WorldWideScience

Sample records for cancer cells harbouring

  1. Senescent cells harbour features of the cancer epigenome

    OpenAIRE

    Cruickshanks, Hazel A; McBryan, Tony; Nelson, David M.; VanderKraats, Nathan D.; Shah, Parisha P.; van Tuyn, John; Rai, Taranjit Singh; Brock, Claire; Donahue, Greg; Dunican, Donncha S; Drotar, Mark E.; Meehan, Richard R.; Edwards, John R.; Berger, Shelley L.; Adams, Peter D.

    2013-01-01

    Altered DNA methylation and associated destabilization of genome integrity and function is a hallmark of cancer. Replicative senescence is a tumour suppressor process that imposes a limit on the proliferative potential of normal cells that all cancer cells must bypass. Here we show by whole-genome single-nucleotide bisulfite sequencing that replicative senescent human cells exhibit widespread DNA hypomethylation and focal hypermethylation. Hypomethylation occurs preferentially at gene-poor, l...

  2. Proliferation and survival molecules implicated in the inhibition of BRAF pathway in thyroid cancer cells harbouring different genetic mutations

    International Nuclear Information System (INIS)

    Thyroid carcinomas show a high prevalence of mutations in the oncogene BRAF which are inversely associated with RAS or RET/PTC oncogenic activation. The possibility of using inhibitors on the BRAF pathway as became an interesting therapeutic approach. In thyroid cancer cells the target molecules, implicated on the cellular effects, mediated by inhibition of BRAF are not well established. In order to fill this lack of knowledge we studied the proliferation and survival pathways and associated molecules induced by BRAF inhibition in thyroid carcinoma cell lines harbouring distinct genetic backgrounds. Suppression of BRAF pathway in thyroid cancer cell lines (8505C, TPC1 and C643) was achieved using RNA interference (RNAi) for BRAF and the kinase inhibitor, sorafenib. Proliferation analysis was performed by BrdU incorporation and apoptosis was accessed by TUNEL assay. Levels of protein expression were analysed by western-blot. Both BRAF RNAi and sorafenib inhibited proliferation in all the cell lines independently of the genetic background, mostly in cells with BRAFV600E mutation. In BRAFV600E mutated cells inhibition of BRAF pathway lead to a decrease in ERK1/2 phosphorylation and cyclin D1 levels and an increase in p27Kip1. Specific inhibition of BRAF by RNAi in cells with BRAFV600E mutation had no effect on apoptosis. In the case of sorafenib treatment, cells harbouring BRAFV600E mutation showed increase levels of apoptosis due to a balance of the anti-apoptotic proteins Mcl-1 and Bcl-2. Our results in thyroid cancer cells, namely those harbouring BRAFV600Emutation showed that BRAF signalling pathway provides important proliferation signals. We have shown that in thyroid cancer cells sorafenib induces apoptosis by affecting Mcl-1 and Bcl-2 in BRAFV600E mutated cells which was independent of BRAF. These results suggest that sorafenib may prove useful in the treatment of thyroid carcinomas, particularly those refractory to conventional treatment and harbouring BRAF

  3. Incidence of Child cancers in the Finistere and around the Brest harbour between 1991 and 2005

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

    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

  5. Mitogen and antigen induced B and T cell responses of peripheral blood mononuclear cells from the harbour seal (Phoca vitulina)

    OpenAIRE

    Swart, Rik; Kluten, Ruud; Huizing, Carla; Vedder, Lies; Reijnders, P.J.H.; Visser, Ilona; Uytdehaag, Fons; Osterhaus, Albert

    1993-01-01

    textabstractIn vitro assays were developed for studies concerning the functioning of the immune system of the harbour seal (Phoca vitulina). Proliferative responses of peripheral blood mononuclear cells (PBMC) were measured after stimulation with different concentrations of the mitogens concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA) or lipopolysaccharide from Salmonella typhimurium (LPS). Con A and PWM induced strong proliferative responses, while PHA and LPS induce...

  6. Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations.

    Science.gov (United States)

    Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte K Y; Geyer, Felipe C; De Filippo, Maria R; Eberle, Carey A; Akram, Muzaffar; Fusco, Nicola; Ichihara, Shu; Sakr, Rita A; Yatabe, Yasushi; Vincent-Salomon, Anne; Rakha, Emad A; Ellis, Ian O; Wen, Y Hannah; Weigelt, Britta; Schnitt, Stuart J; Reis-Filho, Jorge S

    2016-04-01

    Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute

  7. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC ...

  8. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  9. 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. PMID:24476000

  10. 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 structur

  11. Squamous cell skin cancer

    Science.gov (United States)

    ... earliest form of squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type ... cancer; Squamous cell carcinoma of the skin Images Bowen's disease on the hand Keratoacanthoma Keratoacanthoma Skin cancer, squamous ...

  12. 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. PMID:27208781

  13. 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.

  14. Hallmarks of cancer stem cell metabolism.

    Science.gov (United States)

    Sancho, Patricia; Barneda, David; Heeschen, Christopher

    2016-06-14

    Cancer cells adapt cellular metabolism to cope with their high proliferation rate. Instead of primarily using oxidative phosphorylation (OXPHOS), cancer cells use less efficient glycolysis for the production of ATP and building blocks (Warburg effect). However, tumours are not uniform, but rather functionally heterogeneous and harbour a subset of cancer cells with stemness features. Such cancer cells have the ability to repopulate the entire tumour and thus have been termed cancer stem cells (CSCs) or tumour-initiating cells (TICs). As opposed to differentiated bulk tumour cells relying on glycolysis, CSCs show a distinct metabolic phenotype that, depending on the cancer type, can be highly glycolytic or OXPHOS dependent. In either case, mitochondrial function is critical and takes centre stage in CSC functionality. Remaining controversies in this young and emerging research field may be related to CSC isolation techniques and/or the use of less suitable model systems. Still, the apparent dependence of CSCs on mitochondrial function, regardless of their primary metabolic phenotype, represents a previously unrecognised Achilles heel amendable for therapeutic intervention. Elimination of highly chemoresistant CSCs as the root of many cancers via inhibition of mitochondrial function bears the potential to prevent relapse from disease and thus improve patients' long-term outcome. PMID:27219018

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

    International Nuclear Information System (INIS)

    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. 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. Our experiments demonstrated an effective action of Dabrafenib (GSK2118436) and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations. These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  18. 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 ...

  19. Cancer Stem Cells

    OpenAIRE

    Katarzyna Wieczorek; Jolanta Niewiarowska

    2008-01-01

    Cancer stem cell theory gains increasingly greater significance in the world of medicine. Numerous findings of scientific research in vivo and in vitro indicate that it is the population of undifferentiated, self-renewing cells which is responsible for recurrence of cancer and metastasis. Similarly to normal stem cells, cancer stem cells (CSC) function in the environment of the other cells of the organism, called the niche, where they receive signals for differentiation and proliferation proc...

  20. Lung Cancer Stem Cells

    OpenAIRE

    Pine, Sharon R.; Blair Marshall; Lyuba Varticovski

    2008-01-01

    Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation p...

  1. Breast cancer stem cells

    OpenAIRE

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    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 tumors 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 th...

  2. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

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

    NARCIS (Netherlands)

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

    2013-01-01

    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 bl

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

    NARCIS (Netherlands)

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

    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 bl

  5. Gastric Cancer Stem Cells

    OpenAIRE

    Takaishi, Shigeo; Okumura, Tomoyuki; Timothy C Wang

    2008-01-01

    Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony format...

  6. Cancer stem cell metabolism

    OpenAIRE

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

    2016-01-01

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. 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. Deter...

  7. 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...

  8. Response to erlotinib in a patient with lung adenocarcinoma harbouring the EML4-ALK translocation: A case report

    OpenAIRE

    Alì, Greta; Chella, Antonio; Lupi, Cristiana; Proietti, Agnese; NICCOLI, CRISTINA; BOLDRINI, LAURA; DAVINI, FEDERICO; Mussi, Alfredo; FONTANINI, GABRIELLA

    2015-01-01

    Lung cancer is the leading cause of cancer-associated mortality worldwide, and the mainstay of treatment remains to be personalised therapy. Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have been reported to exert a significant impact in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harbouring mutations in the EGFR gene. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocatio...

  9. Small cell lung cancer transformation and T790M mutation: complimentary roles in acquired resistance to kinase inhibitors in lung cancer

    OpenAIRE

    Kenichi Suda; Isao Murakami; Kazuko Sakai; Hiroshi Mizuuchi; Shigeki Shimizu; Katsuaki Sato; Kenji Tomizawa; Shuta Tomida; Yasushi Yatabe; Kazuto Nishio; Tetsuya Mitsudomi

    2015-01-01

    Lung cancers often harbour a mutation in the epidermal growth factor receptor (EGFR) gene. Because proliferation and survival of lung cancers with EGFR mutation solely depend on aberrant signalling from the mutated EGFR, these tumours often show dramatic responses to EGFR tyrosine kinase inhibitors (TKIs). However, acquiring resistance to these drugs is almost inevitable, thus a better understanding of the underlying resistance mechanisms is critical. Small cell lung cancer (SCLC) transformat...

  10. Gefitinib in Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Raffaele Costanzo

    2011-01-01

    Full Text Available Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR that plays a key role in the biology of non small cell lung cancer (NSCLC. Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

  11. Cancer Stem Cells, Cancer Cell Plasticity and Radiation Therapy

    OpenAIRE

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    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 ...

  12. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    MatthewJNaylor

    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.

  13. 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.)

  14. Fingerprints in cancer cells

    International Nuclear Information System (INIS)

    Gene research has shown that factors causing cancer, or carcinogens, may leave marks typical of each particular carcinogen (fingerprints) in the genotype of the cell. Radiation, for instance, may leave such fingerprints in a cancer cell. In particular, the discovery of a gene called p53 has yielded much new information on fingerprints. It has been discovered, for example, that toxic fungus and UV-radiation each leave fingerprints in the p53 gene. Based on the detection of fingerprints, it may be possible in the future to tell a cancer patient what factor had trigged the maglinancy

  15. Prostate cancer stem cells

    OpenAIRE

    Tu, Shi-Ming; Lin, Sue-Hwa

    2011-01-01

    Stem cells have long been implicated in prostate glandular 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 AR− status of prostate stem cells renders them inherently insensitive to androgen blockade ther...

  16. Stem Cells and Cancer

    International Nuclear Information System (INIS)

    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)

  17. Cancer Stem Cells in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer

  18. Cancer Stem Cells

    OpenAIRE

    Aurelio Lorico; Eric Deutsch; Bo Lu; Shih-Hwa Chiou

    2011-01-01

    Cancer Stem Cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into an animal host. A number of cell surface markers such as CD44, CD24, and CD133 are often used to identify and enrich CSCs. A regulatory network consisting of microRNAs and Wnt/β-catenin, Notch, and Hedgehog signaling pathways controls the CSC properties. The clinical relevance of CSCs has been strengthened by emerging evidence,...

  19. Functional recovery of human cells harbouring the mitochondrial DNA mutation MERRF A8344G via peptide-mediated mitochondrial delivery.

    Science.gov (United States)

    Chang, Jui-Chih; Liu, Ko-Hung; Li, Yu-Chi; Kou, Shou-Jen; Wei, Yau-Huei; Chuang, Chieh-Sen; Hsieh, Mingli; Liu, Chin-San

    2013-01-01

    We explored the feasibility of mitochondrial therapy using the cell-penetrating peptide Pep-1 to transfer mitochondrial DNA (mtDNA) between cells and rescue a cybrid cell model of the mitochondrial disease myoclonic epilepsy with ragged-red fibres (MERRF) syndrome. Pep-1-conjugated wild-type mitochondria isolated from parent cybrid cells incorporating a mitochondria-specific tag were used as donors for mitochondrial delivery into MERRF cybrid cells (MitoB2) and mtDNA-depleted Rho-zero cells (Mitoρ°). Forty-eight hours later, translocation of Pep-1-labelled mitochondria into the mitochondrial regions of MitoB2 and Mitoρ° host cells was observed (delivery efficiencies of 77.48 and 82.96%, respectively). These internalized mitochondria were maintained for at least 15 days in both cell types and were accompanied by mitochondrial function recovery and cell survival by preventing mitochondria-dependent cell death. Mitochondrial homeostasis analyses showed that peptide-mediated mitochondrial delivery (PMD) also increased mitochondrial biogenesis in both cell types, but through distinct regulatory pathways involving mitochondrial dynamics. Dramatic decreases in mitofusin-2 (MFN2) and dynamin-related protein 1/fission 1 were observed in MitoB2 cells, while Mitoρ° cells showed a significant increase in optic atrophy 1 and MFN2. These findings suggest that PMD can be used as a potential therapeutic intervention for mitochondrial disorders. PMID:23006856

  20. Cancer Stem Cells in Breast Cancer

    OpenAIRE

    Fumitaka Takeshita; Tomohiro Fujiwara; Takahiro Ochiya; Makiko Ono; Ryou-u Takahashi

    2011-01-01

    The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cel...

  1. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

    ... Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell ... seen in young adults. Patients with mediastinal nonseminomatous EGC are typically classed as poor risk patients because ...

  2. Cancer stem cells in prostate cancer

    OpenAIRE

    Moltzahn, Felix; Thalmann, George N

    2013-01-01

    Prostate cancer (P-Ca) remains a leading cause of cancer-related death in men. Lately, increasing evidence for a hierarchically organized cancer stem cell (CSC) model emerged for different tumors entities, including P-Ca. CSCs are defined by several characteristics including self-renewal, pluripotency and tumorigenicity and are thought to be responsible for tumor recurrence, metastasis and cancer related death. In this review we discuss the recent research in the field of CSCs, its limitation...

  3. Cancer Stem Cells in Pancreatic Cancer

    OpenAIRE

    Karl-Walter Jauch; Hendrik Seeliger; Hanno Niess; Qi Bao; Andrea Renner; Yue Zhao; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC t...

  4. Intratumour variation of biomarker expression by immunohistochemistry in resectable non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Ravn, Jesper;

    2013-01-01

    truly reflect the pattern of biomarker expression. It may also be an important factor in chemo resistance, as tumours with heterogeneous biomarker expression may potentially harbour chemo resistant tumour clones. MATERIALS AND METHODS: Immunohistochemical evaluation of the expression of excision repair...... intratumour heterogeneity in 33-87% of tumours examined. This heterogeneity may influence results in studies investigating the therapeutic impact of predictive biomarkers in non-small cell lung cancer (NSCLC)....

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

    OpenAIRE

    Mafalda Costa Neves; Gordon Stamp; Satvinder Mudan

    2015-01-01

    Introduction: Gastrointestinal stromal tumours (GISTs) are thought to derive from or differentiate towards the interstitial cells of Cajal (ICC) as most demonstrate a similar immunoprofile: CD117+, CD34+ and DOG1+. ICC hyperplasia refers to KIT-expressing microscopic spindle cell proliferations involving the myenteric plexus. Case report: 74 year-old male presented with a 5-year history of heartburn and dysphagia. Imaging revealed a 4 cm GIST in the gastric fundus. Pathology of the resecte...

  6. Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles.

    Science.gov (United States)

    Mkandawire, M M; Lakatos, M; Springer, A; Clemens, A; Appelhans, D; Krause-Buchholz, U; Pompe, W; Rödel, G; Mkandawire, M

    2015-06-28

    A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer. PMID:26022234

  7. Cancer stem cell subsets and their relationships

    OpenAIRE

    Pan Yi-Fei; Yang Han; Chen Chong; Liu Hai-Guang; Zhang Xiao-Hua

    2011-01-01

    Abstract Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells, migrating cancer stem cells and chemoradioresistant cancer stem cells, playing different roles in cancer initiati...

  8. Urothelial Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Irena Dimov

    2010-01-01

    Full Text Available There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs, which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies.

  9. 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.

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

    OpenAIRE

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

    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 resea...

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

    Institute of Scientific and Technical Information of China (English)

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

    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.

  12. Immunotargeting of cancer stem cells

    OpenAIRE

    Kwiatkowska-Borowczyk, Eliza P.; Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

    2015-01-01

    Cancer stem cells (CSCs) represent a distinctive population of tumour cells that control tumour initiation, progression, and maintenance. Their influence is great enough to risk the statement that successful therapeutic strategy must target CSCs in order to eradicate the disease. Because cancer stem cells are highly resistant to chemo- and radiotherapy, new tools to fight against cancer have to be developed. Expression of antigens such as ALDH, CD44, EpCAM, or CD133, which distinguish CSCs fr...

  13. Prostate stem cells and cancer

    OpenAIRE

    Nikitin, Alexander Y.; Matoso, A; Roy-Burman, P

    2007-01-01

    Properties shared by neoplastic and stem cells indicate a possibility that somatic stem cells or transit-amplifying cells that have reacquired stem cell properties, particularly the ability for self-renewal, represent favorable targets for malignant transformation. In this review we discuss significance of the stem cell model for understanding prostate cancer pathogenesis and describe relevant studies in animals. It is proposed that dissemination of rare cancer stem ce...

  14. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  15. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  16. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  17. Ovarian cancer: emerging concept on cancer stem cells

    OpenAIRE

    Ponnusamy Moorthy P; Batra Surinder K

    2008-01-01

    Abstract Emerging evidence suggests that the capacity of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a dysregulated cellular self-renewal capacity. Cancer stem cells may originate due to the distribution into self-renewal and differentiation pathways occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells and cancer cell...

  18. THE HARBOUR DEFENCE MOTOR LAUNCHES

    Directory of Open Access Journals (Sweden)

    W.H. Rice

    2012-02-01

    Full Text Available One of the handiest small craft to emerge from the Second World War was the 72 fet Harbour Defence Motor Launch. It's purpose was to patrol harbours and their approaches and to guard against attack by swimmers or underwater vehicles such as 'chariots' or even submarines. For this task the craft was fitted with a small ASDIC outfit and carried eight depth charges. Surface armament comprised a three-pounder gun on the foredeck, twin Lewis guns on the bridge and a 20 mm Oerlikon aft.

  19. 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 ...

  20. Prostate cancer stem cell biology

    OpenAIRE

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  1. C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling

    OpenAIRE

    Zhu, Pingping; Wang, Yanying; Du, Ying; He, Lei; Huang, Guanling; Zhang, Geng; Yan, Xinlong; Fan, Zusen

    2015-01-01

    Liver cancer stem cells (CSCs) harbour self-renewal and differentiation properties, accounting for chemotherapy resistance and recurrence. However, the molecular mechanisms to sustain liver CSCs remain largely unknown. In this study, based on analysis of several hepatocellular carcinoma (HCC) transcriptome datasets and our experimental data, we find that C8orf4 is weakly expressed in HCC tumours and liver CSCs. C8orf4 attenuates the self-renewal capacity of liver CSCs and tumour propagation. ...

  2. Mouse models for cancer stem cell research

    OpenAIRE

    Cheng, Le; Ramesh, Anirudh V.; Flesken-Nikitin, Andrea; Choi, Jinhyang; Nikitin, Alexander Yu.

    2009-01-01

    Cancer stem cell concept assumes that cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor initiating cells, which are able to reproduce themselves and produce phenotypically heterogeneous cells with lesser tumorigenic potential. Cancer stem cells represent an appealing target for development of more selective and efficient therapies. However, direct testing of the cancer stem cell concept and assessment of its therapeutic implications in human...

  3. Eradicating cancer cells: struggle with a chameleon

    OpenAIRE

    Di, Jiabo; Boer, Tjitske Duiveman-de; Figdor, Carl G.; Torensma, Ruurd

    2011-01-01

    Eradication of cancer stem cells to abrogate tumor growth is a new treatment modality. However, like normal cells cancer cells show plasticity. Differentiated tumor stem cells can acquire stem cell properties when they gain access to the stem cell niche. This indicates that eradicating of stem cells (emptying of the niche) alone will not lead to eradication of the tumor. Treatment should be directed to cancer stem cells ànd more mature cancer cells.

  4. Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

    OpenAIRE

    Wang, Jian-Lin; Yu, Jing-Ping; Zhi-qiang SUN; Sun, Su-Ping

    2014-01-01

    AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics.

  5. Chemotherapy targeting cancer stem cells

    OpenAIRE

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cance...

  6. Single cancer cell analysis on a chip

    OpenAIRE

    Yang, Yoonsun

    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 blood. We designed and developed various microfluidic devices for genetic and phenotypic characterization of single cancer cells. The limited DNA content in a single cell requires DNA amplification t...

  7. Cell of origin of lung cancer

    OpenAIRE

    Hanna, Jennifer M.; Onaitis, Mark W.

    2013-01-01

    Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s) of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell o...

  8. Head and Neck Cancer Stem Cells

    OpenAIRE

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signalin...

  9. A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis

    OpenAIRE

    Gao, Yanzhe; Mutter-Rottmayer, Elizabeth; Greenwalt, Alicia M.; Goldfarb, Dennis; Yan, Feng; Yang, Yang; Martinez-Chacin, Raquel C.; Pearce, Kenneth H.; Tateishi, Satoshi; Major, Michael B.; Vaziri, Cyrus

    2016-01-01

    Trans-lesion synthesis (TLS) is an important DNA-damage tolerance mechanism that permits ongoing DNA synthesis in cells harbouring damaged genomes. The E3 ubiquitin ligase RAD18 activates TLS by promoting recruitment of Y-family DNA polymerases to sites of DNA-damage-induced replication fork stalling. Here we identify the cancer/testes antigen melanoma antigen-A4 (MAGE-A4) as a tumour cell-specific RAD18-binding partner and an activator of TLS. MAGE-A4 depletion from MAGE-A4-expressing cancer...

  10. 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. PMID:26727965

  11. Cancer Stem Cell Hypothesis: Implication for Cancer Prevention and Treatment

    OpenAIRE

    Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya

    2016-01-01

    BACKGROUND: Cancer is a disease of genomic instability, evasion of immune cells, and adaptation of the tumor cells to the changing environment. Genetic heterogeneity caused by tumors and tumor microenvironmental factors forms the basis of aggressive behavior of some cancer cell populations. CONTENT: Cancers arise in self-renewing cell populations and that the resulting cancers, like their normal organ counterparts, are composed of hierarchically organized cell populations. Self–renewing “...

  12. Prostate Cancer Stem Cells: Research Advances

    OpenAIRE

    Dagmara Jaworska; Wojciech Król; Ewelina Szliszka

    2015-01-01

    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 th...

  13. Stem cells in human breast cancer

    OpenAIRE

    Roberto Oliveira, Lucinei; Jeffrey, Stefanie S; Ribeiro Silva, Alfredo

    2010-01-01

    Increasing data support cancer as a stem cell-based disease. Cancer stem cells (CSCs) have beenfound in different human cancers, and recent evidenceindicates that breast cancer originates from and ismaintained by its own CSCs, as well as the normalmammary gland. Mammary stem cells and breast CSCshave been identified and purified in in vitroculturesystems, transplantation assays and/or by cell surfaceantigen identification. Cell surface markers enable thefunctional isolation of stem cells that...

  14. 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......, the last part of the review discusses future directions of this intriguing new research field in the context of new diagnostic and therapeutic opportunities....

  15. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

    OpenAIRE

    Chang W. Song; Hyemi Lee; Dings, Ruud P. M.; Brent Williams; John Powers; Troy Dos Santos; Bo-Hwa Choi; Heon Joo Park

    2012-01-01

    The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, ...

  16. Water circulation forecasting in Spanish harbours

    OpenAIRE

    Grifoll, Manel; Jordá, Gabriel; Sotillo, Marcos G.; Ferrer, Luis; Espino, Manuel; Sánchez-Arcilla, Agustín; Álvarez-Fanjul, Enrique

    2012-01-01

    This paper describes the first harbour circulation forecasting system implemented in Spain. The configuration design was based on previous analyses of the morphologic and hydrodynamic behaviour of three harbours: Barcelona, Tarragona and Bilbao. A nested system of oceanic models was implemented, with a scope ranging from the regional scale (with a mean horizontal resolution of 5 km) to the harbour scale (with a mean horizontal resolution of 40 m). A set of sensitivity tests was carried out in...

  17. Nanomechanical analysis of cells from cancer patients

    Science.gov (United States)

    Cross, Sarah E.; Jin, Yu-Sheng; Rao, Jianyu; Gimzewski, James K.

    2007-12-01

    Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread. Despite several studies on architectural changes in cultured cell lines, no ex vivo mechanical analyses of cancer cells obtained from patients have been reported. Using atomic force microscopy, we report the stiffness of live metastatic cancer cells taken from the body (pleural) fluids of patients with suspected lung, breast and pancreas cancer. Within the same sample, we find that the cell stiffness of metastatic cancer cells is more than 70% softer, with a standard deviation over five times narrower, than the benign cells that line the body cavity. Different cancer types were found to display a common stiffness. Our work shows that mechanical analysis can distinguish cancerous cells from normal ones even when they show similar shapes. These results show that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.

  18. Role of cancer stem cells in hepatocarcinogenesis

    OpenAIRE

    Wang, Bo; Jacob, Samson T.

    2011-01-01

    There has been considerable interest in cancer stem cells (CSCs) among cancer biologists and clinicians, most likely because of their role in the heterogeneity of cancer and their potential application in cancer therapeutics. Recent studies suggest that CSCs play a key role in liver carcinogenesis. A small subpopulation of cancer cells with CSC properties has been identified and characterized from hepatocellular carcinoma (HCC) cell lines, animal models and human primary HCCs. Considering the...

  19. 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...

  20. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  1. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  2. 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

  3. Colon cancer stem cells: implications in carcinogenesis

    OpenAIRE

    Sanders, Matthew A.; Majumdar, Adhip P. N.

    2011-01-01

    The cancer stem cell model was described for hematologic malignancies in 1997 and since then evidence has emerged to support it for many solid tumors as well, including colon cancer. This model proposes that certain cells within the tumor mass are pluripotent and capable of self-renewal and have an enhanced ability to initiate distant metastasis. The cancer stem cell model has important implications for cancer treatment, since most current therapies target actively proliferating cells and may...

  4. What makes cancer stem cell markers different?

    OpenAIRE

    Karsten, Uwe; Goletz, Steffen

    2013-01-01

    Since the cancer stem cell concept has been widely accepted, several strategies have been proposed to attack cancer stem cells (CSC). Accordingly, stem cell markers are now preferred therapeutic targets. However, the problem of tumor specificity has not disappeared but shifted to another question: how can cancer stem cells be distinguished from normal stem cells, or more specifically, how do CSC markers differ from normal stem cell markers? A hypothesis is proposed which might help to solve t...

  5. 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 ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  6. Colorectal Cancer Stem Cells and Cell Death

    International Nuclear Information System (INIS)

    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

  7. The relationship of cancer stem cells in urological cancers

    OpenAIRE

    Marta Pokrywczyńska; Jan Adamowicz; Jakub Tworkiewicz; Zbigniew Wolski; Tomasz Drewa

    2013-01-01

    Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  8. The relationship of cancer stem cells in urological cancers

    Directory of Open Access Journals (Sweden)

    Marta Pokrywczyńska

    2013-08-01

    Full Text Available Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  9. Glutathione in Cancer Cell Death

    International Nuclear Information System (INIS)

    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

  10. 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.

  11. [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. PMID:26486534

  12. Understanding the cancer stem cell

    OpenAIRE

    Bomken, S; Fišer, K; Heidenreich, O; Vormoor, J

    2010-01-01

    The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be as rare as thought first, at least in some malignancies. Improved experimental models are beginning to uncover a less rigid structure to CSC biology, in which the concepts of fun...

  13. 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.

  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

    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 epitheli

  15. Extinction Models for Cancer Stem Cell Therapy

    OpenAIRE

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet ,; Lange, Kenneth

    2009-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tool...

  16. Cancer stem cells: the lessons from pre-cancerous stem cells

    OpenAIRE

    Gao, Jian-Xin

    2007-01-01

    Abstract How a cancer is initiated and established remains elusive despite all the advances in decades of cancer research. Recently the cancer stem cell (CSC) hypothesis has been revived, challenging the long-standing model of ‘clonal evolution’ for cancer development and implicating the dawning of a potential cure for cancer [1]. The recent identification of pre-cancerous stem cells (pCSCs) in cancer, an early stage of CSC development, however, implicates that the clonal evolution is not con...

  17. FR901228 in Treating Patients With Refractory or Progressive Small Cell Lung Cancer or Non-small Cell Lung Cancer

    Science.gov (United States)

    2013-08-14

    Extensive Stage Small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer

  18. Breast cancer stem cells: implications for therapy of breast cancer

    OpenAIRE

    Morrison, Brian J.; Schmidt, Chris W.; Lakhani, Sunil R; Reynolds, Brent A.; Lopez, J. Alejandro

    2008-01-01

    The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to...

  19. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models......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...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...

  20. Cancer Stem Cells Converted from Pluripotent Stem Cells and the Cancerous Niche

    OpenAIRE

    Kasai, T; Chen, L.; Mizutani, AZ; Kudoh, T.; Murakami, H; Fu, L.; Seno, M

    2014-01-01

    Nowadays, the cancer stem cells are considered to be significantly responsible for growth, metastasis, invasion and recurrence of all cancer. Cancer stem cells are typically characterized by continuous proliferation and self-renewal as well as by differentiation potential, while stem cells are considered to differentiate into tissue- specific phenotype of mature cells under the influence of micro-environment. Cancer stem cells should be traced to the stem cells under the influence of a micro-...

  1. Cancer stem cells in head and neck cancer

    OpenAIRE

    Trapasso S; Allegra E

    2012-01-01

    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 differe...

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

    OpenAIRE

    Lennard, Thomas W.J.; Meeson, Annette P; Britton, Kelly M.; Kirby, John A.

    2011-01-01

    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....

  3. Cancer stem cells, tumor dormancy, and metastasis

    OpenAIRE

    EmilyChen

    2012-01-01

    Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs) in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignanc...

  4. Cancer stem cells and brain tumors

    OpenAIRE

    Pérez Castillo, Ana; Aguilar Morante, Diana; Morales-García, José A.; Dorado, Jorge

    2008-01-01

    Besides the role of normal stem cells in organogenesis, cancer stem cells are thought to be crucial for tumorigenesis. Most current research on human tumors is focused on molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and, more recently, in solid tumors suggests that the tumor cell population is heterogeneous. In recent years, several groups have described the existence of a cancer stem cell population in different brain tumors. These neural cancer stem ...

  5. Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells

    OpenAIRE

    Gschweng, Eric Hans

    2015-01-01

    Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, t...

  6. Metastasis-Initiating Cells in Renal Cancer

    OpenAIRE

    Khan, Mohammed I.; Czarnecka, Anna M; Duchnowska, Renata; Kukwa, Wojciech; Szczylik, Cezary

    2013-01-01

    Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of rena...

  7. Mitotic Control of Cancer Stem Cells

    OpenAIRE

    Venere, Monica; Miller, Tyler E.; Rich, Jeremy N.

    2013-01-01

    Cancer stem cells are self-renewing, tumorigenic cells at the apex of tumor hierarchies, and postulated to be quiescent in many tumor types. This issue of Cancer Discovery highlights a study that links the presentation of kinetochores within mitosis to an essential requirement for BUB1B/BubR1, broadening our understanding of the cell-cycle machinery in cancer stem cells.

  8. Head and neck cancer stem cells.

    Science.gov (United States)

    Krishnamurthy, S; Nör, J E

    2012-04-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  9. Implications of Stem Cells and Cancer Stem Cells for Understanding Fomation and Therapy of Cancer

    Institute of Scientific and Technical Information of China (English)

    Guanghui Li; Donglin Wang

    2005-01-01

    Most cancers are heterogeneous with respect to proliferation and differentiation. There is increasing evidence suggesting that only a minority of cancer cells, tumorigenic or tumor initiating cells, possess the capacity to proliferate extensively and form new hematopoietic cancer or solid tumors. Tumor initiating cells share characteristics required for normal stem cells. The dysregulation of self-renewal and proliferation of stem cells is a likely requirement for cancer development. This review formulates a model for the origin of cancer stem cells and regulating self-renewal which influences the way we study and treat cancer.

  10. Gossypol Induced Cell Death in DU 145 Prostate Cancer Cells

    OpenAIRE

    Kennelly, Susan

    2010-01-01

    Cancer Biology Tumourigenesis is a multistep process which includes the transformation of healthy cells into extremely malignant cells, caused by the disruption of normal tissue homeostasis. Hanahan and Weinberg propose that there are a common set of 'acquired capabilities' that most if not all cancers posses's in order to survive and proliferate despite changes in their normal cell physiology during cancer development (Hanahan and Weinberg, 2000). These "Hallmarks of Cancer", according to...

  11. Dendritic cell-based cancer immunotherapy for colorectal cancer

    OpenAIRE

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are curr...

  12. Targeted therapies in small cell lung cancer

    OpenAIRE

    LU, HONG-YANG; Wang, Xiao-Jia; Mao, Wei-Min

    2012-01-01

    Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted...

  13. Mitochondria, cholesterol and cancer cell metabolism.

    Science.gov (United States)

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C

    2016-12-01

    Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways. PMID:27455839

  14. Cell of origin of lung cancer

    Directory of Open Access Journals (Sweden)

    Jennifer M Hanna

    2013-01-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell of origin, and cancer stem cells has been hampered by the heterogeneity of the disease, the lack of good in vivo transplantation models to assess stem cell behavior, and an overall incomplete understanding of the epithelial stem cell hierarchy. As such, a systematic computerized literature search of the MEDLINE database was used to identify articles discussing current knowledge about normal lung and lung cancer stem cells or progenitor cells. In this review, we discuss what is currently known about the role of cancer-initiating cells and normal stem cells in the development of lung tumors.

  15. CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells

    OpenAIRE

    Xu, Haineng; Mu, Jiasheng; Xiao, Jing; Wu, Xiangsong; Li, Maolan; Liu, Tianrun; Liu, Xinyuan

    2015-01-01

    Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, che...

  16. Mechanisms of Therapeutic Resistance in Cancer (Stem) Cells with Emphasis on Thyroid Cancer Cells

    OpenAIRE

    Hombach-Klonisch, Sabine; Natarajan, Suchitra; Thanasupawat, Thatchawan; Medapati, Manoj; PATHAK, ALOK; Ghavami, Saeid; Klonisch, Thomas

    2014-01-01

    The two main reasons for death of cancer patients, tumor recurrence and metastasis, are multi-stage cellular processes that involve increased cell plasticity and coincide with elevated resistance to anti-cancer treatments. Epithelial-to-mesenchymal transition (EMT) is a key contributor to metastasis in many cancer types, including thyroid cancer and is known to confer stem cell-like properties onto cancer cells. This review provides an overview of molecular mechanisms and factors known to con...

  17. The biology of cancer stem cells.

    Science.gov (United States)

    Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F

    2007-01-01

    Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies. PMID:17645413

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

    OpenAIRE

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

    2010-01-01

    Abstract Background 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 b...

  19. Cancer Stem Cells: From Bench to Bedside

    OpenAIRE

    Jones, Richard J.; Matsui, William

    2007-01-01

    Objective clinical responses to anticancer treatments often do not translate into substantial improvements in overall survival. Recent data suggesting many cancers arise from rare self-renewing cells (cancer stem cells) that are biologically distinct from their more numerous differentiated progeny, may explain this paradox. Current anticancer therapies have been developed to target the bulk of the tumor mass (i.e., the differentiated cancer cells). Although treatments directed against the bul...

  20. Dielectrophoretic separation of colorectal cancer cells

    OpenAIRE

    Yang, Fang; Yang, Xiaoming; Jiang, Hong; Bulkhaults, Phillip; Wood, Patricia; Hrushesky, William; Wang, Guiren

    2010-01-01

    Separation of colorectal cancer cells from other biological materials is important for stool-based diagnosis of colorectal cancer. In this paper, we use conventional dielectrophoresis in a microfluidic chip to manipulate and isolate HCT116 colorectal cancer cells. It is noticed that at a particular alternating current frequency band, the HCT116 cells are clearly deflected to a side channel from the main channel after the electric activation of an electrode pair. This motion caused by negative...

  1. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

    Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

  2. Cancer Stem Cells in Lung Tumorigenesis

    OpenAIRE

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2010-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continue...

  3. Role of stem cells in cancer therapy and cancer stem cells: a review

    OpenAIRE

    Sales Kevin; Chaib Boussad; Sagar Jayesh; Winslet Marc; Seifalian Alexander

    2007-01-01

    Abstract For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research fi...

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

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  5. Breast cancer stem-like cells and breast cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

    @@ Until the early 1990s, human cancers were considered a morphologically heterogeneous population of cells. In 1997, Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone was organized as a hierarchy; this was subsequently denoted as cancer stem like cells (CSCs). CSCs are cancer cells that possess characteristics associated with normal stem cells and have the specific ability to give rise to all cell types found in a particular cancer. One reason for the failure of traditional anti tumor therapies might be their inability to eradicate CSCs. Therefore, therapies must identify and destroy CSCs in both primary and metastatic tumors.

  6. Adipocyte activation of cancer stem cell signaling in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

    Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

  7. Confocal Raman imaging for cancer cell classification

    Science.gov (United States)

    Mathieu, Evelien; Van Dorpe, Pol; Stakenborg, Tim; Liu, Chengxun; Lagae, Liesbet

    2014-05-01

    We propose confocal Raman imaging as a label-free single cell characterization method that can be used as an alternative for conventional cell identification techniques that typically require labels, long incubation times and complex sample preparation. In this study it is investigated whether cancer and blood cells can be distinguished based on their Raman spectra. 2D Raman scans are recorded of 114 single cells, i.e. 60 breast (MCF-7), 5 cervix (HeLa) and 39 prostate (LNCaP) cancer cells and 10 monocytes (from healthy donors). For each cell an average spectrum is calculated and principal component analysis is performed on all average cell spectra. The main features of these principal components indicate that the information for cell identification based on Raman spectra mainly comes from the fatty acid composition in the cell. Based on the second and third principal component, blood cells could be distinguished from cancer cells; and prostate cancer cells could be distinguished from breast and cervix cancer cells. However, it was not possible to distinguish breast and cervix cancer cells. The results obtained in this study, demonstrate the potential of confocal Raman imaging for cell type classification and identification purposes.

  8. Epigenetic targeting of ovarian cancer stem cells.

    Science.gov (United States)

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  9. 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.

  10. Breathless cancer cells get fat on glutamine

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Anastasiou; Lewis C Cantley

    2012-01-01

    Many cancer cells depend on glutamine as a fuel for proliferation,yet the mechanisms by which glutamine supports cancer metabolism are not fully understood.Two recent studies highlight an important role for glutamine in the synthesis of lipids and provide novel insights into how glutamine metabolism could be targeted for cancer therapy.

  11. Cancer stem cell targeted therapy: progress amid controversies

    OpenAIRE

    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 illu...

  12. Resveratrol induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jia-hua; CHENG Hai-yan; YU Ze-qian; HE Dao-wei; PAN Zheng; YANG De-tong

    2011-01-01

    Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years.Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer.The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.Results In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells,capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.Conclusion Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.

  13. Markers of small cell lung cancer

    OpenAIRE

    Sharma SK; Taneja Tarvinder

    2004-01-01

    Abstract Lung cancer is the number one cause of cancer death; however, no specific serum biomarker is available till date for detection of early lung cancer. Despite good initial response to chemotherapy, small-cell lung cancer (SCLC) has a poor prognosis. Therefore, it is important to identify molecular markers that might influence survival and may serve as potential therapeutic targets. The review aims to summarize the current knowledge of serum biomarkers in SCLC to improve diagnostic effi...

  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. Targeting prostate cancer stem cells for cancer therapy

    OpenAIRE

    Wang, Guocan; Wang, Zhiwei; Sarkar, Fazlul H; Wei, Wenyi

    2012-01-01

    Prostate cancer (PCa) is the most common malignant neoplasm in men and the second most frequent cause of cancer death for males in the United States. Recently, emerging evidence suggests that prostate cancer stem cells (CSCs) may play a critical role in the development and progression of PCa. Therefore, targeting prostate CSCs for the prevention of tumor progression and treatment of PCa could become a novel strategy for better treatment of patients diagnosed with PCa. In this review article, ...

  16. Metastatic renal cell cancer treatments.

    Science.gov (United States)

    Sternberg, C N

    2003-01-01

    Metastatic renal cell carcinoma has been considered to be resistant to chemotherapy, with responses observed in only limited numbers of patients. For this reason, therapeutic options have ranged from no treatment, to immunotherapy with cytokines such as IL-2 and interferon-alpha, chemotherapy alone or in combination with cytokines, and to a variety of new investigational approaches. Interferon and interleukin-2 (IL-2) have led to long-term survival in selected patients. Immunotherapy with cytokines, monoclonal antibodies, new agents, dendritic cell therapy, and allotransplantation offer promise. Novel therapeutic strategies include combining cytokines, and antiangiogenic approaches such as thalidomide and antivascular endothelial growth factor therapy. Pathologic, cytogenic and molecular studies have proven that renal cell carcinoma is not a single tumor entity. Efforts to improve results also include the identification of prognostic factors, which allow treatment to be better directed towards those patients most likely to benefit. Increasing understanding of cancer biology is beginning to allow for a more targeted approach to the therapy of metastatic renal cell carcinoma. Adequate positioning of known treatments is essential and many trials of new targeted therapies are underway. PMID:14988745

  17. 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

  18. Tracheal metastasis of small cell lung cancer

    OpenAIRE

    De, Sajal

    2009-01-01

    Endotracheal metastases of primary lung cancer are rare. Only one case of tracheal metastasis from small cell lung cancer has been reported in literature. Here, we report a rare case of a 45-year-old woman who was admitted for sudden-onset breathlessness with respiratory failure and required ventilatory support. Endotracheal growth was identified during bronchoscopy, and biopsy revealed endotracheal metastasis of small cell lung cancer.

  19. Repopulation of Ovarian Cancer Cells After Chemotherapy

    OpenAIRE

    Telleria, Carlos M.

    2013-01-01

    The high mortality rate caused by ovarian cancer has not changed for the past thirty years. Although most patients diagnosed with this disease respond to cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci of cells almost always escape therapy, manage to survive, and acquire the capacity to repopulate the tumor. Repopulation of ovarian cancer cells that escape front-line chemotherapy, however, is a poorly understood phenomenon. Here I analyze cancer-initiating ce...

  20. Cell phones - do they cause cancer?

    Science.gov (United States)

    ... cancer URL of this page: //medlineplus.gov/ency/article/007151.htm Cell phones and cancer To use the sharing features ... adults. For this reason, some agencies and government organizations recommend that children avoid prolonged use of cell phones. REDUCING RISKS Although health problems related to ...

  1. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    OpenAIRE

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-01-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and sup...

  2. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    OpenAIRE

    Wenke YUE; JIAO, FENG; Liu, Bin; Jiacong YOU; Zhou, Qinghua

    2011-01-01

    Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung can...

  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 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.

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

    International Nuclear Information System (INIS)

    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

  6. Wnt Signaling in Cancer Stem Cell Biology

    Science.gov (United States)

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  7. Breast cancer stem cells and radiation

    Science.gov (United States)

    Phillips, Tiffany Marie

    2007-12-01

    The present studies explore the response of breast cancer stem cells (BCSC's) to radiation and the implications for clinical cancer treatment. Current cancer therapy eliminates bulky tumor mass but may fail to eradicate a critical tumor initiating cell population termed "cancer stem cells". These cells are potentially responsible for tumor formation, metastasis, and recurrence. Recently cancer stem cells have been prospectively identified in various malignancies, including breast cancer. The breast cancer stem cell has been identified by the surface markers CD44+/CD24 -(low). In vitro mammosphere cultures allow for the enrichment of the cancer stem cell population and were utilized in order to study differential characteristics of BCSC's. Initial studies found that BCSC's display increased radiation resistance as compared to other non-stem tumor cells. This resistance was accompanied by decreased H2AX phosphorylation, decreased reactive oxygen species formation, and increased phosphorylation of the checkpoint protein Chk1. These studies suggest differential DNA damage and repair within the BCSC population. Studies then examined the consequences of fractionated radiation on the BCSC population and found a two-fold increase in BCSC's following 5 x 3Gy. This observation begins to tie cancer stem cell self-renewal to the clinical stem cell phenomenon of accelerated repopulation. Accelerated repopulation is observed when treatment gaps increase between sequential fractions of radiotherapy and may be due to cancer stem cell symmetric self-renewal. The balance between asymmetric and symmetric stem cell division is vital for proper maintenance; deregulation is likely linked to cancer initiation and progression. The developmental Notch-1 pathway was found to regulate BCSC division. Over-expressing the constitutively active Notch-1-ICD in MCF7 cells produced an increase in the BCSC population. Additionally, radiation was observed to increase the expression of the Notch-1

  8. Haloarchaeal myovirus φCh1 harbours a phase variation system for the production of protein variants with distinct cell surface adhesion specificities.

    Science.gov (United States)

    Klein, R; Rössler, N; Iro, M; Scholz, H; Witte, A

    2012-01-01

    The φCh1 myovirus, which infects the haloalkaliphilic archaeon Natrialba magadii, contains an invertible region that comprises the convergent open reading frames (ORFs) 34 and 36, which code for the putative tail fibre proteins gp34 and gp36 respectively. The inversion leads to an exchange of the C-termini of these proteins, thereby creating different types of tail fibres. Gene expression experiments revealed that only ORF34 is transcribed, indicating that φCh1 produces tail fibre proteins exclusively from this particular ORF. Only one of the two types of tail fibres encoded by ORF34 is able to bind to Nab. magadii in vitro. This is reflected by the observation that during the early phases of the infection cycle, the lysogenic strain L11 carries its invertible region exclusively in the orientation that produces that specific type of tail fibre. Obviously, Nab. magadii can only be infected by viruses carrying this particular type of tail fibre. By mutational analysis, the binding domain of gp34 was localized to the C-terminal part of the protein, particularly to a galactose-binding domain. The involvement of galactose residues in cell adhesion was supported by the observation that the addition of α-D-galactose to purified gp34 or whole virions prevented their attachment to Nab. magadii. PMID:22111759

  9. Fentanyl inhibits cell viability in human pancreatic cancer cell line and tumor growth in pancreatic cancer cell-transplanted mice

    OpenAIRE

    Miao, Jianxia; Wang, Liangrong; Chen, Lei; Yang, Tao; Jin, Lida; Lin, Lina

    2015-01-01

    Pancreatic cancer is a kind of devastating disease with a high mortality rate. Fentanyl has been widely applied to anesthesia and analgesia in pancreatic cancer therapy, and is also demonstrated to inhibit the growth of some kinds of cancer cells in existed studies. To investigate the functions of fentanyl in pancreatic cancer, we conducted a series of in vivo and in vitro experiments using human pancreatic cancer cells SW1990 and fentanyl treatment. The cells were transplanted to BALB/c nude...

  10. Dendritic cell-based cancer immunotherapy for colorectal cancer

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  11. Cancer Stem Cells in the Thyroid

    Science.gov (United States)

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  12. Therapeutic strategies targeting cancer stem cells.

    Science.gov (United States)

    Ning, Xiaoyan; Shu, Jianchang; Du, Yiqi; Ben, Qiwen; Li, Zhaoshen

    2013-04-01

    Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy. PMID:23358473

  13. Ultrasound Effect on Cancerous versus Non-Cancerous Cells.

    Science.gov (United States)

    Azagury, Aharon; Amar-Lewis, Eliz; Yudilevitch, Yana; Isaacson, Carol; Laster, Brenda; Kost, Joseph

    2016-07-01

    Previous studies have found that cancer cells whose metastatic potential is low are more vulnerable to mechanical stress-induced trauma to their cytoskeleton compared with benign cells. Because ultrasound induces mechanical stresses on cells and tissues, it is postulated that there may be a way to apply ultrasound to tumors to reduce their ability to metastasize. The difference between low-malignant-potential cancer cells and benign cells could be a result of their different responses to the mechanical stress insonation induced. This hypothesis was tested in vitro and in vivo. Low-malignant-potential cells were found to be more sensitive to insonation, resulting in a significantly higher mortality rate compared with that of benign cells, 89% versus 21%, respectively. This effect can be controlled by varying ultrasound parameters: intensity, duration, and duty cycle. Thus, the results presented in this study suggest the application of ultrasound to discriminate between benign and malignant cells. PMID:27067417

  14. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    OpenAIRE

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is ...

  15. 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...

  16. Every Single Cell Clones from Cancer Cell Lines Growing Tumors In Vivo May Not Invalidate the Cancer Stem Cell Concept

    OpenAIRE

    Li, Fengzhi

    2009-01-01

    We present the result of our research on the tumorigenic ability of single cell clones isolated from an aggressive murine breast cancer cell line in a matched allografting mouse model. Tumor formation is basically dependent on the cell numbers injected per location. We argue that in vivo tumor formation from single cell clones, isolated in vitro from cancer cell lines, may not provide conclusive evidence to disprove the cancer stem cell (CSC) theory without additional data.

  17. Cancer stem cells in head and neck cancer.

    Science.gov (United States)

    Allegra, Eugenia; Trapasso, Serena

    2012-01-01

    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 the presence of specific surface markers for selective cytotoxic agent vehicles. Finally, some research groups are trying to induce these cells to

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

    OpenAIRE

    Narumol Bhummaphan; Pithi Chanvorachote

    2015-01-01

    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 ...

  19. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    Science.gov (United States)

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-08-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and supporting experiments suggest that there exist non-linear growth kinetics of CSCs and negative feedback mechanisms to control the balance between the population of CSCs and that of non-stem cancer cells. The model predictions can help us explain a few long-standing questions in the field of cancer stem cell research, and can be potentially used to predict the efficicacy of anti-cancer therapy.

  20. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  1. Metformin induces apoptosis of pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To assess the role and mechanism of mefformin in inducing apoptosis of pancreatic cancer cells. METHODS: The human pancreatic cancer cell lines ASPC-1, BxPc-3, PANC-1 and SW1990 were exposed to mefformin. The inhibition of cell proliferation and colony formation via apoptosis induction and S phase arrest in pancreatic cancer cell lines of mefformin was tested.RESULTS: In each pancreatic cancer cell line tested, metformin inhibited cell proliferation in a dose dependent manner in MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays). Flow cytometric analysis showed that metformin reduced the number of cells in G1 and increased the percentage of cells in S phase as well as the apoptotic fraction. Enzymelinked immunosorbent assay (EUSA) showed that metformin induced apaptosis in all pancreatic cancer cell lines. In Western blot studies, metformin induced oly-ADP-ribose polymerase(PARP) cleavage (an indicator of aspase activation) in all pancreatic cancer cell lines. The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells. We also observed that metformin treatment ramatically reduced epidermal growth factor receptor (EGFR) and phosphorylated mitogen activated protein kinase (P-MAPK) in both a time- and dose-dependent manner in all cell lines tested.CONCLUSION: Metformin significantly inhibits cell proliferation and apoptosis in all pancreatic cell lines. And the metformin-induced apoptosis is associated with PARP leavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner. Hence, both caspase-8 and -9-initiated apoptotic signaling pathways contribute to metforrnin-induced apoptosis in pancreatic cell lines.

  2. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    Science.gov (United States)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  3. AKT Inhibition Promotes Nonautonomous Cancer Cell Survival.

    Science.gov (United States)

    Salony; Solé, Xavier; Alves, Cleidson P; Dey-Guha, Ipsita; Ritsma, Laila; Boukhali, Myriam; Lee, Ju H; Chowdhury, Joeeta; Ross, Kenneth N; Haas, Wilhelm; Vasudevan, Shobha; Ramaswamy, Sridhar

    2016-01-01

    Small molecule inhibitors of AKT (v-akt murine thymoma viral oncogene homolog) signaling are being evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with subtherapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multiscale, molecular snapshot of this "AKT(low)" cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously upregulate a host of other proteins and metabolites posttranscriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. PMID:26637368

  4. 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)

  5. Identifying cancer origin using circulating tumor cells.

    Science.gov (United States)

    Lu, Si-Hong; Tsai, Wen-Sy; Chang, Ying-Hsu; Chou, Teh-Ying; Pang, See-Tong; Lin, Po-Hung; Tsai, Chun-Ming; Chang, Ying-Chih

    2016-04-01

    Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti-EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti-CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD-1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK(+) and CK18(+) CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7(+) or TTF-1(+), (CK20/ CDX2)(+), or (PSA/ PSMA)(+) corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin. PMID:26828696

  6. 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.

  7. Treatment Option Overview (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  8. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  9. General Information about Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  10. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

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

    International Nuclear Information System (INIS)

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► 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.

  12. 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

  13. Measuring the metastatic potential of cancer cells

    Science.gov (United States)

    Morrison, Dennis R.; Gratzner, Howard; Atassi, M. Z.

    1993-01-01

    Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

  14. T Cells in Gastric Cancer: Friends or Foes

    OpenAIRE

    Mario M. D'Elios; Elena Silvestri; Chiara Della Bella; Amedeo Amedei; Domenico Prisco

    2012-01-01

    Gastric cancer is the second cause of cancer-related deaths worldwide. Helicobacter pylori is the major risk factor for gastric cancer. As for any type of cancer, T cells are crucial for recognition and elimination of gastric tumor cells. Unfortunately T cells, instead of protecting from the onset of cancer, can contribute to oncogenesis. Herein we review the different types, “friend or foe”, of T-cell response in gastric cancer.

  15. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme.

    Science.gov (United States)

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T; Peng, Lifeng; Davis, Paul F; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM's cancer biology. PMID:27148537

  16. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    Science.gov (United States)

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM’s cancer biology.

  17. Learning about Cancer by Studying Stem Cells

    Science.gov (United States)

    ... View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem Cells By Sharon ... culture. Credit: Anne Weston, London Research Institute, CRUK (image available under a Creative Commons Attribution, Non-Commercial, ...

  18. Cancer: repositioned to kill stem cells

    OpenAIRE

    Holyoake, Tessa; Vetrie, David

    2015-01-01

    Chemotherapy-resistant cancer stem cells make it hard to cure many forms of the disease. Repositioning an existing drug to tackle this problem could significantly improve treatment for one form of leukaemia.

  19. 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)

    2016-05-05

    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 Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  20. Stemming Cancer: Functional Genomics of Cancer Stem Cells in Solid Tumors

    OpenAIRE

    Regenbrecht, C. R. A.; Lehrach, H; Adjaye, J.

    2008-01-01

    Cancer stem cells (CSCs) were discovered about 15 years ago in hematopoietic cancers. Subsequently, cancer stem cells were discovered in various solid tumors. Based on parallels with normal stem cells, a developmental process of cancer stem cells follows paths of organized, hierarchical structure of cells with different degrees of maturity. While some investigators have reported particular markers as identification of cancer stem cells, these markers require further research. In this review, ...

  1. Limited small cell lung cancer

    International Nuclear Information System (INIS)

    This paper assesses the prognosis of patients with limited small cell lung cancer (LSCLC) not achieving complete response (CR) to induction combination chemotherapy (ICC) but who achieve CR after thoracic irradiation (TI). Twenty-four patients had CRs to ICC (CR- ICC) of two cycles of cytoxan, Adriamycin, and vincristine alternating with two cycles of cisplatin with VP-16. Another 24 had CR after consolidation with subsequent T1 (CR-T1): 45 Gy in daily fractions of 2.5 Gy or twice-daily fractions of 1.5 Gy. The CR-ICC and CR-TI patients had similar prognostic factors and treatment. Comparing CR-ICC and CR-TI, survival was 40% versus 26% at 2 years and 35% versus 4% at 5 years (P < .05). There were eight (33%) long-term survivors (≥3 years) in the CR-ICC group versus three (13%) in the CR-TI group. Local control for CR-ICC patients was 59% at 5 years versus 21% for the CR-TI patients (not significant). Freedom from DM for the CR-ICC patients was 41% at 5 years versus 8% for the CR-TI patients (P < .05)

  2. Noncoding RNAs in cancer and cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Tianzhi Huang; Angel Alvarez; Bo Hu; Shi-Yuan Cheng

    2013-01-01

    In recent years, it has become increasingly apparent that noncoding RNAs (ncRNA) are of crucial importance for human cancer. The functional relevance of ncRNAs is particularly evident for microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). miRNAs are endogenously expressed small RNA sequences that act as post-transcriptional regulators of gene expression and have been extensively studied for their roles in cancers, whereas lncRNAs are emerging as important players in the cancer paradigm in recent years. These noncoding genes are often aberrantly expressed in a variety of human cancers. However, the biological functions of most ncRNAs remain largely unknown. Recently, evidence has begun to accumulate describing how ncRNAs are dysregulated in cancer and cancer stem cells, a subset of cancer cells harboring self-renewal and differentiation capacities. These studies provide insight into the functional roles that ncRNAs play in tumor initiation, progression, and resistance to therapies, and they suggest ncRNAs as attractive therapeutic targets and potential y useful diagnostic tools.

  3. Redox Regulation in Cancer Stem Cells

    OpenAIRE

    Shijie Ding; Chunbao Li; Ninghui Cheng; Xiaojiang Cui; Xinglian Xu; Guanghong Zhou

    2015-01-01

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of can...

  4. 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.

  5. Sediment transport in rivers, estuaries and harbours

    International Nuclear Information System (INIS)

    Proper understanding of sediment transport phenomena both in terms of quality i.e. direction of sediment transport and quantity i.e. rate of sediment transport and deposition is necessary in : (1) development and maintenance of coastal harbours and appurtenance works such as approach channels, location of sand traps and selection of spoil dumping grounds, (2) deepening of harbours and dredging of channels in estuarine environment, (3) assessing life of a reservoir of a power/irrigation project and (4) silting study of irrigation system. Radioactive tracers have been mainly used in studying the movement of sediment in the coastal areas. Techniques are being developed for quantitative estimation of sediment transport. These techniques and their limitations are discussed. (M.G.B.)

  6. CD133: A cancer stem cells marker, is used in colorectal cancers

    OpenAIRE

    Fei Ren; Wei-Qi Sheng; Xiang Du

    2013-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and self-renewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD1...

  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. Markers of small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Sharma SK

    2004-05-01

    Full Text Available Abstract Lung cancer is the number one cause of cancer death; however, no specific serum biomarker is available till date for detection of early lung cancer. Despite good initial response to chemotherapy, small-cell lung cancer (SCLC has a poor prognosis. Therefore, it is important to identify molecular markers that might influence survival and may serve as potential therapeutic targets. The review aims to summarize the current knowledge of serum biomarkers in SCLC to improve diagnostic efficiency in the detection of tumor progression in lung cancer. The current knowledge on the known serum cytokines and tumor biomarkers of SCLC is emphasized. Recent findings in the search for novel diagnostic and therapeutic molecular markers using the emerging genomic technology for detecting lung cancer are also described. It is believed that implementing these new research techniques will facilitate and improve early detection, prognostication and better treatment of SCLC.

  9. 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.

  10. Biomechanical investigation of colorectal cancer cells

    Science.gov (United States)

    Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro

    2014-09-01

    The nanomechanical properties of SW480 colon cancer cells were investigated using Atomic Force Microscopy. SW480 cells are composed of two sub-populations with different shape and invasiveness. These two cells populations showed similar adhesion properties while appeared significantly different in term of cells stiffness. Since cell stiffness is related to invasiveness and growth, we suggest elasticity as a useful parameter to distinguish invasive cells inside the colorectal tumor bulk and the high-resolution mechanical mapping as a promising diagnostic tool for the identification of malignant cells.

  11. 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......, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress...... in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which...

  12. Cancer stem cells and chemoradiation resistance

    International Nuclear Information System (INIS)

    Cancer is a disease of genetic and epigenetic alterations, which are emphasized as the central mechanisms of tumor progression in the multistepwise model. Discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. The heterogeneity of tumors can be explained with the help of CSCs supported by antiapoptotic signaling. CSCs mimic normal adult stem cells by demonstrating resistance to toxic injuries and chemoradiation therapy. Moreover, they might be responsible for tumor relapse following apparent beneficial treatments. Compared with hematopoietic malignancies, conventional therapy regimes in solid tumors have improved the overall survival marginally, illustrating the profound impact of treatment resistance. This implies that the present therapies, which follow total elimination of rapidly dividing and differentiated tumor cells, need to be modified to target CSCs that repopulate the tumor. In this review article, we report on recent findings regarding the involvement of CSCs in chemoradiation resistance and provide new insights into their therapeutic implications in cancer. (author)

  13. Alteration of pancreatic cancer cell functions by tumor-stromal cell interaction

    OpenAIRE

    Shin eHamada; Atsushi eMasamune; Tooru eShimosegawa

    2013-01-01

    Pancreatic cancer shows a characteristic tissue structure called desmoplasia, which consists of dense fibrotic stroma surrounding cancer cells. Interactions between pancreatic cancer cells and stromal cells promote invasive growth of cancer cells and establish a specific microenvironment such as hypoxia which further aggravates the malignant behavior of cancer cells. Pancreatic stellate cells (PSCs) play pivotal role in the development of fibrosis within the pancreatic cancer tissue, and also...

  14. Alteration of pancreatic cancer cell functions by tumor-stromal cell interaction

    OpenAIRE

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2013-01-01

    Pancreatic cancer shows a characteristic tissue structure called desmoplasia, which consists of dense fibrotic stroma surrounding cancer cells. Interactions between pancreatic cancer cells and stromal cells promote invasive growth of cancer cells and establish a specific microenvironment such as hypoxia which further aggravates the malignant behavior of cancer cells. Pancreatic stellate cells (PSCs) play a pivotal role in the development of fibrosis within the pancreatic cancer tissue, and al...

  15. DNA From Dead Cancer Cells Induces TLR9-Mediated Invasion and Inflammation In Living Cancer Cells

    Science.gov (United States)

    Tuomela, Johanna; Sandholm, Jouko; Kaakinen, Mika; Patel, Ankita; Kauppila, Joonas H.; Ilvesaro, Joanna; Chen, Dongquan; Harris, Kevin W.; Graves, David; Selander, Katri S.

    2014-01-01

    TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple negative, human MDA-MB-231 breast cancer cells stably expressing control or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. PMID:24212717

  16. Gap Junctions: The Claymore for Cancerous Cells

    Directory of Open Access Journals (Sweden)

    Ailar Nakhlband

    2011-07-01

    Full Text Available Introduction: Gap junctions play an important role in the cell proliferation in mammalian cells as well as carcinogenesis. However, there are controversial issues about their role in cancer pathogenesis. This study was designed to evaluate genotoxicity and cytotoxicity of Carbenoxolone (CBX as a prototype of inter-cellular gap junction blocker in MCF7 and BT20 human breast cancer cells. Methods: The MCF7and BT20 human breast cancer cell lines were cultivated, and treated at designated confluency with different doses of CBX. Cellular cytotoxicity was examined using standard colorimetric assay associated with cell viability tests. Gene expression evaluation was carried out using real time polymerase chain reaction (PCR. Results: MCF7 and BT20 cells were significantly affected by CBX in a dose dependent manner in cell viability assays. Despite varying expression of genes, down regulation of pro- and anti-apoptotic genes was observed in these cells. Conclusion: Based upon this investigation, it can be concluded that CBX could affect both low and high proliferative types of breast cancer cell lines and disproportionate down regulation of both pre- and anti-apoptotic genes may be related to interacting biomolecules, perhaps via gap junctions.

  17. 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.

  18. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  19. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    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

  20. Squamous cell cancer of the rectum

    Institute of Scientific and Technical Information of China (English)

    Tara Dyson; Peter V Draganov

    2009-01-01

    Squamous cell carcinoma of the rectum is a rare malignancy. It appears to be associated with chronic inflammatory conditions and infections. The clear association seen between Human Papilloma Virus and various squamous cancers has not been firmly established for the squamous cell cancer of the rectum. The presentation is nonspecific and patients tend to present with advanced stage disease. Diagnosis relies on endoscopic examination with biopsy of the lesion. Distinction from squamous cell cancer of the anus can be difficult, but can be facilitated by immunohistochemical staining for cytokeratins. Staging of the cancer with endoscopic ultrasound and computed tomography provides essential information on prognosis and can guide therapy. At present, surgery remains the main therapeutic option; however recent advances have made chemoradiation a valuable therapeutic addition. Squamous cell carcinoma of the rectum is a distinct entity and it is of crucial importance for the practicing Gastroenterologist to be thoroughly familiar with this disease. Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal, squamous cell carcinoma of the rectum has different epidemiology, etiology, pathogenesis, and prognosis but, most importantly, requires a different therapeutic approach. This review will examine and summarize the available information regarding this disease from the perspective of the practicing gastroenterologist.

  1. High prevalence of side population in human cancer cell lines

    OpenAIRE

    Boesch, Maximilian; Zeimet, Alain G; Fiegl, Heidi; Wolf, Barbara; Huber, Julia; Klocker, Helmut; Gastl, Guenther; Sopper, Sieghart; Wolf, Dominik

    2016-01-01

    Cancer cell lines are essential platforms for performing cancer research on human cells. We here demonstrate that, across tumor entities, human cancer cell lines harbor minority populations of putative stem-like cells, molecularly defined by dye extrusion resulting in the side population phenotype. These findings establish a heterogeneous nature of human cancer cell lines and argue for their stem cell origin. This should be considered when interpreting research involving these model systems.

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

    OpenAIRE

    Bjerregaard, Bolette; Holck, S.; Christensen, I. J.; Larsson, Lars-Inge

    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 specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to ex...

  3. Cancer Stem Cells: From Identification To Eradication

    International Nuclear Information System (INIS)

    A fundamental problem in cancer research is identification of the cells within a tumor that sustain the growth of the neoplastic clone. The concept that only a subpopulation of rare cancer stem cells (CSCs) is responsible for maintenance of the neoplasm emerged nearly 50 years ago: however, conclusive proof for the existence of a CSC was obtained only relatively recently. As definition, cancer stem cells (CSCs) are a sub-population of cancer cells (found within solid tumors or hematological malignancies) that possess characteristics normally associated with stem cells as high self-renewal potential. These cells are believed to be tumorige forming) in contrast to the bulk of cancer cells, which are thought to be non-tumorigenic. The first conclusive evidence for CSCs was published in 1997 in Nature Medicine by Bonnet and Dick who isolated a subpopulation of leukemic cells in AML that express a specific surface marker CD34 but lacks the CD38 marker. The authors established that the CD34+/CD38– subpopulation is capable of initiating leukemia in NOD/SCID mice that is histologically similar to the donor [1]. This subpopulation of cells is termed SCID Leukemia-initiating cells (SLIC). A theory suggests that such cells act as a reservoir for disease recurrence, are the origin of metastasis and exert resistance towards classical antitumor regimens. This resistance was attributed to a combination of several factors [2], suggesting that conventional antitumor regimens are targeting the bulk of the tumor not the dormant stubborn CSCs. Purpose Better understanding of the leukemogenic process and the biology of CSCS to define the most applicable procedures for their identification and isolation in order to design specific targeted therapies aiming at reducing disease burden to very low levels .. up to eradication of the tumor

  4. Electrodynamic activity of healthy and cancer cells

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří

    Vol. 329. Bristol : IOP, 2011 - (Cifra, M.; Pokorny, J.; Kučera, O.), 012007 ISSN 1742-6588. [9th International Frohlich's Symposium on Electrodynamic Activity of Living Cells - Including Microtubule Coherent Modes and Cancer Cell Physics. Praha (CZ), 01.07.2011-03.07.2011] R&D Projects: GA ČR(CZ) GAP102/11/0649 Institutional research plan: CEZ:AV0Z20670512 Keywords : Boundary elements * Cancer cells * Electric dipole Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  5. Targeted therapy for squamous cell lung cancer

    OpenAIRE

    Liao, Rachel G.; Watanabe, Hideo; Meyerson, Matthew; Hammerman, Peter S.

    2012-01-01

    Lung squamous cell carcinoma (SqCC) is the second most common subtype of non-small-cell lung cancer and leads to 40,000–50,000 deaths per year in the USA. Management of non-small-cell lung cancer has dramatically changed over the past decade with the introduction of targeted therapeutic agents for genotypically selected individuals with lung adenocarcinoma. These agents lead to improved outcomes, and it has now become the standard of care to perform routine molecular genotyping of lung adenoc...

  6. 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

  7. 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...

  8. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Directory of Open Access Journals (Sweden)

    Purvi ePatel

    2012-10-01

    Full Text Available Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Although overlapping molecules and pathways have been reported to regulate the stem-like phenotype of CSCs and metastasis, accumulated evidence has suggested additional clonal diversity within the stem-like cancer cell subpopulation. This review will describe the current hypothesis linking CSCs and metastasis and summarize mechanisms important for metastatic CSCs to re-initiate tumors in the secondary sites. A better understanding of CSCs’ contribution to clinical tumor dormancy and metastasis will provide new therapeutic revenues to eradicate metastatic tumors and significantly reduce the mortality of cancer patients.

  9. 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

  10. 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.

  11. High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer

    OpenAIRE

    Liu, Shu-Yan; Zheng, Peng-Sheng

    2013-01-01

    High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDHhigh and ALDHlow cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALD...

  12. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response.

    Science.gov (United States)

    Koizumi, Keiichi; Hojo, Shozo; Akashi, Takuya; Yasumoto, Kazuo; Saiki, Ikuo

    2007-11-01

    The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8(+) and CD4(+) T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. PMID:17894551

  13. Surgery for small cell lung cancer.

    Science.gov (United States)

    de Hoyos, Alberto; DeCamp, Malcolm M

    2014-11-01

    Small-cell lung cancer (SCLC) comprises approximately 14% of all lung cancer cases. Most patients present with locally advanced or metastatic disease and are therefore treated nonoperatively with chemotherapy, radiotherapy, or both. A small subset of patients with SCLC present with early-stage disease and will benefit from surgical resection plus chemotherapy. The rationale for radiotherapy in these patients remains controversial. PMID:25441133

  14. Targeting cancer stem cells in hepatocellular carcinoma

    OpenAIRE

    MISHRA, LOPA

    2014-01-01

    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 fun...

  15. How Taxol/paclitaxel kills cancer cells

    OpenAIRE

    Weaver, Beth A

    2014-01-01

    Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, endometrial, cervical, prostate, and head and neck cancers, in addition to sarcoma, lymphoma, and leukemia. Paclitaxel has long been recognized to induce mitotic arrest, which leads to cell death in a subset of the arrested population. However, r...

  16. Cell Membrane Softening in Cancer Cells

    Science.gov (United States)

    Schmidt, Sebastian; Händel, Chris; Käs, Josef

    Biomechanical properties are useful characteristics and regulators of the cell's state. Current research connects mechanical properties of the cytoskeleton to many cellular processes but does not investigate the biomechanics of the plasma membrane. We evaluated thermal fluctuations of giant plasma membrane vesicles, directly derived from the plasma membranes of primary breast and cervical cells and observed a lowered rigidity in the plasma membrane of malignant cells compared to non-malignant cells. To investigate the specific role of membrane rigidity changes, we treated two cell lines with the Acetyl-CoA carboxylase inhibitor Soraphen A. It changed the lipidome of cells and drastically increased membrane stiffness by up regulating short chained membrane lipids. These altered cells had a decreased motility in Boyden chamber assays. Our results indicate that the thermal fluctuations of the membrane, which are much smaller than the fluctuations driven by the cytoskeleton, can be modulated by the cell and have an impact on adhesion and motility.

  17. Reversibility of apoptosis in cancer cells

    OpenAIRE

    Tang, H. L.; Yuen, K L; Tang, H M; Fung, M C

    2008-01-01

    Apoptosis is a cell suicide programme characterised by unique cellular events such as mitochondrial fragmentation and dysfunction, nuclear condensation, cytoplasmic shrinkage and activation of apoptotic protease caspases, and these serve as the noticeable apoptotic markers for the commitment of cell demise. Here, we show that, however, the characterised apoptotic dying cancer cells can regain their normal morphology and proliferate after removal of apoptotic inducers. In addition, we demonstr...

  18. Lung cancer-initiating cells: a novel target for cancer therapy

    OpenAIRE

    Morrison, Brian J.; Morris, John C.; Steel, Jason C

    2013-01-01

    Lung cancer is a major public health problem causing more deaths than any other cancer. A better understanding of the biology of this disease and improvements in treatment are greatly needed. Increasing evidence supports the concept that a rare and specialized population of cancer cells, so-called cancer-initiating cells with stem cell-like characteristics, is responsible for tumor growth, maintenance, and recurrence. Cancer-initiating cells also exhibit characteristics that render them resis...

  19. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang

    2007-01-01

    The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However,numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte infiltration and inflammation. Therefore, an important question to be answered is how the host immune system responds to engrafted autologous stem cells or allogeneous stem cells. In this brief review, we summarize the progress in several related areas in this field, including some of our data, in four sections: (1) immunogenicity of stem cells; (2)strategies to inhibit immune rejection to allograft stem cells; (3) immune responses to cancer stem cells; and (4)mesenchymal stem cells in immune regulation. Improvement of our understanding on these and other aspects of immune system-stem cell interplay would greatly facilitate the development of stem cell-based therapeutics for regenerative purposes.

  20. Chemotherapy in heterogeneous cultures of cancer cells with interconversion

    International Nuclear Information System (INIS)

    Recently, the interconversion between differentiated and stem-like cancer cells has been observed. Here, we model the in vitro growth of heterogeneous cell cultures in the presence of interconversion from differentiated cancer cells to cancer stem cells (CSCs), showing that, by targeting only CSC with cytotoxic agents, it is not always possible to eradicate cancer. We have determined the kinetic conditions under which cytotoxic agents in in vitro heterogeneous cultures of cancer cells eradicate cancer. In particular, we have shown that the chemotherapeutic elimination of in vitro cultures of heterogeneous cancer cells is effective only if it targets all cancer cell types, and if the induced death rates for the different subpopulations of cancer cell types are large enough. The quantitative results of the model are compared and validated with experimental data. (paper)

  1. Mapping proteolytic cancer cell-extracellular matrix interfaces.

    NARCIS (Netherlands)

    Wolf, K.A.; Friedl, P.H.A.

    2009-01-01

    For cancer progression and metastatic dissemination, cancer cells migrate and penetrate through extracellular tissues. Cancer invasion is frequently facilitated by proteolytic processing of components of the extracellular matrix (ECM). The cellular regions mediating proteolysis are diverse and depen

  2. Uranium isotopes in El hamraween harbour sediments

    International Nuclear Information System (INIS)

    Isotopes of uranium in marine sediments collected from El Hamraween harbour and Ras El-Bhar areas on the Egyptian coast of the Red Sea have been studied using radiochemical separation procedures and alpha-particle spectrometry. Activity concentrations of 238U, 235U, 234U were calculated. The activities observed indicating the enhancement of radioactivity level in El Hamraween harbor area due to the activities of phosphate shipment operation. Secular equilibrium between 234U and 238U was found in the analyzed samples. The average activity ratio of 235U/ 238U was close to the value 0.046 for uranium in nature

  3. The metabolic landscape of cancer stem cells.

    Science.gov (United States)

    Dando, Ilaria; Dalla Pozza, Elisa; Biondani, Giulia; Cordani, Marco; Palmieri, Marta; Donadelli, Massimo

    2015-09-01

    Cancer stem cells (CSCs) are a sub-population of quiescent cells endowed with self-renewal properties that can sustain the malignant behavior of the tumor mass giving rise to more differentiated cancer cells. For this reason, the specific killing of CSCs represents one of the most important challenges of the modern molecular oncology. However, their particular resistance to traditional chemotherapy and radiotherapy imposes a thorough understanding of their biological and biochemical features. The metabolic peculiarities of CSCs may be a therapeutic and diagnostic opportunity in cancer research. In this review, we summarize the most significant discoveries on the metabolism of CSCs describing and critically analyzing the studies supporting either glycolysis or mitochondrial oxidative phosphorylation as a primary source of energy for CSCs. PMID:26337609

  4. Stem cell technology and engineering for cancer treatment

    OpenAIRE

    Sinh Truong Nguyen; Phuc Van Pham

    2015-01-01

    Stem cells are not only widely used for regenerative medicine, but are also considered as a useful tool for cancer treatment. For a long time, stem cells have been utilized to renew the immune system for radiation or chemotherapy treated patients. Recently, stem cells are being engineered to carry therapeutic reagents to target tumor sites. Cancer vaccines based on the knowledge of cancer stem cells have been studied and applied for cancer treatment. Induced pluripotent stem cells have been u...

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

    Institute of Scientific and Technical Information of China (English)

    Hai-hong ZHANG; Ai-zhen CAI; Xue-ming WEI; Li DING; Feng-zhi LI; Ai-ming ZHENG; Da-jiang DAI

    2013-01-01

    Objective: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.Methods: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.Results: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.Conclusions: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.

  6. Cancer Stem Cells and Pediatric Solid Tumors

    International Nuclear Information System (INIS)

    Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC

  7. Navigational aspects of calling to the Great Harbour of Alexandria

    OpenAIRE

    Belov, Alexander

    2014-01-01

    More than ten years of archaeological surveys of the Great Harbour of Alexandria have completely changed the conception of the ancient topography of the port area of the city. The remains of ancient port structures show the high level of port's organization and well correspond to the descriptions of ancient authors. This new archaeological data permits to consider general aspects of navigation within the Great Harbour. The most probable courses of the ships calling to the Great Harbour and le...

  8. 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 on the...

  9. Cancer Stem Cells in Breast: Current Opinion and Future Challenges

    OpenAIRE

    Charafe-Jauffret, Emmanuelle; Monville, Florence; Ginestier, Christophe; Dontu, Gabriela; Birnbaum, Daniel; Wicha, Max S.

    2008-01-01

    There is increasing evidence for the cancer stem cell hypothesis, which holds that cancers are driven by a cellular subcomponent that has stem cell properties, that is, self-renewal, tumorigenicity and multilineage differentiation capacity. The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the speci...

  10. Epirubicin-Adsorbed Nanodiamonds Kill Chemoresistant Hepatic Cancer Stem Cells

    OpenAIRE

    Wang, Xin; Low, Xinyi Casuarine; Hou, Weixin; Abdullah, Lissa Nurrul; Toh, Tan Boon; Mohd Abdul Rashid, Masturah; Ho, Dean; Chow, Edward Kai-Hua

    2014-01-01

    Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Ep...

  11. Understanding cancer stem cell heterogeneity and plasticity

    Institute of Scientific and Technical Information of China (English)

    Dean G Tang

    2012-01-01

    Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo.It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells.Somatic stem cells in adult organs are also heterogeneous,containing many subpopulations of self-renewing cells with distinct regenerative capacity.The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches.Like normal stem cells,recent data suggest that cancer stem cells(CSCs)similarly display significant phenotypic and functional heterogeneity,and that the CSC progeny can manifest diverse plasticity.Here,I discuss CSC heterogeneity and plasticity in the context of tumor development and progression,and by comparing with normal stem cell development.Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted.By understanding the interrelationship between CSCs and their differentiated progeny,we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.

  12. 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

  13. Molecular Pathways: Reactive Oxygen Species Homeostasis in Cancer Cells and Implications for Cancer Therapy

    OpenAIRE

    Nogueira, Veronique; Hay, Nissim

    2013-01-01

    Reactive oxygen species (ROS) are important in regulating normal cellular processes, but deregulated ROS contribute to the development of various human diseases including cancers. Cancer cells have increased ROS levels compared to normal cells, because of their accelerated metabolism. The high ROS levels in cancer cells, which distinguish them from normal cells, could be pro-tumorigenic, but are also their Achilles’ heel. The high ROS content in cancer cells renders them more susceptible to o...

  14. 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

  15. Foxp3 expression in human cancer cells

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos I

    2008-04-01

    Full Text Available Abstract Objective Transcription factor forkhead box protein 3 (Foxp3 specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs. Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. Materials and methods Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. Results Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. Conclusion We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

  16. Cell membrane softening in human breast and cervical cancer cells

    Science.gov (United States)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    AIM: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.METHODS: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.RESULTS: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.CONCLUSION:SP cells have some cancer stem celllike characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.

  18. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    Energy Technology Data Exchange (ETDEWEB)

    Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A. Ivana; Mondello, Chiara, E-mail: mondello@igm.cnr.it [Institute of Molecular Genetics, CNR, via Abbiategrasso 207, 27100 Pavia (Italy)

    2011-03-04

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs.

  19. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    International Nuclear Information System (INIS)

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs

  20. Circulating tumor cells in lung cancer.

    Science.gov (United States)

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. PMID:23207444

  1. Absence of selenium protection against methylmercury toxicity in harbour seal leucocytes in vitro.

    Science.gov (United States)

    Das, Krishna; Dupont, Aurélie; De Pauw-Gillet, Marie-Claire; Debier, Cathy; Siebert, Ursula

    2016-07-15

    Previous studies described high concentrations of mercury (Hg) and selenium (Se) in the blood of harbour seals, Phoca vitulina from the North Sea. In the present study, we evaluated the in vitro potential protective effects of sodium selenite (Na2SeO3) and selenomethionine (SeMet) on cell proliferation of harbour seal lymphocytes exposed to MeHgCl 0.75μM. In vitro exposure of ConA-stimulated T lymphocytes resulted in severe inhibition of DNA synthesis, likely linked to severe loss of mitochondrial membrane potential at 0.75μM. Neither selenite nor SeMet showed a protective effect against MeHg toxicity expressed at the T lymphocyte proliferation level for harbour seals. Selenite and SeMet did not show negative effects regarding lymphocyte proliferation and mitochondrial membrane potential. To conclude, our results clearly demonstrated that MeHg affected in vitro immune cells exposure with no protective effects of selenium at a molar ratio Hg:Se of 1:10 in harbour seals from the North Sea. PMID:27197766

  2. Circulating Tumor Cells in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Brian [Institute of Urology, University of Southern California, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90033 (United States); Rochefort, Holly [Department of Surgery, University of Southern California, 1520 San Pablo Street, HCT 4300, Los Angeles, CA 90033 (United States); Goldkorn, Amir, E-mail: agoldkor@usc.edu [Department of Internal Medicine and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033 (United States)

    2013-12-04

    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.

  3. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    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

  4. 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.

  5. 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.

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

    International Nuclear Information System (INIS)

    Research highlights: → Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). → Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. → Monoclonal cell lines showed reduced sensitivity for Paclitaxel. → In situ CD133+ cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. → CD133+ 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+ 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.

  7. Human Colon Cancer Cells Cultivated in Space

    Science.gov (United States)

    1995-01-01

    Within five days, bioreactor cultivated human colon cancer cells (shown) grown in Microgravity on the STS-70 mission in 1995, had grown 30 times the volume of the control specimens on Earth. The samples grown in space had a higher level of cellular organization and specialization. Because they more closely resemble tumors found in the body, microgravity grown cell cultures are ideal for research purposes.

  8. Renal cell cancer without a renal primary

    OpenAIRE

    Cumani B; Bratcher J; Wang W.; Wayne M.; Kasmin F; Cooperman A

    2010-01-01

    Abstract Renal cell carcinoma has been increasing in incidence over the past two decades. Men are affected more than women and metastatic disease at presentation occurs in up to one third of patients. Metastasis can occur to virtually any organ, and involvement of multiple organs is not uncommon. To date, no reports have been found of metastatic disease without a renal primary. We present a case of renal cell cancer initially presenting as a subcutaneous mass with subsequent pancreatic and pa...

  9. Orthotopic Injection of Pancreatic Cancer Cells.

    Science.gov (United States)

    Aiello, Nicole M; Rhim, Andrew D; Stanger, Ben Z

    2016-01-01

    Pancreatic ductal adenocarcinoma is an aggressive disease with a 5-yr survival rate of only 5%. The location of the pancreas in the abdomen, where it is obscured by other organs, makes it a difficult tissue to study and manipulate. This protocol describes in detail how to orthotopically inject cancer cells into the pancreas in mice. This technique is particularly useful when the cells must be manipulated in ways that cannot be modeled genetically. PMID:26729902

  10. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  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. Cancer Stem Cells: Cell Culture, Markers and Targets for New Therapies

    OpenAIRE

    Gilbert, Candace A.; Ross, Alonzo H.

    2009-01-01

    A cancer stem cell is defined as an undifferentiated cell with the ability to self-renew, differentiate to multiple lineages and initiate tumors that mimic the parent tumor. In this review, we focus on glioblastomas, describing recent progress and problems in characterizing these cells. There have been advances in cancer stem cell culture, but tumor cell heterogeneity has made purification of cancer stem cells difficult. Indeed, it may be that cancer stem cells significantly vary from tumor t...

  13. Membrane proteomic analysis of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Liu Xiaojun

    2010-09-01

    Full Text Available Abstract Background Pancreatic cancer is one of the most aggressive human tumors due to its high potential of local invasion and metastasis. The aim of this study was to characterize the membrane proteomes of pancreatic ductal adenocarcinoma (PDAC cells of primary and metastatic origins, and to identify potential target proteins related to metastasis of pancreatic cancer. Methods Membrane/membrane-associated proteins were isolated from AsPC-1 and BxPC-3 cells and identified with a proteomic approach based on SDS-PAGE, in-gel tryptic digestion and liquid chromatography with tandem mass spectrometry (LC-MS/MS. X! Tandem was used for database searching against the SwissProt human protein database. Results We identified 221 & 208 proteins from AsPC-1 and BxPC-3 cells, respectively, most of which are membrane or membrane-associated proteins. A hundred and nine proteins were found in both cell lines while the others were present in either AsPC-1 or BxPC-3 cells. Differentially expressed proteins between two cell lines include modulators of cell adhesion, cell motility or tumor invasion as well as metabolic enzymes involved in glycolysis, tricarboxylic acid cycle, or nucleotide/lipid metabolism. Conclusion Membrane proteomes of AsPC-1 (metastatic and BxPC-3 (primary cells are remarkably different. The differentially expressed membrane proteins may serve as potential targets for diagnostic and therapeutic interventions.

  14. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Hu C

    2015-03-01

    Full Text Available Chenxia Hu,1 Martin Niestroj,2,3 Daniel Yuan,4 Steven Chang,5 Jie Chen5,6 1Faculty of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Canadian Light Source, Saskatoon, SK, Canada; 3Physics Department, Bonn University, Bonn, Germany; 4Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; 5Faculty of Engineering, University of Alberta, Edmonton, AB, Canada; 6Canadian National Research Council/National Institute for Nanotechnology, Edmonton, AB, Canada Abstract: Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain. Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs with thio-PEG (polyethylene glycol and thio-glucose, the resulting functionalized GNPs (Glu-GNPs were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption

  15. Stemness is derived from thyroid cancer cells

    Directory of Open Access Journals (Sweden)

    RishengMa

    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.

  16. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    Directory of Open Access Journals (Sweden)

    Wenke YUE

    2011-06-01

    Full Text Available Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung cancer cell line-L9981 was cultured in serum-free and growth factors added medium, and spheres were obtained. Then the morphological differences of sphere cells and adherent L9981 cells cultured in serum-containing mediums are observed. Cell proliferation was analyzed by Vi-cell viability analyzer; invasion ability was tested by transwell assay; and in vivo tumorigenicity of the two groups of cells was studied in nude mouse. Results Compared with adherent L9981 cells cultured in serum-containing mediums, cells cultured in serum-free medium display sphere appearance. Doubling time of adherent cells and sphere cells are (56.05±1.95 h and (33.00±1.44 h respectively; Spheroid cells had higher invasion and tumorigenicity ability, 5 times and 20 times respectively, than adherent cells. Conclusion Suspension cultured L9981 in Serum-free medium could form spheroid populations. Cells in spheres had higher ability of invasion and Tumorigenicity than adherent L9981 cells. These results indicated spheroid L9981 cells contained enriched lung cancer stem cells, and Serum-free suspension culture can be a candidate method for enriching lung cancer stem cell.

  17. Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer

    OpenAIRE

    Roh, Jong-Lyel; Kim, Eun Hye; Park, Jin Young; Kim, Ji Won; Kwon, Minsu; Lee, Byung-Heon

    2014-01-01

    Adaptation to cellular stress is not a vital function of normal cells but is required of cancer cells, and as such might be a sensible target in cancer therapy. Piperlongumine is a naturally occurring small molecule selectively toxic to cancer cells. This study assesses the cytotoxicity of piperlongumine and its combination with cisplatin in head-and-neck cancer (HNC) cells in vitro and in vivo. The effect of piperlongumine, alone and in combination with cisplatin, was assessed in human HNC c...

  18. Non-Small Cell Lung Cancer: Screening, Diagnosis, and Staging

    OpenAIRE

    Ferreira, J; Magalhães, M; Rocha, E; Marques, F

    2012-01-01

    Lung cancer is the leading cause of cancer deaths worldwide. Tobacco consumption is the primary cause of lung cancer, accounting for more than 85% 90% of all lung cancer deaths. Non-small cell lung cancer accounts for about 85% of all lung cancers. Several studies have shown that low-dose helical CT of the lung detects more nodules and lung cancers, including early-stage cancers, than does chest radiography. The National Lung Cancer Screening Trial results show that three annual roun...

  19. 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 es

  20. Reuse of harbour sediments in the Greenlandic construction industry

    DEFF Research Database (Denmark)

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

    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 to...

  1. New insights into pancreatic cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Chinthalapally V Rao; Altaf Mohammed

    2015-01-01

    Pancreatic cancer (PC) has been one of the deadliest of allcancers, with almost uniform lethality despite aggressivetreatment. Recently, there have been important advancesin the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recentnew targeted agents and the use of multiple therapeuticcombinations, no treatment option is viable in patients withadvanced cancer. Developing novel strategies to targetprogression of PC is of intense interest. A small populationof pancreatic cancer stem cells (CSCs) has been foundto be resistant to chemotherapy and radiation therapy.CSCs are believed to be responsible for tumor initiation,progression and metastasis. The CSC research has recentlyachieved much progress in a variety of solid tumors,including pancreatic cancer to some extent. This leads tofocus on understanding the role of pancreatic CSCs. Thefocus on CSCs may offer new targets for prevention andtreatment of this deadly cancer. We review the most salientdevelopments in important areas of pancreatic CSCs. Here,we provide a review of current updates and new insightson the role of CSCs in pancreatic tumor progression withspecial emphasis on DclK1 and Lgr5, signaling pathwaysaltered by CSCs, and the role of CSCs in prevention andtreatment of PC.

  2. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  3. Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction

    OpenAIRE

    Shabo, Ivan; Midtbö, Kristine Maria; Andersson, Henrik; Åkerlund, Emma; Olsson, Hans; Wegman, Pia; Gunnarsson, Cecilia; Lindström, Annelie

    2015-01-01

    Background: Cell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor st...

  4. Types of Stem Cell Transplants for Treating Cancer

    Science.gov (United States)

    ... Sources of stem cells for transplant Types of stem cell transplants for treating cancer In a typical stem ... come from your identical twin or triplet Autologous stem cell transplants These stem cells come from you alone. ...

  5. 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.

  6. Tamoxifen-resistant breast cancer cells possess cancer stem-like cell properties

    Institute of Scientific and Technical Information of China (English)

    LIU Hui; ZHANG Heng-wei; SUN Xian-fu; GUO Xu-hui; HE Ya-ning; CUI Shu-de; FAN Qing-xia

    2013-01-01

    Background Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis.Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy.Although acquired resistance to endocrine treatment has been extensively studied,the underlying mechanisms are unclear.We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy.Therefore,we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells.Methods Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively.Stem-cell markers (SOX-2,OCT-4,and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR.Morphological observation was performed to characterize EMT.Results After induction of TAM resistance,TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P <0.05),indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells.TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P <0.01),demonstrating the elevated CSC properties of TAM-R MCF7 cells.Consistently,qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2,OCT-4,and CD133,compared to those of WT MCF7 cells (P <0.05).Morphologically,TAM-R MCF7 cells showed a fibroblastic phenotype,but WT MCF7 cells were epithelial-like.After induction of TAM resistance,qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail,vimentin,and N-cadherin and decreased levels of E-cadherin,which are considered as EMT characteristics (P <0

  7. Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.

    Science.gov (United States)

    Zhang, Wenwen; Cao, Lulu; Sun, Zijia; Xu, Jing; Tang, Lin; Chen, Weiwei; Luo, Jiayan; Yang, Fang; Wang, Yucai; Guan, Xiaoxiang

    2016-05-18

    The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy. PMID:27111245

  8. Role of Oxidative Stress in Stem, Cancer, and Cancer Stem Cells

    International Nuclear Information System (INIS)

    The term ‘‘oxidative stress” refers to a cell’s state characterized by excessive production of reactive oxygen species (ROS) and oxidative stress is one of the most important regulatory mechanisms for stem, cancer, and cancer stem cells. The concept of cancer stem cells arose from observations of similarities between the self-renewal mechanism of stem cells and that of cancer stem cells, but compared to normal stem cells, they are believed to have no control over the cell number. ROS have been implicated in diverse processes in various cancers, and generally the increase of ROS in cancer cells is known to play an important role in the initiation and progression of cancer. Additionally, ROS have been considered as the most significant mutagens in stem cells; when elevated, blocking self-renewal and at the same time, serving as a signal stimulating stem cell differentiation. Several signaling pathways enhanced by oxidative stress are suggested to have important roles in tumorigenesis of cancer or cancer stem cells and the self-renewal ability of stem or cancer stem cells. It is now well established that mitochondria play a prominent role in apoptosis and increasing evidence supports that apoptosis and autophagy are physiological phenomena closely linked with oxidative stress. This review elucidates the effect and the mechanism of the oxidative stress on the regulation of stem, cancer, and cancer stem cells and focuses on the cell signaling cascades stimulated by oxidative stress and their mechanism in cancer stem cell formation, as very little is known about the redox status in cancer stem cells. Moreover, we explain the link between ROS and both of apoptosis and autophagy and the impact on cancer development and treatment. Better understanding of this intricate link may shed light on mechanisms that lead to better modes of cancer treatment

  9. Immune cell interplay in colorectal cancer prognosis

    Institute of Scientific and Technical Information of China (English)

    Samuel; E; Norton; Kirsten; A; Ward-Hartstonge; Edward; S; Taylor; Roslyn; A; Kemp

    2015-01-01

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, par-ticularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship betweencancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.

  10. Radiation response in prostate cancer stem cells

    International Nuclear Information System (INIS)

    The full text of the publication follows. Introduction: Currently, there is no successful treatment for secondary prostate cancer. Resistance of secondary tumours and metastases to radiotherapy and chemotherapy might be explained by cancer stem cells (CSCs). Prostate (P) CSCs are rare cells defined by cell surface markers, CD133+, a2b1integrinhi and CD44+, and are capable of self-renewal, differentiation and invasion in vitro and tumour initiation in vivo. Hypothesis: PCSCs have an alternative DNA damage response following radiation and are resistant to radiation treatment. Methods: Primary prostate (benign and cancer) epithelial stem (SC) transit amplifying (TA, CD133-/a2b1integrinhi/CD44+) and committed basal (CB, CD133-/a2b1integrinlo/CD44+) cells were exposed to 2 Gy of radiation (IR) to induce a DNA damage response. Immunofluorescence was used to quantify nuclear foci, representative of DNA damage response proteins (g-H2AX, 53BP1, phosphorylated ATM/ATR substrates, phospho-Chk2Th68). Immunofluorescence was also used to co-stain for heterochromatin and DNA damage markers. Comet assays (neutral and alkaline) were used to directly assess DNA damage. Results: In benign and cancer cells, the SCs had a lower percentage of cells containing initial foci (30 min post-IR), compared to the TA and CB cells. At 24 h post-IR there was a reduced percentage of cells positive for foci in TA and CB cells suggesting repair. Whilst there were also signs of repair in benign SCs, in the PCSCs there was an increase in percentage of cells positive for foci at 24 h, indicative of a delayed damage response. Comet assays indicated that SCs sustain different kinds of DNA damage to TA and CB cells. Heterochromatin staining indicated that DNA damage foci preferentially formed in euchromatin. Future work: Further studies will include apoptosis and clonogenic assays to measure PCSC survival. In addition, PCSC chromatin status will be examined to elucidate DNA repair kinetics. If we are able

  11. Harbour bathing and the urban transition of water in Copenhagen

    DEFF Research Database (Denmark)

    Jensen, Jens Stissing; Lauridsen, Erik Hagelskjær; Farné Fratini, Chiara;

    2015-01-01

    . In order to conceptualise what provoked these navigational actions and how they translated into transformative urban change, we develop the notions of junctions and transition mediators. We introduce the notion of junctions to understand how navigations are provoked. Junctions are signified by...... might translate into coordinated urban transformations, we introduce the notion of transition mediators. A transition mediator is an artefact—such as the harbour baths—that succeeds in generating transformative change by displacing the boundaries and interdependencies within and among the established......n 2002 the first public harbour swimming bath in the inner harbour of Copenhagen opened. By translating the old industrial harbour into a site of urban living and recreation, the practice of swimming in the harbour has been instrumental in aligning and catalysing a series of broader urban...

  12. Highly parallel identification of essential genes in cancer cells

    OpenAIRE

    Luo, Biao; Cheung, Hiu Wing; Subramanian, Aravind; Sharifnia, Tanaz; Okamoto, Michael; Yang, Xiaoping; Hinkle, Greg; Boehm, Jesse S.; Beroukhim, Rameen; Weir, Barbara A.; Mermel, Craig; Barbie, David A; Awad, Tarif; Zhou, Xiaochuan; Nguyen, Tuyen Van

    2008-01-01

    More complete knowledge of the molecular mechanisms underlying cancer will improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome Atlas are systematically characterizing the structural basis of cancer, by identifying the genomic mutations associated with each cancer type. A powerful complementary approach is to systematically characterize the functional basis of cancer, by identifying the genes essential for growth and related phenotypes in different cancer cells. Such...

  13. 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

  14. Lymphocyte Infusion in Treating Patients With Relapsed Cancer After Bone Marrow or Peripheral Stem Cell Transplantation

    Science.gov (United States)

    2011-11-28

    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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

    , the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+ and CD8+ T cells...

  16. Cancer Stem Cells: Distinct Entities or Dynamically Regulated Phenotypes?

    OpenAIRE

    Li, Yunqing; Laterra, John

    2012-01-01

    The origins of tumor propagating neoplastic stem-like cells (cancer stem cells, CSCs) and their relationship to the bulk population of tumor cells that lack stem-like tumor-propagating features(i.e. transit-amplifying cancer progenitor cells) remain unclear. Recent findings from multiple laboratories show that cancer progenitor cells have the capacity to dedifferentiate and acquire a stem-like phenotype in response to either genetic manipulation or environmental cues. These findings suggest t...

  17. Thyroid stem cells: lessons from normal development and thyroid cancer

    OpenAIRE

    Thomas, Dolly; Friedman, Susan; Lin, Reigh-Yi

    2008-01-01

    Ongoing advances in stem cell research have opened new avenues for therapy for many human disorders. Until recently, however, thyroid stem cells have been relatively understudied. Here, we review what is known about thyroid stem cells and explore their utility as models of normal and malignant biological development. We also discuss the cellular origin of thyroid cancer stem cells and explore the clinical implications of cancer stem cells in the thyroid gland. Since thyroid cancer is the most...

  18. Selective killing of cancer cells by nanoparticle-assisted ultrasound

    OpenAIRE

    Kosheleva, Olga K.; Lai, Tsung-Ching; Chen, Nelson G.; Hsiao, Michael; Chen, Chung-Hsuan

    2016-01-01

    Background Intense ultrasound, such as that used for tumor ablation, does not differentiate between cancerous and normal cells. A method combining ultrasound and biocompatible gold or magnetic nanoparticles (NPs) was developed under in vitro conditions using human breast and lung epithelial cells, which causes ultrasound to preferentially destroy cancerous cells. Results Co-cultures of BEAS-2B normal lung cells and A549 cancerous lung cells labeled with green and red fluorescent proteins, res...

  19. Regulation of cell death in cancer - possible implications for immunotherapy

    OpenAIRE

    Simone eFulda

    2013-01-01

    Since most anticancer therapies including immunotherapy trigger programmed cell death in cancer cells, defective cell death programs can lead to treatment resistance and tumor immune escape. Therefore, evasion of programmed cell death may provide one possible explanation as to why cancer immunotherapy has so far only shown modest clinical benefits for children with cancer. A better understanding of the molecular mechanisms that regulate sensitivity and resistance to programmed cell death is e...

  20. Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells

    OpenAIRE

    Hellsten, Rebecka; Johansson, Martin; Dahlman, Anna; Sterner, Olov; Bjartell, Anders

    2011-01-01

    Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+...

  1. [Asbestos import in Italy: the transit through Livorno harbour from 1957 to 1995].

    Science.gov (United States)

    Nemo, Alessandro; Boccuzzi, Maria Teresa; Silvestri, Stefano

    2009-01-01

    This work aims to describe quantities, type of packaging and geographical area of origin of the asbestos fibres unloaded in Livorno harbour between 1957 and 1995. Historical data, available for this period, were collected from Il Messaggero Marittimo, a periodical journal dealing with Livorno harbour activities. Collaboration between the local Health and Safety Unit (ASL 6) and the Institute for Study and Prevention of Cancer (ISPO), both Regional Institutions of the National Health Service, made it possible to carry out this work. The computation of the collected data for the whole period allows the description of the quantities, year by year and the assessment of the percentage imported through Livorno on the total tonnage imported in Italy during the same period. The detection of the geographical areas of origin allowed to estimate the quantities subdivided by type of fibre (serpentine/amphiboles). These results will help the historical assessment of occupational asbestos exposure of the Livorno dockers. PMID:19585878

  2. Gastric cancer stem cells: A novel therapeutic target

    OpenAIRE

    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, ...

  3. T-helper-1-cell cytokines drive cancer into senescence

    OpenAIRE

    Braumüller, Heidi; Wieder, Thomas; Brenner, Ellen; Aßmann, Sonja; Hahn, Matthias; Alkhaled, Mohammed; Schilbach, Karin; Essmann, Frank; Kneilling, Manfred; Griessinger, Christoph; Ranta, Felicia; Ullrich, Susanne; Mocikat, Ralph; Braungart, Kilian; Mehra, Tarun

    2013-01-01

    Cancer control by adaptive immunity involves a number of defined death and clearance mechanisms. However, efficient inhibition of exponential cancer growth by T cells and interferon-γ (IFN-γ) requires additional undefined mechanisms that arrest cancer cell proliferation. Here we show that the combined action of the T-helper-1-cell cytokines IFN-γ and tumour necrosis factor (TNF) directly induces permanent growth arrest in cancers. To safely separate senescence induced by tumour immunity from ...

  4. Small cell lung cancer transformation and T790M mutation: complimentary roles in acquired resistance to kinase inhibitors in lung cancer.

    Science.gov (United States)

    Suda, Kenichi; Murakami, Isao; Sakai, Kazuko; Mizuuchi, Hiroshi; Shimizu, Shigeki; Sato, Katsuaki; Tomizawa, Kenji; Tomida, Shuta; Yatabe, Yasushi; Nishio, Kazuto; Mitsudomi, Tetsuya

    2015-01-01

    Lung cancers often harbour a mutation in the epidermal growth factor receptor (EGFR) gene. Because proliferation and survival of lung cancers with EGFR mutation solely depend on aberrant signalling from the mutated EGFR, these tumours often show dramatic responses to EGFR tyrosine kinase inhibitors (TKIs). However, acquiring resistance to these drugs is almost inevitable, thus a better understanding of the underlying resistance mechanisms is critical. Small cell lung cancer (SCLC) transformation is a relatively rare acquired resistance mechanism that has lately attracted considerable attention. In the present study, through an in-depth analysis of multiple EGFR-TKI refractory lesions obtained from an autopsy case, we observed a complementary relationship between SCLC transformation and EGFR T790M secondary mutation (resistance mutation). We also identified analogies and differences in genetic aberration between a TKI-refractory lesion with SCLC transformation and one with EGFR T790M mutation. In particular, target sequencing revealed a TP53 P151S mutation in all pre- and post-treatment lesions. PTEN M264I mutation was identified only in a TKI-refractory lesion with SCLC transformation, while PIK3CA and RB1 mutations were identified only in pre-treatment primary tumour samples. These results provide the groundwork for understanding acquired resistance to EGFR-TKIs via SCLC transformation. PMID:26400668

  5. Albendazole sensitizes cancer cells to ionizing radiation

    International Nuclear Information System (INIS)

    Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted

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

    OpenAIRE

    Tae Hun Kim; Dong Hoon Suh; Mi-Kyung Kim; Yong Sang Song

    2014-01-01

    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 wi...

  7. Clinical perspectives of cancer stem cell research in radiation oncology

    International Nuclear Information System (INIS)

    Radiotherapy has a proven potential to eradicate cancer stem cells which is reflected by its curative potential in many cancer types. Considerable progress has been made in identification and biological characterisation of cancer stem cells during the past years. Recent biological findings indicate significant inter- and intratumoural and functional heterogeneity of cancer stem cells and lead to more complex models which have potential implications for radiobiology and radiotherapy. Clinical evidence is emerging that biomarkers of cancer stem cells may be prognostic for the outcome of radiotherapy in some tumour entities. Perspectives of cancer stem cell based research for radiotherapy reviewed here include their radioresistance compared to the mass of non-cancer stem cells which form the bulk of all tumour cells, implications for image- and non-image based predictive bio-assays of the outcome of radiotherapy and a combination of novel systemic treatments with radiotherapy

  8. 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.

  9. Cancer stem cells, metabolism, and therapeutic significance.

    Science.gov (United States)

    Yang, Mengqi; Liu, Panpan; Huang, Peng

    2016-05-01

    Cancer stem cells (CSCs) have attracted much attention of the research community in the recent years. Due to their highly tumorigenic and drug-resistant properties, CSCs represent important targets for developing novel anticancer agents and therapeutic strategies. CSCs were first described in hematopoietic malignancies and subsequently identified in various types of solid tumors including brain, breast, lung, colon, melanoma, and ovarian cancer. CSCs possess special biological properties including long-term self-renewal capacity, multi-lineage differentiation, and resistance to conventional chemotherapy and radiotherapy. As such, CSCs are considered as a major source of residual disease after therapy leading to disease occurrence. Thus, it is very important to understand the cellular survival mechanisms specific to CSCs and accordingly develop effective therapeutic approaches to eliminate this subpopulation of cancer cells in order to improve the treatment outcome of cancer patients. Possible therapeutic strategies against CSCs include targeting the self-renewal pathways of CSCs, interrupting the interaction between CSCs and their microenvironment, and exploiting the unique metabolic properties of CSCs. In this review article, we will provide an overview of the biological characteristics of CSCs, with a particular focus on their metabolic properties and potential therapeutic strategies to eliminate CSCs. PMID:26864589

  10. Sialylation: an Avenue to Target Cancer Cells.

    Science.gov (United States)

    Vajaria, Bhairavi N; Patel, Kinjal R; Begum, Rasheedunnisa; Patel, Prabhudas S

    2016-07-01

    Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration. PMID:26685886

  11. Heat induces gene amplification in cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. ► Hyperthermia induces DNA double strand breaks. ► DNA double strand breaks are considered to be required for the initiation of gene amplification. ► 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 °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) γH2AX immunostaining to detect γH2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 °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 °C for 30 min induces DNA double strand breaks in HCT116 cells as shown by γH2AX 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 telomere functions are denatured. To our knowledge, this is the first study to provide direct evidence of hyperthermia induced gene amplification.

  12. 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

  13. Electrodynamic activity of healthy and cancer cells

    International Nuclear Information System (INIS)

    Microtubules in the cell form a structure capable of generating electrodynamic field and mitochondria form their supporting system for physical processes including energy supply. Mitochondria transfer protons from their matrix space into cytosol, create strong static field around them that causes ordering of water and altering it into quasi-elastic medium with reduced viscous damping. Microtubules are composed of heterodimers that are electric dipoles. Microtubule oscillations generate an electrodynamic field. The greatest energy supply may be provided by liberation of non-utilized energy from mitochondria. Microtubules and mitochondria form a unique cooperating system in the cell. Mitochondria form a boundary element whose function depends on chemical-genetic control but their output is essential for physical processes in the cell. Mitochondrial dysfunction in cancer cells results in diminished intensity of the static electric field, disturbed water ordering, increased damping of microtubule oscillations and their shift towards linear region, and decreased energy supply. Power and coherence of oscillations and generated electrodynamic field is weakened. Malignant properties of cancer cell, in particular local invasion and metastasis, may depend on disturbed electrodynamic field. Nanotechnology is promising for investigation of electrodynamic activity in living cells.

  14. Cancer, stem cells and cancer stem cells: old ideas, new developments

    OpenAIRE

    Ghaffari, Saghi

    2011-01-01

    It has been suggested that, at least in some forms of cancer, a sub-population of slow-cycling, therapy-resistant cancer stem cells exists that has the ability to reconstitute the tumor in its entirety. If true, this model implies that conventional therapies based on targeting highly cycling cells within the tumor will leave the slow-cycling stem cell population intact, giving them the opportunity to reinitiate the tumor at a later date. This review discusses the evidence for this model and t...

  15. Clinical significance of T cell metabolic reprogramming in cancer.

    Science.gov (United States)

    Herbel, Christoph; Patsoukis, Nikolaos; Bardhan, Kankana; Seth, Pankaj; Weaver, Jessica D; Boussiotis, Vassiliki A

    2016-12-01

    Conversion of normal cells to cancer is accompanied with changes in their metabolism. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect, which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis functions in parallel with the TCA cycle and other metabolic pathways to enhance biosynthetic processes and thus support proliferation and growth. Similar metabolic features are observed in T cells during activation but, in contrast to cancer, metabolic transitions in T cells are part of a physiological process. Currently, there is intense interest in understanding the cause and effect relationship between metabolic reprogramming and T cell differentiation. After the recent success of cancer immunotherapy, the crosstalk between immune system and cancer has come to the forefront of clinical and basic research. One of the key goals is to delineate how metabolic alterations of cancer influence metabolism-regulated function and differentiation of tumor resident T cells and how such effects might be altered by immunotherapy. Here, we review the unique metabolic features of cancer, the implications of cancer metabolism on T cell metabolic reprogramming during antigen encounters, and the translational prospective of harnessing metabolism in cancer and T cells for cancer therapy. PMID:27510264

  16. Experience of ReCell in Skin Cancer Reconstruction

    OpenAIRE

    Onur Gilleard; Nicholas Segaren; Ciaran Healy

    2013-01-01

    The ReCell system (Avita Medical) is a cell culture product that allows the immediate processing of a small split-thickness skin biopsy to produce a complete population of cells including keratinocytes, melanocytes, Langerhans cells and fibroblasts. This series is the first to highlight the reconstructive applications of ReCell following ablative skin cancer surgery. The ReCell system was utilized for three patients following skin cancer excision. In two cases, the cells were applied to foreh...

  17. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    Science.gov (United States)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  18. NK cells, pregnancy, cancer. A short review

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Pospíšil, Miloslav; Fišerová, Anna

    2005-01-01

    Roč. 8, č. 4 (2005), s. 147-152. ISSN 1506-4794 R&D Projects: GA AV ČR IAA500200509; GA AV ČR IAA5020403; GA ČR GA524/04/0102; GA AV ČR IAA500200510 Institutional research plan: CEZ:AV0Z50200510 Keywords : natural killer cells * immune tolerance * cancer Subject RIV: EE - Microbiology, Virology

  19. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois; Souček, Karel

    Budapest, 2008. s. 194. [ISAC XXIV International Congress, Cytometry in the Age of Systems Biology. 17.05.2008-21.05.2008, Budapest] R&D Projects: GA ČR(CZ) GA204/07/0834 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * neuroendocrine-like cells * prostate cancer Subject RIV: BO - Biophysics

  20. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    Science.gov (United States)

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  1. CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but not in non-small cell lung cancer.

    Science.gov (United States)

    Cui, Fei; Wang, Jian; Chen, Duan; Chen, Yi-Jiang

    2011-03-01

    Lung cancer is the most common cause of cancer-related death worldwide. Current investigations in the field of cancer research have intensively focused on the 'cancer stem cell' or 'tumor-initiating cell'. While CD133 was initially considered as a stem cell marker only in the hematopoietic system and the nervous system, the membrane antigen also identifies tumorigenic cells in certain solid tumors. In this study, we investigated the human lung cancer cell lines A549, H157, H226, Calu-1, H292 and H446. The results of real-time PCR analysis after chemotherapy drug selection and the fluorescence-activated cell sorting analysis showed that CD133 only functioned as a marker in the small cell lung cancer line H446. The sorted CD133+ subset presented stem cell-like features, including self-renewal, differentiation, proliferation and tumorigenic capacity in subsequent assays. Furthermore, a proportion of the CD133+ cells had a tendency to remain stable, which may explain the controversies arising from previous studies. Therefore, the CD133+ subset should provide an enriched source of tumor-initiating cells among H446 cells. Moreover, the antigen could be used as an investigative marker of the tumorigenic process and an effective treatment for small cell lung cancer. PMID:21174061

  2. 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.

  3. Can a Cancer Cell Turn into a Normal Cell?

    Directory of Open Access Journals (Sweden)

    Ranan Gülhan Aktas

    2014-09-01

    Full Text Available HepG2 cells, a human liver cancer cell line (hepatocellular carcinoma, are being considered as a future model for bioartificial liver studies. They have the ability to differentiate and demonstrate some features of normal liver cells. Our previous studies focused on examination of the morphological and functional properties of these cells under different extracellular environmental conditions. We have created a culture model that these cells demonstrate remarkable changes after 30 days. These changes include an increase in the cytoplasmic organelles, formation of bile canaliculi, occurrence of junctional complexes between the adjacent cells, existence of microvilli on the apical surfaces, accumulation of glycogen particles in the cytoplasm, an increase at the density of albumin labeled areas and a rise at the Na-K ATPase level on cellular membranes.

  4. 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.

  5. 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.

  6. Stromal-cell and cancer-cell exosomes leading the metastatic exodus for the promised niche

    OpenAIRE

    Hoffman, Robert M.

    2013-01-01

    Exosomes are thought to play an important role in metastasis. Luga and colleagues have described the production of exosomes by stromal cells such as cancer-associated fibroblasts that are taken up by breast cancer cells and are then loaded with Wnt 11, which is associated with stimulation of the invasiveness and metastasis of the breast cancer cells. Previous studies have shown that exosomes produced by breast cancer cells are taken up by stromal fibroblasts and other stromal cells, suggestin...

  7. Lack of correlation of stem cell markers in breast cancer stem cells

    OpenAIRE

    Liu, Y; Nenutil, R; Appleyard, M V; Murray, K; Boylan, M; Thompson, A. M.; Coates, P J

    2014-01-01

    Background: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. Methods: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and t...

  8. Cancer stem cells in haematological malignancies

    OpenAIRE

    Zagozdzon, Radoslaw; Golab, Jakub

    2015-01-01

    At least several types of human haematological malignancies can now be seen as ‘stem-cell diseases’. The best-studied in this context is acute myeloid leukaemia (AML). It has been shown that these diseases are driven by a pool of ‘leukaemia stem cells (LSC)’, which remain in the quiescent state, have the capacity to survive and self-renew, and are responsible for the recurrence of cancer after classical chemotherapy. It has been understood that LSC must be eliminated in order to cure patients...

  9. Microrheology of keratin networks in cancer cells

    International Nuclear Information System (INIS)

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a deceasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. (paper)

  10. Microrheology of keratin networks in cancer cells.

    Science.gov (United States)

    Paust, T; Paschke, S; Beil, M; Marti, O

    2013-12-01

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a decreasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. PMID:24305115

  11. Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

    International Nuclear Information System (INIS)

    Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.

  12. Ovarian Cancer Stem Cell Markers: Prognostic and Therapeutic Implications

    OpenAIRE

    Burgos-Ojeda, Daniela; Rueda, Bo R.; Buckanovich, Ronald J.

    2012-01-01

    Cancer stem cells are rare chemotherapy resistant cells within a tumor which can serve to populate the bulk of a tumor with more differentiated daughter cells and potentially contribute to recurrent disease. Ovarian cancer is a disease for which at the time of initial treatment we can obtain complete clinical remission in the majority of patients. Unfortunately, most will relapse and succumb to their disease. This clinical course is in line with the cancer stem cell model. In the past five ye...

  13. Cancer Stem Cells in Brain Tumors and Their Lineage Hierarchy

    OpenAIRE

    Kong, Doo-Sik

    2012-01-01

    Despite recent advances in the development of novel targeted chemotherapies, the prognosis of malignant glioma remains dismal. The chemo-resistance of this tumor is attributed to tumor heterogeneity. To explain this unique chemo- resistance, the concept of cancer stem cells has been evoked. Cancer stem cells, a subpopulation of whole tumor cells, are now regarded as candidate therapeutic targets. Here, the author reviews and discusses the cancer stem cell concept.

  14. Risk Factors for Renal Cell Cancer in a Japanese Population

    OpenAIRE

    Washio, Masakazu; Mori, Mitsuru

    2009-01-01

    The incidence of renal cell cancer has been increasing worldwide. Although the incidence of renal cell cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. In this paper, we would like to introduce the result of our studies, which evaluate the risk factors for renal cell cancer in Japan. Hypertension, diabetes mellitus, kidney diseases, fondness for fatty food and black tea showed an increased risk of renal cell carcinoma whil...

  15. Cancer stem cell plasticity and tumor hierarchy

    Institute of Scientific and Technical Information of China (English)

    Marina Carla Cabrera; Robert E Hollingsworth; Elaine M Hurt

    2015-01-01

    The origins of the complex process of intratumoralheterogeneity have been highly debated and differentcellular mechanisms have been hypothesized to accountfor the diversity within a tumor. The clonal evolution andcancer stem cell (CSC) models have been proposed asdrivers of this heterogeneity. However, the concept ofcancer stem cell plasticity and bidirectional conversionbetween stem and non-stem cells has added additionalcomplexity to these highly studied paradigms and may helpexplain the tumor heterogeneity observed in solid tumors.The process of cancer stem cell plasticity in which cancercells harbor the dynamic ability of shifting from a non-CSCstate to a CSC state and vice versa may be modulated byspecific microenvironmental signals and cellular interactionsarising in the tumor niche. In addition to promoting CSCplasticity, these interactions may contribute to the cellulartransformation of tumor cells and affect response tochemotherapeutic and radiation treatments by providingCSCs protection from these agents. Herein, we review theliterature in support of this dynamic CSC state, discussthe effectors of plasticity, and examine their role in thedevelopment and treatment of cancer.

  16. Cancer Stem Cells: Foe or Reprogrammable Cells for Efficient Cancer Therapy?

    Directory of Open Access Journals (Sweden)

    Carlo Ventura

    2015-11-01

    Full Text Available Embryonic development and carcinogenesis share many molecular pathways and regulatory molecules. While the induction of a pluripotent state involves a significant oncogenic risk, as in induced pluripotent stem cells (iPSCs, the embryonic environment in vivo has been shown to suppress tumor development. In this review, we discuss the subtle equilibrium between the nanotopography (niche of the hosting tissue resident stem cells and their biological dynamics, including the transformation in cancer stem cells. We review consistent findings indicating the potential for modulating the biology of human cancer stem cells by the aid of naturally occurring or synthetic molecules, including developmental stage zebrafish embryo extracts, hyaluronan, butyric acid (BA and retinoic acid (RA, hyaluronan mixed esters of BA and RA, melatonin, vitamin D3, and endorphin peptides. Within this context, we dissect the multifaceted mechanisms orchestrated by endorphinergic systems, including paracrine cellto- cell communication, as well as the establishment of autocrine and intracrine (intracellular peptide actions driving transcriptional responses and self-sustaining loops that behave as long-lived signals imparting features characteristic of differentiation, growth regulation and cell memory. Based upon the remarkable action of electromagnetic fields and mechanical vibration on (stem cell signaling, differentiation, and senescence, we also consider the potential for using these physical energies as a tool to afford a fine tuning of cancer stem cell fate. On the whole, we forecast future deployment of the physical and/or chemical approaches described herein aiming at reprogramming, rather than destroying cancer stem cells, eventually placing cancer therapy within the context of Regenerative Medicine.

  17. Prevalence of Epithelial Ovarian Cancer Stem Cells Correlates with Recurrence in Early-Stage Ovarian Cancer

    OpenAIRE

    Gil Mor; Anders Jakobsen; Thomas Rutherford; Dan-Arin Silasi; Holmberg, Jennie C.; Pei Hui; Marianne Waldstrøm; Karina Dahl Steffensen; Alvero, Ayesha B.; Yang Yang

    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 h...

  18. Role of Oxidative Stress in Stem, Cancer, and Cancer Stem Cells

    OpenAIRE

    Ahmed Abdal Dayem; Hye-Yeon Choi; Jung-Hyun Kim; Ssang-Goo Cho

    2010-01-01

    The term ‘‘oxidative stress” refers to a cell’s state characterized by excessive production of reactive oxygen species (ROS) and oxidative stress is one of the most important regulatory mechanisms for stem, cancer, and cancer stem cells. The concept of cancer stem cells arose from observations of similarities between the self-renewal mechanism of stem cells and that of cancer stem cells, but compared to normal stem cells, they are believed to have no control over the cell number. ROS have bee...

  19. Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes.

    Science.gov (United States)

    Chen, Bingdi; Le, Wenjun; Wang, Yilong; Li, Zhuoquan; Wang, Dong; Ren, Lei; Lin, Ling; Cui, Shaobin; Hu, Jennifer J; Hu, Yihui; Yang, Pengyuan; Ewing, Rodney C; Shi, Donglu; Cui, Zheng

    2016-01-01

    A set of electrostatically charged, fluorescent, and superparamagnetic nanoprobes was developed for targeting cancer cells without using any molecular biomarkers. The surface electrostatic properties of the established cancer cell lines and primary normal cells were characterized by using these nanoprobes with various electrostatic signs and amplitudes. All twenty two randomly selected cancer cell lines of different organs, but not normal control cells, bound specifically to the positively charged nanoprobes. The relative surface charges of cancer cells could be quantified by the percentage of cells captured magnetically. The activities of glucose metabolism had a profound impact on the surface charge level of cancer cells. The data indicate that an elevated glycolysis in the cancer cells led to a higher level secretion of lactate. The secreted lactate anions are known to remove the positive ions, leaving behind the negative changes on the cell surfaces. This unique metabolic behavior is responsible for generating negative cancer surface charges in a perpetuating fashion. The metabolically active cancer cells are shown to a unique surface electrostatic pattern that can be used for recovering cancer cells from the circulating blood and other solutions. PMID:27570558

  20. Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes

    Science.gov (United States)

    Chen, Bingdi; Le, Wenjun; Wang, Yilong; Li, Zhuoquan; Wang, Dong; Ren, Lei; Lin, Ling; Cui, Shaobin; Hu, Jennifer J.; Hu, Yihui; Yang, Pengyuan; Ewing, Rodney C.; Shi, Donglu; Cui, Zheng

    2016-01-01

    A set of electrostatically charged, fluorescent, and superparamagnetic nanoprobes was developed for targeting cancer cells without using any molecular biomarkers. The surface electrostatic properties of the established cancer cell lines and primary normal cells were characterized by using these nanoprobes with various electrostatic signs and amplitudes. All twenty two randomly selected cancer cell lines of different organs, but not normal control cells, bound specifically to the positively charged nanoprobes. The relative surface charges of cancer cells could be quantified by the percentage of cells captured magnetically. The activities of glucose metabolism had a profound impact on the surface charge level of cancer cells. The data indicate that an elevated glycolysis in the cancer cells led to a higher level secretion of lactate. The secreted lactate anions are known to remove the positive ions, leaving behind the negative changes on the cell surfaces. This unique metabolic behavior is responsible for generating negative cancer surface charges in a perpetuating fashion. The metabolically active cancer cells are shown to a unique surface electrostatic pattern that can be used for recovering cancer cells from the circulating blood and other solutions. PMID:27570558

  1. Cavitary Lung Cancer Lined with Normal Bronchial Epithelium and Cancer Cells

    OpenAIRE

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells.

  2. Improvement of Mooring Configurations in Geraldton Harbour

    Directory of Open Access Journals (Sweden)

    Wim van der Molen

    2015-12-01

    Full Text Available Ports exposed to high energy long wave conditions can experience significantly reduced berth operability. Geraldton is perhaps one of the best known examples. Recent studies to mitigate the problems have concentrated on the reduction of the long waves by extending the breakwater. However, this is quite costly. Various countermeasures related to the mooring configuration are defined and analysed in this paper. The analysed alternatives are use of shore-based mooring lines, installation of softer fenders, a combination of these two, and deployment of Cavotec MoorMaster™ units. These alternatives were compared with the existing mooring configuration and with the option to extend the breakwater. The best improvement (50% increase of threshold long wave height inside the harbour is reached by installing a combination of pneumatic fenders and constant tension winches set to 30 t, or nylon breast lines on a brake winch with a pretension of 25 t. In this way, the vessel is pulled into the fenders and fender friction prevents excessive surging of the ship along the berth.

  3. Direct targeting of cancer cells: a multiparameter approach.

    Science.gov (United States)

    Heinrich, Eileen L; Welty, Lily Anne Y; Banner, Lisa R; Oppenheimer, Steven B

    2005-01-01

    Lectins have been widely used in cell surface studies and in the development of potential anticancer drugs. Many past studies that have examined lectin toxicity have only evaluated the effects on cancer cells, not their non-cancer counterparts. In addition, few past studies have evaluated the relationship between lectin-cell binding and lectin toxicity on both cell types. Here we examine these parameters in one study: lectin-cell binding and lectin toxicity with both cancer cells and their normal counterparts. We found that the human colon cancer cell line CCL-220/Colo320DM bound to agarose beads derivatized with Phaseolus vulgaris agglutinin (PHA-L) and wheat germ agglutinin (WGA), while the non-cancer human colon cell line CRL-1459/CCD-18Co did not. When these lectins were tested for their effects on cell viability in culture, both cell lines were affected by the lectins but at 6, 48 and 72 h incubation times, PHA-L was most toxic to the cancer cell line in a concentration dependent manner. At 48 h incubation, WGA was more toxic to the cancer cell line. The results suggest that it may be possible to develop lectin protocols that selectively target cancer cells for death. In any case, examination of both malignant cells and their non-malignant counterparts, analysis of their binding characteristics to immobilized lectins, and examination of the toxicity of free lectins in culture, provides a multiparameter model for obtaining more comprehensive information than from more limited approaches. PMID:16181664

  4. Murine Lung Cancer Induces Generalized T Cell Exhaustion

    Science.gov (United States)

    Mittal, Rohit; Chen, Ching-Wen; Lyons, John D; Margoles, Lindsay M; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L

    2015-01-01

    Background Cancer is known to modulate tumor-specific immune responses by establishing a micro-environment that leads to the upregulation of T cell inhibitory receptors, resulting in the progressive loss of function and eventual death of tumor-specific T cells. However, the ability of cancer to impact the functionality of the immune system on a systemic level is much less well characterized. Because cancer is known to predispose patients to infectious complications including sepsis, we hypothesized that the presence of cancer alters pathogen-directed immune responses on a systemic level. Materials and Methods We assessed systemic T cell coinhibitory receptor expression, cytokine production, and apoptosis in mice with established subcutaneous lung cancer tumors and in unmanipulated mice without cancer. Results Results indicated that the frequencies of PD-1+, BTLA+, and 2B4+ cells in both the CD4+ and CD8+ T cell compartments were increased in mice with localized cancer relative to non-cancer controls, and the frequencies of both CD4+ and CD8+ T cells expressing multiple different inhibitory receptors was increased in cancer animals relative to non-cancer controls. Additionally, 2B4+CD8+ T cells in cancer mice exhibited reduced IL-2 and IFN-γ, while BTLA+CD8+ T cells in cancer mice exhibited reduced IL-2 and TNF. Conversely, CD4+ T cells in cancer animals demonstrated an increase in the frequency of Annexin V+ apoptotic cells. Conclusion Taken together, these data suggest that the presence of cancer induces systemic T cell exhaustion and generalized immune suppression. PMID:25748104

  5. 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 be...

  6. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

    OpenAIRE

    Tiffany M. Phillips; Kwanghee Kim; Erina Vlashi; McBride, William H.; Frank Pajonk

    2007-01-01

    BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs). In breast can...

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

    OpenAIRE

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

    2011-01-01

    Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. 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 cells — through networks of cytokines and growth factors. Since these components have a direct...

  8. Overexpression of cyclin Y in non-small cell lung cancer is associated with cancer cell proliferation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Cyclin Y (CCNY) is a key cell cycle regulator that acts as a growth factor sensor to integrate extracellular signals with the cell cycle machinery. The expression status of CCNY in lung cancer and its clinical significance remain unknown. The data indicates that CCNY may be deregulated in non-small cell lung cancer, where it may act to promote cell proliferation. These studies suggest that CCNY may be a candidate biomarker of NSCLC and a possible therapeutic target for lung cancer treatment.

  9. Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples

    OpenAIRE

    Wang, Shunqi; Huang, Shengsong; Zhao, Xin; Zhang, Qimin; Wu, Min; Sun, Feng; Han, Gang; Wu, Denglong

    2013-01-01

    This study was to enrich prostate cancer stem cells (PrCSC) from primary prostate cancer cultures (PPrCC). Primary prostate cancer cells were amplified in keratinocyte serum-free medium with epidermal growth factor (EGF) and bovine pituitary extract (BPE), supplemented with leukemia inhibitory factor (LIF), stem cell factor (SCF) and cholera toxin. After amplification, cells were transferred into ultra-low attachment dishes with serum-free DMEM/F12 medium, supplemented with EGF, basic fibrobl...

  10. Niche construction game cancer cells play

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

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

    Directory of Open Access Journals (Sweden)

    Apostolou P

    2015-07-01

    Full Text Available 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 to determine genes that are expressed in breast cancer and breast CSCs and to investigate their correlation with stemness. RNA was extracted from established breast cancer cell lines and from CSCs derived from five different breast cancer patients. DNA microarray analysis was performed and any upregulated genes were also studied in other cancer types, including colorectal and lung cancer. For genes that were expressed only in breast cancer, knockdown-based experiments were performed. Finally, the gene expression levels of stemness transcription factors were measured. The outcome of the analysis indicated a group of genes that were aberrantly expressed mainly in breast cancer cells with stemness properties. Knockdown experiments confirmed the impact of several of these on NANOG, OCT3/4, and SOX2 transcription factors. It seems that several genes that are not directly related with hormone metabolism and basic signal transduction pathways might have an important role in relapse and disease progression and, thus, can be targeted for new treatment approaches for breast cancer. Keywords: breast cancer, cancer stem cells, stemness, DNA microarray

  12. Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells

    OpenAIRE

    Yang, Feng-Qiang; Wang, Ji-Jiao; Yan, Jia-Sheng; Huang, Jian-Hua; Li, Wei; Che, Jian-Ping; Wang, Guang-Chun; Liu, Min; Zheng, Jun-Hua

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the ef...

  13. Metabolic alterations in cancer cells and therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Naima Hammoudi; Kausar Begam Riaz Ahmed; Celia Garcia-Prieto; Peng Huang

    2011-01-01

    Cancer metabolism has emerged as an important area of research in recent years. Elucidation of the metabolic differences between cancer and normal cells and the underlying mechanisms will not only advance our understanding of fundamental cancer cell biology but also provide an important basis for the development of new therapeutic strategies and novel compounds to selectively eliminate cancer cells by targeting their unique metabolism. This article reviews several important metabolic alterations in cancer cells, with an emphasis on increased aerobic glycolysis (the Warburg effect) and glutamine addiction, and discusses the mechanisms that may contribute to such metabolic changes. In addition, metabolic alterations in cancer stem cells, mitochondrial metabolism and its influence on drug sensitivity, and potential therapeutic strategies and agents that target cancer metabolism are also discussed.

  14. Breast and other cancer dormancy as a therapeutic endpoint: speculative recombinant T cell receptor ligand (RTL) adjuvant therapy worth considering?

    International Nuclear Information System (INIS)

    Most individuals who died of trauma were found to harbour microscopic primary cancers at autopsies. Surgical excision of the primary tumour, unfortunately, seems to disturb tumour dormancy in over half of all metastatic relapses. A recently developed immune model suggested that the evolutionary pressure driving the creation of a T cell receptor repertoire was primarily the homeostatic surveillance of the genome. The model is based on the homeostatic role of T cells, suggesting that molecular complementarity between the positively selected T cell receptors and the self peptide-presenting major histocompatibility complex molecules establishes and regulates homeostasis, strictly limiting variations of its components. The repertoire is maintained by continuous peripheral stimulation via soluble forms of self-peptide-presenting major histocompatibility complex molecules governed by the law of mass action. The model states that foreign peptides inhibit the complementary interactions between the major histocompatibility complexes and T cell receptors. Since the vast majority of clinically detected cancers present self-peptides the model assumes that tumour cells are, paradoxically, under homeostatic T cell control. The novelty of our hypothesis therefore is that resection of the primary tumour mass is perceived as loss of 'normal' tissue cells. Consequently, T cells striving to reconstitute homeostasis stimulate rather than inhibit the growth of dormant tumour cells and avascular micrometastases. Here we suggest that such kick-start growths could be prevented by a recombinant T cell receptor ligand therapy that modifies T cell behaviour through a partial activation mechanism. The homeostatic T cell regulation of tumours can be tested in a tri-transgenic mice model engineered to express potent oncogenes in a doxycycline-dependent manner. We suggest seeding dissociated, untransformed mammary cells from doxycycline naïve mice into the lungs of two mice groups: one

  15. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    Science.gov (United States)

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  16. Targeted Elimination of Breast Cancer Cells with Low Proteasome Activity is Sufficient for Tumor Regression

    OpenAIRE

    Vlashi, Erina; Lagadec, Chann; Chan, Mabel; Frohnen, Patricia; Jean McDonald, Alexandra; Pajonk, Frank

    2013-01-01

    Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells, able to regrow a tumor after sublethal treatment while their progeny lack this feature. Furthermore, breast cancer stem cells are highly resistant to conventional anti-cancer treatments. According to the cancer stem cell hypothesis, all cancer stem cells in a tumor have to be eliminated to achieve cancer cure. In this study we tested if targeted elimination of breast cancer stem cells le...

  17. DUAL ROLES OF CANCER CELL-EXPRESSED IMMUNOGLOBULINS IN CANCER IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Gregory Lee

    2014-01-01

    Full Text Available While the expression of immunoglobulins and T cell receptors on cancer cells has been well-established for decades, the potential roles and mechanisms of action of these cancerous antigen receptors have not been fully elucidated. A monoclonal antibody designated as RP215, which reacts specifically with the carbohydrate-associated epitope located on the heavy chain region of cancerous immunoglobulins and T cell receptors, was used as a unique probe to study the roles of antigen receptors in the immunology of cancer cells. Through extensive cell-based biological and immunological studies, it was found that both anti-antigen receptors and RP215 demonstrated similar actions on the gene regulations involved in the growth/proliferation of cancer cells, as well as on toll-like receptors involved in innate immunity. In addition, RP215-specific cancerous immunoglobulins are believed to capture or neutralize circulating antigen/antibodies which may be harmful to cancer cells within the human body. In contrast to normal B and T cells and their respective receptors in the conventional immune system, cancer cells co-express both immunoglobulins and T cell receptors and immune protection is exercised by unique mechanisms. For example, these cancer cell-expressed antigen receptors display a lack of class switching, limited hyper-mutation, aberrant glycosylations and a strong influence on the toll-like receptors of cancer cells. Therefore, it is hypothesized that both normal and cancerous immune systems may co-exist and operate simultaneously within the human body. The balance of these two immune factors for respective surveillance and protection may be relevant to the outcome of cancer immunotherapy in humans. A potential therapeutic strategy is being developed by using RP215 as a drug candidate to target cancer cells based on these observations.

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

    International Nuclear Information System (INIS)

    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. 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. 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 < 0.01). Some of these genes have already been directly linked with breast cancer, metastasis and malignant progression, whilst others encode receptors linked to signal transduction pathways or are otherwise related to cell proliferation. Fifty genes showed at least a 2.5-fold difference between MSSMs and T-est cells according to AtlasImage, 2-fold according to SAM. Most of these classified as genes related to metabolism and cell communication. 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. 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.

  20. Convergence of normal stem cell and cancer stem cell developmental stage: Implication for differential therapies

    OpenAIRE

    Shengwen Calvin Li; Lee, Katherine L.; Jane Luo; Jiang F. Zhong; William G Loudon

    2011-01-01

    Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements. We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation. CSC can be the key to the elaboration of anti-cancer-based therapy. In this article, we focus on a controversial new theme relating to CSC. Tumorigenesis may have a c...

  1. Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation

    OpenAIRE

    Cheng, Kunrong; Samimi, Roxana; Xie, Guofeng; Shant, Jasleen; Drachenberg, Cinthia; Wade, Mark; Davis, Richard J.; Nomikos, George; Raufman, Jean-Pierre

    2008-01-01

    Most colon cancers overexpress M3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor...

  2. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  3. Targeting the cancer cell cycle by cold atmospheric plasma

    Science.gov (United States)

    Volotskova, O.; Hawley, T. S.; Stepp, M. A.; Keidar, M.

    2012-09-01

    Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.

  4. Mitochondria as therapeutic targets for cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    In Sung Song; Jeong Yu Jeong; Seung Hun Jeong; Hyoung Kyu Kim; Kyung Soo Ko; Byoung Doo Rhee; Nari Kim; Jin Han

    2015-01-01

    Cancer stem cells (CSCs) are maintained by theirsomatic stem cells and are responsible for tumorinitiation, chemoresistance, and metastasis. Evidencefor the CSCs existence has been reported for a numberof human cancers. The CSC mitochondria have beenshown recently to be an important target for cancertreatment, but clinical significance of CSCs and theirmitochondria properties remain unclear. Mitochondriatargetedagents are considerably more effectivecompared to other agents in triggering apoptosis ofCSCs, as well as general cancer cells, via mitochondrialdysfunction. Mitochondrial metabolism is altered incancer cells because of their reliance on glycolyticintermediates, which are normally destined for oxidativephosphorylation. Therefore, inhibiting cancer-specificmodifications in mitochondrial metabolism, increasingreactive oxygen species production, or stimulatingmitochondrial permeabilization transition could bepromising new therapeutic strategies to activate celldeath in CSCs as well, as in general cancer cells. Thisreview analyzed mitochondrial function and its potentialas a therapeutic target to induce cell death in CSCs.Furthermore, combined treatment with mitochondriatargeteddrugs will be a promising strategy for thetreatment of relapsed and refractory cancer.

  5. 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. PMID:22043817

  6. Minor Harbours of the East Coast of Ireland

    OpenAIRE

    Spratt-Murphy, William; Shotton, Elizabeth

    2015-01-01

    Considerable progress in the engineering of maritime structures occurred between the 18th and 20th centuries in Ireland. While major harbours have been well documented, there remain considerable structures that due to their small size have been overlooked. These minor harbours represent a considerable source of information, many having originated through local efforts only to be later modified through government works in the 19th and 20th centuries. The danger posed to these structures from d...

  7. Cancer Stem Cells: A Novel Paradigm for Cancer Prevention and Treatment

    OpenAIRE

    Subramaniam, D; Ramalingam, S; Houchen, C.W.; Anant, S

    2010-01-01

    Cancer is the second leading cause for mortality in US only after heart disease and lacks a good or effective therapeutic paradigm. Despite the emergence of new, targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is supporting the idea that human cancers can be considered as a stem cell disease. Malignancies are believed to originate from a fraction of cancer cells th...

  8. 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...

  9. Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer.

    Science.gov (United States)

    Tan, Chee-Seng; Gilligan, David; Pacey, Simon

    2015-09-01

    Discovery of activating mutations in EGFR and their use as predictive biomarkers to tailor patient therapy with EGFR tyrosine kinase inhibitors (TKIs) has revolutionised treatment of patients with advanced EGFR-mutant non-small-cell lung cancer (NSCLC). At present, first-line treatment with EGFR TKIs (gefitinib, erlotinib, and afatinib) has been approved for patients harbouring exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. These agents improve response rates, time to progression, and overall survival. Unfortunately, patients develop resistance, limiting patient benefit and posing a challenge to oncologists. Optimum treatment after progression is not clearly defined. A more detailed understanding of the biology of EGFR-mutant NSCLC and the mechanisms of resistance to targeted therapy mean that an era of treatment approaches based on rationally developed drugs or therapeutic strategies has begun. Combination approaches-eg, dual EGFR blockade-to overcome resistance have been trialled and seem to be promising but are potentially limited by toxicity. Third-generation EGFR-mutant-selective TKIs, such as AZD9291 or rociletininb, which target Thr790Met-mutant tumours, the most common mechanism of EGFR TKI resistance, have entered clinical trials, and exciting, albeit preliminary, efficacy data have been reported. In this Review, we summarise the scientific literature and evidence on therapy options after EGFR TKI treatment for patients with NSCLC, aiming to provide a guide to oncologists, and consider how to maximise therapeutic advances in outcomes in this rapidly advancing area. PMID:26370354

  10. Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells.

    Science.gov (United States)

    Yongsanguanchai, Nuttida; Pongrakhananon, Varisa; Mutirangura, Apiwat; Rojanasakul, Yon; Chanvorachote, Pithi

    2015-01-15

    Even though tremendous advances have been made in the treatment of cancers during the past decades, the success rate among patients with cancer is still dismal, largely because of problems associated with chemo/radioresistance and relapse. Emerging evidence has indicated that cancer stem cells (CSCs) are behind the resistance and recurrence problems, but our understanding of their regulation is limited. Rapid reversible changes of CSC-like cells within tumors may result from the effect of biological mediators found in the tumor microenvironment. Here we show how nitric oxide (NO), a key cellular modulator whose level is elevated in many tumors, affects CSC-like phenotypes of human non-small cell lung carcinoma H292 and H460 cells. Exposure of NO gradually altered the cell morphology toward mesenchymal stem-like shape. NO exposure promoted CSC-like phenotype, indicated by increased expression of known CSC markers, CD133 and ALDH1A1, in the exposed cells. These effects of NO on stemness were reversible after cessation of the NO treatment for 7 days. Furthermore, such effect was reproducible using another NO donor, S-nitroso-N-acetylpenicillamine. Importantly, inhibition of NO by the known NO scavenger 2-(4-carboxy-phenyl)-4,4,5,5 tetramethylimidazoline-1-oxy-3-oxide strongly inhibited CSC-like aggressive cellular behavior and marker expression. Last, we unveiled the underlying mechanism of NO action through the activation of caveolin-1 (Cav-1), which is upregulated by NO and is responsible for the aggressive behavior of the cells, including anoikis resistance, anchorage-independent cell growth, and increased cell migration and invasion. These findings indicate a novel role of NO in CSC regulation and its importance in aggressive cancer behaviors through Cav-1 upregulation. PMID:25411331

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

    OpenAIRE

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

    2014-01-01

    Background 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 b...

  12. 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...

  13. 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.

  14. The role of myeloid cells in cancer therapies.

    Science.gov (United States)

    Engblom, Camilla; Pfirschke, Christina; Pittet, Mikael J

    2016-07-01

    Recent clinical trials have demonstrated the ability to durably control cancer in some patients by manipulating T lymphocytes. These immunotherapies are revolutionizing cancer treatment but benefit only a minority of patients. It is thus a crucial time for clinicians, cancer scientists and immunologists to determine the next steps in shifting cancer treatment towards better cancer control. This Review describes recent advances in our understanding of tumour-associated myeloid cells. These cells remain less studied than T lymphocytes but have attracted particular attention because their presence in tumours is often linked to altered patient survival. Also, experimental studies indicate that myeloid cells modulate key cancer-associated activities, including immune evasion, and affect virtually all types of cancer therapy. Consequently, targeting myeloid cells could overcome limitations of current treatment options. PMID:27339708

  15. Natural Products That Target Cancer Stem Cells.

    Science.gov (United States)

    Moselhy, Jim; Srinivasan, Sowmyalakshmi; Ankem, Murali K; Damodaran, Chendil

    2015-11-01

    The cancer stem cell model suggests that tumor initiation is governed by a small subset of distinct cells with stem-like character termed cancer stem cells (CSCs). CSCs possess properties of self-renewal and intrinsic survival mechanisms that contribute to resistance of tumors to most chemotherapeutic drugs. The failure to eradicate CSCs during the course of therapy is postulated to be the driving force for tumor recurrence and metastasis. Recent studies have focused on understanding the unique phenotypic properties of CSCs from various tumor types, as well as the signaling pathways that underlie self-renewal and drug resistance. Natural products (NPs) such as those derived from botanicals and food sources may modulate vital signaling pathways involved in the maintenance of CSC phenotype. The Wingless/Integrated (WNT), Hedgehog, Notch and PI3K/AKT/mTOR pathways have all been associated with quiescence and self-renewal of CSCs, as well as execution of CSC function including differentiation, multidrug resistance and metastasis. Recent studies evaluating NPs against CSC support the epidemiological evidence linking plant-based diets with reduced malignancy rates. This review covers the key aspects of NPs as modulators of CSC fate. PMID:26503998

  16. HS-4, a highly potent inhibitor of cell proliferation of human cancer cell

    Institute of Scientific and Technical Information of China (English)

    Gui-Lan Xing; Shu-Hong Tian; Xue-Li Xie; Jian Fu

    2015-01-01

    Objective:To investigate the antitumor activity of the compound HS-4 and the action mechanism.Methods:MTT method was used to testin vitroantitumor activity of the compound HS-4. Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice, and,in vivoantitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system. Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics, using high-throughput sequencing technology. Results:HS-4 was found to have relatively highin-vitro antitumor activity against liver cancer cells, gastric cancer cells, renal cancer cells, lung cancer cells, breast cancer cells and colon cancer cells. The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively, while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L, respectively. It was demonstrated that HS- 4 possessed a better therapeutic effect in liver cancer.Conclusions: A new reliable orthotopic xenotransplantation tumor model of liver cancer in nude mice is established. The new compounds HS-4 was found to possess relatively highin vivo andin vitroantitumor activity against liver cancer cells.

  17. HS-4,a highly potent inhibitor of cell proliferation of human cancer cell

    Institute of Scientific and Technical Information of China (English)

    Gui-Lan; Xing; Shu-Hong; Tian; Xue-Li; Xie; Jian; Fu

    2015-01-01

    Objective:To investigate the antitumor activity of the compound HS-4 and the action mechanism.Methods:MTT method was used to test in vitro antitumor activity of the compound HS-4.Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice,and.in vivo antitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system.Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics,using high-throughput sequencing technology.Results:HS-4 was found to have relatively high in-vitro antitumor activity against liver cancer cells,gastric cancer cells,renal cancer cells,lung cancer cells,breast cancer cells and colon cancer cells.The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively,while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L,respectively.It was demonstrated that HS- 4 possessed a betler therapeutic effect in liver cancer.Conclusions:A new reliable orthotopicxenotransplantation tumor model of liver cancer in nude mice is established.The new compounds HS-4 was found to possess relatively high in vivo and in vitro antitumor activity against liver cancer cells.

  18. Cancer Stem Cells: The Final Frontier for Glioma Virotherapy

    OpenAIRE

    Dey, Mahua; Ulasov, Ilya V.; Tyler, Matthew A.; Sonabend, Adam M.; Lesniak, Maciej S.

    2011-01-01

    Cancer stem cells (CSC) are a very small subset of all cancer cells and possess characteristics very similar to normal stem cells, in particular, the capacity for self-renewal, multipotency and relative quiescence. These chemo- and radiation resistant cells are responsible for maintaining tumor volume leading to therapy failure and recurrence. In glioblastoma multiforme (GBM), the most common primary intracranial malignancy, glioma stem cells have been implicated as one of the key players in ...

  19. Cancer Stem Cells – Basics, Progress and Future Potential

    OpenAIRE

    Bapat S.A

    2010-01-01

    The primary characteristics of adult stem cells are maintaining prolonged quiescence, ability to self-renew and plasticity to differentiate into multiple cell types. These properties are evolutionarily conserved from fruit fly to humans. Similar to normal tissue repair in organs, the stem cell concept is inherently impregnated in the etiology of cancer. Tumors contain a minor population of tumor-initiating cells, called "cancer stem cells" that maintain some similarities in self-renewal and d...

  20. Dynamic Switch Between Two Adhesion Phenotypes in Colorectal Cancer Cells

    OpenAIRE

    Geng, Yue; Chandrasekaran, Siddarth; Agastin, Sivaprakash; Li, Jiahe; King, Michael R.

    2013-01-01

    The hematogenous metastatic cascade is mediated by the interaction of cancer cells and the endothelial cell lining of blood vessels. In this work, we examine the colon cancer cell line COLO 205, which grows simultaneously in both adherent and suspended states in culture and can serve as a good model for studying tumor heterogeneity. The two subpopulations of cells have different molecular characteristics despite being from the same parent cell line. We found that the ratio of adherent to susp...

  1. TRANSCRIPTIONAL LANDSCAPE OF NEURONAL and CANCER STEM CELLS

    OpenAIRE

    Miele, Evelina

    2013-01-01

    Tumor mass is composed by heterogeneous cell population including a subset of “cancer stem cells” (CSC). Oncogenic signals foster CSC by transforming tissue stem cells or by reprogramming progenitor/differentiated cells towards stemness. Thus, CSC share features with cancer and stem cells (e.g. self-renewal, hierarchical developmental program leading to differentiated cells, epithelial/mesenchimal transition) and these latter are maintained by the constitutive activation of stemne...

  2. Human prostate cancer stem cells: new features unveiled

    Institute of Scientific and Technical Information of China (English)

    Yuting Sun; Wei-Qiang Gao

    2011-01-01

    @@ Cancer stem cells (CSCs) are a rare sub-population of phenotypically distinct cancer cells exhibiting stem cell characteristics.They are tumourigenic, meanwhile capable of self-renewal and forming differentiated progenies.CSCs are believed to be resistant to the standard therapeutics, and provide the cell reservoir for tumour initiation.1 Understanding CSCs or in another word, tumour-initiating cells, is of critical therapeutic importance.

  3. 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

    increase in the number of gamma-H2AX ‘DNA damage foci’, indicating replicative stress, which may lead to genomic instability. As the p53 tumor suppressor is an inducer of G1 arrest after DNA damage and often deregulated in cancer cells, we investigated if the growth reduction due to SSX2 expression was p53...... 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......The SSX family of cancer and germline antigens is mainly expressed in the germ cells of healthy individuals as well as wide range of cancers and is therefore potential targets for immunotherapy. However, little is known about the role of SSX proteins in tumorigenesis and normal cell function. Here...

  4. 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.

  5. MEMBRANE LEc EXPRESSION IN BREAST CANCER CELLS

    Directory of Open Access Journals (Sweden)

    Ya. A. Udalova

    2014-09-01

    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.

  6. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois

    2008-01-01

    Roč. 102, č. 5 (2008), s. 393. ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * prostate cancer * neuroendocrine-like cells Subject RIV: BO - Biophysics

  7. Adhesion between peptides/antibodies and breast cancer cells

    Science.gov (United States)

    Meng, J.; Paetzell, E.; Bogorad, A.; Soboyejo, W. O.

    2010-06-01

    Atomic force microscopy (AFM) techniques were used to measure the adhesion forces between the receptors on breast cancer cells specific to human luteinizing hormone-releasing hormone (LHRH) peptides and antibodies specific to the EphA2 receptor. The adhesion forces between LHRH-coated AFM tips and human MDA-MB-231 cells (breast cancer cells) were shown to be about five times greater than those between LHRH-coated AFM tips and normal Hs578Bst breast cells. Similarly, those between EphA2 antibody-coated AFM tips and breast cancer cells were over five times greater than those between EphA2 antibody-coated AFM tips and normal breast cells. The results suggest that AFM can be used for the detection of breast cancer cells in biopsies. The implications of the results are also discussed for the early detection and localized treatment of cancer.

  8. Cancer Stem Cells: Biological Functions and Therapeutically Targeting

    Directory of Open Access Journals (Sweden)

    Marius Eugen Ciurea

    2014-05-01

    Full Text Available Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be important in treatment of malignant diseases both as targets and drug carriers. The efforts to understand the role of different signalling in cancer stem cells requires in depth knowledge about the mechanisms that control their self-renewal, differentiation and malignant potential. The aim of this paper is to discuss insights into cancer stem cells historical background and to provide a brief review of the new therapeutic strategies for targeting cancer stem cells.

  9. Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells

    Science.gov (United States)

    Suman, S; Das, T P; Damodaran, C

    2013-01-01

    Background: Breast cancer stem cells (BCSCs) are characterized by high aldehyde dehydrogenase (ALDH) enzyme activity and are refractory to current treatment modalities, show a higher risk for metastasis, and influence the epithelial to mesenchymal transition (EMT), leading to a shorter time to recurrence and death. In this study, we focused on examination of the mechanism of action of a small herbal molecule, psoralidin (Pso) that has been shown to effectively suppress the growth of BSCSs and breast cancer cells (BCCs), in breast cancer (BC) models. Methods: ALDH− and ALDH+ BCCs were isolated from MDA-MB-231 cells, and the anticancer effects of Pso were measured using cell viability, apoptosis, colony formation, invasion, migration, mammosphere formation, immunofluorescence, and western blot analysis. Results: Psoralidin significantly downregulated NOTCH1 signaling, and this downregulation resulted in growth inhibition and induction of apoptosis in both ALDH− and ALDH+ cells. Molecularly, Pso inhibited NOTCH1 signaling, which facilitated inhibition of EMT markers (β-catenin and vimentin) and upregulated E-cadherin expression, resulting in reduced migration and invasion of both ALDH− and ALDH+ cells. Conclusion: Together, our results suggest that inhibition of NOTCH1 by Pso resulted in growth arrest and inhibition of EMT in BCSCs and BCCs. Psoralidin appears to be a novel agent that targets both BCSCs and BCCs. PMID:24129237

  10. Dominant B-cell epitopes from cancer/stem cell antigen SOX2 recognized by serum samples from cancer patients

    OpenAIRE

    Shih, Julia; Rahman, Munira; Luong, Quang T; Lomeli, Shirley H.; Riss, Joseph; Prins, Robert M.; Gure, Ali O.; Zeng, Gang

    2014-01-01

    Human sex determining region Y-box 2 (SOX2) is an important transcriptional factor involved in the pluripotency and stemness of human embryonic stem cells. SOX2 plays important roles in maintaining cancer stem cell activities of melanoma and cancers of the brain, prostate, breast, and lung. SOX2 is also a lineage survival oncogene for squamous cell carcinoma of the lung and esophagus. Spontaneous cellular and humoral immune responses against SOX2 present in cancer patients classify it as a tu...

  11. 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.; Suranganie F. Dharmawardhane

    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...

  12. Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

    OpenAIRE

    Weifeng Huang; Chunpeng Wan; Qicong Luo; Zhengjie Huang; Qi Luo

    2014-01-01

    Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere f...

  13. Targeting cancer stem cells: a new therapy to cure cancer patients

    OpenAIRE

    Hu, Yapeng; Fu, Liwu

    2012-01-01

    Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. They have been identified in blood, breast, brain, colon, melanoma, pancreatic, prostate, ovarian, lung cancers and so on. It is often considered to be associated with chemo-resistance and radio-resistance that lead to the failure of traditional therapies. Most therapies are directed at the fast growing tumor ...

  14. Stem cells in radiation and oral cancer research

    International Nuclear Information System (INIS)

    Cancer stem cells (CSCs) are defined as a small sub population of cancer cells that constitute a pool of self sustaining cells with the exclusive ability to cause the heterogeneous lineages of cancer cells that comprise the tumour. There are three main characteristics of CSCs. Initially the cell must show potent tumour initiation in that it can regenerate the tumour which it was derived from a limited number of cells. In addition, the cells should demonstrate self renewal in vivo, which is practically observed via regrowth of phenotypically indistinguishable and heterogeneous tumours following serial transplantation of re-isolated CSCs in secondary and tertiary recipients. Finally, the cells must show a differentiation capacity, allowing them to give rise to a heterogeneous progeny, which represents a phenocopy of the original tumour. This article highlights the radiation therapy resulting in radiation resistance in cancer stem cells. (author)

  15. Investigation of the selenium metabolism in cancer cell lines

    DEFF Research Database (Denmark)

    Lunøe, Kristoffer; Gabel-Jensen, Charlotte; Stürup, Stefan; Andresen, Lars; Skov, Søren; Gammelgaard, Bente

    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...... 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...... exclusion chromatography and ICP-MS detection. The selenium compounds exhibited large differences in their ability to induce cell death in the three cell lines and the susceptibilities of the cell lines were different. Full recovery of selenium in the cellular fractions was observed for all Se compounds...

  16. 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...

  17. Characterization of normal and cancer stem cells: One experimental paradigm for two kinds of stem cells

    OpenAIRE

    Mayol, Jean-François; Loeuillet, Corinne; Hérodin, Francis; Wion, Didier

    2009-01-01

    The characterization of normal stem cells and cancer stem cells uses the same paradigm. These cells are isolated by a Fluorescent-Activated Cell Sorting step and their stemness is assayed following implantation into animals. However, differences exist between these two kinds of stem cells. Therefore, the translation of the experimental procedures used for normal stem cell isolation into the cancer stem cell research field is a potential source of artefacts. In addition, normal stem cell thera...

  18. Experimental studies on ultralow frequency pulsed gradient magnetic field inducing apoptosis of cancer cell and inhibiting growth of cancer cell

    Institute of Scientific and Technical Information of China (English)

    曾繁清; 郑从义; 张新晨; 李宗山; 李朝阳; 王川婴; 张新松; 黄晓玲; 张沪生

    2002-01-01

    The morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time. The apoptotic cancer cell contracted, became rounder and divorced from adjacent cells; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane; the endoplasmic reticulums(ER) expanded and fused with the cellular membrane; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma. Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediated in situ nick end labeling(TUNEL). It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample. The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency(ULF) pulsed gradient magnetic field; the nuclei DNA contents decreased, indicating that magnetic field can block DNA replication and inhibit mitosis of cancer cells. It was suggested that magnetic field could inhibit the metabolism of cancer cell, lower its malignancy, and restrain its rapid and heteromorphic growth. Since ULF pulsed gradient magnetic field can induce apoptosis of cancer cells and inhibit the growth of malignant tumour, it could be used as a new method to treat cancer.

  19. Cancer Stem Cells in Small Cell Lung Cancer Cell Line H446: Higher Dependency on Oxidative Phosphorylation and Mitochondrial Substrate-Level Phosphorylation than Non-Stem Cancer Cells

    OpenAIRE

    Gao, Cuicui; Shen, Yao; Jin, Fang; Miao, Yajing; Qiu, Xiaofei

    2016-01-01

    Recently, targeting cancer stem cells (CSCs) metabolism is becoming a promising therapeutic approach to improve cancer treatment outcomes. However, knowledge of the metabolic state of CSCs in small cell lung cancer is still lacking. In this study, we found that CSCs had significantly lower oxygen consumption rate and extracellular acidification rate than non-stem cancer cells. Meanwhile, this subpopulation of cells consumed less glucose, produced less lactate and maintained lower ATP levels. ...

  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. The role of bisphosphonates in breast cancer: Direct effects of bisphosphonates on breast cancer cells

    International Nuclear Information System (INIS)

    In addition to inhibiting bone resorption, bisphosphonates have also been shown to exhibit antitumour effects. In vitro, bisphosphonates inhibit proliferation and induce apoptosis in cultured human breast cancer cells. In addition, bisphosphonate treatment interferes with breast cancer cell adhesion to bone matrix, and inhibits cell migration and invasion. The combination of bisphosphonates with other anticancer drugs such as the taxoids markedly enhances these effects. These newly recognized direct actions of bisphosphonates on breast cancer cells indicate that these agents may have a greater role to play in treatment of patients suffering from cancers with a propensity to metastasize to bone

  2. Pancreatic involvement in small cell lung cancer

    International Nuclear Information System (INIS)

    Few data are available concerning incidence, clinical picture, and prognosis for pancreatic metastases of small cell lung carcinoma. In this paper we review the related literature available in English language. Although pancreatic metastases are generally asymptomatic, they can rarely produce clinical symptoms or functional abnormalities. The widespread use of multi-detector computerised tomography (CT) in contemporary medical practice has led to an increased detection of pancreatic metastases in oncology patients. Tissue diagnosis is imperative because radiological techniques alone are incapable of differentiating them from primary pancreatic tumours. Pancreatic metastases occur in the relative end stage of small cell lung cancer. The main complications of these lesions, although rare, are acute pancreatitis and obstructive jaundice. Early chemotherapy can provide a survival benefit even in patients with mild acute pancreatitis or extrahepatic biliary obstruction

  3. 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 ...

  4. Liver Label Retaining Cancer Cells Are Relatively Resistant to the Reported Anti-Cancer Stem Cell Drug Metformin

    OpenAIRE

    Xin, Hong-Wu; Ambe, Chenwi M.; Miller, Tyler C.; Chen, Jin-Qiu; Wiegand, Gordon W.; Anderson, Andrew J.; Ray, Satyajit; Mullinax, John E.; Hari, Danielle M; Koizumi, Tomotake; Godbout, Jessica D.; Goldsmith, Paul K.; Stojadinovic, Alexander; Rudloff, Udo; Thorgeirsson, Snorri S.

    2016-01-01

    Background & Aims: Recently, we reported that liver Label Retaining Cancer Cells (LRCC) can initiate tumors with only 10 cells and are relatively resistant to the targeted drug Sorafenib, a standard of practice in advanced hepatocellular carcinoma (HCC). LRCC are the only cancer stem cells (CSC) isolated alive according to a stem cell fundamental function, asymmetric cell division. Metformin has been reported to preferentially target many other types of CSC of different organs, including live...

  5. Stem cells and cancer: Evidence for bone marrow stem cells in epithelial cancers

    Institute of Scientific and Technical Information of China (English)

    Han-Chen Li; Calin Stoicov; Arlin B Rogers; JeanMarie Houghton

    2006-01-01

    Cancer commonly arises at the sites of chronic inflammation and infection. Although this association has long been recognized, the reason has remained unclear. Within the gastrointestinal tract, there are many examples of inflammatory conditions associated with cancer, and these include reflux disease and Barrett's adenocarcinoma of the esophagus, Helicobacter infection and gastric cancer, inflammatory bowel disease and colorectal cancer and viral hepatitis leading to hepatocellular carcinoma.There are several mechanisms by which chronic inflammation has been postulated to lead to cancer which includes enhanced proliferation in an endless attempt to heal damage, the presence of a persistent inflammatory environment creating a pro-carcinogenic environment and more recently a role for engraftment of circulating marrow-derived stem cells which may contribute to the stromal components of the tumor as well as the tumor mass itself. Here we review the recent advances in our understanding of the contributions of circulating bone marrow-derived stem cells to the formation of tumors in animal models as well as in human beings.

  6. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells

    Science.gov (United States)

    Xu, Wenwei; Mezencev, Roman; Kim, Byungkyu; Wang, Lijuan; McDonald, John; Sulchek, Todd; Sulchek Team; McDonald Team

    2013-03-01

    The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed study of highly invasive ovarian cancer cells (HEY A8) and their less invasive parental cells (HEY), demonstrates that deformability can serve as an accurate biomarker of metastatic potential. Comparative gene expression profiling indicate that the reduced stiffness of highly metastatic HEY A8 cells is associated with actin cytoskeleton remodeling, microscopic examination of actin fiber structure in these cell lines is consistent with this prediction. Our results indicate that cell stiffness not only distinguishes ovarian cancer cells from non-malignant cells, but may also be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells.

  7. Personalized Therapy of Small Cell Lung Cancer.

    Science.gov (United States)

    Schneider, Bryan J; Kalemkerian, Gregory P

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive, poorly differentiated neuroendocrine carcinoma with distinct clinical, pathological and molecular characteristics. Despite robust responses to initial chemotherapy and radiation, the prognosis of patients with SCLC remains poor with an overall 5-year survival rate of less than 10 %. Despite the fact that numerous molecularly targeted approaches have thus far failed to demonstrate clinical utility in SCLC, further advances will rely on better definition of the biological pathways that drive survival, proliferation and metastasis. Recent next-generation, molecular profiling studies have identified many new therapeutic targets in SCLC, as well as extreme genomic instability which explains the high degree of resistance. A wide variety of anti-angiogenic agents, growth factor inhibitors, pro-apoptotic agents, and epigenetic modulators have been evaluated in SCLC and many studies of these strategies are on-going. Perhaps the most promising approaches involve agents targeting cancer stem cell pathways and immunomodulatory drugs that interfere with the PD1 and CTLA-4 pathways. SCLC offers many barriers to the development of successful therapy, including limited tumor samples, inadequate preclinical models, high mutational burden, and aggressive tumor growth which impairs functional status and hampers enrollment on clinical trials. PMID:26703804

  8. 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.

  9. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Xiao-Ling Ding; Jie-Fei Huang; Hong Zhang; Sheng-Bao Wu; Jian-Ping Cheng; Qun Wei

    2008-01-01

    AIM:To investigate apoptosis in human pancreatic cancer ceils induced by Triptolide (TL),and the relationship between this apoptosis and expression of caspase-3' bcl-2 and bax.METHODS:Human pancreatic cancer cell line SW1990 was cultured in DIEM media for this study.MTT assay was used to determine the cell growth inhibitory rate in vitro.Flow cytometry and TUNEL assay were used to detect the apoptosis of human pancreatic cancer cells before and after TL treatment.RT-PCR was used to detect the expression of apoptosis-associated gene caspase-3' bcl-2 and bax.RESULTS:TL inhibited the growth of human pancreatic cancer cells in a dose-and time-dependent manner.TL induced human pancreatic cancer cells to undergo apoptosis with typically apoptotic characteristics.TUNEL assay showed that after the treatment of human pancreatic cancer cells with 40 ng/mL TL for 12 h and 24 h,the apoptotic rates of human pancreatic cancer cells increased significantly.RT-PCR demonstrated that caspase-3 and bax were significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was not.CONCLUSION:TL is able to induce the apoptosis in human pancreatic cancer cells.This apoptosis may be mediated by up-regulating the expression of apoptosisassociated caspase-3 and bax gene.

  10. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Chun-min GE; Qing-hui MENG; Jian-ping CAO; Jian TONG; Sai-jun FAN

    2007-01-01

    Aim: To investigate the anticancer activity of dihydroartemisinin (DHA), a deriva-tive of antimalaria drug artemisinin in a panel of human ovarian cancer cell lines. Methods: Cell growth was determined by the MTT viability assay. Apoptosis and cell cycle progression were evaluated by a DNA fragmentation gel electro-phoresis, flow cytometry assay, and TUNEL assay; protein and mRNA expression were analyzed by Western blotting and RT-PCR assay. Results: Artemisinin and its derivatives, including artesunate, arteether, artemether, arteannuin, and DHA, exhibit anticancer growth activities in human ovarian cancer cells. Among them, DHA is the most effective in inhibiting cell growth. Ovarian cancer cell lines are more sensitive (5-10-fold) to DHA treatment compared to normal ovarian cell lines. DHA at micromolar dose levels exhibits a dose- and time-dependent cyto-toxicity in ovarian cancer cell lines. Furthermore, DHA induced apoptosis and G2 cell cycle arrest, accompanied by a decrease of Bcl-xL and Bcl-2 and an increase of Bax and Bad. Conclusion: The promising results show for the first time that DHA inhibits the growth of human ovarian cancer cells. The selective inhibition of ovarian cancer cell growth, apoptosis induction, and G2 arrest provide in vitro evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of ovarian cancer.

  11. 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

  12. 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...

  13. Double Stem Cell Transplant May Help Fight a Childhood Cancer

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159243.html Double Stem Cell Transplant May Help Fight a Childhood Cancer Tandem ... better chance of survival if they receive two stem cell transplants, a new study reports. The double stem ...

  14. Double Stem Cell Transplant May Help Fight a Childhood Cancer

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_159243.html Double Stem Cell Transplant May Help Fight a Childhood Cancer Tandem ... better chance of survival if they receive two stem cell transplants, a new study reports. The double stem ...

  15. Role of Inflammation and Substrate Stiffness in Cancer Cell Transmigration

    Science.gov (United States)

    Hamilla, Susan; Stroka, Kimberly; Aranda-Espinoza, Helim

    2013-03-01

    Cancer metastasis, the ability for cancer cells to break away from the primary tumor site and spread to other organs of the body, is one of the main contributing factors to the deadliness of the disease. One of the rate-limiting steps in cancer metastasis that is not well understood is the adhesion of tumor cells to the endothelium followed by transmigration. Other factors include substrate stiffness and inflammation. To test these parameters, we designed an in vitro model of transendothelial migration. Our results suggest that cancer cell transmigration is a two-step process in which they first incorporate into the endothelium before migrating through. It was observed that the cumulative fraction of cancer cells that incorporate into the endothelium increases over time. Unlike leukocytes, which can directly transmigrate through the endothelium, cancer cells appear to have a two-step process of transmigration. Our results indicate that inflammation does not act as a signal for cancer cells to localize at specific sites and transmigrate similarly to leukocytes. Cancer cell transmigration also does not vary with substrate stiffness indicating that tissue stiffness may not play a role in cancer's propensity to metastasize to certain tissues.

  16. Mitochondrial DNA determines androgen dependence in prostate cancer cell lines

    OpenAIRE

    Higuchi, M; Kudo, T; Suzuki, S.; Evans, TT; Sasaki, R.; Wada, Y; Shirakawa, T.; Sawyer, JR; Gotoh, A

    2006-01-01

    Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large-deletion mitochondrial DNA is verycommon in prostate cancer. To investigate the role of mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted mitochondrial DNA in accordance with the progression of prostate cancer. We demonstra...

  17. The role of regulatory T cells in cancer immunology

    OpenAIRE

    Whiteside TL

    2015-01-01

    Theresa L Whiteside University of Pittsburgh Cancer Institute, Pittsburgh, PA, US Abstract: Regulatory T cells (Treg) are generally considered to be significant contributors to tumor escape from the host immune system. Emerging evidence suggests, however, that in some human cancers, Treg are necessary to control chronic inflammation, prevent tissue damage, and limit inflammation-associated cancer development. The dual role of Treg in cancer and underpinnings of Treg diversity are not well und...

  18. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-08-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  19. ATP citrate lyase knockdown impacts cancer stem cells in vitro

    OpenAIRE

    Hanai, J-i; Doro, N; Seth, P; Sukhatme, V P

    2013-01-01

    ATP citrate lyase (ACL) knockdown (KD) causes tumor suppression and induces differentiation. We have previously reported that ACL KD reverses epithelial–mesenchymal transition (EMT) in lung cancer cells. Because EMT is often associated with processes that induce stemness, we hypothesized that ACL KD impacts cancer stem cells. By assessing tumorsphere formation and expression of stem cell markers, we showed this to be the case in A549 cells, which harbor a Ras mutation, and in two other non-sm...

  20. Cancer Stem Cells: Biological Functions and Therapeutically Targeting

    OpenAIRE

    Marius Eugen Ciurea; Ada Maria Georgescu; Stefana Oana Purcaru; Stefan-Alexandru Artene; Ghazaleh Hooshyar Emami; Mihai Virgil Boldeanu; Daniela Elise Tache; Anica Dricu

    2014-01-01

    Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be importan...

  1. Detection of cancer cells using SapC-DOPS nanovesicles

    OpenAIRE

    Davis, Harold W.; Hussain, Nida; Qi, Xiaoyang

    2016-01-01

    Unlike normal cells, cancer cells express high levels of phosphatidylserine on the extracellular leaflet of their cell membrane. Exploiting this characteristic, our lab developed a therapeutic agent that consists of the fusogenic protein, saposin C (SapC) which is embedded in dioleoylphosphatidylserine (DOPS) vesicles. These nanovesicles selectively target cancer cells and induce apoptosis. Here we review the data supporting use of SapC-DOPS to locate tumors for surgical resection or for trea...

  2. Dynamics of Cancer Cell near Collagen Fiber Chain

    Science.gov (United States)

    Kim, Jihan; Sun, Bo

    Cell migration is an integrated process that is important in life. Migration is essential for embryonic development as well as homeostatic processes such as wound healing and immune responses. When cell migrates through connective extracellular matrix (ECM), it applies cellular traction force to ECM and senses the rigidity of their local environment. We used human breast cancer cell (MDA-MB-231) which is highly invasive and applies strong traction force to ECM. As cancer cell applies traction force to type I collage-based ECM, it deforms collagen fibers near the surface. Patterns of deforming collagen fibers are significantly different with pairs of cancer cells compared to a single cancer cell. While a pair of cancer cells within 60 um creates aligned collagen fiber chains between them permanently, a single cancer cell does not form any fiber chains. In this experiment we measured a cellular response and an interaction between a pair of cells through the chain. Finally, we analyzed correlation of directions between cancer cell migration and the collagen chain alignment.

  3. Pitavastatin suppressed liver cancer cells in vitro and in vivo.

    Science.gov (United States)

    You, He-Yi; Zhang, Wei-Jian; Xie, Xue-Meng; Zheng, Zhi-Hai; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-01-01

    Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy. PMID:27621652

  4. Comprehensive copy number profiles of breast cancer cell model genomes

    OpenAIRE

    Shadeo, Ashleen; Lam, Wan L.

    2006-01-01

    Introduction Breast cancer is the most commonly diagnosed cancer in women worldwide and consequently has been extensively investigated in terms of histopathology, immunochemistry and familial history. Advances in genome-wide approaches have contributed to molecular classification with respect to genomic changes and their subsequent effects on gene expression. Cell lines have provided a renewable resource that is readily used as model systems for breast cancer cell biology. A thorough characte...

  5. Stem Cell Based Gene Therapy in Prostate Cancer

    OpenAIRE

    Jae Heon Kim; Hong Jun Lee; Yun Seob Song

    2014-01-01

    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 ...

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

    Directory of Open Access Journals (Sweden)

    Lipworth Loren

    2011-04-01

    Full Text Available Abstract 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.

  7. Squamous Cell Lung Cancer Presenting as a Malar Mass

    OpenAIRE

    Ganesh Veerappan; Christopher Lettieri; Brian Cuneo

    2003-01-01

    Introduction: Lung cancer metastasizing to the face has rarely been reported and is an even more unusual presentation. Case: This is the case of a 49-year-old man diagnosed with squamous cell carcinoma of the face, scheduled for resection. Preoperative radiographs revealed a left upper lobe mass, found to be squamous cell carcinoma. Diagnosis was changed to Stage IV primary lung cancer. The patient did not undergo resection. Discussion: No previous cases of primary lung cancer presenting as a...

  8. Comprehensive genomic characterization of squamous cell lung cancers

    NARCIS (Netherlands)

    Hammerman, Peter S.; Lawrence, Michael S.; Voet, Douglas; Jing, Rui; Cibulskis, Kristian; Sivachenko, Andrey; Stojanov, Petar; McKenna, Aaron; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Sougnez, Carrie; Imielinski, Marcin; Helman, Elena; Hernandez, Bryan; Pho, Nam H.; Meyerson, Matthew; Chu, Andy; Chun, Hye-Jung E.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Sipahimalani, Payal; Stoll, Dominik; Balasundaram, Miruna; Birol, Inanc; Butterfield, Yaron S. N.; Chuah, Eric; Coope, Robin J. N.; Corbett, Richard; Dhalla, Noreen; Guin, Ranabir; Hirst, Anhe Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Karen; Nip, Ka Ming; Olshen, Adam; Schein, Jacqueline E.; Slobodan, Jared R.; Tam, Angela; Thiessen, Nina; Varhol, Richard; Zeng, Thomas; Zhao, Yongjun; Jones, Steven J. M.; Marra, Marco A.; Saksena, Gordon; Cherniack, Andrew D.; Schumacher, Stephen E.; Tabak, Barbara; Carter, Scott L.; Pho, Nam H.; Nguyen, Huy; Onofrio, Robert C.; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Hammerman, Peter S.; Getz, Gad; Meyerson, Matthew; Protopopov, Alexei; Zhang, Jianhua; Hadjipanayis, Angela; Lee, Semin; Xi, Ruibin; Yang, Lixing; Ren, Xiaojia; Zhang, Hailei; Shukla, Sachet; Chen, Peng-Chieh; Haseley, Psalm; Lee, Eunjung; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Socci, Nicholas D.; Liang, Yupu; Schultz, Nikolaus; Borsu, Laetitia; Lash, Alex E.; Viale, Agnes; Sander, Chris; Ladanyi, Marc; Auman, J. Todd; Hoadley, Katherine A.; Wilkerson, Matthew D.; Shi, Yan; Liquori, Christina; Meng, Shaowu; Li, Ling; Turman, Yidi J.; Topal, Michael D.; Tan, Donghui; Waring, Scot; Buda, Elizabeth; Walsh, Jesse; Jones, Corbin D.; Mieczkowski, Piotr A.; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Dolina, Peter; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; O'Connor, Brian D.; Prins, Jan F.; Liu, Jinze; Chiang, Derek Y.; Hayes, D. Neil; Perou, Charles M.; Cope, Leslie; Danilova, Ludmila; Weisenberger, Daniel J.; Maglinte, Dennis T.; Pan, Fei; Van den Berg, David J.; Triche, Timothy; Herman, James G.; Baylin, Stephen B.; Laird, Peter W.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Jinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Schultz, Nikolaus; Sinha, Rileen; Ciriello, Giovanni; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Gao, Jianjiong; Aksoy, B. Arman; Weinhold, Nils; Ramirez, Ricardo; Taylor, Barry S.; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Mo, Qianxing; Seshan, Venkatraman; Paik, Paul K.; Ladanyi, Marc; Sander, Chris; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod; Unruh, Anna; Wakefield, Chris; Cason, R. Craig; Baggerly, Keith A.; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Zhu, Jingchun; Szeto, Christopher; Scott, Gary K.; Yau, Christina; Ng, Sam; Goldstein, Ted; Waltman, Peter; Sokolov, Artem; Ellrott, Kyle; Collisson, Eric A.; Zerbino, Daniel; Wilks, Christopher; Ma, Singer; Craft, Brian; Wilkerson, Matthew D.; Auman, J. Todd; Hoadley, Katherine A.; Du, Ying; Cabanski, Christopher; Walter, Vonn; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Marron, J. S.; Liu, Yufeng; Wang, Kai; Liu, Jinze; Prins, Jan F.; Hayes, D. Neil; Perou, Charles M.; Creighton, Chad J.; Zhang, Yiqun; Travis, William D.; Rekhtman, Natasha; Yi, Joanne; Aubry, Marie C.; Cheney, Richard; Dacic, Sanja; Flieder, Douglas; Funkhouser, William; Illei, Peter; Myers, Jerome; Tsao, Ming-Sound; Penny, Robert; Mallery, David; Shelton, Troy; Hatfield, Martha; Morris, Scott; Yena, Peggy; Shelton, Candace; Sherman, Mark; Paulauskis, Joseph; Meyerson, Matthew; Baylin, Stephen B.; Govindan, Ramaswamy; Akbani, Rehan; Azodo, Ijeoma; Beer, David; Bose, Ron; Byers, Lauren A.; Carbone, David; Chang, Li-Wei; Chiang, Derek; Chu, Andy; Chun, Elizabeth; Collisson, Eric; Cope, Leslie; Creighton, Chad J.; Danilova, Ludmila; Ding, Li; Getz, Gad; Hammerman, Peter S.; Hayes, D. Neil; Hernandez, Bryan; Herman, James G.; Heymach, John; Ida, Cristiane; Imielinski, Marcin; Johnson, Bruce; Jurisica, Igor; Kaufman, Jacob; Kosari, Farhad; Kucherlapati, Raju; Kwiatkowski, David; Ladanyi, Marc; Lawrence, Michael S.; Maher, Christopher A.; Mungall, Andy; Ng, Sam; Pao, William; Peifer, Martin; Penny, Robert; Robertson, Gordon; Rusch, Valerie; Sander, Chris; Schultz, Nikolaus; Shen, Ronglai; Siegfried, Jill; Sinha, Rileen; Sivachenko, Andrey; Sougnez, Carrie; Stoll, Dominik; Stuart, Joshua; Thomas, Roman K.; Tomaszek, Sandra; Tsao, Ming-Sound; Travis, William D.; Vaske, Charles; Weinstein, John N.; Weisenberger, Daniel; Wheeler, David; Wigle, Dennis A.; Wilkerson, Matthew D.; Wilks, Christopher; Yang, Ping; Zhang, Jianjua John; Jensen, Mark A.; Sfeir, Robert; Kahn, Ari B.; Chu, Anna L.; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric E.; Pontius, Joan; Pihl, Todd D.; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique L.; Nicholls, Matthew C.; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter A.; Alonso, Shelley; Sanbhadti, Rashmi N.; Barletta, Sean P.; Greene, John M.; Pot, David A.; Tsao, Ming-Sound; Bandarchi-Chamkhaleh, Bizhan; Boyd, Jeff; Weaver, JoEllen; Wigle, Dennis A.; Azodo, Ijeoma A.; Tomaszek, Sandra C.; Aubry, Marie Christine; Ida, Christiane M.; Yang, Ping; Kosari, Farhad; Brock, Malcolm V.; Rogers, Kristen; Rutledge, Marian; Brown, Travis; Lee, Beverly; Shin, James; Trusty, Dante; Dhir, Rajiv; Siegfried, Jill M.; Potapova, Olga; Fedosenko, Konstantin V.; Nemirovich-Danchenko, Elena; Rusch, Valerie; Zakowski, Maureen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Fan, Zhen; Todaro, Nicole; Eckman, John; Myers, Jerome; Rathmell, W. Kimryn; Thorne, Leigh B.; Huang, Mei; Boice, Lori; Hill, Ashley; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Morrison, Carl; Gaudioso, Carmelo; Bartlett, Johnm. S.; Kodeeswaran, Sugy; Zanke, Brent; Sekhon, Harman; David, Kerstin; Juhl, Hartmut; Van Le, Xuan; Kohl, Bernard; Thorp, Richard; Tien, Nguyen Viet; Van Bang, Nguyen; Sussman, Howard; Phu, Bui Duc; Hajek, Richard; PhiHung, Nguyen; Khan, Khurram Z.; Muley, Thomas; Shaw, Kenna R. Mills; Sheth, Margi; Yang, Liming; Buetow, Ken; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin; Dillon, Laura A. L.; Schaefer, Carl; Guyer, Mark S.; Ozenberger, Bradley A.; Palchik, Jacqueline D.; Peterson, Jane; Sofia, Heidi J.; Thomson, Elizabeth; Meyerson, Matthew

    2012-01-01

    Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment.

  9. Reliable in vitro studies require appropriate ovarian cancer cell lines.

    Science.gov (United States)

    Jacob, Francis; Nixdorf, Sheri; Hacker, Neville F; Heinzelmann-Schwarz, Viola A

    2014-01-01

    Ovarian cancer is the fifth most common cause of cancer death in women and the leading cause of death from gynaecological malignancies. Of the 75% women diagnosed with locally advanced or disseminated disease, only 30% will survive five years following treatment. This poor prognosis is due to the following reasons: limited understanding of the tumor origin, unclear initiating events and early developmental stages of ovarian cancer, lack of reliable ovarian cancer-specific biomarkers, and drug resistance in advanced cases. In the past, in vitro studies using cell line models have been an invaluable tool for basic, discovery-driven cancer research. However, numerous issues including misidentification and cross-contamination of cell lines have hindered research efforts. In this study we examined all ovarian cancer cell lines available from cell banks. Hereby, we identified inconsistencies in the reporting, difficulties in the identification of cell origin or clinical data of the donor patients, restricted ethnic and histological type representation, and a lack of tubal and peritoneal cancer cell lines. We recommend that all cell lines should be distributed via official cell banks only with strict guidelines regarding the minimal available information required to improve the quality of ovarian cancer research in future. PMID:24936210

  10. Induction of pyroptosis in colon cancer cells by LXRβ

    Science.gov (United States)

    Rébé, Cédric; Derangère, Valentin; Ghiringhelli, François

    2015-01-01

    Liver X receptors (LXRs) have been proposed to have some anticancer properties. We recently identified a new non-genomic role of LXRβ in colon cancer cells. Under LXR agonist treatment, LXRβ induces pyroptosis of these cells in vitro and in vivo, raising the possibility of targeting this isoform in cancer treatment.

  11. Colorectal cancer stem cells : regulation of the phenotype and implications for therapy resistance

    OpenAIRE

    Emmink, B.L.

    2014-01-01

    In this thesis different aspects of cancer stem cells in colorectal cancer are discribed. We focus on the therapy resistance of cancer stem cells and the effect that reactive oxygen species and hypoxia have on the cancer stem cell phenotype. For this purpose a novel culture method to propagate cancer stem cells form resected tumor specimens was used.

  12. NK cells and cancer: You can teach innate cells new tricks

    OpenAIRE

    Morvan, MG; Lanier, LL

    2015-01-01

    © 2016 Macmillan Publishers Limited. Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer.

  13. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  14. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon [Korea Institute of Radiologicaland Medical Sciences, Seoul (Korea, Republic of)

    2010-11-15

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  15. Water Quality Observations in the Dekhaila Harbour, Alexandria, Egypt

    International Nuclear Information System (INIS)

    The Dekhaila Harbour, which was recently constructed in Alexandria, had become a highly eutrophied areas due to intensive maritime activities, and the effect of a mixture of nutrients and different pollutants reaching the harbour through land-based effluent. Environmental observations which were carried monthly from April 1998 to March 1999 demonstrated extremely high nutrient level and productive phytoplankton, showing wide temporal and spatial variations. The variability of surface salinity was one of the characteristic features of the harbour, falling within the range of 17.3-39.2 ppt. Nutrients sustained pronouncedly high values, with annual average of 19.22uM for nitrate, 4.16um for nitrite, 38.69uM for ammonia, 6.44uM for phosphate and 49.52 for silicate. Chlorophyll a was exceptionally high (up to 13.23ug/1), having an annual average of 107.5ug/1. The harbour water was relatively turbid most of the year. The concentrations of dissolved oxygen revealed the alternations of good (5-10ml/1) aeration conditions. Consequently, low zooplankton abundance was found in the Dekhalia Harbour (annual average: 22,640 ind./m3). Statistical analysis showed that the envirnomental factors controlling both phyplankton and zooplankton biomass had different seasonal patterns. (author)

  16. Unlocking Pandora's box: personalising cancer cell death in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Fennell Dean A

    2012-06-01

    Full Text Available Abstract Evasion of apoptosis is a hallmark of tumorigenesis and a recognised cause of multidrug resistance. Over the last decade, insights into how apoptosis might be exploited in non-small cell lung cancer (NSCLC and how cancer therapeutics might be used to engage apoptotic signalling in a personalised manner have changed markedly. We are now in the wake of a paradigm shift in stratified therapeutic approaches related to NSCLC. At the heart of this shift in thinking is the emerging knowledge that even the most drug-resistant cancers exhibit a functional death pathway and, critically, that this pathway can be efficiently engaged, leading to clinical benefit. This review will summarise current knowledge of mitochondrial apoptotic pathway dysfunction in NSCLC and how the next generation of targeted therapeutics might be used to exploit deficiencies in apoptotic signalling in a personalised manner to improve clinical outcome and predict therapeutic benefit.

  17. Combinatorial treatment of mammospheres with trastuzumab and salinomycin efficiently targets HER2-positive cancer cells and cancer stem cells.

    Science.gov (United States)

    Oak, Prajakta S; Kopp, Florian; Thakur, Chitra; Ellwart, Joachim W; Rapp, Ulf R; Ullrich, Axel; Wagner, Ernst; Knyazev, Pjotr; Roidl, Andreas

    2012-12-15

    A major obstacle in the successful treatment of cancer is the occurrence of chemoresistance. Cancer cells surviving chemotherapy and giving rise to a recurrence of the tumor are termed cancer stem cells and can be identified by elevated levels of certain stem cell markers. Eradication of this cell population is a priority objective in cancer therapy. Here, we report elevated levels of stem cell markers in MCF-7 mammospheres. Likewise, an upregulation of HER2 and its differential expression within individual cells of mammospheres was observed. Sorting for HER2(high) and HER2(low) cells revealed an upregulation of stem cell markers NANOG, OCT4 and SOX2 in the HER2(low) cell fraction. Accordingly, HER2(low) cells also showed reduced proliferation, ductal-like outgrowths and an increased number of colonies in matrigel. Xenografts from subcutaneously injected HER2(low) sorted cells exihibited earlier onset but slower growth of tumors and an increase in stem cell markers compared to tumors developed from the HER2(high) fraction. Treatment of mammospheres with salinomycin reduced the expression of SOX2 indicating a selective targeting of cancer stem cells. Trastuzumab however, did not reduce the expression of SOX2 in mammospheres. Furthermore, a combinatorial treatment of mammospheres with trastuzumab and salinomycin was superior to single treatment with each drug. Thus, targeting HER2 expressing tumors with anti-HER2 therapies will not necessarily eliminate cancer stem cells and may lead to a more aggressive cancer cell phenotype. Our study demonstrates efficient killing of both HER2 positive cells and cancer stem cells, hence opening a possibility for a new combinatorial treatment strategy. PMID:22511343

  18. A Milk Protein, Casein, as a Proliferation Promoting Factor in Prostate Cancer Cells

    OpenAIRE

    Park, Sung-Woo; Kim, Joo-Young; Kim, You-sun; Lee, Sang Jin; Lee, Sang Don; CHUNG, MOON KEE

    2014-01-01

    Purpose Despite most epidemiologic studies reporting that an increase in milk intake affects the growth of prostate cancer, the results of experimental studies are not consistent. In this study, we investigated the proliferation of prostate cancer cells treated with casein, the main protein in milk. Materials and Methods Prostate cancer cells (LNCaP and PC3), lung cancer cells (A459), stomach cancer cells (SNU484), breast cancer cells (MCF7), immortalized human embryonic kidney cells (HEK293)...

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

    International Nuclear Information System (INIS)

    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

  1. Cellular spectroscopy: applications to cancer stem cell characterization

    Science.gov (United States)

    Wiegand, G.; Xin, H.; Anderson, A.; Mullinax, J.; Jaiswal, K.; Wiegand, A.; Avital, Itzhak

    2011-02-01

    Spectroscopic and light scattering methods were used to gain insight into the existence and characterization of the cancer stem cell. Fundamental technical description of devices used have been reported elsewhere. We included alterations and implementation of these biophotonic instruments as applied to our objectives. We disassociated human tumor and submitted the cells to optical characterization to support our working hypothesis of stem cell origins to cancer and mechanisms. Single cell combined with population based analysis within the Pancreatic cancer system led us to information regarding the polarization state of cells possessing anchor proteins and drug influx pumps. Multispectral imaging combined with flow cytometry enabled us to target rare cells that appear to retain template DNA. rendering them resistant to anti-cancer drug therapy. In this study we describe an optical method that combines high-throughput population pattern and correlates each cell with an individual fluorescent and bright-field image.

  2. Shared signaling pathways in normal and breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Gautam K Malhotra

    2011-01-01

    Full Text Available Recent advances in our understanding of breast cancer biology have led to the identification of a subpopulation of cells within tumors that appear to be responsible for initiating and propagating the cancer. These tumor initiating cells are not only unique in their ability to generate tumors, but also share many similarities with elements of normal adult tissue stem cells, and have therefore been termed cancer stem cells (CSCs. These CSCs often inappropriately use many of the same signaling pathways utilized by their normal stem cell counterparts which may present a challenge to the development of CSC specific therapies. Here, we discuss three major stem cell signaling pathways (Notch, Wnt, and Hedgehog; with a focus on their function in normal mammary gland development and their misuse in breast cancer stem cell fate determination.

  3. Xylitol induces cell death in lung cancer A549 cells by autophagy.

    Science.gov (United States)

    Park, Eunjoo; Park, Mi Hee; Na, Hee Sam; Chung, Jin

    2015-05-01

    Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells. PMID:25650339

  4. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    Science.gov (United States)

    2015-03-17

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  5. Cancer stem cells – a new chance for successful treatment of cancer

    OpenAIRE

    Badowska-Kozakiewicz, Anna M.; Michał P. Budzik

    2015-01-01

    Cancer stem cells are undifferentiated cells capable of being transformed into all types of cells comprising the tumour mass. As demonstrated by recent findings, they are responsible for the development of both haematopoietic malignancies and solid lesions. Cancer stem cells determine the unlimited growth of tumours and the variety of their morphology; they are also suspected of being the factor responsible for metastases. Their capability for renewal is the cause of disease recurrences even ...

  6. 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.

  7. Selective Cancer Targeting via Aberrant Behavior of Cancer Cell-associated Glucocorticoid Receptor

    OpenAIRE

    Mukherjee, Amarnath; Narayan, Kumar P; Pal, Krishnendu; Kumar, Jerald M.; Rangaraj, Nandini; Shasi V Kalivendi; Banerjee, Rajkumar

    2009-01-01

    Glucocorticoid receptors (GRs) are ubiquitous, nuclear hormone receptors residing in cell types of both cancer and noncancerous origin. It is not known whether cancer cell–associated GR alone can be selectively manipulated for delivery of exogenous genes to its nucleus for eliciting anticancer effect. We find that GR ligand, dexamethasone (Dex) in association with cationic lipoplex (termed as targeted lipoplex) could selectively manipulate GR in cancer cells alone for the delivery of transgen...

  8. 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. PMID:26272183

  9. Drug delivery system and breast cancer cells

    Science.gov (United States)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  10. Pinpoint attack on cancer cell with ions

    International Nuclear Information System (INIS)

    Microbeam technology is indispensable in bio-scientific research, for example the investigation of cell-to-cell communications such as bystander effects, the analysis of cellular spatial sensitivity, the interaction of damage caused by individual irradiation, cellular repair dynamics, and intra-cellular processes such as apoptosis. A single-ion hit technique using the heavy-ion microbeam is being developed at JAEA AVF cyclotron facility for elucidate of biofunctions. A heavy ion microbeam system was developed using a beam collimator with a 5 μm diameter hole. In the new system the microbeam spot was focused to 0.7 μm in diameter using focusing lenses. The PIXE analysis has been widely applied in the fields of biology and medicine. The use of micro-beams allows analyzing trace elements on the cellular level as well. In Air Micro-PIXE images the elemental distribution in the cell by scanning the micro-beams. Biological effects of heavy ion particle beams are markedly more potent, and the dose distribution of heavy ion particle beams is more concentrated than those of X-ray and gamma ray. Therefore, radiotherapy using heavy ion particle beams not only improves the prognosis of cancer patients, but significantly contributes to improvement of their quality of life by conserving the function and morphology of affected organs. A highly precise carbon ion microsurgery system will be developed to treat various small tumours based on the technique of microbeam formation. (author)

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    KH.M. ABDEL-SALAM

    2012-12-01

    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.

  13. 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. PMID:21888505

  14. Enhanced Heme Function and Mitochondrial Respiration Promote the Progression of Lung Cancer Cells

    OpenAIRE

    Hooda, Jagmohan; Cadinu, Daniela; Alam, Md. Maksudul; Shah, Ajit; Cao, Thai M.; Sullivan, Laura A.; Brekken, Rolf; Zhang, Li

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair...

  15. 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...

  16. Gene expression profiles in irradiated cancer cells

    International Nuclear Information System (INIS)

    Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell lines subjected to hadrontherapy treatments with a genomewide approach by using cDNA microarray technology to identify gene expression profiles and candidate genes responsible of differential cellular responses

  17. 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.

  18. 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.

  19. 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.

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

    International Nuclear Information System (INIS)

    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. Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism.

    Science.gov (United States)

    Ai, Zhihong; Lu, Yang; Qiu, Songbo; Fan, Zhen

    2016-04-01

    Cisplatin is currently one of the most effective chemotherapeutic drugs used for treating ovarian cancer; however, resistance to cisplatin is common. In this study, we explored an experimental strategy for overcoming cisplatin resistance of human ovarian cancer from the new perspective of cancer cell metabolism. By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. We found that cisplatin downregulated the level of the regulatable α subunit of HIF-1, HIF-1α, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1α degradation but did not downregulate HIF-1α in their cisplatin-resistant counterparts. Overexpression of a degradation-resistant HIF-1α (HIF-1α ΔODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1α or pharmacological promotion of HIF-1α degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. We further demonstrated that knockdown of HIF-1α improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Our findings suggest that the HIF-1α-regulated cancer metabolism pathway could be a novel target for overcoming cisplatin resistance in ovarian cancer. PMID:26801746

  2. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    International Nuclear Information System (INIS)

    Highlights: • As2O3 inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As2O3 than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As2O3 than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As2O3 is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As2O3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As2O3 is a potential anticancer drug for cervical cancer

  3. Phagocytosis in pup and adult harbour, grey and harp seals.

    Science.gov (United States)

    Frouin, Héloïse; Lebeuf, Michel; Hammill, Mike; Fournier, Michel

    2010-04-15

    Knowledge on pinniped immunology is still in its infancy. For instance, age-related and developmental aspects of the immune system in pinnipeds need to be better described. The present study examined the phagocytic activity and efficiency of harbour, grey and harp seal leukocytes. In the first part of the study, peripheral blood was collected from captive female harbour seals of various ages. Data showed an age-related decrease in phagocytosis in female harbour seals from sub-adult to adulthood. In the second part of the study, changes in phagocytosis were quantified during lactation in wild newborn harbour, grey and harp seals and in their mothers (harp and grey seals). In newborns of the same age, leukocytes of harbour and harp seals phagocytosed less than those of grey seal pups. The phagocytic activity and efficiency increased significantly from early to mid-lactation in newborn harbour seals, and from early to late lactation in newborn grey seals, which could suggest that the transfer of phagocytosis-promoting factor(s) in colostrum is an important feature of temporary protection for pups. In contrast, no changes in phagocytic activity and efficiency were observed in lactating females of the two seal species, harp and grey, examined. At late lactation, phagocytic activity in both grey and harp seal pups and phagocytic efficiency in grey seal pups were significantly higher than in their mothers. These results could reflect either the capacity of phagocytes of the newborn harp and grey seals to respond to pathogens. Results from this study suggest that the phagocytosis of the seal species examined is not fully developed at birth as it generally increases in pups during lactation. Thereafter, the phagocytic activity of seals appears to decrease throughout adulthood. PMID:19766324

  4. Anticancer effect of arsenite on cell migration, cell cycle and apoptosis in human pancreatic cancer cells

    Science.gov (United States)

    HORIBE, YOHEI; ADACHI, SEIJI; YASUDA, ICHIRO; YAMAUCHI, TAKAHIRO; KAWAGUCHI, JUNJI; KOZAWA, OSAMU; SHIMIZU, MASAHITO; MORIWAKI, HISATAKA

    2016-01-01

    The standard treatment for advanced pancreatic cancer is chemotherapy, but its clinical outcome remains unsatisfactory. Therefore, the development of novel treatments for this malignancy is urgently required. In the present study, the anticancer effect of arsenite on platelet-derived growth factor (PDGF)-BB-induced migration, cell cycle and apoptosis was investigated in pancreatic cancer cells (AsPC-1 and BxPC-3), and compared with the effect on normal pancreatic epithelial (PE) cells. In the cell migration assay, arsenite clearly inhibited PDGF-BB-induced cell migration in AsPC-1 cells, but not in BxPC-3 or PE cells. Arsenite also caused cell apoptosis in AsPC-1 cells, but not in BxPC-3 or PE cells. In AsPC-1 cells, the levels of cyclin D1 and phosphorylated retinoblastoma protein decreased following treatment with arsenite, but this was not observed in BxPC-3 cells. To further examine the differences between these two cell lines, the effect of arsenite on upstream p44/p42 mitogen-activated protein kinase (MAPK) and Akt was investigated. PDGF-BB caused phosphorylation of p44/p42 MAPK and Akt in both cell lines. Pretreatment with arsenite significantly suppressed PDGF-BB-induced phosphorylation of Akt, but not of p44/p42 MAPK in AsPC-1 cells. By contrast, arsenite did not affect these molecules in BxPC-3 cells. Since the inhibition of the Akt signaling pathway markedly reduced PDGF-BB-induced migration in AsPC-1 cells, the present results strongly suggest that arsenite inhibits PDGF-BB-induced migration by suppressing the Akt signaling pathway in AsPC-1 cells. Therefore, arsenite may be a useful tool for the treatment of patients with certain types of pancreatic cancer, without causing adverse effects on normal pancreatic cells.

  5. Cancer stem cells and resistance to chemo and radio therapy.

    Science.gov (United States)

    Malik, Babar; Nie, Daotai

    2012-01-01

    Cancer stem cells (CSCs, or tumor initiating cells) are responsible for tumor initiation. If cancer treatment kills most of cancer cells in the stage of transit amplifying and differentiation without killing the stem cells, the surviving CSCs will eventually lead to recurrence of tumors. Studies have suggested that CSCs may be the primary mediators of resistance to chemo- and radio-therapy, leading to failure in cancer therapy. Numerous targets are being investigated for their potential involvement in the self-renewal and chemo- and radio-resistance of cancer cells. However, despite the intensive efforts invested into characterizing the role of cancer stem cells, there is a sense of uncertainty regarding the identity and number of these cells as well as the implications in cancer treatment. In this review, we will discuss the identification of CSCs by cell surface markers, the biology of CSCs, and the role of CSCs in resistance to radio- and chemo-therapy. This review will discuss the advances in targeting CSCs to improve the efficacy of chemo- and radio-therapy. PMID:22202026

  6. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

  7. Cancer stem cells: a new approach to tumor development

    Directory of Open Access Journals (Sweden)

    Natália Cristina Ciufa Kobayashi

    2015-02-01

    Full Text Available Many theories have been proposed to explain the origins of cancer. Currently, evidences show that not every tumor cell is capable of initiating a tumor. Only a small part of the cancer cells, called cancer stem cells (CSCs, can generate a tumor identical to the original one, when removed from human tumors and transplanted into immunosuppressed mice. The name given to these cells comes from the resemblance to normal stem cells, except for the fact that their ability to divide is infinite. These cells are also affected by their microenvironment. Many of the signaling pathways, such as Wnt, Notch and Hedgehog, are altered in this tumoral subpopulation, which also contributes to abnormal proliferation. Researchers have found several markers for CSCs; however, much remains to be studied, or perhaps a universal marker does not even exist, since they vary among tumor types and even from patient to patient. It was also found that cancer stem cells are resistant to radiotherapy and chemotherapy. This may explain the re-emergence of the disease, since they are not completely eliminated and minimal amounts of CSCs can repopulate a tumor. Once the diagnosis in the early stages greatly increases the chances of curing cancer, identifying CSCs in tumors is a goal for the development of more effective treatments. The objective of this article is to discuss the origin of cancer according to the theory of stem cell cancer, as well as its markers and therapies used for treatment.

  8. 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.

  9. Oncotripsy: Targeting cancer cells selectively via resonant harmonic excitation

    Science.gov (United States)

    Heyden, S.; Ortiz, M.

    2016-07-01

    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.

  10. Fermented red ginseng extract inhibits cancer cell proliferation and viability.

    Science.gov (United States)

    Oh, Jisun; Jeon, Seong Bin; Lee, Yuri; Lee, Hyeji; Kim, Ju; Kwon, Bo Ra; Yu, Kang-Yeol; Cha, Jeong-Dan; Hwang, Seung-Mi; Choi, Kyung-Min; Jeong, Yong-Seob

    2015-04-01

    Red ginseng (Panax ginseng C.A. Meyer) is the most widely recognized medicinal herb due to its remedial effects in various disorders, such as cancers, diabetes, and heart problems. In this study, we investigated the anticancer effect of fermented red ginseng extract (f-RGE; provided by Jeonju Biomaterials Institute, Jeonju, South Korea) in a parallel comparison with the effect of nonfermented red ginseng extract (nf-RGE; control) on several cancer cell lines--MCF-7 breast cancer cells, HepG2 hepatocellular carcinoma cells, and reprogrammed MCF-7 cells (mimicking cancer stem cells). Cells were cultured at various concentrations of RGE (from 0.5 up to 5 mg/mL) and their viabilities and proliferative properties were examined. Our data demonstrate the following: (1) nf-RGE inhibited cell viability at ≥1 mg/mL for MCF-7 cells and ≥2 mg/mL for HepG2 cells, (2) in the presence of a carcinogenic agent, 12-O-tetradecanoylphorbol-13-acetate (TPA), nf-RGE treatment in combination with paclitaxel synergistically decreased MCF-7 as well as HepG2 cell viability, (3) f-RGE (which contained a greater level of Rg3 content) more effectively decreased the viability of MCF-7 and HepG2 cells compared to nf-RGE, and (4) f-RGE appeared more potent for inhibiting cancerous differentiation of reprogrammed MCF-7 cells in a synergistic fashion with paclitaxel, especially in the presence of TPA, compared to nf-RGE. These findings suggest that f-RGE treatment may be more effective for decreasing cancer cell survival by inducing apoptotic cell death and also presumably for preventing cancer stem cell differentiation compared to nf-RGE. PMID:25658580

  11. The Evolving Concepts of Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

    OpenAIRE

    Amit Shah; Shilpa Patel; Jigna Pathak; Niharika Swain; Shwetha Kumar

    2014-01-01

    There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs)—the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumor cell population. CSCs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the ...

  12. Methyl Antcinate A Suppresses the Population of Cancer Stem-Like Cells in MCF7 Human Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Wen-Wei Chang

    2013-02-01

    Full Text Available Methyl antcinate A (MAA is an ergostane-type triterpenoid extracted from the fruiting bodies of Antrodia camphorate that has been reported to be a cytotoxic agent towards some types of cancer cells, such as oral cancer and liver cancer. Cancer stem cells (CSCs are a particular population within cancer cells which are responsible for tumor initiation, drug resistance and metastasis and targeting CSCs is an emerging area in cancer therapy. In this study, we examine the effect of MAA on cancer stem-like cells in the MCF7 human breast cancer cell line. Although MAA displayed very low cytotoxic effect towards MCF7 under normal culture conditions, it did show good inhibitory effects on the self-renewal capability which was examined by mammosphere culture including primary and secondary sphere. MAA also inhibited cell migration ability of MCF7 sphere cells. By western blot analysis, MAA was shown to suppress the expression of heat shock protein 27 and increase the expression of IkBα and p53. In conclusion, our data demonstrate that MAA has anti-CSC activity and is worthy of future development of potent anticancer agents.

  13. Expression Compilation of Several Putative Cancer Stem Cell Markers by Primary Ovarian Carcinoma

    OpenAIRE

    Di Jiabo; Yigit Refika; G. Figdor Carl; Duiveman-de Boer Tjitske; Massuger Leon; Torensma Ruurd

    2010-01-01

    Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer stem cell markers were reported to be expressed by ovarian cancer. Those cancer stem cells are gifted with lower vulnerability to irradiation and cytostatic drugs explaining the high incidence of recurrence after treatment. A variety of different cancer stem cell markers were desc...

  14. Squamous Cell Lung Cancer Presenting as a Malar Mass

    Directory of Open Access Journals (Sweden)

    Ganesh Veerappan

    2003-09-01

    Full Text Available Introduction: Lung cancer metastasizing to the face has rarely been reported and is an even more unusual presentation. Case: This is the case of a 49-year-old man diagnosed with squamous cell carcinoma of the face, scheduled for resection. Preoperative radiographs revealed a left upper lobe mass, found to be squamous cell carcinoma. Diagnosis was changed to Stage IV primary lung cancer. The patient did not undergo resection. Discussion: No previous cases of primary lung cancer presenting as a malar mass have been reported. Facial lesions can be the presenting feature of primary lung cancer. Discovery of the true primary lesion can alter therapy and prognosis.

  15. 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.

  16. Heating cancer stem cells to reduce tumor relapse

    OpenAIRE

    PG. Pelicci; P. Dalton; R. Orecchia

    2011-01-01

    Tumour relapse is believed to be caused by rare cancer-cells with stem-cell properties (cancer stem cells) that are intrinsically resistant to available treatments. The identification of novel strategies to increase their sensitivity has major clinical implications. Latest clinical trials have shown a positive antitumoral effect of hyperthermia in combination with chemotherapy or radiotherapy. In a recent paper, the combination of increased temperature at the tumour site, generated by laser t...

  17. An RNA editing fingerprint of cancer stem cell reprogramming

    OpenAIRE

    Crews, Leslie A; Jiang, Qingfei; Zipeto, Maria A; de Lazzari, Elisa; Court, Angela C.; Ali, Shawn; Barrett, Christian L.; Frazer, Kelly A; Jamieson, Catriona HM

    2015-01-01

    Background Deregulation of RNA editing by adenosine deaminases acting on dsRNA (ADARs) has been implicated in the progression of diverse human cancers including hematopoietic malignancies such as chronic myeloid leukemia (CML). Inflammation-associated activation of ADAR1 occurs in leukemia stem cells specifically in the advanced, often drug-resistant stage of CML known as blast crisis. However, detection of cancer stem cell-associated RNA editing by RNA sequencing in these rare cell populatio...

  18. Proteasomal regulation of caspase-8 in cancer cell apoptosis

    OpenAIRE

    Fiandalo, Michael V.; Schwarze, Steven R.; Kyprianou, Natasha

    2013-01-01

    Previous studies demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of caspase-8. The present study investigated the impact of proteasome inhibition on caspase-8 stability, ubiquitination, trafficking, and activation in cancer cells. Using caspase-8 deficient neuroblastoma (NB7) cells for reconstituting non-cleavable mutant forms of caspase-8, we demonstrated that the non-cleavable fo...

  19. Integrated molecular portrait of non-small cell lung cancers

    OpenAIRE

    Lazar, Vladimir; Suo, Chen; Orear, Cedric; van den Oord, Joost; Balogh, Zsofia; Guegan, Justine; Job, Bastien; Meurice, Guillaume; Ripoche, Hugues; Calza, Stefano; Hasmats, Johanna; Lundeberg, Joakim; Lacroix, Ludovic; Vielh, Philippe; Dufour, Fabienne

    2013-01-01

    Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridiz...

  20. Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells

    OpenAIRE

    Kristine Glunde; Sandra E. Guggino; Meiyappan Solaiyappan; Pathak, Arvind P.; Yoshitaka Ichikawa; Bhujwalla, Zaver M.

    2003-01-01

    Cancer cells invade by secreting degradative enzymes, which are sequestered in lysosomal vesicles. In this study, the impact of an acidic extracellular environment on lysosome size, number, and distance from the nucleus in human mammary epithelial cells (HMECs) and breast cancer cells of different degrees of malignancy was characterized because the physiological microenvironment of tumors is frequently characterized by extracellular acidity. An acidic extracellular pH (pHe) resulted in a dist...

  1. 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.

  2. Hypoxia regulates stemness of breast cancer MDA-MB-231 cells

    OpenAIRE

    Xie, Jing; Xiao, Yong; Zhu, Xiao-Yan; Ning, Zhou-yu; Xu, Hai-fan; Wu, Hui-Min

    2016-01-01

    Human breast cancers include cancer stem cell populations as well as non-tumorigenic cancer cells. Breast cancer stem cells possess self-renewal capability and thus are the root cause of recurrence and metastasis of malignant tumors. Hypoxia is a fundamental pathological feature of solid tumor tissues and exerts a wide range of effects on the biological behavior of cancer cells. However, there is little information on the role of hypoxia in modulating the stemness of breast cancer cells. In t...

  3. 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

  4. Exosomes Released from Breast Cancer Carcinomas Stimulate Cell Movement

    OpenAIRE

    Dinari A Harris; Patel, Sajni H.; Gucek, Marjan; Hendrix, An; Westbroek, Wendy; Taraska, Justin W.

    2015-01-01

    For metastasis to occur cells must communicate with to their local environment to initiate growth and invasion. Exosomes have emerged as an important mediator of cell-to-cell signalling through the transfer of molecules such as mRNAs, microRNAs, and proteins between cells. Exosomes have been proposed to act as regulators of cancer progression. Here, we study the effect of exosomes on cell migration, an important step in metastasis. We performed cell migration assays, endocytosis assays, and e...

  5. Iron induces cancer stem cells and aggressive phenotypes in human lung cancer cells.

    Science.gov (United States)

    Chanvorachote, Pithi; Luanpitpong, Sudjit

    2016-05-01

    Evidence has accumulated in support of the critical impact of cancer stem cells (CSCs) behind the chemotherapeutic failure, cancer metastasis, and subsequent disease recurrence and relapse, but knowledge of how CSCs are regulated is still limited. Redox status of the cells has been shown to dramatically influence cell signaling and CSC-like aggressive behaviors. Here, we investigated how subtoxic concentrations of iron, which have been found to specifically induce cellular hydroxyl radical, affected CSC-like subpopulations of human non-small cell lung carcinoma (NSCLC). We reveal for the first time that subchronic iron exposure and higher levels of hydroxyl radical correlated well with increased CSC-like phenotypes. The iron-exposed NSCLC H460 and H292 cells exhibited a remarkable increase in propensities to form CSC spheroids and to proliferate, migrate, and invade in parallel with an increase in level of a well-known CSC marker, ABCG2. We further observed that such phenotypic changes induced by iron were not related to an epithelial-to-mesenchymal transition (EMT). Instead, the sex-determining region Y (SRY)-box 9 protein (SOX9) was substantially linked to iron treatment and hydroxyl radical level. Using gene manipulations, including ectopic SOX9 overexpression and SOX9 short hairpin RNA knockdown, we have verified that SOX9 is responsible for CSC enrichment mediated by iron. These findings indicate a novel role of iron via hydroxyl radical in CSC regulation and its importance in aggressive cancer behaviors and likely metastasis through SOX9 upregulation. PMID:26911281

  6. Consensus nomenclature for CD8+ T cell phenotypes in cancer

    Science.gov (United States)

    Apetoh, Lionel; Smyth, Mark J.; Drake, Charles G.; Abastado, Jean-Pierre; Apte, Ron N.; Ayyoub, Maha; Blay, Jean-Yves; Bonneville, Marc; Butterfield, Lisa H.; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Esteban; Chen, Lieping; Colombo, Mario P.; Comin-Anduix, Begoña; Coukos, Georges; Dhodapkar, Madhav V.; Dranoff, Glenn; Frazer, Ian H.; Fridman, Wolf-Hervé; Gabrilovich, Dmitry I.; Gilboa, Eli; Gnjatic, Sacha; Jäger, Dirk; Kalinski, Pawel; Kaufman, Howard L.; Kiessling, Rolf; Kirkwood, John; Knuth, Alexander; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Marincola, Francesco; Melero, Ignacio; Melief, Cornelis J.; Mempel, Thorsten R.; Mittendorf, Elizabeth A.; Odun, Kunle; Overwijk, Willem W.; Palucka, Anna Karolina; Parmiani, Giorgio; Ribas, Antoni; Romero, Pedro; Schreiber, Robert D.; Schuler, Gerold; Srivastava, Pramod K.; Tartour, Eric; Valmori, Danila; van der Burg, Sjoerd H.; van der Bruggen, Pierre; van den Eynde, Benoît J.; Wang, Ena; Zou, Weiping; Whiteside, Theresa L.; Speiser, Daniel E.; Pardoll, Drew M.; Restifo, Nicholas P.; Anderson, Ana C.

    2015-01-01

    Whereas preclinical investigations and clinical studies have established that CD8+ T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8+ T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8+ T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8+ T cell immunity, leading to the emergence of dysfunctional CD8+ T cells. The existence of different types of CD8+ T cells in cancer calls for a more precise definition of the CD8+ T cell immune phenotypes in cancer and the abandonment of the generic terms “pro-tumor” and “antitumor.” Based on recent studies investigating the functions of CD8+ T cells in cancer, we here propose some guidelines to precisely define the functional states of CD8+ T cells in cancer. PMID:26137416

  7. Prostate cancer cells metastasize to the hematopoietic stem cell niche in bone

    Institute of Scientific and Technical Information of China (English)

    Evan T Keller

    2011-01-01

    @@ The majority of men with advanced prostate cancer develop bone metastases as opposed to metastases at other sites.1 It has been unclear why prostate cancer selectively metastasizes to and proliferates in bone.Recently, Shiozawa et al.Delineated a mechanism that may account for the establishment of prostate cancer in bone.2 Specifically, they identified that prostate cancer cells compete with hematopoietic stem cells (HSC) for the osteoblast in the HSC niche of the bone.Defining the mechanisms through which prostate cancer cells establish themselves in bone is critical towards developing effective therapeutic strategies to prevent or target bone metastases.

  8. Metformin and prostate cancer stem cells: a novel therapeutic target.

    Science.gov (United States)

    Mayer, M J; Klotz, L H; Venkateswaran, V

    2015-12-01

    Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies. PMID:26215782

  9. Stem cell biology in thyroid cancer: Insights for novel therapies

    Institute of Scientific and Technical Information of China (English)

    Parisha; Bhatia; Koji; Tsumagari; Zakaria; Y; Abd; Elmageed; Paul; Friedlander; Joseph; F; Buell; Emad; Kandil

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

  10. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-14

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  11. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Research highlights: → Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. → Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. → PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. → 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 β-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 by treatment with anti

  12. FH535 inhibited metastasis and growth of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Wu MY

    2015-07-01

    Full Text Available Meng-Yao Wu,1,* Rong-Rui Liang,1,* Kai Chen,1 Meng Shen,1 Ya-Li Tian,1,2 Dao-Ming Li,1 Wei-Ming Duan,1 Qi Gui,1 Fei-Ran Gong,3 Lian Lian,1,2 Wei Li,1,6 Min Tao1,4–61Department of Oncology, The First Affiliated Hospital of Soochow University, 2Department of Oncology, Suzhou Xiangcheng People’s Hospital, 3Department of Hematology, The First Affiliated Hospital of Soochow University, 4Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 5Institute of Medical Biotechnology, Soochow University, Suzhou, 6PREMED Key Laboratory for Precision Medicine, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workAbstract: FH535 is a small-molecule inhibitor of the Wnt/β-catenin signaling pathway, which a substantial body of evidence has proven is activated in various cancers, including pancreatic cancer. Activation of the Wnt/β-catenin pathway plays an important role in tumor progression and metastasis. We investigated the inhibitory effect of FH535 on the metastasis and growth of pancreatic cancer cells. Western blotting and luciferase reporter gene assay indicated that FH535 markedly inhibited Wnt/β-catenin pathway viability in pancreatic cancer cells. In vitro wound healing, invasion, and adhesion assays revealed that FH535 significantly inhibited pancreatic cancer cell metastasis. We also observed the inhibitory effect of FH535 on pancreatic cancer cell growth via the tetrazolium and plate clone formation assays. Microarray analyses suggested that changes in the expression of multiple genes could be involved in the anti-cancer effect of FH535 on pancreatic cancer cells. Our results indicate for the first time that FH535 inhibits pancreatic cancer cell metastasis and growth, providing new insight into therapy of pancreatic cancer.Keywords: pancreatic cancer, FH535, β-catenin, metastasis, growth

  13. Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells

    DEFF Research Database (Denmark)

    Liang, Yuh-Jin; Ding, Yao; Levery, Steven B;

    2013-01-01

    Previous studies demonstrated that certain glycosphingolipids (GSLs) are involved in various cell functions, such as cell growth and motility. Recent studies showed changes in GSL expression during differentiation of human embryonic stem cells; however, little is known about expression profiles of...... GSLs in cancer stem cells (CSCs). CSCs are a small subpopulation in cancer and are proposed as cancer-initiating cells, have been shown to be resistant to numerous chemotherapies, and may cause cancer recurrence. Here, we analyzed GSLs expressed in human breast CSCs by applying a CSC model induced...... through epithelial-mesenchymal transition, using mass spectrometry, TLC immunostaining, and cell staining. We found that (i) Fuc-(n)Lc4Cer and Gb3Cer were drastically reduced in CSCs, whereas GD2, GD3, GM2, and GD1a were greatly increased in CSCs; (ii) among various glycosyltransferases tested, m...

  14. 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; Issinger, Olaf-Georg; Stenvang, Jan

    2007-01-01

    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 are...... 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.......Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for...

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

    Directory of Open Access Journals (Sweden)

    Masamitsu Kanada

    2014-12-01

    Full Text Available 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. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies.

  16. Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    EvaKaramitopoulou

    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.

  17. The thioredoxin system in breast cancer cell invasion and migration.

    Science.gov (United States)

    Bhatia, Maneet; McGrath, Kelly L; Di Trapani, Giovanna; Charoentong, Pornpimol; Shah, Fenil; King, Mallory M; Clarke, Frank M; Tonissen, Kathryn F

    2016-08-01

    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. PMID:26760912

  18. 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.

  19. Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines

    OpenAIRE

    Terasawa, K.; Toyota, M; Sagae, S.; Ogi, K; Suzuki, H.; Sonoda, T.; Akino, K; Maruyama, R.; Nishikawa, N.; Imai, K; Shinomura, Y; T. Saito; Tokino, T

    2006-01-01

    Transcription factor 2 gene (TCF2) encodes hepatocyte nuclear factor 1β (HNF1β), a transcription factor associated with development and metabolism. Mutation of TCF2 has been observed in renal cell cancer, and by screening aberrantly methylated genes, we have now identified TCF2 as a target for epigenetic inactivation in ovarian cancer. TCF2 was methylated in 53% of ovarian cancer cell lines and 26% of primary ovarian cancers, resulting in loss of the gene's expression. TCF2 expression was res...

  20. 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.)

  1. Astragalus extract inhibits destruction of gastric cancer cells to mesothelial cells by anti-apoptosis

    Institute of Scientific and Technical Information of China (English)

    Di Na; Fu-Nan Liu; Zhi-Feng Miao; Zong-Min Du; Hui-Mian Xu

    2009-01-01

    AIM: To determine the inhibitory effect of Astragalus memebranaceushas on gastric cancer cell supernatantinduced apoptosis of human peritoneal mesothelial cells. METHODS: Human peritoneal mesothelial cell (HPMC) line HMrSV5 was co-incubated with gastric cancer cell supernatant (MKN45) and/or Astragalus memebranaceushas. Morphological changes in gastric cancer cells were observed under phase-contrast microscope. Quantitative cell damage was determined by MTT assay. Apoptosis was determined under transmission electron microscope and quantified by detecting acridine orange/ethidium bromide-stained (AO/EB) condensed nuclei under fluorescent microscope or by flow cytometry. Expressions of Bcl-2 and Bax were evaluated with immunostaining. RESULTS: Morphological changes and exfoliation occurred and naked areas appeared in cultured HMrSV5 cells 24 h after they were treated with gastric cancer cell supernatant. Cell supernatant from MKN45 gastric cancer cells induced apoptosis of HMrSV5 cells in a time-dependent manner. Obvious morphological changes were observed in cell apoptosis, such as condensation of chromatin, nuclear fragmentations and apoptotic bodies. Astragalus memebranaceus could partly suppress these changes and regulate the expressions of Bcl-2 and Bax in HMrSV5 cells. CONCLUSION: Gastric cancer cells induce apoptosis of HPMCs through the supernatant. Astragalus memebranaceushas inhibits this phenomenon and can be used an adjuvant chemothera-peutic agent in gastric cancer therapy.

  2. Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

    OpenAIRE

    Hwang-Verslues, Wendy W.; Wen-Hung Kuo; Po-Hao Chang; Chi-Chun Pan; Hsing-Hui Wang; Sheng-Ta Tsai; Yung-Ming Jeng; Jin-Yu Shew; Kung, John T.; Chung-Hsuan Chen; Lee, Eva Y-H. P.; King-Jen Chang; Wen-Hwa Lee

    2009-01-01

    Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vi...

  3. 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

  4. Wound Healing and Cancer Stem Cells: Inflammation as a Driver of Treatment Resistance in Breast Cancer

    OpenAIRE

    Arnold, Kimberly M; Opdenaker, Lynn M.; Daniel Flynn; Jennifer Sims-Mourtada

    2015-01-01

    The relationship between wound healing and cancer has long been recognized. The mechanisms that regulate wound healing have been shown to promote transformation and growth of malignant cells. In addition, chronic inflammation has been associated with malignant transformation in many tissues. Recently, pathways involved in inflammation and wound healing have been reported to enhance cancer stem cell (CSC) populations. These cells, which are highly resistant to current treatments, are capable o...

  5. Cancer Stem and Progenitor-Like Cells as Pharmacological Targets in Breast Cancer Treatment

    OpenAIRE

    Valéria B. de Souza; Schenka, André A

    2015-01-01

    The present review is focused on the current role of neoplastic stem and progenitor-like cells as primary targets in the pharmacotherapy of cancer as well as in the development of new anticancer drugs. We begin by summarizing the main characteristics of these tumor-initiating cells and key concepts that support their participation in therapeutic failure. In particular, we discuss the differences between the major carcinogenesis models (ie, clonal evolution vs cancer stem cell (CSC) model) wit...

  6. The thioredoxin system in breast cancer cell invasion and migration

    OpenAIRE

    Maneet Bhatia; Kelly L. McGrath; Giovanna Di Trapani; Pornpimol Charoentong; Fenil Shah; Mallory M. King; Clarke, Frank M.; Tonissen, Kathryn F

    2016-01-01

    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 ...

  7. Nanodrug-Mediated Thermotherapy of Cancer Stem-Like Cells.

    Science.gov (United States)

    Rao, Wei; Wang, Hai; Zhong, Allison; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2016-03-01

    Cancer stem-like cells (CSCs) are rare subpopulations of cancer cells that are resistant to conventional chemotherapy and radiotherapy and contribute to cancer metastases and tumor recurrence. Therefore, it is of significance to develop an effective therapy to eliminate the CSCs. Cancer thermotherapy realized by depositing heat into tumor in a minimally invasive way is a promising alternative to the conventional therapies for cancer treatment. However, this method is limited by its inability to target CSCs, potentially allowing the CSCs to survive and re-initiate tumor growth. More recently, nanodrug-mediated thermotherapy has been explored to selectively eliminate CSCs and specifically deposit heat in tumor to spare healthy tissue. Here, we provide a brief overview of the targeting moieties and nanoplatforms used in developing nanodrug-mediated thermotherapy of cancer with particular emphasis on the CSCs, as well as the challenges and potential directions for future research in this emerging field. PMID:27455612

  8. Deterministic sequential isolation of floating cancer cells under continuous flow.

    Science.gov (United States)

    Tran, Quang D; Kong, Tian Fook; Hu, Dinglong; Marcos; Lam, Raymond H W

    2016-08-01

    Isolation of rare cells, such as circulating tumor cells, has been challenging because of their low abundance and limited timeframes of expressions of relevant cell characteristics. In this work, we devise a novel hydrodynamic mechanism to sequentially trap and isolate floating cells in biosamples. We develop a microfluidic device for the sequential isolation of floating cancer cells through a series of microsieves to obtain up to 100% trapping yield and >95% sequential isolation efficiency. We optimize the trappers' dimensions and locations through both computational and experimental analyses using microbeads and cells. Furthermore, we investigated the functional range of flow rates for effective sequential cell isolation by taking the cell deformability into account. We verify the cell isolation ability using the human breast cancer cell line MDA-MB-231 with perfect agreement with the microbead results. The viability of the isolated cells can be maintained for direct identification of any cell characteristics within the device. We further demonstrate that this device can be applied to isolate the largest particles from a sample containing multiple sizes of particles, revealing its possible applicability in isolation of circulating tumor cells in cancer patients' blood. Our study provides a promising sequential cell isolation strategy with high potential for rapid detection and analysis of general floating cells, including circulating tumor cells and other rare cell types. PMID:27387093

  9. General Information about Renal Cell Cancer

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...

  10. NAC selectively inhibit cancer telomerase activity: A higher redox homeostasis threshold exists in cancer cells

    OpenAIRE

    Pengying Li; Meilin Wu; Jing Wang; Yilun Sui; Shanlin Liu; Dongyun Shi

    2016-01-01

    Telomerase activity controls telomere length, and this plays an important role in stem cells, aging and tumors. Antioxidant was shown to protect telomerase activity in normal cells but inhibit that in cancer cells, but the underlying mechanism is elusive. Here we found that 7721 hepatoma cells held a higher redox homeostasis threshold than L02 normal liver cells which caused 7721 cells to have a higher demand for ROS; MnSOD over-expression in 7721 decreased endogenous reactive oxygen species ...

  11. Normal human colon cells suppress malignancy when fused with colon cancer cells

    International Nuclear Information System (INIS)

    Normal human colon mucosa cells and cells obtained from histologically normal tissues near that cancer were fused with human colon cancer cells. Resultant hybrid populations of normal and malignant cell fusions behaved as nonmalignant cells in culture, were unable to grow in soft agar, did not express tumor-associated antigens, and were nontumorigenic in nude mice. Autofusion of the cancer cell population led to a phenotype intermediate between normal and malignant cells. That is, the cultures had a much lower plating efficiency in soft agar, and the tumors had a longer latency and slower growth rate in nude mice. This is the first cell culture system to demonstrate that normal epithelial cells can suppress malignancy of their autologous cancer cells, and is a prelude to more extensive studies of genetic events involved in malignant conversion of human colonic epithelium

  12. 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

  13. Viable capture and release of cancer cells in human whole blood

    Science.gov (United States)

    Doh, Il; Yoo, Hwan-il; Cho, Young-Ho; Lee, Jinseon; Kwan Kim, Hong; Kim, Jhingook

    2012-07-01

    We present viable cancer cell isolation devices utilizing the physical properties of cells. The tapered slit structure is proposed to isolate cancer cells from blood cells and collect them by reversed flow. From the experimental study using the spiked cancer cells in human whole blood, we verified the capability of the present cancer cell isolation chip in terms of capture efficiency, viability, and release rate. The viable cancer cells obtained from the present chip can be used for the further applications of cancer diagnosis, treatment monitoring, and new target drug development for cancer stem cells.

  14. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Gilbert Bernier

    2011-03-01

    Full Text Available 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.

  15. 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. PMID:27262760

  16. Biofunctionalized magnetic vortex microdisks for targeted cancer cell destruction.

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D.-H.; Rozhkova, E. A.; Ulasov, I. V.; Bader, S. D.; Rajh, T.; Lesniak, M. S.; Novosad, V.; Univ. of Chicago Pritzker School of Medicine

    2010-01-01

    Nanomagnetic materials offer exciting avenues for probing cell mechanics and activating mechanosensitive ion channels, as well as for advancing cancer therapies. Most experimental works so far have used superparamagnetic materials. This report describes a first approach based on interfacing cells with lithographically defined microdiscs that possess a spin-vortex ground state. When an alternating magnetic field is applied the microdisc vortices shift, creating an oscillation, which transmits a mechanical force to the cell. Because reduced sensitivity of cancer cells toward apoptosis leads to inappropriate cell survival and malignant progression, selective induction of apoptosis is of great importance for the anticancer therapeutic strategies. We show that the spin-vortex-mediated stimulus creates two dramatic effects: compromised integrity of the cellular membrane, and initiation of programmed cell death. A low-frequency field of a few tens of hertz applied for only ten minutes was sufficient to achieve {approx}90% cancer-cell destruction in vitro.

  17. Common stemness regulators of embryonic and cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Christiana; Hadjimichael; Konstantina; Chanoumidou; Natalia; Papadopoulou; Panagiota; Arampatzi; Joseph; Papamatheakis; Androniki; Kretsovali

    2015-01-01

    Pluripotency of embryonic stem cells(ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal trans-ducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors(cancer stem cells), provides a common conceptual and research frame-work for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.

  18. 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.

  19. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    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

  20. 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

    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...... 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...... 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....