell. A normal healthy cell's survival relies on a sensitive balance between the primordial glycolysis and a more regulated mitochondrial bioenergetics. The salient difference between these two bioenergetics pathways is that oxygen availability is an obligatory requirement for mitochondrial pathway while glycolysis can function without oxygen. Early observations that some cancer cells up-regulate glycolytic activity even in the presence of oxygen (aerobic glycolysis) led to a hypothesis that such an altered cancer cell metabolism stems from inherent mitochondrial dysfunction. While a general validity of this hypothesis is still being debated, a number of recent research efforts have yielded clarity on the physiological origins of this aerobic glycolysis phenotype in cancer cells. Building on these recent studies, we present a generalized scheme of cancer cell metabolism and propose a novel hypothesis that might rationalize new avenues of cancer intervention.

  19. Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480.

    Directory of Open Access Journals (Sweden)

    Akari Takaya

    Full Text Available Human cancer stem-like cells (CSCs/cancer-initiating cells (CICs can be isolated as side population (SP cells, aldehyde dehydrogenase high (ALDHhigh cells or cell surface marker-positive cells including CD44+ cells and CD133+ cells. CSCs/CICs and non-CSCs/CICs are unstable in in vitro culture, and CSCs/CICs can differentiate into non-CSCs/CICs and some non-CSCs/CICs can dedifferentiate into CSCs/CICs. Therefore, experiments using a large amount of CSCs/CICs are technically very difficult. In this study, we isolated single cell clones from SP cells and main population (MP cells derived from the human colon cancer cell line SW480. SP analysis revealed that SP clone cells had relatively high percentages of SP cells, whereas MP clone cells showed very few SP cells, and the phenotypes were sustainable for more than 2 months of in vitro culture. Xenograft transplantation revealed that SP clone cells have higher tumor-initiating ability than that of MP clone cells and SP clone cell showed higher chemo-resistance compared with MP clone cells. These results indicate that SP clone cells derived from SW480 cells are enriched with CSCs/CICs, whereas MP clone cells are pure non-CSCs/CICs. SP clone cells and MP clone cells are a very stable in vitro CSC/CIC-enriched and non-CSC/CIC model for further analysis.

  20. [Isolation and in vitro characterization of CD133(+) side population cells from laryngeal cancer cell line].

    Science.gov (United States)

    Wu, Chun-ping; Zhou, Liang; Xie, Ming; Tao, Lei; Zhang, Ming; Tian, Jie

    2011-09-01

    To investigate an approach enriching cancer stem cells (CSCs) more effectively from laryngeal cancer cell line. CD133(+)SP and CD133(-)SP subpopulation was detected and isolated from Hep-2 cell line using Hoechst33342 dye and phycoerythrin (PE)-conjugated CD133 monoclonal antibody assisted by fluorescence activated cell sorting technology. Sorted CD133(+)SP and CD133(-)SP cells were compared in CSCs-related assays including proliferation, differentiation, spheroid formation and drug sensitivity. CD133(+)SP cells accounted for a very small fraction of (0.30 ± 0.12)% in Hep-2 cell line, far less than the proportion of CD133(+) subgroup and side population subgroup, which were (3.15 ± 0.83)% and (17.1 ± 2.0)% respectively. Intriguingly, CD133(+)SP cells proliferated much faster than CD133(-)SP cells in RPMI1640 and gave rise to CD133(-)SP cells and other heterogeneous cells that formed the bulk of the tumor. In contrast, CD133(-)SP cells were not able to differentiate into CD133(+)SP cells. In serum-free medium CD133(+)SP cells grew as spherical clusters and remained floating. In addition, CD133(+)SP cells manifested the marked resistance to chemotherapy than CD133(-)SP cells. Compared with CD133(-)SP cells, CD133(+)SP subpopulation exhibited extraordinary cancer stem-like properties, were enriched for cancer stem cells more effectively and might serve as an ideal putative candidate for CSCs research in laryngeal cancer.

  1. Characterization of side population cells isolated from the colon cancer cell line SW480.

    Science.gov (United States)

    Xiong, Binghong; Ma, Li; Hu, Xiang; Zhang, Caiquan; Cheng, Yong

    2014-09-01

    Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many types of cell lines and tissues have demonstrated the presence of SP cells, including colon cancer cell lines. This study aimed to identify cancer stem cells (CSCs) in the SP of the colon cancer cell line SW480. SP cells were isolated by fluorescence-activated cell sorting (FACS), followed by serum-free medium (SFM) culture. The self-renewal, differentiated progeny, clone formation, proliferation, invasion ability, cell cycle, chemosensitivity and tumorigenic properties in SP and non-SP (NSP) cells were investigated through in vitro culture and in vivo serial transplantation. The expression profiles of ATP-binding cassette (ABC) protein transporters and stem cell-related genes were examined by RT-PCR and western blot analysis. The human colon cancer cell lines SW480, Lovo and HCT116 contain 1.1 ± 0.10, 0.93 ± 0.11 and 1.33 ± 0.05% SP cells, respectively. Flow cytometry analysis revealed that SP cells could differentiate into SP and NSP cells. SP cells had a higher proliferation potency and CFE than NSP cells. Compared to NSP cells, SP cells were also more resistant to CDDP and 5-FU, and were more invasive and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA and protein expression of ABCG2, MDR1, OCT-4, NANOG, SOX-2, CD44 and CD133. SP cells isolated from human colon cancer cell lines harbor CSC properties that may be related to the invasive potential and therapeutic resistance of colon cancer.

  2. Microfluidic channel for characterizing normal and breast cancer cells

    Science.gov (United States)

    TruongVo, T. N.; Kennedy, R. M.; Chen, H.; Chen, A.; Berndt, A.; Agarwal, M.; Zhu, L.; Nakshatri, H.; Wallace, J.; Na, S.; Yokota, H.; Ryu, J. E.

    2017-03-01

    A microfluidic channel was designed and fabricated for the investigation of behaviors of normal and cancer cells in a narrow channel. A specific question addressed in this study was whether it is possible to distinguish normal versus cancer cells by detecting their stationary and passing behaviors through a narrow channel. We hypothesized that due to higher deformability, softer cancer cells will pass through the channel further and quicker than normal cells. Two cell lines, employed herein, were non-tumor breast epithelial cells (MCF-10A; 11.2  ±  2.4 µm in diameter) and triple negative breast cancer cells (MDA-MB-231; 12.4  ±  2.1 µm in diameter). The microfluidic channel was 300 µm long and linearly tapered with a width of 30 µm at an inlet to 5 µm at an outlet. The result revealed that MDA-MB-231 cells entered and stuck further toward the outlet than MCF-10A cells in response to a slow flow (2 µl min-1). Further, in response to a fast flow (5 µl min-1), the passage time (mean  ±  s.d.) was 26.6  ±  43.9 s for normal cells (N  =  158), and 1.9  ±  1.4 s for cancer cells (N  =  128). The measurement of stiffness by atomic force microscopy as well as model-based predictions pointed out that MDA-MB-231 cells are significantly softer than MCF-10A cells. Collectively, the result in this study suggests that analysis of an individual cell’s behavior through a narrow channel can characterize deformable cancer cells from normal ones, supporting the possibility of enriching circulating tumor cells using novel microfluidics-based analysis.

  3. Susceptibility of ATM-deficient pancreatic cancer cells to radiation.

    Science.gov (United States)

    Ayars, Michael; Eshleman, James; Goggins, Michael

    2017-05-19

    Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.

  4. Isolation, identification, and characterization of cancer stem cells: A review.

    Science.gov (United States)

    Abbaszadegan, Mohammad Reza; Bagheri, Vahid; Razavi, Mahya Shariat; Momtazi, Amir Abbas; Sahebkar, Amirhossein; Gholamin, Mehran

    2017-08-01

    Cancer stem cells (CSCs) or tumor-initiating cells (TICs) as a small subset of neoplastic cells are able to produce a tumor (tumorigenesis), maintain the population of tumorigenic cells (self-renewal), and generate the heterogeneous cells constructing the entire tumor (pluripotency). The research on stationary and circulating CSCs due to resistance to conventional therapies and inability in complete eradication of cancer is critical for developing novel therapeutic strategies for a more effective reduction in the risk of tumor metastasis and cancer recurrence. This review compiles information about different methods of detection and dissociation, side population, cellular markers, and establishment culture of CSCs, as well as characteristics of CSCs such as tumorigenicity, and signaling pathways associated with self-renewal and the capability of the same histological tumor regeneration in various cancers. © 2016 Wiley Periodicals, Inc.

  5. Compatibility of cancer cells with nanostructured oxidized porous silicon substrates

    Energy Technology Data Exchange (ETDEWEB)

    Zeidman, Tal; Parush, Ran; Massad, Na' ama [Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000 (Israel); Segal, Ester [Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa 32000 (Israel); Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa 32000 (Israel)

    2011-06-15

    The attachment and long-term viability of three types of human cancer cell lines (glioma U87, breast cancer MDA-MB-231, and cervical cancer HeLa) onto nanostructured oxidized porous Si substrates is investigated. The porous layers are fabricated to give cylindrically-shaped structures with pore diameters in the tunable range of 10 to 150 nm by anodizing a heavily-doped p-type Si. The Alamar Blue viability assay and optical microscopy are employed to assess the attachment, viability and the morphology of the cells. The results show that cells remain viable and proliferate on all surfaces. The nano-architecture of the studied scaffolds does not exert a deleterious effect on cancer cells. Cell coverage levels comparable to standard culture preparations on tissue culture polystyrene are observed (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  6. A systematic study of wave conditions and sediment transport near Mormugao harbour

    Digital Repository Service at National Institute of Oceanography (India)

    Reddy, M.P.M.

    Wave conditions and the nature of sediment transport in the Mormugao Harbour area have been evaluated in view of the proposed development project of this harbour It has been found from this study that generally high waves will be experienced...

  7. Suspended sediment transport and shoaling in the Munambam fishery harbour, Kerala

    Digital Repository Service at National Institute of Oceanography (India)

    Revichandran, C.; Abraham, P.; Josanto, V.; Sankaranarayanan, V.N.

    phenomena in the harbour region. Based on various physical and geomorphological data available on the harbour and near shore region, remedial measures are suggested to prevent the siltation and shoaling at the entrance channel and the sandbar formation...

  8. Third Indian National Conference on Harbour and Ocean Engineering (INCHOE - 2004). Proceedings

    Digital Repository Service at National Institute of Oceanography (India)

    Mandal, S.; SanilKumar, V.; Jayakumar, S.

    The two volumes contain 103 scientific papers in the field of harbour and ocean engineering, presented at the Third Indian National Conference on Harbour and Ocean Engineering (INCHOE - 2004), held at National Institute of Oceanography (NIO), Dona...

  9. A comparative study of macrobenthic community from harbours along the central west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Ingole, B.S.; Sivadas, S.; Nanajkar, M.; Sautya, S.; Nag, A.

    compared the macrobenthic community between different Indian harbours. The present study was therefore conducted in three important harbour (Ratnagiri, Goa, Karwar) along the central west coast of India. The paper discusses the health status of the three...

  10. Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both liver cancer cells and cancer stem cells.

    Science.gov (United States)

    Wang, Meiping; Xie, Fangyuan; Wen, Xikai; Chen, Han; Zhang, Hai; Liu, Junjie; Zhang, He; Zou, Hao; Yu, Yuan; Chen, Yan; Sun, Zhiguo; Wang, Xinxia; Zhang, Guoqing; Yin, Chuan; Sun, Duxin; Gao, Jie; Jiang, Beige; Zhong, Yanqiang; Lu, Ying

    2017-05-01

    Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells. The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo. SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells. In vivo, SCM showed the best tumor inhibitory effect with a safety profile. Thus, PEG-ceramide nanomicelles could serve as an effective and safe therapeutic drug carrier to deliver SAL into liver cancer, opening up the avenue of using PEG-ceramide as therapeutic drug carriers.

  11. Heparan sulfate mediates trastuzumab effect in breast cancer cells

    Science.gov (United States)

    2013-01-01

    Background Trastuzumab is an antibody widely used in the treatment of breast cancer cases that test positive for the human epidermal growth factor receptor 2 (HER2). Many patients, however, become resistant to this antibody, whose resistance has become a major focus in breast cancer research. But despite this interest, there are still no reliable markers that can be used to identify resistant patients. A possible role of several extracellular matrix (ECM) components—heparan sulfate (HS), Syn-1(Syndecan-1) and heparanase (HPSE1)—in light of the influence of ECM alterations on the action of several compounds on the cells and cancer development, was therefore investigated in breast cancer cell resistance to trastuzumab. Methods The cDNA of the enzyme responsible for cleaving HS chains from proteoglycans, HPSE1, was cloned in the pEGFP-N1 plasmid and transfected into a breast cancer cell lineage. We evaluated cell viability after trastuzumab treatment using different breast cancer cell lines. Trastuzumab and HS interaction was investigated by confocal microscopy and Fluorescence Resonance Energy Transfer (FRET). The profile of sulfated glycosaminoglycans was also investigated by [35S]-sulfate incorporation. Quantitative RT-PCR and immunofluorescence were used to evaluate HPSE1, HER2 and Syn-1 mRNA expression. HPSE1 enzymatic activity was performed using biotinylated heparan sulfate. Results Breast cancer cell lines responsive to trastuzumab present higher amounts of HER2, Syn-1 and HS on the cell surface, but lower levels of secreted HS. Trastuzumab and HS interaction was proven by FRET analysis. The addition of anti-HS to the cells or heparin to the culture medium induced resistance to trastuzumab in breast cancer cells previously sensitive to this monoclonal antibody. Breast cancer cells transfected with HPSE1 became resistant to trastuzumab, showing lower levels of HER2, Syn-1 and HS on the cell surface. In addition, HS shedding was increased significantly in

  12. Side population cells separated from A549 lung cancer cell line possess cancer stem cell-like properties and inhibition of autophagy potentiates the cytotoxic effect of cisplatin.

    Science.gov (United States)

    Yang, Yang; Fan, Yuxia; Qi, Yu; Liu, Donglei; Wu, Kai; Wen, Fengbiao; Zhao, Song

    2015-08-01

    Recent studies have suggested that cancer stem cells (CSCs) may be responsible for tumorigenesis and contribute to resistance to chemotherapy. Side population (SP) cells are thought to be enriched for CSCs in most types of human tumors. Therefore, the aim of the present study was to sort SP cells using an A549 lung cancer cell line, identify the cancer stem cell-like properties of SP and determine the role of autophagy in the survival of SP cells of lung cancer. SP cells were isolated by fluorescence-activated cell sorter (FACS) from A549 lung cancer cells, and the CSC-like properties were verified through confocal fluorescence imaging, sphere formation assays, cell proliferation and colony formation assay, gene expression in vitro and tumor formation in vivo. The role of autophagy in the survival of SP cells was assessed by western blotting and flow cytometric analysis. A549 lung cancer cells contained 1.10% SP cells. SP cells showed higher abilities of sphere and colony formation, cell proliferation and self-renewal. Moreover, compared to non-SP, SP cells demonstrated a higher mRNA expression of stem cell markers (MDR1, ABCG2 and OCT-4). The clone formation efficiency of SP cells was significantly higher than that non-SP cells under the same conditions. Expression of autophagosomes in SP cells was markedly lower than that in non-SP cells. However, the level of autophagy in SP cells was found to be markedly increased in the presence of cisplatin. In addition, inhibition of autophagy enhanced the effects of apoptosis induced by cisplatin. SP cells from the A549 lung cancer cell line possessed the properties of CSCs and were used to investigate the further characteristics of lung CSCs. SP cells were more resistant to chemotherapy and inhibition of autophagy enhanced the effects of apoptosis induced by the chemotherapeutic agent, cisplatin. These results may provide insight into novel therapeutic targets.

  13. Hypothesis of mitochondrial oncogenesis as the trigger of normal cells to cancer cells.

    Science.gov (United States)

    Du, Jianping

    2014-06-01

    The Warburg Effect showed that energy metabolism of cancer cells was similar to prokaryotic cells, which were different from normal eucaryotic cells. The Endosymbiotic Theory offered a plausible explanation that the eucaryotic cells were evolved from prokaryotic cells, by which host cells (ancient prokaryotic cells) had ingested mitochondria (ancient aerobic bacteria), which depended on oxidative phosphorylation rather than glycolysis for generating energy. The alteration of energy metabolism might mean that the survival style of cancer cells were the re-evolution from eucaryotic cells to prokaryotic cells. But how this alteration happened was still unknown. This hypothesis tries to explain how mitochondria take part in the re-evolution from normal cell to cancer cell. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Cancer cell sensitivity to bortezomib is associated with survivin expression and p53 status but not cancer cell types

    Directory of Open Access Journals (Sweden)

    Chanan-Khan Asher A

    2010-01-01

    Full Text Available Abstract Background Survivin is known playing a role in drug resistance. However, its role in bortezomib-mediated inhibition of growth and induction of apoptosis is unclear. There are conflicting reports for the effect of bortezomib on survivin expression, which lacks of a plausible explanation. Methods: In this study, we tested cancer cells with both p53 wild type and mutant/null background for the relationship of bortezomib resistance with survivin expression and p53 status using MTT assay, flow cytometry, DNA fragmentation, caspase activation, western blots and RNAi technology. Results We found that cancer cells with wild type p53 show a low level expression of survivin and are sensitive to treatment with bortezomib, while cancer cells with a mutant or null p53 show a high level expression of survivin and are resistant to bortezomib-mediated apoptosis induction. However, silencing of survivin expression utilizing survivin mRNA-specific siRNA/shRNA in p53 mutant or null cells sensitized cancer cells to bortezomib mediated apoptosis induction, suggesting a role for survivin in bortezomib resistance. We further noted that modulation of survivin expression by bortezomib is dependent on p53 status but independent of cancer cell types. In cancer cells with mutated p53 or p53 null, bortezomib appears to induce survivin expression, while in cancer cells with wild type p53, bortezomib downregulates or shows no significant effect on survivin expression, which is dependent on the drug concentration, cell line and exposure time. Conclusions Our findings, for the first time, unify the current inconsistent findings for bortezomib treatment and survivin expression, and linked the effect of bortezomib on survivin expression, apoptosis induction and bortezomib resistance in the relationship with p53 status, which is independent of cancer cell types. Further mechanistic studies along with this line may impact the optimal clinical application of bortezomib in

  15. Cancer Stem Cells in Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Amy Ruth Bradshaw

    2016-08-01

    Full Text Available Aim To identify and characterize cancer stem cells (CSC in glioblastoma multiforme (GBM.Methods 4μm-thick formalin-fixed paraffin-embedded GBM samples from six patients underwent 3,3-diaminobenzidine (DAB and immunofluorescent (IF immunohistochemical (IHC staining for the embryonic stem cell (ESC markers NANOG, OCT4, SALL4, SOX2 and pSTAT3. IF IHC staining was performed to demonstrate co-expression of these markers with GFAP. The protein expression and the transcriptional activities of the genes encoding NANOG, OCT4, SOX2, SALL4 and STAT3 were investigated using Western blotting (WB and NanoString gene expression analysis, respectively. Results DAB and IF IHC staining demonstrated the presence of a CSC population expressing NANOG, OCT4, SOX2, SALL4 and STAT3 with the almost ubiquitous presence of SOX2 and a relatively low abundance of OCT4, within GBM. The expression of NANOG, SOX2 and pSTAT3 but, not OCT and SALL4, was confirmed by WB. NanoString gene analysis demonstrated transcriptional activation of NANOG, OCT4, SALL4, STAT3 and SOX2 in GBM. Conclusion This study demonstrated a population of CSCs within GBM characterized by the expression of the CSC markers NANOG, SALL4, SOX2, pSTAT3 and OCT4 at the protein and mRNA levels. The almost ubiquitous presence of SOX2 and a relatively low abundance of OCT4 would support the putative existence of a stem cell hierarchy within GBM.

  16. Intestinal stem cell imaging in colorectal cancer screening.

    Science.gov (United States)

    Moossavi, S; Ansari, R

    2013-01-01

    Colorectal cancer (CRC) is a common cancer and cause of cancer-related death worldwide. Although, the step-wise genetic alteration in the course of adenoma-carcinoma progression is well-understood, the mechanism of the tumour initiation and promotion is yet to be elucidated. Murine studies indicate that intestinal tumour originates from normal intestinal stem cells which acquire the oncogenic hits. It is plausible to consider the abnormality of the stem cell compartment as the earliest potentially detectable phenotypic change in the course of intestinal tumourigenesis. Hereby, it is hypothesised that imaging of the abnormal state of the intestinal stem cell compartment could potentially be integrated in CRC screening strategy.

  17. Role of Pancreatic Stellate Cells in Chemoresistance in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Joshua eMcCarroll

    2014-04-01

    Full Text Available Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumour volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumour microenvironment following activation of pancreatic stellate cells, tumour progression and chemoresistance is enhanced. This review will discuss how PSCs contribute to chemoresistance in pancreatic cancer.

  18. Exercise-Dependent Regulation of NK Cells in Cancer Protection

    DEFF Research Database (Denmark)

    Idorn, Manja; Hojman, Pernille

    2016-01-01

    Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we...... a mechanistic explanation for the protective effect of exercise on cancer, and we propose that exercise represents a potential strategy as adjuvant therapy in cancer, by improving NK cell recruitment and infiltration in solid tumors....... review the link between exercise and NK cell function, focusing on circulating exercise factors and additional effects, including vascularization, hypoxia, and body temperature in mediating the effects on NK cell functionality. Exercise-dependent mobilization and activation of NK cells provides...

  19. Exercise-Dependent Regulation of NK Cells in Cancer Protection.

    Science.gov (United States)

    Idorn, Manja; Hojman, Pernille

    2016-07-01

    Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we review the link between exercise and NK cell function, focusing on circulating exercise factors and additional effects, including vascularization, hypoxia, and body temperature in mediating the effects on NK cell functionality. Exercise-dependent mobilization and activation of NK cells provides a mechanistic explanation for the protective effect of exercise on cancer, and we propose that exercise represents a potential strategy as adjuvant therapy in cancer, by improving NK cell recruitment and infiltration in solid tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Electrostrictive Effect in Cancer Cell Reflected in Capacitance Relaxation Phenomena

    Directory of Open Access Journals (Sweden)

    Tapas Kumar Basak

    2008-12-01

    Full Text Available The present paper has focus on the composite dielectric property of the cancer cell on concomitant with the capacitance relaxation phenomena. In this respect it has been found from MAT lab simulation the electrostrictive process in cancer cell is a complex one for which the electrostatic surfaces surrounding the cell changes with the incremental changes in the capacitance present in the capacitance relaxation curve. From these incremental changes in capacitance it is also possible to find out the electrostrictive energy of the cancer cell. It is interesting to note that the electrostrictive energy corresponding to the cell incremental changes in the capacitance is more in the first order system than that present in the second order system representing the equivalent configuration of the composite dielectric associated with the cell membrane. This is due the fact that during the process DNA synthesis and cell division the change in capacitance of the membrane for the first order system is relatively slow.

  1. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Facchino, Sabrina; Abdouh, Mohamed [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Bernier, Gilbert, E-mail: gbernier.hmr@ssss.gouv.qc.ca [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Faculté de Médecine, Université de Montréal, Montréal, H3T 1J4 (Canada)

    2011-03-30

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

  2. Localization of thymosin ß10 in breast cancer cells

    DEFF Research Database (Denmark)

    Mælan, A.ase Elisabeth; Rasmussen, Trine Kring; Larsson, Lars-Inge

    2007-01-01

    as in cell motility and spreading. We have studied the distribution of endogenously expressed thymosin ß10 in cultured human breast cancer cell lines. Both unperturbed monolayer cultures and wound-healing models were examined using double-staining for thymosin ß10 and polymerized (F-) actin. Our findings...... for thymosin ß10 was inverse of staining for F-actin. These data support a physiological role for thymosin ß10 in sequestration of G-actin as well as in cancer cell motility....... show that thymosin ß10 is expressed in all three-cancer cell lines (SK-BR-3, MCF-7 and MDA-MB-231) studied. No or little staining was detected in confluent cells, whereas strong staining occurred in semiconfluent cells and in cells populating monolayer wounds. Importantly, the distribution of staining...

  3. Cell lineage determinants as regulators of breast cancer metastasis.

    Science.gov (United States)

    Lu, Wei; Kang, Yibin

    2016-12-01

    The mammary epithelium is organized in a hierarchy of mammary stem cells (MaSCs), progenitors, and differentiated cells. The development and homeostasis of mammary gland are tightly controlled by a complex network of cell lineage regulators. These determinants of cellular hierarchy are frequently deregulated in breast tumor cells and closely associated with cancer progression and metastasis. They also contribute to the diversity of breast cancer subtypes and their distinct metastatic patterns. Cell fate regulators that normally promote stem/progenitor activities can serve as drivers for epithelial-mesenchymal transition and metastasis whereas regulators that promote terminal differentiation generally suppress metastasis. In this review, we discuss how some of the key factors function in normal mammary lineage determination and how these processes are hijacked by tumor cells to enhance metastasis. Understanding the molecular connections between normal development and cancer metastasis will enable the development of more specific and effective therapeutic approaches targeting metastatic tumor cells.

  4. [Radiosensitization effect of black garlic extract on lung cancer cell line Lewis cells].

    Science.gov (United States)

    Yang, Gui-qing; Wang, Dong; Wang, Yi-shan; Wang, Yuan-yuan; Yang, Ke

    2013-08-01

    To explore the radiosensitization effect of black garlic extract (BGE) on lung cancer cell line Lewis cells. The inhibition rate of lung cancer cells after BGE action was detected by MTT. Effect of BGE combined radiotherapy on the colony formation rate was observed by cloning formation assay. Changes of the cell morphology were observed by Hoechst staining. Changes of the cell cycle were detected by flow cytometry. Real time PCR was used to detect mRNA expressions of bcl-2 and bax. BGE could have significant inhibitory action on the growth of lung cancer Lewis cells. The combination of BGE and radiotherapy (by 60Co gamma) significantly induced Lewis cells' apoptosis in G2/M stage, obviously decreased the expression of bcl-2, and up-regulated the expression of bax. BGE could sensitize the lung cancer Lewis cells to ionizing irradiation. This effect might be probably caused by changing the cell cycles and affecting expressions of bax and bcl-2.

  5. Advances of Molecular Targeted Therapy in Squamous Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2013-12-01

    Full Text Available Squamous cell lung cancer (SQCLC is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR inhibitors or anaplastic lymphoma kinase (ALK inhibitors that show exquisite activity in lungadenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1 gene, the discoidin domain receptor 2 (DDR2 gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lungcancer assessing the value of novel therapeutics addressing these targets.

  6. Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy.

    Science.gov (United States)

    Dandawate, Prasad R; Subramaniam, Dharmalingam; Jensen, Roy A; Anant, Shrikant

    2016-10-01

    Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth. In addition, CSCs are believed to be responsible for cancer recurrence, anticancer drug resistance, and metastasis. Hence, compounds targeting breast CSCs may be better therapeutic agents for treating breast cancer and control recurrence and metastasis. Naturally occurring compounds, mainly phytochemicals have gained immense attention in recent times because of their wide safety profile, ability to target heterogeneous populations of cancer cells as well as CSCs, and their key signaling pathways. Therefore, in the present review article, we summarize our current understanding of breast CSCs and their signaling pathways, and the phytochemicals that affect these cells including curcumin, resveratrol, tea polyphenols (epigallocatechin-3-gallate, epigallocatechin), sulforaphane, genistein, indole-3-carbinol, 3, 3'-di-indolylmethane, vitamin E, retinoic acid, quercetin, parthenolide, triptolide, 6-shogaol, pterostilbene, isoliquiritigenin, celastrol, and koenimbin. These phytochemicals may serve as novel therapeutic agents for breast cancer treatment and future leads for drug development. Copyright © 2016. Published by Elsevier Ltd.

  7. CNT Nanobombs for Specific Eradication of Cancer Cells: A New Concept in Cancer Theranostics.

    Science.gov (United States)

    Omidi, Yadollah

    2011-01-01

    Whole extermination of cancerous cells/tissue seems no longer to be a dream. Exploiting advanced photoactive nanomaterials such as functionalized fullerenes and carbon nano-tubes (CNTs) can act as CNT nanobombs (CNT-NBs) when exposed to the near infrared (NIR) radiation. PEGylated CNTs tagged with an antibody/aptamer can target cancer cells. Once attached to cancer cells, the NIR emission (700-1100 nm), in which body tissues are mostly transparent, can be applied to CNT-NBs which can absorb the light and get heated up. The resultant enhanced temperature can abolish the cancer. Once stealth CNT-NBs are tagged with imaging moieties, it would be a matter of computer gaming for physician who can inject it for real time visualization and destruction of cancer by activation of the NIR laser. While, many nanosystems (NSs) are still in waiting list for clinical translation, our dreams may come true by applying stealth CNT-NBs against cancer.

  8. CNT Nanobombs for Specific Eradication of Cancer Cells: A New Concept in Cancer Theranosticss

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2011-11-01

    Full Text Available Whole extermination of cancerous cells/tissue seems no longer to be a dream. Exploiting advanced photoactive nanomaterials such as functionalized fullerenes and carbon nanotubes (CNTs can act as CNT nanobombs (CNT-NBs when exposed to the near infrared (NIR radiation. PEGylated CNTs tagged with an antibody/aptamer can target cancer cells. Once attached to cancer cells, the NIR emission (700-1100 nm, in which body tissues are mostly transparent, can be applied to CNT-NBs which can absorb the light and get heated up. The resultant enhanced temperature can abolish the cancer. Once stealth CNT-NBs are tagged with imaging moieties, it would be a matter of computer gaming for physician who can inject it for real time visualization and destruction of cancer by activation of the NIR laser. While, many nanosystems (NSs are still in waiting list for clinical translation, our dreams may come true by applying stealth CNT-NBs against cancer.

  9. Prevalence of Epithelial Ovarian Cancer Stem Cells Correlates with Recurrence in Early-Stage Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Karina Dahl Steffensen

    2011-01-01

    Full Text Available Epithelial ovarian cancer stem cells (EOC stem cells have been associated with recurrence and chemoresistance. CD44 and CK18 are highly expressed in cancer stem cells and function as tools for their identification and characterization. We investigated the association between the number of CD44+ EOC stem cells in ovarian cancer tumors and progression-free survival. EOC stem cells exist as clusters located close to the stroma forming the cancer stem cell “niche”. 17.1% of the samples reveled high number of CD44+ EOC stem cells (>20% positive cells. In addition, the number of CD44+ EOC stem cells was significantly higher in patients with early-stage ovarian cancer (FIGO I/II, and it was associated with shorter progression-free survival (P=0.026. This study suggests that quantification of the number of EOC stem cells in the tumor can be used as a predictor of disease and could be applied for treatment selection in early-stage ovarian cancer.

  10. Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

    Science.gov (United States)

    Yazdannejat, H; Hosseinimehr, S J; Ghasemi, A; Pourfallah, T A; Rafiei, A

    2016-01-11

    Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

  11. Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery

    Science.gov (United States)

    Khan, Sarwat T.; Kilgour, Marisa K.; Xu, Rebecca; Kennedy, Michael A.; Auer, Rebecca C.

    2017-01-01

    The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. Natural Killer (NK) cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance. Here, we describe the post-operative environment and how the release of sympathetic stress-related factors (e.g., cortisol, prostaglandins, catecholamines), anti-inflammatory cytokines (e.g., IL-6, TGF-β), and myeloid derived suppressor cells, mediate NK cell dysfunction. A snapshot of current and recently completed clinical trials specifically addressing NK cell dysfunction post-surgery is also discussed. In collecting and summarizing results from these different aspects of the surgical stress response, a comprehensive view of the NK cell suppressive effects of surgery is presented. Peri-operative therapies to mitigate NK cell suppression in the post-operative period could improve curative outcomes following cancer surgery. PMID:28817109

  12. Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery

    Directory of Open Access Journals (Sweden)

    Leonard Angka

    2017-08-01

    Full Text Available The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. Natural Killer (NK cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance. Here, we describe the post-operative environment and how the release of sympathetic stress-related factors (e.g., cortisol, prostaglandins, catecholamines, anti-inflammatory cytokines (e.g., IL-6, TGF-β, and myeloid derived suppressor cells, mediate NK cell dysfunction. A snapshot of current and recently completed clinical trials specifically addressing NK cell dysfunction post-surgery is also discussed. In collecting and summarizing results from these different aspects of the surgical stress response, a comprehensive view of the NK cell suppressive effects of surgery is presented. Peri-operative therapies to mitigate NK cell suppression in the post-operative period could improve curative outcomes following cancer surgery.

  13. DDB2 Suppresses Tumorigenicity by Limiting the Cancer Stem Cell Population in Ovarian Cancer

    Science.gov (United States)

    Han, Chunhua; Zhao, Ran; Liu, Xingluo; Srivastava, Amit; Gong, Li; Mao, Hsiaoyin; Qu, Meihua; Zhao, Weiqiang; Yu, Jianhua; Wang, Qi-En

    2014-01-01

    Ovarian cancer is an extremely aggressive disease associated with a high percentage of tumor recurrence and chemotherapy resistance. Understanding the underlying mechanism of tumor relapse is crucial for effective therapy of ovarian cancer. DNA damage-binding protein 2 (DDB2) is a DNA repair factor mainly involved in nucleotide excision repair. Here, a novel role was identified for DDB2 in the tumorigenesis of ovarian cancer cells and the prognosis of patients with ovarian cancer. Overexpressing DDB2 in human ovarian cancer cells suppressed its capability to recapitulate tumors in athymic nude mice. Mechanistic investigation demonstrated that DDB2 is able to reduce the cancer stem cell (CSC) population characterized with high aldehyde dehydrogenase activity in ovarian cancer cells, probably through disrupting the self-renewal capacity of CSCs. Low DDB2 expression correlates with poor outcomes among patients with ovarian cancer, as revealed from the analysis of publicly available gene expression array datasets. Given the finding that DDB2 protein expression is low in ovarian tumor cells, enhancement of DDB2 expression is a promising strategy to eradicate CSCs and would help to halt ovarian cancer relapse. PMID:24574518

  14. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

    Science.gov (United States)

    Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

    2017-08-10

    One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Reprogramming cancer cells: a novel approach for cancer therapy or a tool for disease-modeling?

    Science.gov (United States)

    Yilmazer, Açelya; de Lázaro, Irene; Taheri, Hadiseh

    2015-12-01

    Chromatin dynamics have been the major focus of many physiological and pathological processes over the past 20 years. Epigenetic mechanisms have been shown to be reshaped during both cellular reprogramming and tumorigenesis. For this reason, cancer cell reprogramming can provide a powerful tool to better understand both regenerative and cancer-fate processes, with a potential to develop novel therapeutic approaches. Recent studies showed that cancer cells can be reprogrammed to a pluripotent state by the overexpression of reprogramming transcription factors. Activation of transcription factors and modification of chromatin regulators may result in the remodeling of epigenetic status and refueling of tumorigenicity in these reprogrammed cancer cells. However, studies focusing on cancer cell reprogramming are contradictory; some studies reported increased tumor progression whereas others showed that cellular reprogramming has a treatment potential for cancer. In this review, first, the current knowledge on the epigenetic mechanisms involved during cancer development and cellular reprogramming will be presented. Later, different reports and key factors about pluripotency-based reprogramming of cancer cells will be reviewed in detail. New insights will be provided on cancer biology and therapy in the light of cellular reprogramming. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Epidemiologic characteristics and risk factors for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Loren Lipworth

    2009-04-01

    Full Text Available Loren Lipworth1,2, Robert E Tarone1,2, Lars Lund2,3, Joseph K McLaughlin1,21International Epidemiology Institute, Rockville, MD, USA; 2Department of Medicine (JKM, RET and Preventive Medicine (LL, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 3Department of Urology, Viborg Hospital, Viborg, DenmarkAbstract: Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches

  17. A preliminary study of side population cells in human gastric cancer cell line HGC-27.

    Science.gov (United States)

    Gao, Ganglong; Sun, Zhenliang; Wenyong, Liu; Dongxia, Ye; Zhao, Runjia; Zhang, Xueli

    2015-03-16

    Cancer stem cell-like side population (SP) cells, which may be responsible for recurrence, tumor metastasis, and resistance to cancer therapy, have been identified and characterized in several types of cell lines from gastric cancer. However, there is no report on isolation of SP cells from human gastric cancer cell line HGC-27. This study aims to analyze the proportion of SP cells in HGC-27 cell line, differentiate SP from non-side population (NSP) cells, and determine whether the SP cells have certain biological properties of stem cells. (1) HGC-27 suspension was prepared and stained with Hoechst33342 and PI for flow cytometric isolation of SP (2). Differences in proliferation and stemness-related gene expression profiles (CD133, CD44, OCT-4, MDR1, EpCAM, and ABCG2) between SP and NSP cells were detected by gastric formation assay and quantitative real-time PCR (3). Oncogenicity of SP and NSP cells was determined in nude mice in vivo. (1) SP cells accounted for 0.1-1.0% of HGC-27 cells, and decreased to 0% after verapamil inhibition. Using flow cytometry, we sorted 7.5×10⁵ SP cells and most HGC-27 cells were NSP cells (2). Gastric formation assay and MTT demonstrated that there was a significant difference in proliferation between SP and NSP cells. Gene expression analysis showed that the expression of genes was significantly higher in SP cells (3). The oncogenicity experiment in nude mice revealed that 105 SP cells were able to form tumors, which demonstrated higher tumorigenicity than non-SP cells. These results collectively suggested that SP cells from HGC-27 cell line have some cancer stem cell properties and could be used for studying the pathogenesis of gastric cancer, which may contribute to discovery of novel therapeutic targets.

  18. Vuosaari Harbour Road Tunnel Traffic Management and Incident Detection System Design Issues

    Directory of Open Access Journals (Sweden)

    Caj Holm

    2006-11-01

    Full Text Available Helsinki is constructing in Vuosaari a new modem and effectivecargo harbour. All cargo harbour activities will be concentratedthere. The total project includes the harbour, a logisticsarea, traffic connections (road, railway and fairway and aBusiness Park. The road connection goes through the Porvarinlahtiroad tunnel. The harbour will commence operatingin 2008. This paper gives an oveTView of the tunnel design phasefunctional studies and risk analysis tunnel incident detectionsystem design issues and some specific environmental featuresof the tunnel.

  19. Vuosaari Harbour Road Tunnel Traffic Management and Incident Detection System Design Issues

    OpenAIRE

    Caj Holm; Ronald Westermark; Mario Anžek

    2006-01-01

    Helsinki is constructing in Vuosaari a new modem and effectivecargo harbour. All cargo harbour activities will be concentratedthere. The total project includes the harbour, a logisticsarea, traffic connections (road, railway and fairway) and aBusiness Park. The road connection goes through the Porvarinlahtiroad tunnel. The harbour will commence operatingin 2008. This paper gives an oveTView of the tunnel design phasefunctional studies and risk analysis tunnel incident detectionsystem design i...

  20. Cancer cell metastasis; perspectives from the focal adhesion

    Directory of Open Access Journals (Sweden)

    Lefteris C Zacharia

    2015-10-01

    Full Text Available In almost all cancers, most patients die from metastatic disease and not from the actual primary tumor. That is why addressing the problem of metastasis is of utmost importance for the successful treatment and improved survival of cancer patients. Metastasis is a complex process that ultimately leads to cancer cells spreading from the tumor to distant sites of the body. During this process, cancer cells tend to lose contact with the extracellular matrix (ECM and neighboring cells within the primary tumor, and are thus able to invade surrounding tissues. Hence, ECM, and the ECM-associated adhesion proteins play a critical role in the metastatic process. This review will focus on recent literature regarding interesting and novel molecules at the cell-ECM adhesion sites, namely migfilin, mitogen-inducible gene-2 (Mig-2 and Ras suppressor-1 (RSU-1, that are also critically involved in cancer cell metastasis, emphasizing on data from experiments performed in vitro in breast cancer and hepatocellular carcinoma cell lines as well as human breast cancer tissue samples.

  1. Glutamine Transport and Mitochondrial Metabolism in Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Mariafrancesca Scalise

    2017-12-01

    Full Text Available The concept that cancer is a metabolic disease is now well acknowledged: many cancer cell types rely mostly on glucose and some amino acids, especially glutamine for energy supply. These findings were corroborated by overexpression of plasma membrane nutrient transporters, such as the glucose transporters (GLUTs and some amino acid transporters such as ASCT2, LAT1, and ATB0,+, which became promising targets for pharmacological intervention. On the basis of their sodium-dependent transport modes, ASCT2 and ATB0+ have the capacity to sustain glutamine need of cancer cells; while LAT1, which is sodium independent will have the role of providing cancer cells with some amino acids with plausible signaling roles. According to the metabolic reprogramming of many types of cancer cells, glucose is mainly catabolized by aerobic glycolysis in tumors, while the fate of Glutamine is completed at mitochondrial level where the enzyme Glutaminase converts Glutamine to Glutamate. Glutamine rewiring in cancer cells is heterogeneous. For example, Glutamate is converted to α-Ketoglutarate giving rise to a truncated form of Krebs cycle. This reprogrammed pathway leads to the production of ATP mainly at substrate level and regeneration of reducing equivalents needed for cells growth, redox balance, and metabolic energy. Few studies on hypothetical mitochondrial transporter for Glutamine are reported and indirect evidences suggested its presence. Pharmacological compounds able to inhibit Glutamine metabolism may represent novel drugs for cancer treatments. Interestingly, well acknowledged targets for drugs are the Glutamine transporters of plasma membrane and the key enzyme Glutaminase.

  2. Variable TERRA abundance and stability in cervical cancer cells.

    Science.gov (United States)

    Oh, Bong-Kyeong; Keo, Ponnarath; Bae, Jaeman; Ko, Jung Hwa; Choi, Joong Sub

    2017-06-01

    Telomeres are transcribed into long non-coding RNA, referred to as telomeric repeat-containing RNA (TERRA), which plays important roles in maintaining telomere integrity and heterochromatin formation. TERRA has been well characterized in HeLa cells, a type of cervical cancer cell. However, TERRA abundance and stability have not been examined in other cervical cancer cells, at least to the best of our knowledge. Thus, in this study, we measured TERRA levels and stability, as well as telomere length in 6 cervical cancer cell lines, HeLa, SiHa, CaSki, HeLa S3, C-33A and SNU-17. We also examined the association between the TERRA level and its stability and telomere length. We found that the TERRA level was several fold greater in the SiHa, CaSki, HeLa S3, C-33A and SNU-17 cells, than in the HeLa cells. An RNA stability assay of actinomycin D-treated cells revealed that TERRA had a short half-life of ~4 h in HeLa cells, which was consistent with previous studies, but was more stable with a longer half-life (>8 h) in the other 5 cell lines. Telomere length varied from 4 to 9 kb in the cells and did not correlate significantly with the TERRA level. On the whole, our data indicate that TERRA abundance and stability vary between different types of cervical cancer cells. TERRA degrades rapidly in HeLa cells, but is maintained stably in other cervical cancer cells that accumulate higher levels of TERRA. TERRA abundance is associated with the stability of RNA in cervical cancer cells, but is unlikely associated with telomere length.

  3. Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor

    Science.gov (United States)

    Nagy, N; Bronckart, Y; Camby, I; Legendre, H; Lahm, H; Kaltner, H; Hadari, Y; Van Ham, P; Yeaton, P; Pector, J-C; Zick, Y; Salmon, I; Danguy, A; Kiss, R; Gabius, H-J

    2002-01-01

    Background and aims: Galectins are β-galactoside binding proteins. This ability may have a bearing on cell adhesion and migration/proliferation in human colon cancer cells. In addition to galectins-1 and -3 studied to date, other members of this family not investigated in detail may contribute to modulation of tumour cell features. This evident gap has prompted us to extend galectin analysis beyond the two prototypes. The present study deals with the quantitative determination of immunohistochemical expression of galectin-8 in normal, benign, and malignant human colon tissue samples and in four human colon cancer models (HCT-15, LoVo, CoLo201, and DLD-1) maintained both in vitro as permanent cell lines and in vivo as nude mice xenografts. The role of galectin-8 (and its neutralising antibody) in cell migration was investigated in HCT-15, LoVo, CoLo201, and DLD-1 cell lines. Methods: Immunohistochemical expression of galectin-8 and its overall ability to bind to sugar ligands (revealed glycohistochemically by means of biotinylated histochemically inert carrier bovine serum albumin with α- and β-d-galactose, α-d-glucose, and lactose derivatives as ligands) were quantitatively determined using computer assisted microscopy. The presence of galectin-8 mRNA in the four human colon cancer cell lines was examined by reverse transcriptase-polymerase chain reaction. In vitro, cellular localisation of exogenously added galectin-8 in the culture media of these colon cancer cells was visualised by fluorescence microscopy. In vitro galectin-8 mediated effects (and the influence of its neutralising antibody) on migration levels of living HCT-15, LoVo, CoLo201, and DLD-1 cells were quantitatively determined by computer assisted phase contrast microscopy. Results: A marked decrease in immunohistochemical expression of galectin-8 occurred with malignancy development in human colon tissue. Malignant colon tissue exhibited a significantly lower galectin-8 level than normal or

  4. LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

    Science.gov (United States)

    Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

    2013-04-05

    Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Host manipulation by cancer cells: Expectations, facts, and therapeutic implications.

    Science.gov (United States)

    Tissot, Tazzio; Arnal, Audrey; Jacqueline, Camille; Poulin, Robert; Lefèvre, Thierry; Mery, Frédéric; Renaud, François; Roche, Benjamin; Massol, François; Salzet, Michel; Ewald, Paul; Tasiemski, Aurélie; Ujvari, Beata; Thomas, Frédéric

    2016-03-01

    Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. © 2016 WILEY Periodicals, Inc.

  6. Apoptosis and cancer stem cells : Implications for apoptosis targeted therapy

    NARCIS (Netherlands)

    Kruyt, Frank A. E.; Schuringa, Jan Jacob

    2010-01-01

    Evidence is accumulating showing that cancer stem cells or tumor-initiating cells are key drivers of tumor formation and progression. Successful therapy must therefore eliminate these cells, which is hampered by their high resistance to commonly used treatment modalities. Thus far, only a limited

  7. DNA breaks early in replication in B cell cancers

    Science.gov (United States)

    Research by scientists at the NCI has identified a new class of DNA sites in cells that break early in the replication process. They found that these break sites correlate with damage often seen in B cell cancers, such as diffuse large B cell lymphoma.

  8. Cytotoxicity of Sambucus ebulus on cancer cell lines and protective ...

    African Journals Online (AJOL)

    DR. TONUKARI NYEROVWO

    2013-05-22

    May 22, 2013 ... Also, protective effects of vitamins C and E against SEE-induced cytotoxicity on normal cell lines were studied. Cytotoxicity of SEE on cancer (HepG2 and CT26) and normal (CHO and rat fibroblast) cell lines was evaluated by MTT assay. IC50 of SEE on the cell lines was assessed. Furthermore, IC50 of ...

  9. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  10. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

    Science.gov (United States)

    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  11. Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

    National Research Council Canada - National Science Library

    Hou, Zhi-Jie; Luo, Xi; Zhang, Wei; Peng, Fei; Cui, Bai; Wu, Si-Jin; Zheng, Fei-Meng; Xu, Jie; Xu, Ling-Zhi; Long, Zi-Jie; Wang, Xue-Ting; Li, Guo-Hui; Wan, Xian-Yao; Yang, Yong-Liang; Liu, Quentin

    2015-01-01

    Cancer stem-like cell (CS-like cell) is considered to be responsible for recurrence and drug resistance events in breast cancer, which makes it a potential target for novel cancer therapeutic strategy...

  12. Bioactive food components, cancer cell growth limitation and reversal of glycolytic metabolism

    NARCIS (Netherlands)

    Keijer, J.; Bekkenkamp-Grovestein, M.; Venema, D.P.; Dommels, Y.E.M.

    2011-01-01

    Cancer cells are resistant to apoptosis and show a shift in energy production from mitochondrial oxidative phosphorylation to cytosolic glycolysis. Apoptosis resistance and metabolic reprogramming are linked in many cancer cells and both processes center on mitochondria. Clearly, mutated cancer

  13. Up-regulation of CIT promotes the growth of colon cancer cells

    OpenAIRE

    Wu, Zehua; Zhu, Xiangying; Xu, Wendi; Zhang,Yu; Chen, Lin; Qiu, Fabo; Zhang, Binyuan; Wu, Liqun; Peng, Zhihai; Tang, Huamei

    2017-01-01

    Colon cancer is one of the major causes of cancer mortality worldwide. However, the underlying mechanism and therapeutic targets of colon cancer have not yet been fully elucidated. In the present study, we demonstrate that citron rho-interacting, serine/threonine kinase 21 (CIT) promotes the growth of human colon cancer cells. CIT is overexpressed in human colon cancer tissues and cell lines. High expression of CIT predicts poor survival for patients with colon cancer. In colon cancer cells, ...

  14. Anti-cancer stem cell activity of a hedgehog inhibitor GANT61 in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Kurebayashi, Junichi; Koike, Yoshikazu; Ohta, Yusuke; Saitoh, Wataru; Yamashita, Tetsumasa; Kanomata, Naoki; Moriya, Takuya

    2017-05-01

    Estradiol (E2) increases not only the cell growth but also the cancer stem cell (CSC) proportion in estrogen receptor (ER)-positive breast cancer cells. It has been suggested that the non-canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER-positive breast cancer cells. We studied anti-CSC activity of a non-canonical Hh inhibitor GANT61 in ER-positive breast cancer cells. Effects of GANT61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER-positive breast cancer cell lines. CSC proportion was measured using either the mammosphere assay or CD44/CD24 assay. Expression levels of pivotal molecules in the Hh pathway were measured. Combined effects of GANT61 with antiestrogens on the anti-cell growth and anti-CSC activities were investigated. E2 significantly increased the cell growth and CSC proportion in all ER-positive cell lines. E2 increased the expression levels of glioma-associated oncogene (GLI) 1 and/or GLI2. GANT61 decreased the cell growth in association with a G1-S cell cycle retardation and increased apoptosis. GANT61 decreased the E2-induced CSC proportion measured by the mammosphere assay in all cell lines. Antiestrogens also decreased the E2-induced cell growth and CSC proportion. Combined treatments of GANT61 with antiestrogens additively enhanced anti-cell growth and/or anti-CSC activities in some ER-positive cell lines. In conclusion, the non-canonical Hh inhibitor GANT61 inhibited not only the cell growth but also the CSC proportion increased by E2 in ER-positive breast cancer cells. GANT61 enhanced anti-cell growth and/or anti-CSC activities of antiestrogens in ER-positive cell lines. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  15. In vitro and in vivo pathogenicity studies of Pasteurella multocida strains harbouring different ompA.

    Science.gov (United States)

    Katoch, Shailja; Sharma, Mandeep; Patil, R D; Kumar, Sandeep; Verma, Subhash

    2014-09-01

    Pasteurella multocida is a pathogenic, Gram-negative bacterium that is commonly found as normal flora in nasopharynx of variety of wild and domestic animals. Numerous virulence factors have been described for P. multocida isolates which include adherence and colonization factors, iron-regulated and acquisition proteins, extracellular enzymes such as neuraminidase, lipopolysaccharide (LPS), capsule and a variety of outer membrane proteins (Omp). OmpA has a significant role in stabilizing the cell envelope structure by providing physical linkage between the outer membrane & peptidoglycan. It has been shown to mediate P. multocida -host cells interaction via heparin and/or fibronectin binding and therefore act as an important invasive molecule which could determine the final outcome of initial infection. Comparative nucleotide sequence analysis of ompA gene of P. multocida has revealed that despite extensive genetic diversity in ompA of P. multocida, most sequences could be classified into two major allele classes namely ompA allele (I) and allele (II). The P. multocida recovered from nasal cavity of bovine and belonging to two ompA classes were tested for their differential virulence. In vitro pathogenicity studies on Madin Darby Bovine Kidney (MDBK) cell line employing adhesion and invasion assays indicated that P. multocida strain with ompA (I) is more invasive than P. multocida strain with ompA (II). In vivo studies in mice further reiterated that the isolates harbouring ompA(I) were comparatively more virulent to isolates harbouring ompA (II).

  16. Biological and management aspects of a Caribbean mangal: West Harbour, Jamaica

    NARCIS (Netherlands)

    Chow, Barbara A.

    1997-01-01

    CHOW, Barbara A., 1997. Biological and management aspects of a Caribbean mangal: West Harbour, Jamaica. Studies Nat. Hist. Caribbean Region 73, Amsterdam, 1997: 1-22. Observations are given for the first time of West Harbour, a pristine south-coast Jamaican mangal. West Harbour is shown to be a

  17. Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death.

    Science.gov (United States)

    Qin, Jianzhong; Kunda, Nicholas; Qiao, Guilin; Calata, Jed F; Pardiwala, Krunal; Prabhakar, Bellur S; Maker, Ajay V

    2017-02-02

    Immunotherapeutic approaches to manage patients with advanced gastrointestinal malignancies are desired; however, mechanisms to incite tumor-specific immune responses remain to be elucidated. Rose bengal (RB) is toxic at low concentrations to malignant cells and may induce damage-associated molecular patterns; therefore, we investigated its potential as an immunomodulator in colon cancer. Murine and human colon cancer lines were treated with RB (10% in saline/PV-10) for cell cycle, cell death, and apoptosis assays. Damage-associated molecular patterns were assessed with western blot, ELISA, and flow cytometry. In an immunocompetent murine model of colon cancer, we demonstrate that tumors regress upon RB treatment, and that RB induces cell death in colon cancer cells through G2/M growth arrest and predominantly necrosis. RB-treated colon cancer cells expressed distinct hallmarks of immunogenic cell death (ICD), including enhanced expression of calreticulin and heat-shock protein 90 on the cell surface, a decrease in intracellular ATP, and the release of HMGB1. To confirm the ICD phenotype, we vaccinated immunocompetent animals with syngeneic colon cancer cells treated with RB. RB-treated tumors served as a vaccine against subsequent challenge with the same CT26 colon cancer tumor cells, and vaccination with in vitro RB-treated cells resulted in slower tumor growth following inoculation with colon cancer cells, but not with syngeneic non-CT26 cancer cells, suggesting a specific antitumor immune response. In conclusion, RB serves as an inducer of ICD that contributes to enhanced specific antitumor immunity in colorectal cancer.

  18. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  19. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Science.gov (United States)

    Majchrzak, Kinga; Lo Re, Daniele; Gajewska, Małgorzata; Bulkowska, Małgorzata; Homa, Agata; Pawłowski, Karol; Motyl, Tomasz; Murphy, Paul V; Król, Magdalena

    2013-01-01

    Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in vivo studies are required to

  20. Stem Cells Antigen-1 Enriches for a Cancer Stem Cell-Like Subpopulation in Mouse Gastric Cancer.

    Science.gov (United States)

    Park, Jun Won; Park, Jung Min; Park, Dong Min; Kim, Dae-Yong; Kim, Hark Kyun

    2016-05-01

    There is a strong need to identify markers to enrich gastric cancer stem cells (CSCs). However, CSC enrichment markers for mouse gastric cancers have not yet been determined. In our previous study, we generated primary mouse gastric cancer cell line NCC-S1 (S1) established from a Villin-cre;Smad4(F/F) ;Trp53(F/F) ;Cdh1(F/wt) mouse and its metastatic variant cell line NCC-S1M (S1M). Interestingly, S1M cells exhibited CSC-like features, such as increased tumorigenic potential and chemoresistance. By comparing gene expression profiles between S1 and S1M cells, we identified Stem Cells Antigen-1 (Sca-1) as a cell surface marker, which was mostly upregulated in S1M. Sca-1 was upregulated in tumorspheres from S1 cells or after cisplatin treatment in S1 cells. Immunofluorescence (IF) analysis showed that approximately 7% of cancer cells exhibited positivity for Sca-1 in primary mouse gastric cancer tissues. An in vivo-limiting dilution assay showed that Sca-1(high) mouse gastric cancer cells demonstrated increased tumorigenicity compared with Sca-1(negative) cells. The Sca-1 expression was downregulated by TGF-β pathway activation and Wnt pathway inhibition in mouse gastric cancer cells. Sca-1(high) cells showed relatively low TGF-β reporter activity and high TCF/LEF1 reporter activity compared with Sca-1(negative) cells. A chromatin immunoprecipitation analysis demonstrated that Sca-1 was a β-catenin/LEF1 target gene. Sca-1(high) allografts were more resistant to cisplatin/fluorouracil chemotherapy than Sca-1(negative) allografts, and overexpressed Bcl-xL. Eighty-five mouse genes overexpressed in Sca-1(high) S1 cells compared with Sca-1(negative) cells clustered 123 pretreatment gastric cancer patient samples according to survival following chemotherapy. Taken together, Sca-1 is a novel CSC enrichment marker that mediates TGF-β and Wnt/β-catenin signaling in mouse gastric cancer. Stem Cells 2016;34:1177-1187. © 2016 AlphaMed Press.