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Sample records for homologue enhances cancer

  1. Regulation and role of post-translational modifications of enhancer of zeste homologue 2 in cancer development.

    Science.gov (United States)

    Lu, Haiqi; Li, Guangliang; Zhou, Chenyi; Jin, Wei; Qian, Xiaoling; Wang, Zhuo; Pan, Hongming; Jin, Hongchuan; Wang, Xian

    2016-01-01

    Post-translational modifications (PTMs) are critical molecular events which alter protein conformation after their synthesis and diversity protein properties by modulating their stability, localization, interacting partners or the activity of their substrates, consequently exerting pivotal roles in regulating the functions of many important eukaryotic proteins. It has been well acknowledged that PTMs are of great importance in a broad range of biological processes such as gene regulation, cell proliferation, differentiation and apoptosis, tissue development, diseases, tumor progression and drug resistance. As the core and contributing catalytic subunit of Polycomb repressive complex 2(PRC2), Enhancer of zeste homolog 2 (EZH2) is a master epigenetic regulator, often serving as a highly conserved histone methyltransferase (HMTase) to induce histone H3 lysine 27 trimethylation (H3K27me3) and repress gene transcription and expression. Dysregulated EZH2 expression is frequently associated with cancer development and poor prognosis in a wide variety of cancers. Considered its essential role in carcinogenesis, EZH2 is a potential candidate for cancer targeted therapy. Remarkably, mounting evidence highlights that EZH2 expression, activity and stability can be regulated by PTMs including phosphorylation, acetylation, ubiquitination, sumoylation and GlcNAcylation aside from its well-validated modifications in transcriptional and post-transcriptional levels. However, the precise regulatory mechanisms underlying EZH2 PTMs and whether other types of PTMs orchestrate in EZH2 remain largely unclear. In this review, we summarize current advances in the understanding of EZH2 regulation by PTMs and their associated biological functions during tumorigenesis.

  2. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers.

    Science.gov (United States)

    Bischoff, J R; Anderson, L; Zhu, Y; Mossie, K; Ng, L; Souza, B; Schryver, B; Flanagan, P; Clairvoyant, F; Ginther, C; Chan, C S; Novotny, M; Slamon, D J; Plowman, G D

    1998-06-01

    Genetic and biochemical studies in lower eukaryotes have identified several proteins that ensure accurate segregation of chromosomes. These include the Drosophila aurora and yeast Ipl1 kinases that are required for centrosome maturation and chromosome segregation. We have identified two human homologues of these genes, termed aurora1 and aurora2, that encode cell-cycle-regulated serine/threonine kinases. Here we demonstrate that the aurora2 gene maps to chromosome 20q13, a region amplified in a variety of human cancers, including a significant number of colorectal malignancies. We propose that aurora2 may be a target of this amplicon since its DNA is amplified and its RNA overexpressed, in more than 50% of primary colorectal cancers. Furthermore, overexpression of aurora2 transforms rodent fibroblasts. These observations implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome-associated proteins as novel targets for cancer therapy.

  3. The urokinase receptor and its structural homologue C4.4A in human cancer

    DEFF Research Database (Denmark)

    Jacobsen, B; Ploug, M

    2008-01-01

    in the human genome. The structural relationship between the two proteins is, however, not reflected at the functional level. Whereas uPAR has a well-established role in regulating and focalizing uPA-mediated plasminogen activation to the surface of those cells expressing the receptor, the biological function...... of C4.4A remains elusive. Nonetheless, both uPAR and C4.4A have been implicated in human pathologies such as wound healing and cancer. A large body of experimental evidence thus demonstrates that high levels of uPAR in resected tumour tissue as well as in plasma are associated with poor prognosis......The urokinase-type plasminogen activator receptor (uPAR) and its structural homologue C4.4A are multidomain members of the Ly6/uPAR/alpha-neurotoxin protein domain family. Both are glycosylphosphatidylinositol-anchored membrane glycoproteins encoded by neighbouring genes located on chromosome 19q13...

  4. Distinct isoforms of the Drosophila Brd4 homologue are present at enhancers, promoters and insulator sites.

    Science.gov (United States)

    Kellner, Wendy A; Van Bortle, Kevin; Li, Li; Ramos, Edward; Takenaka, Naomi; Corces, Victor G

    2013-11-01

    Brd4 is a double bromodomain protein that has been shown to interact with acetylated histones to regulate transcription by recruiting Positive Transcription Elongation Factor b to the promoter region. Brd4 is also involved in gene bookmarking during mitosis and is a therapeutic target for the treatment of acute myeloid leukemia. The Drosophila melanogaster Brd4 homologue is called Fs(1)h and, like its vertebrate counterpart, encodes different isoforms. We have used ChIP-seq to examine the genome-wide distribution of Fs(1)h isoforms. We are able to distinguish the Fs(1)h-L and Fs(1)h-S binding profiles and discriminate between the genomic locations of the two isoforms. Fs(1)h-S is present at enhancers and promoters and its amount parallels transcription levels. Correlations between the distribution of Fs(1)h-S and various forms of acetylated histones H3 and H4 suggest a preference for binding to H3K9acS10ph. Surprisingly, Fs(1)h-L is located at sites in the genome where multiple insulator proteins are also present. The results suggest that Fs(1)h-S may be responsible for the classical role assigned to this protein, whereas Fs(1)h-L may have a new and unexpected role in chromatin architecture by working in conjunction with insulator proteins to mediate intra- or inter-chromosome interactions.

  5. The archaeal TFIIE homologue facilitates transcription initiation by enhancing TATA-box recognition

    NARCIS (Netherlands)

    Bell, S.D.; Brinkman, A.B.; Oost, van der J.; Jackson, S.P.

    2001-01-01

    Transcription from many archaeal promoters can be reconstituted in vitro using recombinant TATA-box binding protein (TBP) and transcription factor B (TFB)—homologues of eukaryal TBP and TFIIB—together with purified RNA polymerase (RNAP). However, all archaeal genomes sequenced to date reveal the

  6. Bcl-2 homologue Debcl enhances α-synuclein-induced phenotypes in Drosophila

    Directory of Open Access Journals (Sweden)

    P. Githure M’Angale

    2016-09-01

    Full Text Available Background Parkinson disease (PD is a debilitating movement disorder that afflicts 1–2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized Debcl and the antiapoptotic Buffy. The expression of the human transgene α-synuclein, a gene that is strongly associated with inherited forms of PD, in dopaminergic neurons (DA of Drosophila, results in loss of neurons and locomotor dysfunction to model PD in flies. The altered expression of Debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of Debcl in mitochondrial-dependent neuronal degeneration and death. Results The directed overexpression of Debcl using the Ddc-Gal4 transgene in the DA of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of Debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of Debcl in the α-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of Debcl along with Buffy partially counteracts the Debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of Debcl along with the expression of α-synuclein in the eye, enhanced the eye ablation that results from the overexpression of Debcl. The co-expression of Buffy along with Debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of Debcl partially restores the eye to a roughened eye phenotype. Discussion The

  7. Bcl-2 homologue Debcl enhances α-synuclein-induced phenotypes in Drosophila.

    Science.gov (United States)

    M'Angale, P Githure; Staveley, Brian E

    2016-01-01

    Parkinson disease (PD) is a debilitating movement disorder that afflicts 1-2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized Debcl and the antiapoptotic Buffy. The expression of the human transgene α-synuclein, a gene that is strongly associated with inherited forms of PD, in dopaminergic neurons (DA) of Drosophila, results in loss of neurons and locomotor dysfunction to model PD in flies. The altered expression of Debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of Debcl in mitochondrial-dependent neuronal degeneration and death. The directed overexpression of Debcl using the Ddc-Gal4 transgene in the DA of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of Debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of Debcl in the α-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of Debcl along with Buffy partially counteracts the Debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of Debcl along with the expression of α-synuclein in the eye, enhanced the eye ablation that results from the overexpression of Debcl. The co-expression of Buffy along with Debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of Debcl partially restores the eye to a roughened eye phenotype. The overexpression of Debcl in DA neurons produces flies with

  8. Tumour cell expression of C4.4A, a structural homologue of the urokinase receptor, correlates with poor prognosis in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Hansen, Line V.; Skov, Birgit G; Ploug, Michael

    2007-01-01

    expression. In the present study, we therefore explored the possible association between C4.4A expression and prognosis in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tissue sections from 108 NSCLC patients were subjected to immunohistochemical staining using a polyclonal antibody......PURPOSE: C4.4A expression has been implicated in human cancer progression. This protein is a structural homologue of the urokinase receptor, uPAR, which constitutes a well-established prognostic marker in various human cancers. Nonetheless, little is known about the prognostic significance of C4.4A...... that specifically recognises human C4.4A. Staining frequency and intensity was scored semiquantitatively and grouped into cancers with high and low expression of C4.4A. Kaplan-Meier survival curves were generated to evaluate the significance of C4.4A expression in prognosis of NSCLC patients. RESULTS: High C4.4A...

  9. Enhanced electron correlations in the binary stannide PdSn4: A homologue of the Dirac nodal arc semimetal PtSn4

    Science.gov (United States)

    Xu, C. Q.; Zhou, W.; Sankar, R.; Xing, X. Z.; Shi, Z. X.; Han, Z. D.; Qian, B.; Wang, J. H.; Zhu, Zengwei; Zhang, J. L.; Bangura, A. F.; Hussey, N. E.; Xu, Xiaofeng

    2017-11-01

    The advent of nodal-line semimetals, i.e., systems in which the conduction and valence bands cross each other along a closed trajectory (line or loop) inside the Brillouin zone, has opened up a new arena for the exploration of topological condensed matter in which, due to a vanishing density of states near the Fermi level, electron correlation effects also may play an important role. Despite this conceptual richness, however, material realization of nodal-line (loop) fermions is rare with PbTaSe2, ZrSiS, and PtSn4 as the only promising known candidates. Here we report the synthesis and physical properties of a semimetal PdSn4 that is isostructural with PtSn4 yet possesses quasiparticles with significantly enhanced effective masses. In addition, PdSn4 displays an unusual polar angular magnetoresistance which, at a certain field orientation, varies linearly with fields up to 55 T. Our paper suggests that, in association with its homologue PtSn4 whose low-lying excitations recently were claimed to possess Dirac nodal arcs, PdSn4 may be a promising candidate in the search for novel topological states with enhanced correlation effects.

  10. Pepsin homologues in bacteria

    Directory of Open Access Journals (Sweden)

    Bateman Alex

    2009-09-01

    Full Text Available Abstract Background Peptidase family A1, to which pepsin belongs, had been assumed to be restricted to eukaryotes. The tertiary structure of pepsin shows two lobes with similar folds and it has been suggested that the gene has arisen from an ancient duplication and fusion event. The only sequence similarity between the lobes is restricted to the motif around the active site aspartate and a hydrophobic-hydrophobic-Gly motif. Together, these contribute to an essential structural feature known as a psi-loop. There is one such psi-loop in each lobe, and so each lobe presents an active Asp. The human immunodeficiency virus peptidase, retropepsin, from peptidase family A2 also has a similar fold but consists of one lobe only and has to dimerize to be active. All known members of family A1 show the bilobed structure, but it is unclear if the ancestor of family A1 was similar to an A2 peptidase, or if the ancestral retropepsin was derived from a half-pepsin gene. The presence of a pepsin homologue in a prokaryote might give insights into the evolution of the pepsin family. Results Homologues of the aspartic peptidase pepsin have been found in the completed genomic sequences from seven species of bacteria. The bacterial homologues, unlike those from eukaryotes, do not possess signal peptides, and would therefore be intracellular acting at neutral pH. The bacterial homologues have Thr218 replaced by Asp, a change which in renin has been shown to confer activity at neutral pH. No pepsin homologues could be detected in any archaean genome. Conclusion The peptidase family A1 is found in some species of bacteria as well as eukaryotes. The bacterial homologues fall into two groups, one from oceanic bacteria and one from plant symbionts. The bacterial homologues are all predicted to be intracellular proteins, unlike the eukaryotic enzymes. The bacterial homologues are bilobed like pepsin, implying that if no horizontal gene transfer has occurred the duplication

  11. BCAR1, a human homologue of the adapter protein p130Cas, and antiestrogen resistance in breast cancer cells

    NARCIS (Netherlands)

    A. Brinkman (Arend); S. van der Flier (Silvia); E.M. Kok (Elisabeth); L.C.J. Dorssers (Lambert)

    2000-01-01

    textabstractBACKGROUND: Treatment of breast cancer with the antiestrogen tamoxifen is effective in approximately one half of the patients with estrogen receptor-positive disease, but tumors recur frequently because of the development of metastases that are resistant to

  12. Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers.

    Science.gov (United States)

    Dallol, Ashraf; Forgacs, Eva; Martinez, Alonso; Sekido, Yoshitaka; Walker, Rosemary; Kishida, Takeshi; Rabbitts, Pamela; Maher, Eamonn R; Minna, John D; Latif, Farida

    2002-05-02

    The human homologue of the Drosophila Roundabout gene DUTT1 (Deleted in U Twenty Twenty) or ROBO1 (Locus Link ID 6091), a member of the NCAM family of receptors, was recently cloned from the lung cancer tumour suppressor gene region 2 (LCTSGR2 or U2020 region) at 3p12. DUTT1 maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer lines (SCLC) and in a breast cancer line. In this report we (a) defined the genomic organization of the DUTT1 gene, (b) performed mutation and expression analysis of DUTT1 in lung, breast and kidney cancers, (c) identified tumour specific promoter region methylation of DUTT1 in human cancers. The gene was found to contain 29 exons and spans at least 240 kb of genomic sequence. The 5' region contains a CpG island, and the poly(A)(+) tail has an atypical 5'-GATAAA-3' signal. We analysed DUTT1 for mutations in lung, breast and kidney cancers, no inactivating mutations were detected by PCR-SSCP. However, seven germline missense changes were found and characterized. DUTT1 expression was not detectable in one out of 18 breast tumour lines analysed by RT-PCR. Bisulfite sequencing of the promoter region of DUTT1 gene in the HTB-19 breast tumour cell line (not expressing DUTT1) showed complete hypermethylation of CpG sites within the promoter region of the DUTT1 gene (-244 to +27 relative to the translation start site). The expression of DUTT1 gene was reactivated in HTB-19 after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The same region was also found to be hypermethylated in six out of 32 (19%) primary invasive breast carcinomas and eight out of 44 (18%) primary clear cell renal cell carcinomas (CC-RCC) and in one out of 26 (4%) primary NSCLC tumours. Furthermore 80% of breast and 75% of CC-RCC tumours showing DUTT1 methylation had allelic losses for 3p12 markers hence obeying Knudson's two hit hypothesis. Our findings suggest that DUTT1 warrants further analysis as a candidate for

  13. Phosphatase and tensin homologue deleted on chromosome 10 ...

    African Journals Online (AJOL)

    Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene deleted or mutated in many human cancers such as glioblastoma, spinal tumors, prostate, bladder, adrenals, thyroid, breast, endometrium, and colon cancers. They result from loss of heterozygosity (LOH) for the PTEN ...

  14. Immunoengineering: how nanotechnology can enhance cancer immunotherapy.

    Science.gov (United States)

    Goldberg, Michael S

    2015-04-09

    Although cancer immunotherapy can lead to durable outcomes, the percentage of patients who respond to this disruptive approach remains modest to date. Encouragingly, nanotechnology can enhance the efficacy of immunostimulatory small molecules and biologics by altering their co-localization, biodistribution, and release kinetics. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. SLIT2, a human homologue of the Drosophila Slit2 gene, has tumor suppressor activity and is frequently inactivated in lung and breast cancers.

    Science.gov (United States)

    Dallol, Ashraf; Da Silva, Nancy Fernandes; Viacava, Paolo; Minna, John D; Bieche, Ivan; Maher, Eamonn R; Latif, Farida

    2002-10-15

    Slit2 plays a vital role in axon guidance by signaling through Robo receptors. Recent evidence suggests that Slit2 protein may function in other settings because human and Xenopus Slit2 has been shown to inhibit leukocyte chemotaxis. SLIT2 protein is a putative ligand for the ROBO receptors. We recently demonstrated that ROBO1 is inactivated by promoter region hypermethylation in cancers; furthermore, tumor suppressor activity has not been shown. Thus, the importance of ROBO1 inactivation in human cancer is uncertain. Therefore, we investigated the status of SLIT2 located at 4p15.2 in lung and breast cancers. Although somatic SLIT2 mutations were not detected, epigenetic inactivation was common. SLIT2 promoter methylation was detected in 59% of breast cancer, 77% of non-small cell lung cancer, and 55% of small cell lung cancer cell lines. In these tumor lines, SLIT2 expression was restored by treatment with a demethylating agent. SLIT2 promoter methylation was detected in 43% of breast cancer, 53% of non-small cell lung cancer, and 36% of small cell lung cancer primary tumors. The majority of methylated tumors demonstrated allelic loss at 4p15.2. In addition, SLIT2 expression was down-regulated in methylated breast tumors, relative to normal control, as demonstrated by quantitative real-time reverse transcription-PCR. Overexpression of SLIT2 suppressed >70% of colony growth in each of three breast tumor lines (with either absent or low SLIT2 expression). Because SLIT2 is primarily a secreted protein, SLIT2-conditioned medium suppressed the growth of several breast cancer lines (with absent or weak SLIT2expression) by 26-51% but had no significant effect on a breast tumor cell line that expresses normal levels of SLIT2. These findings demonstrate that SLIT2 is frequently inactivated in lung and breast cancer by promoter region hypermethylation and allele loss and is an excellent candidate for the lung and breast tumor suppressor gene previously mapped to 4p15.2.

  16. Epidermal growth factor receptor and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue-specific amino acid substitutions are associated with different histopathological prognostic factors in resected non-small-cell lung cancer.

    Science.gov (United States)

    Seitlinger, Joseph; Renaud, Stéphane; Falcoz, Pierre-Emmanuel; Schaeffer, Mickaël; Olland, Anne; Reeb, Jérémie; Santelmo, Nicola; Legrain, Michèle; Voegeli, Anne-Claire; Weingertner, Noëlle; Chenard, Marie-Pierre; Beau-Faller, Michèle; Massard, Gilbert

    2016-12-01

    Epidermal growth factor receptor (mEGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogen homologue (mKRAS) mutations are the two main oncogenic drivers in resected non-small-cell lung cancer (NSCLC). We aimed to evaluate the correlation between histopathological prognostic factors and these mutations in resected NSCLC. We retrospectively reviewed data from 841 patients who underwent a surgical resection with a curative intent for NSCLC between 2007 and 2012. KRAS mutations were observed in 255 patients (32%) and mEGFR in 103 patients (12%). A correlation was observed between mKRAS patients and lymph node involvement [Cramer's V: 0.451, P V: 0.235, P = 0.02, OR: 3.04 (95% CI: 1.5-6.3), P = 0.004]. High lymph node ratio and angioinvasion were also significantly more frequent in mKRAS [Cramer's V: 0.373, P V: 0.269, P V: 0.459, P V: 0.45, P < 0.001 OR: 21.14 (95% CI: 9.2-48.3), P < 0.001, respectively]. We observed a correlation between mKRAS and negative histopathological prognostic factors and between mEGFR and positive prognostic factors. One can wonder whether histopathological prognostic factors are only clinical reflections of molecular alterations. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  17. Loss of Phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and IGF-IR signaling to promote antiestrogen resistance in breast cancer

    Science.gov (United States)

    Miller, Todd W.; Pérez-Torres, Marianela; Narasanna, Archana; Guix, Marta; Stål, Olle; Pérez-Tenorio, Gizeh; Gonzalez-Angulo, Ana M.; Hennessy, Bryan T.; Mills, Gordon B.; Kennedy, J. Phillip; Lindsley, Craig W.; Arteaga, Carlos L.

    2009-01-01

    Knockdown of the tumor suppressor phosphatase PTEN with shRNA in three estrogen receptor (ER)-positive breast cancer cell lines resulted in increased PI3K and AKT activities, resistance to tamoxifen and fulvestrant, and hormone-independent growth. PTEN knockdown induced the upregulation of ER transcriptional activity in MCF-7 cells, but decreased ER protein levels and transcriptional activity in T47D and MDA-361 cells. Tamoxifen and fulvestrant treatment inhibited estradiol-induced ER transcriptional activity in all shPTEN cell lines but did not abrogate the increased cell proliferation induced by PTEN knockdown. PTEN knockdown increased basal and ligand-induced activation of the IGF-I and ErbB3 receptor tyrosine kinases, and prolonged the association of the p85 PI3K subunit with the IGF-IR effector IRS-1 and with ErbB3, implicating PTEN in the modulation of signaling upstream of PI3K. Consistent with these data, PTEN levels inversely correlated with levels of tyrosine-phosphorylated IGF-IR in tissue lysate arrays of primary breast cancers. Inhibition of IGF-IR and/or ErbB2-mediated activation of ErbB3 with tyrosine kinase inhibitors restored hormone-dependence and the growth inhibitory effect of tamoxifen and fulvestrant on shPTEN cells, suggesting that co-targeting both ER and receptor tyrosine kinase pathways holds promise for the treatment of patients with ER+, PTEN-deficient breast cancers. PMID:19435893

  18. Harnessing the Microbiome to Enhance Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Michelle H. Nelson

    2015-01-01

    Full Text Available The microbiota plays a key role in regulating the innate and adaptive immune system. Herein, we review the immunological aspects of the microbiota in tumor immunity in mice and man, with a focus on toll-like receptor (TLR agonists, vaccines, checkpoint modulators, chemotherapy, and adoptive T cell transfer (ACT therapies. We propose innovative treatments that may safely harness the microbiota to enhance T cell-based therapies in cancer patients. Finally, we highlight recent developments in tumor immunotherapy, particularly novel ways to modulate the microbiome and memory T cell responses to human malignancies.

  19. Crystal chemistry of sartorite homologues and related sulfosalts

    DEFF Research Database (Denmark)

    Berlepsch, Peter; Makovicky, Emil; Balic-Zunic, Tonci

    2001-01-01

    sartorite homologues, sulfosalt, crystal chemistry, coordination polyhedra, bond-pairs, crankshaft chains......sartorite homologues, sulfosalt, crystal chemistry, coordination polyhedra, bond-pairs, crankshaft chains...

  20. Dynamic contrast enhanced MRI in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Alonzi, Roberto [Marie Curie Research Wing, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN (United Kingdom)], E-mail: robertoalonzi@btinternet.com; Padhani, Anwar R. [Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex, HA6 2RN (United Kingdom); Synarc Inc. 575 Market Street, San Francisco, CA 94105 (United States)], E-mail: anwar.padhani@paulstrickland-scannercentre.org.uk; Allen, Clare [Department of Imaging, University College Hospital, London, 235 Euston Road, NW1 2BU (United Kingdom)], E-mail: clare.allen@uclh.nhs.uk

    2007-09-15

    Angiogenesis is an integral part of benign prostatic hyperplasia (BPH), is associated with prostatic intraepithelial neoplasia (PIN) and is key to the growth and for metastasis of prostate cancer. Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) using small molecular weight gadolinium chelates enables non-invasive imaging characterization of tissue vascularity. Depending on the technique used, data reflecting tissue perfusion, microvessel permeability surface area product, and extracellular leakage space can be obtained. Two dynamic MRI techniques (T{sub 2}*-weighted or susceptibility based and T{sub 1}-weighted or relaxivity enhanced methods) for prostate gland evaluations are discussed in this review with reference to biological basis of observations, data acquisition and analysis methods, technical limitations and validation. Established clinical roles of T{sub 1}-weighted imaging evaluations will be discussed including lesion detection and localisation, for tumour staging and for the detection of suspected tumour recurrence. Limitations include inadequate lesion characterisation particularly differentiating prostatitis from cancer, and in distinguishing between BPH and central gland tumours.

  1. Enhancing Immune Checkpoint Inhibitor Therapy In Kidney Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0141 TITLE: Enhancing Immune Checkpoint Inhibitor therapy in Kidney Cancer PRINCIPAL INVESTIGATOR: Hans-Joerg Hammers...Immune Checkpoint Inhibitor therapy in Kidney Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH- 15-1-0141 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...to develop strategies to enhance immune checkpoint inhibition in kidney cancer . The work is designed to test different strategies to induce or

  2. Subendometrial enhancement and peritumoral enhancement for assessing endometrial cancer on dynamic contrast enhanced MR imaging.

    Science.gov (United States)

    Fujii, Shinya; Kido, Aki; Baba, Tsukasa; Fujimoto, Koji; Daido, Sayaka; Matsumura, Noriomi; Konishi, Ikuo; Togashi, Kaori

    2015-04-01

    To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1-46.4%, 85.8-88.5%, 69.2-76.5%, and 84.4-87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p<0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p<0.05) and depth (p<0.01). Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the overestimation by strong focal enhancement of PTE Type 1. PTE Type 2 correlates both with the presence and depth of myometrial invasion and also may play an important role in the diagnosis of LVSI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Subendometrial enhancement and peritumoral enhancement for assessing endometrial cancer on dynamic contrast enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Shinya [Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Yonago (Japan); Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kido, Aki, E-mail: akikido@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Baba, Tsukasa [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Fujimoto, Koji; Daido, Sayaka [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Matsumura, Noriomi; Konishi, Ikuo [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Togashi, Kaori [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2015-04-15

    Highlights: •We have assessed the peritumoral enhancement (PTE), which mimics SEE on DCE. •We evaluated the diagnostic accuracy of SEE for the myometrial invasion and the frequency of PTE. •We assessed the relationship between these enhancements and important pathologic factors. •PTE Type 1 is the main factor causing the overestimation of myometrial invasion using SEE on DCE. •PTE Type 2 correlates the myometrial invasion and may play an important role in the diagnosis of LVSI. -- Abstract: Objectives: To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. Materials and methods: MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1–46.4%, 85.8–88.5%, 69.2–76.5%, and 84.4–87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p < 0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p < 0.05) and depth (p < 0.01). Conclusion: Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the

  4. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images.

    Science.gov (United States)

    Gupta, Suneet; Porwal, Rabins

    2016-01-01

    Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  5. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images

    Directory of Open Access Journals (Sweden)

    Suneet Gupta

    2016-01-01

    Full Text Available Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  6. The Mycobacterium tuberculosis homologue of the Mycobacterium ...

    African Journals Online (AJOL)

    With the completion of genome sequencing of Mycobacterium tuberculosis and upsurge in the incidence of M. tuberculosis infection worldwide partly as a result of HIV pandemic, there is need for rationale approach to vaccine and chemotherapy discoveries for M. tuberculosis. The homologue of mig gene of. Mycobacterium ...

  7. Tailored Communication to Enhance Adaptation Across the Breast Cancer Spectrum

    Science.gov (United States)

    2007-10-01

    breast cancer communications to enhance screening adherence, decision-making, and quality of life across the spectrum of disease ( i . e . , from risk...breast cancer . Aim 2: To examine the moderating effects of individual differences in attentional style (i.e., high vs. low monitoring) on the impact...the CAP intervention. The session would conclude with a brief introduction to the Life After Cancer Treatment book that was sent to all participants

  8. Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis.

    Science.gov (United States)

    Roe, Jae-Seok; Hwang, Chang-Il; Somerville, Tim D D; Milazzo, Joseph P; Lee, Eun Jung; Da Silva, Brandon; Maiorino, Laura; Tiriac, Hervé; Young, C Megan; Miyabayashi, Koji; Filippini, Dea; Creighton, Brianna; Burkhart, Richard A; Buscaglia, Jonathan M; Kim, Edward J; Grem, Jean L; Lazenby, Audrey J; Grunkemeyer, James A; Hollingsworth, Michael A; Grandgenett, Paul M; Egeblad, Mikala; Park, Youngkyu; Tuveson, David A; Vakoc, Christopher R

    2017-08-24

    Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies, owing in part to its propensity for metastasis. Here, we used an organoid culture system to investigate how transcription and the enhancer landscape become altered during discrete stages of disease progression in a PDA mouse model. This approach revealed that the metastatic transition is accompanied by massive and recurrent alterations in enhancer activity. We implicate the pioneer factor FOXA1 as a driver of enhancer activation in this system, a mechanism that renders PDA cells more invasive and less anchorage-dependent for growth in vitro, as well as more metastatic in vivo. In this context, FOXA1-dependent enhancer reprogramming activates a transcriptional program of embryonic foregut endoderm. Collectively, our study implicates enhancer reprogramming, FOXA1 upregulation, and a retrograde developmental transition in PDA metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Enhancing photodynamic therapy of refractory solid cancers

    NARCIS (Netherlands)

    Weijer, R.

    2017-01-01

    Photodynamic therapy (PDT) is based on the activation of a photosensitizer by (laser) light to locally produce highly destructive reactive oxygen species. When employed for cancer treatment, PDT is able to induce tumor cell death, microvascular damage, and an anti-tumor immune response. All these

  10. Internet tools to enhance breast cancer care.

    Science.gov (United States)

    Shachar, Shlomit Strulov; Muss, Hyman B

    2016-01-01

    Internet tools have become a great aid in the daily practice of physicians who treat breast cancer patients. In cancer care there are frequent and important intersections where major decisions need to be made; these include (1) whether or not to give chemotherapy; (2) how much toxicity to expect, and (3) the life expectancy of the patient, considering non-breast cancer comorbidities. These decisions can be made more accurately using calculators based on data sets of thousands of patients as opposed to physician intuition. Such tools also help patients and caregivers in optimal decision making, as they estimate the absolute benefits and risks of treatment. In this perspective we describe selected internet sites that are useful across several domains of care, including the potential benefits of different adjuvant regimens for early breast cancer, prognosis after neoadjuvant therapy, prognosis for ductal carcinoma in situ, and toxicity and life expectancy estimates. We review the variables required to use the tools, the results obtained, the methods of validation, and the advantages and disadvantages of each tool.

  11. Photocatalyzing CO2 to CO for Enhanced Cancer Therapy.

    Science.gov (United States)

    Zheng, Di-Wei; Li, Bin; Li, Chu-Xin; Xu, Lu; Fan, Jin-Xuan; Lei, Qi; Zhang, Xian-Zheng

    2017-11-01

    Continuous exposure to carbon monoxide (CO) can sensitize cancer cells to chemotherapy while protect normal cells from apoptosis. The Janus face of CO thus provides an ideal strategy for cancer therapy. Here, a photocatalytic nanomaterial (HisAgCCN) is introduced to transform endogenous CO2 to CO for improving cancer therapy in vivo. The CO production rate of HisAgCCN reaches to 65 µmol h-1 gmat-1 , which can significantly increase the cytotoxicity of anticancer drug (doxorubicin, DOX) by 70%. Interestingly, this study finds that HisAgCCN can enhance mitochondria biogenesis and aggravate oxidative stress in cancer cells, whereas protect normal cells from chemotherapy-induced apoptosis as well. Proteomics and metabolomics studies reveal that HisAgCCN can enhance mitochondria biogenesis and aggravate oxidative stress in cancer cells specifically. In vivo studies indicate that HisAgCCN/DOX combination therapy presents a synergetic tumor inhibition, which might provide a new direction for clinical cancer therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Cognitive problems among breast cancer survivors: loneliness enhances risk.

    Science.gov (United States)

    Jaremka, Lisa M; Peng, Juan; Bornstein, Robert; Alfano, Catherine M; Andridge, Rebecca R; Povoski, Stephen P; Lipari, Adele M; Agnese, Doreen M; Farrar, William B; Yee, Lisa D; Carson, William E; Kiecolt-Glaser, Janice K

    2014-12-01

    Cancer survivors often experience cognitive difficulties after treatment completion. Although chemotherapy enhances risk for cognitive problems, it is likely only one piece of a complex puzzle that explains survivors' cognitive functioning. Loneliness may be one psychosocial risk factor. The current studies included both subjective and objective cognitive measures and tested whether lonelier breast cancer survivors would have more concentration and memory complaints and experience more concentration difficulties than their less lonely counterparts. The relationship between loneliness and cognitive function was tested among three samples of breast cancer survivors. Study 1 was a sample of breast cancer survivors (n = 200) who reported their concentration and memory problems. Study 2a was a sample of breast cancer survivors (n = 185) and noncancer controls (n = 93) who reported their concentration and memory problems. Study 2b was a subsample of Study 2a breast cancer survivors (n = 22) and noncancer controls (n = 21) who completed a standardized neuropsychological test assessing concentration. Studies 1 and 2a revealed that lonelier women reported more concentration and memory problems than less lonely women. Study 2b utilized a standardized neuropsychological continuous performance test and demonstrated that lonelier women experienced more concentration problems than their less lonely counterparts. These studies demonstrated that loneliness is linked to concentration and memory complaints and the experience of concentration problems among breast cancer survivors. The results were also highly consistent across three samples of breast cancer survivors. These data suggest that loneliness may be a risk factor for cognitive difficulties among cancer survivors. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Phosphatase and Tensin Homologue: Novel Regulation by Developmental Signaling

    Directory of Open Access Journals (Sweden)

    Travis J. Jerde

    2015-01-01

    Full Text Available Phosphatase and tensin homologue (PTEN is a critical cell endogenous inhibitor of phosphoinositide signaling in mammalian cells. PTEN dephosphorylates phosphoinositide trisphosphate (PIP3, and by so doing PTEN has the function of negative regulation of Akt, thereby inhibiting this key intracellular signal transduction pathway. In numerous cell types, PTEN loss-of-function mutations result in unopposed Akt signaling, producing numerous effects on cells. Numerous reports exist regarding mutations in PTEN leading to unregulated Akt and human disease, most notably cancer. However, less is commonly known about nonmutational regulation of PTEN. This review focuses on an emerging literature on the regulation of PTEN at the transcriptional, posttranscriptional, translational, and posttranslational levels. Specifically, a focus is placed on the role developmental signaling pathways play in PTEN regulation; this includes insulin-like growth factor, NOTCH, transforming growth factor, bone morphogenetic protein, wnt, and hedgehog signaling. The regulation of PTEN by developmental mediators affects critical biological processes including neuronal and organ development, stem cell maintenance, cell cycle regulation, inflammation, response to hypoxia, repair and recovery, and cell death and survival. Perturbations of PTEN regulation consequently lead to human diseases such as cancer, chronic inflammatory syndromes, developmental abnormalities, diabetes, and neurodegeneration.

  14. Enhanced MRI of breast cancer smaller than 3 cm

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Yukio; Yoshida, Shouji (Hyogo Medical Center for Adults (Japan)); Narabayashi, Isamu (and others)

    1991-11-01

    Twenty-two patients with breast cancers were studied using magnetic resonance (MR) imaging with a cylindrical surface coil at 1.5 Tesla. All were examined with the FE sequence and Gd-DTPA as a contrast medium. These images were compared with micrographs of the specimens. All cancers were enhanced clearly, and demarcated margins or spiculations of the tumors were seen as clearly on MR images as on micrographs of the specimens. In 12 patients (9 carcinomas, 2 fibroadenomas and 1 benign phyllodes tumor), dynamic studies were performed after the intravenous injection of Gd-DTPA. All nine carcinomas showed enhancement characterized by a sudden increase in signal intensity on the order of 100% or more with the first 2 minutes after injection. Two fibroadenomas were enhanced slowly. Thirteen patients with breast cancers were examined with several sequences (FE, T{sub 1}-weighted SE, T{sub 2}-weighted SE and STIR) with or without Gd-DTPA. The most clearly delineated images of the tumors were those of FE images with Gd-DTPA enhancement. A phantom constituted of various concentrations of Gd-DTPA in 20% albumin solution was measured by signal intensities with T{sub 1}-weighted SE sequence and FE sequence. The ratio of enhancement of the 20% albumin solution relative to the Gd-DTPA concentration was higher with the FE sequence than with the SE sequence. The sensitivity of the FE sequence to Gd-DTPA enhancement was 1.5 times that of the SE sequence under the usual concentration of Gd-DTPA. (author).

  15. MRI Background Parenchymal Enhancement Is Not Associated with Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Barbara Bennani-Baiti

    Full Text Available Previously, a strong positive association between background parenchymal enhancement (BPE at magnetic resonance imaging (MRI and breast cancer was reported in high-risk populations. We sought to determine, whether this was also true for non-high-risk patients.540 consecutive patients underwent breast MRI for assessment of breast findings (BI-RADS 0-5, non-high-risk screening (no familial history of breast cancer, no known genetic mutation, no prior chest irradiation, or previous breast cancer diagnosis and subsequent histological work-up. For this IRB-approved study, BPE and fibroglandular tissue FGT were retrospectively assessed by two experienced radiologists according to the BI-RADS lexicon. Pearson correlation coefficients were calculated to explore associations between BPE, FGT, age and final diagnosis of breast cancer. Subsequently, multivariate logistic regression analysis, considering covariate colinearities, was performed, using final diagnosis as the target variable and BPE, FGT and age as covariates.Age showed a moderate negative correlation with FGT (r = -0.43, p<0.001 and a weak negative correlation with BPE (r = -0.28, p<0.001. FGT and BPE correlated moderately (r = 0.35, p<0.001. Final diagnosis of breast cancer displayed very weak negative correlations with FGT (r = -0.09, p = 0.046 and BPE (r = -0.156, p<0.001 and weak positive correlation with age (r = 0.353, p<0.001. On multivariate logistic regression analysis, the only independent covariate for prediction of breast cancer was age (OR 1.032, p<0.001.Based on our data, neither BPE nor FGT independently correlate with breast cancer risk in non-high-risk patients at MRI. Our model retained only age as an independent risk factor for breast cancer in this setting.

  16. Expression of EZH2 and Ki-67 in colorectal cancer and associations with treatment response and prognosis

    NARCIS (Netherlands)

    Fluge, Ø.; Gravdal, K.; Carlsen, E.; Vonen, B.; Kjellevold, K.; Refsum, S.; Lilleng, R.; Eide, T.J.; Halvorsen, T.B.; Tveit, K.M.; Otte, A.P.; Akslen, L.A.; Dahl, O.

    2009-01-01

    Background: Enhancer of zeste homologue 2 (EZH2) is a member of the Polycomb group of genes that is involved in epigenetic silencing and cell cycle regulation. Methods: We studied EZH2 expression in 409 patients with colorectal cancer stages II and III. The patients were included in a randomised

  17. Enhanced Radiation Therapy of Gold Nanoparticles in Liver Cancer

    Directory of Open Access Journals (Sweden)

    Meili Guo

    2017-03-01

    Full Text Available Gold nanoparticles (GNPs were widely used in X-ray imaging and radiation therapy due to strong photoelectric effects and secondary electrons under high energy irradiation. As liver cancer is one of the most common forms of cancer, the use of GNPs could enhance liver cancer radiotherapy. We synthesized polyethylene glycol (PEG-coated GNPs of two different sizes by chemical reduction reaction. Blood stability, cellular uptake, cytotoxicity and radiation therapy were investigated. A 3–5 nm red shift of SPR caused by interactions between PEG-coated GNPs and plasma indicated their good stability. Cellular uptake assay showed that PEG-coated GNPs would enhance an appreciable uptake. GNPs preferred to combine with blood proteins, and thus induced the formation of 30–50 nm Au-protein corona. GNPs were endocytosed by cytoplasmic vesicles, localized in intracellular region, and presented concentration dependent cell viability. Clonogenic assay illustrated that the PEG-coated GNPs could sensitize two liver cancer cell lines to irradiation.

  18. Natural killer cells enhance the immune surveillance of cancer

    Directory of Open Access Journals (Sweden)

    Faisal Nouroz

    2016-04-01

    Full Text Available Immune system (IS is comprised of molecules, cells, tissues and organs involved in host defense mechanism from infectious agents or tumor cells. On crossing the cell barriers by these infectious agents, the defense mechanism is alerted by the immune system to respond against these invading microbes. Innate immune response (IIR and acquired immune response (AIR are working in parallel to control these invading microbes. IIR is composed of various types of phagocytes and lymphocytes, while AIR is comprised of T and B lymphocytes. All the cells of the immune system cooperatively work against infectious agents and cancerous cells but Natural killer (NK cells are playing an important role to respond to tumor by enhancing the expression of complementary domain (CD86 on dendritic cells (DCs and production of IL-12. NK cells demolished tumor through perforin and granzyme, which are important for immune surveillance and death of tumor cells induced by cytokines such as tumor necrosis factor (TNF, Fas ligand (CD178, interferon-γ (IFN-γ and IL-10. These cytokines have inhibited proliferation of tumor by inducing anti-angiogenic factors and maintaining cross talk with other immune cells. Natural products like transfer factor plus, immune modulator mix, ascorbic acid, Ganoderma lucidum, Agaricus blazei teas, nitrogenated soy extract, Andrographis paniculata and several phytochemicals enhanced the efficiency of NK cells in controlling cancers. Further studies will unravel the impact of NK cells in cancer control and how NK efficiency can be further enhanced.

  19. LIGHT Elevation Enhances Immune Eradication of Colon Cancer Metastases.

    Science.gov (United States)

    Qiao, Guilin; Qin, Jianzhong; Kunda, Nicholas; Calata, Jed F; Mahmud, Dolores L; Gann, Peter; Fu, Yang-Xin; Rosenberg, Steven A; Prabhakar, Bellur S; Maker, Ajay V

    2017-04-15

    The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could empower antitumor immune responses in this setting remain to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor cell-specific antitumor immune responses. In this model, increasing LIGHT expression in the microenvironment of either primary tumors or liver metastases triggered regression of established tumors and slowed the growth of liver metastases, driven by cytotoxic T-lymphocyte-mediated antitumor immunity. These responses corresponded with significant increases in tumor-infiltrating lymphocytes and increased expression of lymphocyte-homing signals in the metastatic tumors. Furthermore, we demonstrated evidence of durable tumor-specific antitumor immunity. In conclusion, increasing LIGHT expression increased T-cell proliferation, activation, and infiltration, resulting in enhanced tumor-specific immune-mediated tumor regressions in primary tumors and colorectal liver metastases. Mechanisms to increase LIGHT in the colon cancer microenvironment warrant further investigation and hold promise as an immunotherapeutic strategy. Cancer Res; 77(8); 1880-91. ©2017 AACR. ©2017 American Association for Cancer Research.

  20. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells.

    Science.gov (United States)

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-12

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na⁺/H⁺ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal-regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors.

  1. Characterization of the C. elegans erlin homologue

    Directory of Open Access Journals (Sweden)

    Hoegg Maja B

    2012-01-01

    Full Text Available Abstract Background Erlins are highly conserved proteins associated with lipid rafts within the endoplasmic reticulum (ER. Biochemical studies in mammalian cell lines have shown that erlins are required for ER associated protein degradation (ERAD of activated inositol-1,4,5-trisphosphate receptors (IP3Rs, implying that erlin proteins might negatively regulate IP3R signalling. In humans, loss of erlin function appears to cause progressive intellectual disability, motor dysfunction and joint contractures. However, it is unknown if defects in IP3R ERAD are the underlying cause of this disease phenotype, whether ERAD of activated IP3Rs is the only function of erlin proteins, and what role ERAD plays in regulating IP3R-dependent processes in the context of an intact animal or embryo. In this study, we characterize the erlin homologue of the nematode Caenorhabditis elegans and examine erlin function in vivo. We specifically set out to test whether C. elegans erlin modulates IP3R-dependent processes, such as egg laying, embryonic development and defecation rates. We also explore the possibility that erlin might play a more general role in the ERAD pathway of C. elegans. Results We first show that the C. elegans erlin homologue, ERL-1, is highly similar to mammalian erlins with respect to amino acid sequence, domain structure, biochemical properties and subcellular location. ERL-1 is present throughout the C. elegans embryo; in adult worms, ERL-1 appears restricted to the germline. The expression pattern of ERL-1 thus only partially overlaps with that of ITR-1, eliminating the possibility of ERL-1 being a ubiquitous and necessary regulator of ITR-1. We show that loss of ERL-1 does not affect overall phenotype, or alter brood size, embryonic development or defecation cycle length in either wild type or sensitized itr-1 mutant animals. Moreover we show that ERL-1 deficient worms respond normally to ER stress conditions, suggesting that ERL-1 is not an

  2. Cancer imaging using surface-enhanced resonance Raman scattering nanoparticles.

    Science.gov (United States)

    Harmsen, Stefan; Wall, Matthew A; Huang, Ruimin; Kircher, Moritz F

    2017-07-01

    The unique spectral signatures and biologically inert compositions of surface-enhanced resonance Raman scattering (SERRS) nanoparticles make them promising contrast agents for in vivo cancer imaging. Our SERRS nanoparticles consist of a 60-nm gold nanoparticle core that is encapsulated in a 15-nm-thick silica shell wherein the resonant Raman reporter is embedded. Subtle aspects of their preparation can shift their limit of detection by orders of magnitude. In this protocol, we present the optimized, step-by-step procedure for generating reproducible SERRS nanoparticles with femtomolar (10-15 M) limits of detection. We provide ways of characterizing the optical properties of SERRS nanoparticles using UV/VIS and Raman spectroscopy, and their physicochemical properties using transmission electron microscopy and nanoparticle tracking analysis. We introduce several applications of these nanoprobes for biomedical research, with a focus on intraoperative cancer imaging via Raman imaging. A detailed account is provided for successful i.v. administration of SERRS nanoparticles such that delineation of cancerous lesions can be achieved in vivo and ex vivo on resected tissues without the need for specific biomarker targeting. This straightforward, yet comprehensive, protocol-from initial de novo gold nanoparticle synthesis to SERRS nanoparticle contrast-enhanced preclinical Raman imaging in animal models-takes ∼96 h.

  3. Mammographic density, MRI background parenchymal enhancement and breast cancer risk.

    Science.gov (United States)

    Pike, M C; Pearce, C L

    2013-11-01

    Mammographic density (MD), representing connective and epithelial tissue (fibroglandular tissue, FGT) is a major risk factor for breast cancer. In an analysis of an autopsy series (Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease. Cancer 1990; 66: 1721-1725, Bartow SA, Pathak DR, Mettler FA et al. Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors. Am J Epidemiol 1995; 142: 813-819), MD was found to be strongly correlated with the collagen and epithelial content of the breast (Li T, Sun L, Miller N et al. The association of measured breast tissue characteristics with MD and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 343-349), and another report showed that breast epithelium was highly concentrated in the areas of collagen concentration (Hawes D, Downey S, Pearce CL et al. Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity. Breast Cancer Res 2006; 8: R24). Collagen comprises the overwhelming majority of the FGT, occupying an area on the slides obtained from the autopsy series some 15 times the area of glandular tissue. The relationship of MD with breast cancer risk appears likely to be due to a major extent to increasing epithelial cell numbers with increasing MD. FGT is also seen in breast magnetic resonance imaging (breast MRI) and, as expected, it has been shown that this measure of FGT (MRI-FGT) is highly correlated with MD. A contrast-enhanced breast MRI shows that normal FGT 'enhances' (background parenchymal enhancement, BPE) after contrast agent is administered(Morris EA. Diagnostic breast MR imaging: current status and future directions. Radiol Clin North Am 2007; 45: 863-880, vii., Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic

  4. Is the prosthetic homologue necessary for embodiment?

    Directory of Open Access Journals (Sweden)

    Chelsea Dornfeld

    2016-12-01

    Full Text Available Embodiment is the process by which patients with limb loss come to accept their peripheral device as a natural extension of self. However, there is little guidance as to how exacting the prosthesis must be in order for embodiment to take place: is it necessary for the prosthetic hand to look just like the absent hand? Here, we describe a protocol for testing whether an individual would select a hand that looks like their own from among a selection of 5 hands, and whether the hand selection (regardless of homology is consistent across multiple exposures to the same (but reordered set of candidate hands. Pilot results using healthy volunteers reveals that hand selection is only modestly consistent, and that selection of the prosthetic homologue is atypical (61 of 192 total exposures. Our protocol can be executed in minutes, and makes use of readily available equipment and softwares. We present both a face-to-face and a virtual protocol, for maximum flexibility of implementation.

  5. Enhancing circadian clock function in cancer cells inhibits tumor growth.

    Science.gov (United States)

    Kiessling, Silke; Beaulieu-Laroche, Lou; Blum, Ian D; Landgraf, Dominic; Welsh, David K; Storch, Kai-Florian; Labrecque, Nathalie; Cermakian, Nicolas

    2017-02-14

    Circadian clocks control cell cycle factors, and circadian disruption promotes cancer. To address whether enhancing circadian rhythmicity in tumor cells affects cell cycle progression and reduces proliferation, we compared growth and cell cycle events of B16 melanoma cells and tumors with either a functional or dysfunctional clock. We found that clock genes were suppressed in B16 cells and tumors, but treatments inducing circadian rhythmicity, such as dexamethasone, forskolin and heat shock, triggered rhythmic clock and cell cycle gene expression, which resulted in fewer cells in S phase and more in G1 phase. Accordingly, B16 proliferation in vitro and tumor growth in vivo was slowed down. Similar effects were observed in human colon carcinoma HCT-116 cells. Notably, the effects of dexamethasone were not due to an increase in apoptosis nor to an enhancement of immune cell recruitment to the tumor. Knocking down the essential clock gene Bmal1 in B16 tumors prevented the effects of dexamethasone on tumor growth and cell cycle events. Here we demonstrated that the effects of dexamethasone on cell cycle and tumor growth are mediated by the tumor-intrinsic circadian clock. Thus, our work reveals that enhancing circadian clock function might represent a novel strategy to control cancer progression.

  6. Pulsed Ultrasound Enhances Nanoparticle Penetration into Breast Cancer Spheroids

    Science.gov (United States)

    Grainger, Stephanie J.; Serna, Juliana Valencia; Sunny, Steffi; Zhou, Yun; Deng, Cheri X.; El-Sayed, Mohamed E.H.

    2010-01-01

    Effective treatment of solid tumors requires homogenous distribution of anticancer drugs within the entire tumor volume to deliver lethal concentrations to resistant cancer cells and tumor-initiating cancer stem cells. However, penetration of small molecular weight chemotherapeutic agents and drug-loaded polymeric and lipid particles into the hypoxic and necrotic regions of solid tumors remains a significant challenge. This article reports the results of pulsed ultrasound enhanced penetration of nano-sized fluorescent particles into MCF-7 breast cancer spheroids (300-350 μm diameter) as a function of particle size and charge. With pulsed ultrasound application in the presence of microbubbles, small (20 nm) particles achieve 6-20 folds higher penetration and concentration in the spheroid's core compared to those not exposed to ultrasound. Increase in particle size to 40 nm and 100 nm results in their effective penetration into the spheroid's core to 9 and 3 folds, respectively. In addition, anionic carboxylate particles achieved higher penetration (2.3, 3.7, and 4.7 folds) into the core (0.25r) of MCF-7 breast cancer spheroids compared to neutral (2.2, 1.9, and 2.4 folds) and cationic particles (1.5, 1.4 and 1.9 folds) upon US exposure for 30, 60, and 90 seconds under the same experimental conditions. These results demonstrate the feasibility of utilizing pulsed ultrasound to increase the penetration of nano-sized particles into MCF-7 spheroids mimicking tumor tissue. The effects of particle properties on the penetration enhancement were also illustrated. PMID:20957996

  7. Dynamic Contrast-Enhanced CT in Patients with Pancreatic Cancer

    DEFF Research Database (Denmark)

    Eriksen, Rie Ø; Strauch, Louise S; Sandgaard, Michael

    2016-01-01

    The aim of this systematic review is to provide an overview of the use of Dynamic Contrast-enhanced Computed Tomography (DCE-CT) in patients with pancreatic cancer. This study was composed according to the PRISMA guidelines 2009. The literature search was conducted in PubMed, Cochrane Library...... tissue, compared with measurements in pancreatic tissue outside of tumor, or normal pancreatic tissue in control groups of healthy volunteers. The studies were heterogeneous in the number of patients enrolled and scan protocols. Perfusion parameters measured and analyzed by DCE-CT might be useful...

  8. Mammographic density, MRI background parenchymal enhancement and breast cancer risk

    Science.gov (United States)

    Pike, M. C.; Pearce, C. L.

    2013-01-01

    Mammographic density (MD), representing connective and epithelial tissue (fibroglandular tissue, FGT) is a major risk factor for breast cancer. In an analysis of an autopsy series (Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification and parenchymal patterns as indicators of histologic “high-risk” benign breast disease. Cancer 1990; 66: 1721–1725, Bartow SA, Pathak DR, Mettler FA et al. Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors. Am J Epidemiol 1995; 142: 813–819), MD was found to be strongly correlated with the collagen and epithelial content of the breast (Li T, Sun L, Miller N et al. The association of measured breast tissue characteristics with MD and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 343–349), and another report showed that breast epithelium was highly concentrated in the areas of collagen concentration (Hawes D, Downey S, Pearce CL et al. Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity. Breast Cancer Res 2006; 8: R24). Collagen comprises the overwhelming majority of the FGT, occupying an area on the slides obtained from the autopsy series some 15 times the area of glandular tissue. The relationship of MD with breast cancer risk appears likely to be due to a major extent to increasing epithelial cell numbers with increasing MD. FGT is also seen in breast magnetic resonance imaging (breast MRI) and, as expected, it has been shown that this measure of FGT (MRI-FGT) is highly correlated with MD. A contrast-enhanced breast MRI shows that normal FGT ‘enhances’ (background parenchymal enhancement, BPE) after contrast agent is administered(Morris EA. Diagnostic breast MR imaging: current status and future directions. Radiol Clin North Am 2007; 45: 863–880, vii., Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation

  9. Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Zhen Hua Wu

    Full Text Available The major challenges we are facing in cancer therapy with paclitaxel (PTX are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ, an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP, an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.

  10. Hypopharyngeal cancer associated with synchronous oesophageal cancer: risk factors and benefits of image-enhanced endoscopic screening.

    Science.gov (United States)

    Ni, X-G; Zhang, Q-Q; Zhu, J-Q; Wang, G-Q

    2017-12-14

    To explore the risk factors associated with the occurrence of synchronous oesophageal cancer in patients with hypopharyngeal cancer, and to investigate the roles of image-enhanced endoscopic screening in the prediction and diagnosis of early oesophageal cancer. The clinical characteristics of patients with hypopharyngeal cancer (n = 160) were analysed. All patients underwent laryngoscopic and gastroscopic examination using image-enhanced endoscopic techniques before treatment. Of 160 hypopharyngeal cancer patients, 43 (27 per cent) had synchronous oesophageal cancer. Heavy drinking (odds ratio = 4.787, p = 0.029) and local invasion of three or more anatomical sites (odds ratio = 14.391, p = 0.000) were independent risk factors for synchronous oesophageal cancer. Narrow-band imaging laryngoscopy could detect more invaded anatomical sites than ordinary white light endoscopy (t = 8.532, p = 0.000). More early oesophageal cancer cases were detected with Lugol chromoendoscopy than with non-Lugol iodine staining examination (χ2 = 4.925, p = 0.026). Synchronous oesophageal cancer is common in patients with hypopharyngeal cancer. The heavy drinking patients with hypopharyngeal cancer should undergo intensive monitoring. Image-enhanced endoscopic screening is helpful in the prediction and early detection of second primary oesophageal cancer.

  11. 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.

  12. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  13. Autologous Immune Enhancement Therapy for Cancer - Our experience since 2004

    Directory of Open Access Journals (Sweden)

    Hiroshi Terunuma

    2012-01-01

    Full Text Available Cancer, the major killer disease of the century requires a multi-pronged approach and among the latest modalities of treatments, Immunotherapy occupies a promising role. Immunotherapy for cancer was first started to be practised in the NIH and cell based immunotherapy for cancer is in practice for the past three decades. [1, 2] There are several literatures from various countries on the successful application of cell based Immunotherapies for various solid tumours and haematological malignancies. [3-8] Our team’s association with immune cells started when I was working on RNA transcriptome analysis to understand the immune system in HIV carriers which in turn required in vitro expansion of human Natural Killer (NK cells. [9] This led to the customization of protocols which has resulted in successful in vitro expansion, activation of NK cells and T cells for Immunotherapy. The purpose of Biotherapy institute of Japan (BIJ is to support research and clinical application of immune cells like NK cells, γδT cells, αβT cells, Cytotoxic T lymphocytes (CTL and Dendritic cells (DC for application as Autologous Immune Enhancement Therapy (AIET to fight against cancer. AIET using NK cells, CTLs, DCs etc have been administered for more than 5000 patients since 2004 till date by BIJ. Principle of AIET: For AIET using NK cells, the process involves separation of lymphocytes from the peripheral blood of the patient followed by selective NK cell expansion using the expansion kit (BINKIT, BIJ, JAPAN without feeder layers and then infusion of the expanded-activated NK cells. [10,11] As reports suggest that the activity of peripheral blood NK cells are lower in cancer patients compared to normal individuals [12] and as in vitro expansion of NK cells increases the cytotoxic ability 5 to 10 fold, [13] the NK cells are expanded in vivo and then infused to the patient in AIET. We are also working on combination immunotherapy using NK cells and CTLs and also NK

  14. Interventions to enhance return-to-work for cancer patients.

    Science.gov (United States)

    de Boer, Angela G E M; Taskila, Tyna K; Tamminga, Sietske J; Feuerstein, Michael; Frings-Dresen, Monique H W; Verbeek, Jos H

    2015-09-25

    Cancer patients are 1.4 times more likely to be unemployed than healthy people. Therefore it is important to provide cancer patients with programmes to support the return-to-work (RTW) process. This is an update of a Cochrane review first published in 2011. To evaluate the effectiveness of interventions aimed at enhancing RTW in cancer patients compared to alternative programmes including usual care or no intervention. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, in the Cochrane Library Issue 3, 2014), MEDLINE (January 1966 to March 2014), EMBASE (January 1947 to March 2014), CINAHL (January 1983 to March, 2014), OSH-ROM and OSH Update (January 1960 to March, 2014), PsycINFO (January 1806 to 25 March 2014), DARE (January 1995 to March, 2014), ClinicalTrials.gov, Trialregister.nl and Controlled-trials.com up to 25 March 2014. We also examined the reference lists of included studies and selected reviews, and contacted authors of relevant studies. We included randomised controlled trials (RCTs) of the effectiveness of psycho-educational, vocational, physical, medical or multidisciplinary interventions enhancing RTW in cancer patients. The primary outcome was RTW measured as either RTW rate or sick leave duration measured at 12 months' follow-up. The secondary outcome was quality of life. Two review authors independently assessed trials for inclusion, assessed the risk of bias and extracted data. We pooled study results we judged to be clinically homogeneous in different comparisons reporting risk ratios (RRs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence for each comparison using the GRADE approach. Fifteen RCTs including 1835 cancer patients met the inclusion criteria and because of multiple arms studies we included 19 evaluations. We judged six studies to have a high risk of bias and nine to have a low risk of bias. All included studies were conducted in high income countries and most studies were

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

    Science.gov (United States)

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

    2015-10-24

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

  16. Detection of a Yersinia pestis gene homologue in rodent samples

    Directory of Open Access Journals (Sweden)

    Timothy A. Giles

    2016-08-01

    Full Text Available A homologue to a widely used genetic marker, pla, for Yersinia pestis has been identified in tissue samples of two species of rat (Rattus rattus and Rattus norvegicus and of mice (Mus musculus and Apodemus sylvaticus using a microarray based platform to screen for zoonotic pathogens of interest. Samples were from urban locations in the UK (Liverpool and Canada (Vancouver. The results indicate the presence of an unknown bacterium that shares a homologue for the pla gene of Yersinia pestis, so caution should be taken when using this gene as a diagnostic marker.

  17. Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression

    Directory of Open Access Journals (Sweden)

    Gutierrez-Hartmann Arthur

    2011-06-01

    expressing all GFP-LIMK1 fusions, compared to GFP alone. Invasion assays revealed that all GFP-LIMK1 fusions increased MDA-MB-231 cell invasion ~1.5-fold, compared to GFP-only control cells. Tumor xenograft studies in nude mice revealed that MDA-MB-231 cells stably expressing GFP-LIMK, NLS-GFP-LIMK1 and NES-GFP-LIMK1 enhanced tumor growth 2.5-, 1.6- and 4.7-fold, respectively, compared to GFP-alone. Conclusion Taken together, these data demonstrate that LIMK1 activity in both the cytoplasmic and nuclear compartments promotes breast cancer progression, underscoring that nuclear LIMK1 contributes to the transforming function of LIMK1.

  18. TPP1 is a homologue of ciliate TEBP-β and interacts with POT1 to recruit telomerase

    Science.gov (United States)

    Xin, Huawei; Liu, Dan; Wan, Ma; Safari, Amin; Kim, Hyeung; Sun, Wen; O'Connor, Matthew S.; Songyang, Zhou

    2007-02-01

    Telomere dysfunction may result in chromosomal abnormalities, DNA damage responses, and even cancer. Early studies in lower organisms have helped to establish the crucial role of telomerase and telomeric proteins in maintaining telomere length and protecting telomere ends. In Oxytricha nova, telomere G-overhangs are protected by the TEBP-α/β heterodimer. Human telomeres contain duplex telomeric repeats with 3' single-stranded G-overhangs, and may fold into a t-loop structure that helps to shield them from being recognized as DNA breaks. Additionally, the TEBP-α homologue, POT1, which binds telomeric single-stranded DNA (ssDNA), associates with multiple telomeric proteins (for example, TPP1, TIN2, TRF1, TRF2 and RAP1) to form the six-protein telosome/shelterin and other subcomplexes. These telomeric protein complexes in turn interact with diverse pathways to form the telomere interactome for telomere maintenance. However, the mechanisms by which the POT1-containing telosome communicates with telomerase to regulate telomeres remain to be elucidated. Here we demonstrate that TPP1 is a putative mammalian homologue of TEBP-β and contains a predicted amino-terminal oligonucleotide/oligosaccharide binding (OB) fold. TPP1-POT1 association enhanced POT1 affinity for telomeric ssDNA. In addition, the TPP1 OB fold, as well as POT1-TPP1 binding, seemed critical for POT1-mediated telomere-length control and telomere-end protection in human cells. Disruption of POT1-TPP1 interaction by dominant negative TPP1 expression or RNA interference (RNAi) resulted in telomere-length alteration and DNA damage responses. Furthermore, we offer evidence that TPP1 associates with the telomerase in a TPP1-OB-fold-dependent manner, providing a physical link between telomerase and the telosome/shelterin complex. Our findings highlight the critical role of TPP1 in telomere maintenance, and support a yin-yang model in which TPP1 and POT1 function as a unit to protect human telomeres, by both

  19. IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer.

    Science.gov (United States)

    Felices, M; Chu, S; Kodal, B; Bendzick, L; Ryan, C; Lenvik, A J; Boylan, K L M; Wong, H C; Skubitz, A P N; Miller, J S; Geller, M A

    2017-06-01

    Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Neurospora crassa fmf-1 encodes the homologue of the ...

    Indian Academy of Sciences (India)

    Neurospora crassa fmf-1 encodes the homologue of the. Schizosaccharomyces pombe Ste11p regulator of sexual development. Srividhya V. Iyer, Mukund Ramakrishnan and Durgadas P. Kasbekar. J. Genet. 88, 33–39. Figure 1. Sequence at the junction of the proximal breakpoint of T(AR173) has homology with Cen-VII ...

  1. Cloning and expression analysis of a partial LEAFY homologue from ...

    African Journals Online (AJOL)

    A partial homologue of LEAFY, designated as AcLFY (Genebank accession no HQ433335), was isolated from pineapple (Ananas comosus L. cv. Comte de Paris) by PCR. The conserved cDNA fragment of AcLFY is 256 bp in length and contained an open reading frame of 248 bp, which encodes 82 amino acids protein.

  2. Isolation and characterization of an AGAMOUS homologue from cocoa

    NARCIS (Netherlands)

    Chaidamsari, T.; Sugiarit, H.; Santoso, D.; Angenent, G.C.; Maagd, de R.A.

    2006-01-01

    We report the cloning of a cDNA from TcAG, an AG (Arabidopsis thaliana MADS-box C-type transcription factor gene AGAMOUS) homologue from cocoa (Theobroma cacao L.). TcAG was in the cocoa flower expressed primarily in stamens and ovaries, comparable to AG in Arabidopsis. Additionally, we found that

  3. A homologue of the defender against the apoptotic death gene ...

    Indian Academy of Sciences (India)

    The 327 bp transcript showed an open reading frame of 87 amino acid residues. The deduced amino acid sequence of the putative C. reinhardtii DAD1 homologue showed 54% identity with Oryza sativa, 56% identity with Drosophila melanogaster, 66% identity with Xenopus laevis, and 64% identity with Homo sapiens, Sus ...

  4. Characterization and cloning of TMV resistance gene N homologues ...

    African Journals Online (AJOL)

    Tobacco cultivars Nicotiana tabacum cv. Samsun NN plants carrying the N gene contain a multitude of N-related genes. We cloned a few N homologues and isolated two full-length cDNAs of NL-C26 and NL-B69 genes from N. tabacum cv. Samsun NN. Nucleotide sequence analysis showed that the coding regions of ...

  5. Breast cancer cells induce cancer-associated fibroblasts to secrete hepatocyte growth factor to enhance breast tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Shiaw-Wei Tyan

    2011-01-01

    Full Text Available It has been well documented that microenvironment consisting of stroma affects breast cancer progression. However, the mechanisms by which cancer cells and fibroblasts, the major cell type in stroma, interact with each other during tumor development remains to be elucidated. Here, we show that the human cancer-associated fibroblasts (CAFs had higher activity in enhancing breast tumorigenecity compared to the normal tissue-associated fibroblasts (NAFs isolated from the same patients. The expression level of hepatocyte growth factor (HGF in these fibroblasts was positively correlated with their ability to enhance breast tumorigenesis in mice. Deprivation of HGF using a neutralizing antibody reduced CAF-mediated colony formation of human breast cancer cells, indicating that CAFs enhanced cancer cell colony formation mainly through HGF secretion. Co-culture with human breast cancer MDA-MB-468 cells in a transwell system enhanced NAFs to secret HGF as well as promote tumorigenecity. The newly gained ability of these "educated" NAFs became irreversible after continuing this process till fourth passage. These results suggested that breast cancer cells could alter the nature of its surrounding fibroblasts to secrete HGF to support its own progression through paracrine signaling.

  6. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

    Directory of Open Access Journals (Sweden)

    Nicolas D. Prionas, MD, PhD

    2015-01-01

    Full Text Available Dedicated breast computed tomography (bCT generates high-resolution, three-dimensional images of the pendent uncompressed breast. Intravenous iodinated contrast during bCT provides additional physiologic information. In this case, a 10.0-mm invasive ductal carcinoma was visualized using contrast-enhanced breast CT one year before mammographic detection. Mammography four months before bCT was negative. The bCT contrast enhancement pattern closely matched the dynamic contrast-enhanced MRI obtained after diagnosis. Lesion enhancement at contrast-enhanced breast CT matched previously published enhancement values of breast cancer. Contrast-enhanced dedicated bCT provided high-resolution tomographic images and physiologic contrast enhancement data that facilitated the detection of an early breast cancer.

  7. Multifunctional liposomes for enhanced anti-cancer therapy

    Science.gov (United States)

    Falcao, Claudio Borges

    2011-12-01

    with half of the concentration needed for G3139 alone in CL to reduce the cell viability by 40%. Also, it was found greater apoptotic signal in cells treated with CLs containing D-(KLAKLAK)2/G3139 complexes than CLs with G3139 only. In vivo, D-(KLAKLAK) 2/G3139 complexes in CL significantly inhibited tumor growth compared to the saline treated group, through apoptosis induction. However, the mechanism involved in cell death by apoptosis seems to be independent of reduction of bcl-2 protein levels. PEG2000 at 1% mol could significantly reduce activity of PCL formulation towards B16(F10) cells compared to CLs. After pre-incubation at pH 7.4, PCL and pH-PCL had decreased activity compared to CL towards B16(F10) cells. After pre-incubation at pH 5.0, while CL and PCL had the same activity with the cells as in neutral pH, pH-PCL formulation had its PEG cleaved and its cytotoxicity was restored against the melanoma cells. Thus, D-(KLAKLAK)2/G3139 complexes in CL had enhanced anti-cancer therapy, through apoptosis, than G3139 alone in CL in vitro and in vivo. In vitro, PCL and pH-PCL particles obtained can have a prolonged blood residence time, and, once a tumor tissue is reached, pH-PCL can have its cytotoxicity restored because of hydrolysis of cleavable PEG at a lowered pH.

  8. Metformin enhances radiosensitivity via inhibition of DNA repair pathway in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Youn Kyoung; Kim, Mi Sook; Lee, Ji Young; Song, Kyung Hee; Choi, Kyul; Kim, Eun Ho; Ha, Hun Joo [Ewha Womans University, Seoul (Korea, Republic of)

    2014-04-15

    In this study, we provide a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer. Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. Currently, it is one of the commonest chemoradiotherapy worked better than the radiotherapy or chemotherapy in colorectal cancer. To enhance radiosensitivity of tumor cells for chemoradiotherapy, it is to use potential anticancer agents that act as radiosensitizers. Metformin, one of the most widely used antidiabetic drugs, has recently been associated with potential antitumorigenic effects. Our data shows that metformin combined with radiation enhances the efficacy of radiotherapy and down-regulates DNA repair proteins. Therefore, we provides a scientific rationale for the clinical application of metformin as a radiosensitizer in colorectal cancer.

  9. Intervention to Enhance Empowerment in Breast Cancer Self-Help Groups

    OpenAIRE

    Stang, Ingun; Mittelmark, Maurice B

    2010-01-01

    As arduous psychological reactions and loss of control almost inevitably represent a challenge for women diagnosed and treated for breast cancer, a participatory intervention study was initiated that aimed to enhance empowerment in breast cancer self-help groups. Women newly diagnosed with breast cancer were invited to participate. The intervention encompassed three professionally led self-help groups running sequentially, each group for approximately four months. Each group of...

  10. Dynamic contrast-enhanced MRI for monitoring response to neoadjuvant chemotherapy in breast cancer

    NARCIS (Netherlands)

    Loo, C.E.

    2016-01-01

    The general aim of this thesis is to investigate the role of dynamic contrast-enhanced MRI in monitoring response of breast cancer during neoadjuvant chemotherapy. The role of MRI with respect to achieving personalized breast cancer treatment by improving response monitoring is examined. Our

  11. Association between Parenchymal Enhancement of the Contralateral Breast in Dynamic Contrast-enhanced MR Imaging and Outcome of Patients with Unilateral Invasive Breast Cancer

    NARCIS (Netherlands)

    van der Velden, Bas; Dmitriev, Ivan; Loo, C.E.; Pijnappel, Ruud; Gilhuijs, Kenneth

    2015-01-01

    Purpose To retrospectively investigate whether parenchymal enhancement in dynamic contrast material–enhanced magnetic resonance (MR) imaging of the contralateral breast in patients with unilateral invasive breast cancer is associated with therapy outcome. Materials and Methods After obtaining

  12. Monolayer structures of alkyl aldehydes: Odd-membered homologues

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, T.K. [BP Institute, Department of Chemistry, University of Cambridge, Cambridge (United Kingdom); Clarke, S.M., E-mail: stuart@bpi.cam.ac.u [BP Institute, Department of Chemistry, University of Cambridge, Cambridge (United Kingdom); Bhinde, T. [BP Institute, Department of Chemistry, University of Cambridge, Cambridge (United Kingdom); Castro, M.A.; Millan, C. [Instituto Ciencia de los Materiales de Sevilla, Departamento de Quimica Inorganica (CSIC-Universidad de Sevilla) (Spain); Medina, S. [Centro de Investigacion, Tecnologia e Innovacion de la Universidad de Sevilla (CITIUS), Sevilla (Spain)

    2011-03-01

    Crystalline monolayers of three aldehydes with an odd number of carbon atoms in the alkyl chain (C{sub 7}, C{sub 9} and C{sub 11}) at low coverages are observed by a combination of X-ray and neutron diffraction. Analysis of the diffraction data is discussed and possible monolayer crystal structures are proposed; although unique structures could not be ascertained for all molecules. We conclude that the structures are flat on the surface, with the molecules lying in the plane of the layer. The C{sub 11} homologue is determined to have a plane group of either p2, pgb or pgg, and for the C{sub 7} homologue the p2 plane group is preferred.

  13. Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Zhengzhi, E-mail: zouzhengzhi@m.scnu.edu.cn [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000 (China); Luo, Xiaoyong [Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang 471000 (China); Nie, Peipei [KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510000 (China); Wu, Baoyan; Zhang, Tao; Wei, Yanchun [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000 (China); Wang, Wenyi [Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China); Geng, Guojun; Jiang, Jie [Xiamen Cancer Center, Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China); Mi, Yanjun, E-mail: myjgj_77@163.com [Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China)

    2016-09-09

    SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuating AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies. - Highlights: • Depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors. • Overexpression of SRC-3 enhanced cancer cell resistance to HDAC inhibitors. • SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. • Bufalin synergized with HDAC inhibitor attenuated AKT activation and reduced Bcl-2 levels in human cancer cell.

  14. Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

    2011-08-05

    Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

  15. Natural killer cells enhance the immune surveillance of cancer

    African Journals Online (AJOL)

    Faisal Nouroz

    2015-09-11

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

  16. Tailored Communication to Enhance Adaption Across the Breast Cancer Spectrum

    Science.gov (United States)

    2005-10-01

    information script is generated covering such topics as diet, dietary supplements and exercise. The Project Coordinator reviews each script to ensure...study protocols related to breast cancer survivorship and lymphedema . She continues to collect data on women diagnosed with early stage breast cancer

  17. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

    2010-01-01

    can be achieved using epigenetic modifiers. AREAS COVERED IN THIS REVIEW: We provide an overview of the potential of CG antigens as targets for cancer immunotherapy, including advantages and disadvantages. We also discuss the current state of development of CG antigen vaccines, and the potential...... antigen vaccines may be a useful approach for treating cancer....

  18. Signal enhancement ratio (SER) quantified from breast DCE-MRI and breast cancer risk

    Science.gov (United States)

    Wu, Shandong; Kurland, Brenda F.; Berg, Wendie A.; Zuley, Margarita L.; Jankowitz, Rachel C.; Sumkin, Jules; Gur, David

    2015-03-01

    Breast magnetic resonance imaging (MRI) is recommended as an adjunct to mammography for women who are considered at elevated risk of developing breast cancer. As a key component of breast MRI, dynamic contrast-enhanced MRI (DCE-MRI) uses a contrast agent to provide high intensity contrast between breast tissues, making it sensitive to tissue composition and vascularity. Breast DCE-MRI characterizes certain physiologic properties of breast tissue that are potentially related to breast cancer risk. Studies have shown that increased background parenchymal enhancement (BPE), which is the contrast enhancement occurring in normal cancer-unaffected breast tissues in post-contrast sequences, predicts increased breast cancer risk. Signal enhancement ratio (SER) computed from pre-contrast and post-contrast sequences in DCE-MRI measures change in signal intensity due to contrast uptake over time and is a measure of contrast enhancement kinetics. SER quantified in breast tumor has been shown potential as a biomarker for characterizing tumor response to treatments. In this work we investigated the relationship between quantitative measures of SER and breast cancer risk. A pilot retrospective case-control study was performed using a cohort of 102 women, consisting of 51 women who had diagnosed with unilateral breast cancer and 51 matched controls (by age and MRI date) with a unilateral biopsy-proven benign lesion. SER was quantified using fully-automated computerized algorithms and three SER-derived quantitative volume measures were compared between the cancer cases and controls using logistic regression analysis. Our preliminary results showed that SER is associated with breast cancer risk, after adjustment for the Breast Imaging Reporting and Data System (BI-RADS)-based mammographic breast density measures. This pilot study indicated that SER has potential for use as a risk factor for breast cancer risk assessment in women at elevated risk of developing breast cancer.

  19. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images

    OpenAIRE

    Suneet Gupta; Rabins Porwal

    2016-01-01

    Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests...

  20. Study on nasopharyngeal cancer tissue using surface-enhanced Raman spectroscopy

    Science.gov (United States)

    Ge, Xiaosong; Lin, Xueliang; Xu, Zhihong; Wei, Guoqiang; Huang, Wei; Lin, Duo

    2016-10-01

    Surface-enhanced Raman spectroscopy (SERS) can provide detailed molecular structure and composition information, and has demonstrated great potential in biomedical filed. This spectroscopy technology has become one of the most important optical techniques in the early diagnosis of cancer. Nasopharyngeal cancer (NPC) is a malignant neoplasm arising in the nasopharyngeal epithelial lining, which has relatively high incidence and death rate in Southeast Asia and southern China. This paper reviews the current progress of SERS in the field of cancer diagnostics, including gastric cancer, colorectal cancer, cervical cancer and nasopharyngeal cancer. In addition to above researches, we recently develop a novel NPC detection method based on tissue section using SERS, and obtain primary results. The proposed method has promising potential for the detection of nasopharyngeal carcinoma.

  1. Hexokinase 2 confers resistance to cisplatin in ovarian cancer cells by enhancing cisplatin-induced autophagy.

    Science.gov (United States)

    Zhang, Xiao-Yan; Zhang, Meng; Cong, Qing; Zhang, Ming-Xing; Zhang, Meng-Yu; Lu, Ying-Ying; Xu, Cong-Jian

    2018-02-01

    The high mortality rate of ovarian cancer is connected with the development of acquired resistance to multiple cancer drugs, especially cisplatin. Activation of cytoprotective autophagy has been implicated as a contributing mechanism for acquired cisplatin resistance in ovarian cancer cells. Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis. Higher HK2 expression has been associated with chemoresistance in ovarian cancer. However, whether HK2 functionally contributes to cisplatin resistance in ovarian cancer is unclear. In this study, we investigated the role of HK2 in regulating ovarian cancer cisplatin resistance. Increased HK2 levels were detected in drug-resistant human ovarian cancer cells and tissues. Cisplatin downregulated HK2 in cisplatin-sensitive but not in resistant ovarian cancer cells. HK2 knockdown sensitized resistant ovarian cancer cells to cisplatin-induced cell death and apoptosis. Conversely, HK2 overexpression in cisplatin-sensitive cells induced cisplatin resistance. Mechanistically, cisplatin increased ERK1/2 phosphorylation as well as autophagic activity. Blocking autophagy with the autophagy inhibitor 3-MA sensitized resistant ovarian cancer cells to cisplatin. HK2 overexpression enhanced cisplatin-induced ERK1/2 phosphorylation and autophagy while HK2 knockdown showed the opposite effects. Blocking the MEK/ERK pathway using the MEK inhibitor U0126 prevented cisplatin-induced autophagy enhanced by HK2 overexpression. Furthermore, HK2 knockdown sensitized resistance ovarian tumor xenografts to cisplatin in vivo. In conclusion, our data supported that HK2 promotes cisplatin resistance in ovarian cancer by enhancing drug-induced, ERK-mediated autophagy. Therefore, targeting HK2 may be a new therapeutic strategy to combat chemoresistance in ovarian cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer.

    Science.gov (United States)

    Yoo, So Young; Bang, Seo Young; Jeong, Su-Nam; Kang, Dae Hwan; Heo, Jeong

    2016-03-29

    Stem cell-like colon cancer cells (SCCs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. Oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on SCCs are not well studied yet. Here, we engineered a cancer-favoring oncolytic vaccinia virus (CVV) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing SCCs. CVV is an evolved Wyeth strain vaccinia virus (EVV) lacking the viral thymidine kinase. SCC models were established using human or mouse colon cancer spheres, which continuously expressed stemness markers. The cancer-favoring characteristics and different cytotoxic pathways for killing cancer cells successfully overrode general drug resistance, thereby killing colon cancer cells regardless of the presence of SCCs. Subcutaneously injected HT29 spheres showed lower growth in CVV-treated models than in 5-Fu-treated models. Intraperitoneally injected CT26 spheres induced tumor masses in the abdominal region. CVV-treated groups showed higher survival rates and smaller tumor mass formation, compared to 5-Fu-treated groups. Interestingly, the combined treatment of CVV with 5-Fu showed improved survival rates and complete suppression of tumor mass. The CVV developed in this study, thus, effectively suppresses SCCs, which can be synergistically enhanced by simultaneous treatment with the anticancer drug 5-Fu. Our novel CVV is highly advantageous as a next-generation therapeutic for treating colon cancer.

  3. TAK1 inhibitor NG25 enhances doxorubicin-mediated apoptosis in breast cancer cells.

    Science.gov (United States)

    Wang, Zhenyu; Zhang, Huiyuan; Shi, Minghao; Yu, Yang; Wang, Hao; Cao, Wen-Ming; Zhao, Yanling; Zhang, Hong

    2016-09-07

    Doxorubicin (Dox, Adriamycin) has been widely used in breast cancer treatment. But its severe cardio-toxic side effects limited the clinical use. Dox treatment can induce DNA damage and other accompanying effects in cancer cells, and subsequently activates nuclear factor κB (NF-κB) pathway which has a strong pro-survival role in different types of malignancy. We hypothesize that blocking NF-κB pathway may sensitize breast cancer cells to Dox chemotherapy. TGFβ-activated kinase-1 (TAK1) is a key intracellular molecule participating in genotoxic stresses-induced NF-κB activation. Targeting TAK1 as a strategy to enhance cancer treatment efficacy has been studied in several malignancies. We showed that NG25, a synthesized TAK1 inhibitor, greatly enhanced Dox treatment efficacy in a panel of breast cancer cell lines. In this pre-clinical study, we found that NG25 partially blocked Dox-induced p38 phosphorylation and IκBα degradation and enhanced Dox-induced cytotoxic effects and apoptosis in all breast cancer cell lines tested. Taken together, we provided clear evidence that NG25 sensitizes the breast cancer cells to Dox treatment in vitro. This combination may be an effective and feasible therapeutic option maximizing Dox efficacy and meanwhile minimizing Dox side effects in treating breast cancer.

  4. Valproic acid enhances bosutinib cytotoxicity in colon cancer cells.

    Science.gov (United States)

    Mologni, Luca; Cleris, Loredana; Magistroni, Vera; Piazza, Rocco; Boschelli, Frank; Formelli, Franca; Gambacorti-Passerini, Carlo

    2009-04-15

    Unbalanced histone deacetylase (HDAC) hyperactivity is a common feature of tumor cells. Inhibition of HDAC activity is often associated with cancer cell growth impairment and death. Valproic acid (VPA) is a HDAC inhibitor used for the treatment of epilepsy. It has recently been recognized as a promising anticancer drug. We investigated the effects of VPA on growth and survival of colon cancer cells. VPA caused growth inhibition and programmed cell death that correlated with histone hyperacetylation. VPA modulated the expression of various factors involved in cell cycle control and apoptosis and induced caspase activation. Interestingly, VPA induced downregulation of c-Src and potentiated the cytotoxic effects of the c-Src inhibitor bosutinib, both in vitro and in vivo. The combination of sublethal doses of VPA and bosutinib led to massive apoptosis of colon cancer cells, irrespective of their genetic background. These results suggest that VPA may be employed as a positive modulator of bosutinib antitumor activity in colorectal cancer.

  5. Enhancement of Anti-Telomerase Immunity Against Prostate Cancer

    National Research Council Canada - National Science Library

    Vieweg, Johannes

    2006-01-01

    .... We have also demonstrated that human Treg can selectively be depleted in cancer patients using the IL- 2/diphtheria toxin conjugate denileukin diftitox, without inducing toxicity on other cellular...

  6. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    Science.gov (United States)

    Szliszka, Ewelina; Czuba, Zenon P; Mazur, Bogdan; Sedek, Lukasz; Paradysz, Andrzej; Krol, Wojciech

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer. PMID:20161998

  7. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ewelina Szliszka

    2009-12-01

    Full Text Available Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

  8. Enhancing citizen engagement in cancer screening through deliberative democracy.

    Science.gov (United States)

    Rychetnik, Lucie; Carter, Stacy M; Abelson, Julia; Thornton, Hazel; Barratt, Alexandra; Entwistle, Vikki A; Mackenzie, Geraldine; Salkeld, Glenn; Glasziou, Paul

    2013-03-20

    Cancer screening is widely practiced and participation is promoted by various social, technical, and commercial drivers, but there are growing concerns about the emerging harms, risks, and costs of cancer screening. Deliberative democracy methods engage citizens in dialogue on substantial and complex problems: especially when evidence and values are important and people need time to understand and consider the relevant issues. Information derived from such deliberations can provide important guidance to cancer screening policies: citizens' values are made explicit, revealing what really matters to people and why. Policy makers can see what informed, rather than uninformed, citizens would decide on the provision of services and information on cancer screening. Caveats can be elicited to guide changes to existing policies and practices. Policies that take account of citizens' opinions through a deliberative democracy process can be considered more legitimate, justifiable, and feasible than those that don't.

  9. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    OpenAIRE

    Ewelina Szliszka; Zenon P. Czuba; Bogdan Mazur; Lukasz Sedek; Andrzej Paradysz; Wojciech Krol

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showe...

  10. Natural products as potential cancer therapy enhancers: A preclinical update

    Directory of Open Access Journals (Sweden)

    Abed Agbarya

    2014-09-01

    Full Text Available Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  11. Diagnostic and prognostic values of contrast-enhanced ultrasound in breast cancer: a retrospective study.

    Science.gov (United States)

    Zhao, Yi-Xuan; Liu, Shuang; Hu, Yan-Bing; Ge, Yan-Yan; Lv, Dong-Mei

    2017-01-01

    This study aimed to explore the diagnostic and prognostic values of contrast-enhanced ultrasound (CEUS) in breast cancer. Between September 2009 and October 2011, a total of 143 breast cancer patients and 161 healthy people were selected as case group and control group, respectively. After the identification of lesions by conventional ultrasound, all patients underwent CEUS. The CEUS images were analyzed, and time-intensity curves (TICs) were obtained. Hematoxylin-eosin and immunohistochemistry staining was performed on tissue specimens, according to which the expressions of estrogen receptor (ER), c-erb-B2, p53, and Ki-67 were measured. Multivariate logistic regression analysis was used to compare CEUS and TIC parameters between the two groups. Compared with the control group, cancer patients showed high enhancement, heterogeneous enhancement or defects in the central region, expansion of lesion diameter after enhancement and crab-like blur lesion edges. The peak intensity (PI), relative start time of enhancement, relative PI, and relative area under the curve in the case group were significantly higher than those in the control group. Logistic analysis showed that the uniformity of enhancement, expansion of lesion diameter, and relative PI were significant diagnostic parameters of breast cancer, with area under the curve being 0.798, 0.776, and 0.919, respectively. There were strong associations between CEUS characteristics and expressions of prognostic factors in breast cancer: the heterogeneous enhancement was common in c-erb-B2-positive tumors; the centripetal enhancement occurred more in ER-negative tumors; perforator vessels were often seen in tumors at high histological grade; perfusion defects were common in ER-negative, c-erb-B2-positive, and Ki-67-positive tumors. CEUS is a useful tool for the early diagnosis and prognosis of breast cancer.

  12. Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage

    Directory of Open Access Journals (Sweden)

    Harsharan Dhillon

    2014-01-01

    Full Text Available Pancreatic cancer is one of the most deadly cancers with a nearly 95% mortality rate. The poor response of pancreatic cancer to currently available therapies and the extremely low survival rate of pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of reactive oxygen species (ROS-inducing agents has emerged as an innovative and effective strategy to treat various cancers. In this study, we investigated the potential of a known ROS inducer, piperlongumine (PPLGM, a bioactive agent found in long peppers, to induce pancreatic cancer cell death in cell culture and animal models. We found that PPLGM inhibited the growth of pancreatic cancer cell cultures by elevating ROS levels and causing DNA damage. PPLGM-induced DNA damage and pancreatic cancer cell death was reversed by treating the cells with an exogenous antioxidant. Similar to the in vitro studies, PPLGM caused a reduction in tumor growth in a xenograft mouse model of human pancreatic cancer. Tumors from the PPLGM-treated animals showed decreased Ki-67 and increased 8-OHdG expression, suggesting PPLGM inhibited tumor cell proliferation and enhanced oxidative stress. Taken together, our results show that PPLGM is an effective inhibitor for in vitro and in vivo growth of pancreatic cancer cells, and that it works through a ROS-mediated DNA damage pathway. These findings suggest that PPLGM has the potential to be used for treatment of pancreatic cancer.

  13. In vitro dentine remineralization with a potential salivary phosphoprotein homologue.

    Science.gov (United States)

    Romero, Maria Jacinta Rosario H; Nakashima, Syozi; Nikaido, Toru; Sadr, Alireza; Tagami, Junji

    2016-08-01

    Advantages of introducing a salivary phosphoprotein homologue under standardized in vitro conditions to simulate the mineral-stabilizing properties of saliva have been proposed. This study longitudinally investigates the effects of casein, incorporated as a potential salivary phosphoprotein homologue in artificial saliva (AS) solutions with/without fluoride (F) on in vitro dentine lesion remineralization. Thin sections of bovine root dentine were demineralized and allocated randomly into 6 groups (n=18) having equivalent mineral loss (ΔZ) after transverse microradiography (TMR). The specimens were remineralized using AS solutions containing casein 0μg/ml, F 0ppm (C0-F0); casein 0μg/ml, F 1ppm (C0-F1); casein 10μg/ml, F 0ppm (C10-F0); casein 10μg/ml, F 1ppm (C10-F1); casein 100μg/ml, F 0ppm (C100-F0) or casein 100μg/ml, F 1ppm (C100-F1) for 28days with TMR taken every 7 days. Surface mineral precipitation, evident in group C0-F1, was apparently inhibited in groups with casein incorporation. Repeated measures ANOVA with Bonferroni correction revealed higher ΔZ for non-F and non-casein groups than for their counterparts (p<0.001). Subsequent multiple comparisons showed that mineral gain was higher (p<0.001) with 10μg/ml casein than with 100μg/ml when F was present in the earlier stages of remineralization, with both groups achieving almost complete remineralization after 28 days. Casein is a potential salivary phosphoprotein homologue that could be employed for in vitro dentine remineralization studies. Concentration related effects may be clinically significant and thus must be further examined. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Enhancer profiling identifies critical cancer genes and characterizes cell identity in adult T-cell leukemia.

    Science.gov (United States)

    Wong, Regina Wan Ju; Ngoc, Phuong Cao Thi; Leong, Wei Zhong; Yam, Alice Wei Yee; Zhang, Tinghu; Asamitsu, Kaori; Iida, Shinsuke; Okamoto, Takashi; Ueda, Ryuzo; Gray, Nathanael S; Ishida, Takashi; Sanda, Takaomi

    2017-11-23

    A number of studies have recently demonstrated that super-enhancers, which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. Super-enhancers are also often enriched at cancer genes in various malignancies. The identification of such enhancers would pinpoint critical factors that directly contribute to pathogenesis. In this study, we performed enhancer profiling using primary leukemia samples from adult T-cell leukemia/lymphoma (ATL), which is a genetically heterogeneous intractable cancer. Super-enhancers were enriched at genes involved in the T-cell activation pathway, including IL2RA/CD25, CD30, and FYN, in both ATL and normal mature T cells, which reflected the origin of the leukemic cells. Super-enhancers were found at several known cancer gene loci, including CCR4, PIK3R1, and TP73, in multiple ATL samples, but not in normal mature T cells, which implicated those genes in ATL pathogenesis. A small-molecule CDK7 inhibitor, THZ1, efficiently inhibited cell growth, induced apoptosis, and downregulated the expression of super-enhancer-associated genes in ATL cells. Furthermore, enhancer profiling combined with gene expression analysis identified a previously uncharacterized gene, TIAM2, that was associated with super-enhancers in all ATL samples, but not in normal T cells. Knockdown of TIAM2 induced apoptosis in ATL cell lines, whereas overexpression of this gene promoted cell growth. Our study provides a novel strategy for identifying critical cancer genes. © 2017 by The American Society of Hematology.

  15. Synergistic enhancement of breast cancer cell death using ultrasound-microbubbles in combination with cisplatin

    Science.gov (United States)

    Jetha, Sheliza; Karshafian, Raffi

    2017-03-01

    Cisplatin (CDDP), an anti-cancer agent, can effectively treat several cancerous tumourstumors such as testicular, bladder, and ovarian cancers. CDDP binds to specific DNA bases causing 1,2-intrastrand cross-links, single strand and double strand breaks inducing apoptosis. However, the effectiveness of CDDP is limited in tumourtumors such as breast cancer due to drug resistance. In this study, the application of ultrasound-microbubble (USMB) in improving the therapeutic effect of CDDP in breast cancer cell line is investigated. Human breast cancer (MDA-MB-231) cells in suspension (2×106 cells/mL concentration and 0.6 mL volume) were treated with CDDP (3 µM, 30 µM and 300 µM) and USMB at 0.5 MHz pulse centered frequency, 60 s insonation time, 16 µs pulse duration, 1 kHz pulse repetition frequency, and 1.7% v/v (volume concentration) of Definity microbubble agent. Following USMB treatment, cells were plated in 96-well plates for 24 and 48-hour incubation, after which cell viability was measured using MTT assay (VMTT). Cell viability decreased significantly with the combined treatment of CDDP and USMB compared to CDDP alone (pcisplatin synergistically enhances chemotherapeutic effectiveness in breast cancer cells. However, this enhanced effectiveness, in breast cancer cells (MDA-MB-231), is dependent on incubation time and cisplatin (CDDP) concentration.

  16. Diagnostic and prognostic values of contrast-enhanced ultrasound in breast cancer: a retrospective study

    OpenAIRE

    Zhao YX; Liu S.; Hu YB; Ge YY; Lv DM

    2017-01-01

    Yi-Xuan Zhao, Shuang Liu, Yan-Bing Hu, Yan-Yan Ge, Dong-Mei Lv Department of Ultrasound, Second Hospital, Jilin University, Changchun, People’s Republic of China Abstract: This study aimed to explore the diagnostic and prognostic values of contrast-enhanced ultrasound (CEUS) in breast cancer. Between September 2009 and October 2011, a total of 143 breast cancer patients and 161 healthy people were selected as case group and control group, respectively. After the identific...

  17. Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells.

    Science.gov (United States)

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Verma, Ajit Kumar; Mukhtar, Hasan

    2016-12-01

    Although treatment of prostate cancer has improved over the past several years, taxanes, such as cabazitaxel, remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule-stabilizing agent and inhibits prostate cancer cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types. In this study, we investigated the effect of fisetin in combination with cabazitaxel with the objective to achieve maximum therapeutic benefit, reduce dose and toxicity, and minimize or delay the induction of drug resistance and metastasis. Our data show for the first time that a combination of fisetin (20 μmol/L) enhances cabazitaxel (5 nmol/L) and synergistically reduces 22Rν1, PC-3M-luc-6, and C4-2 cell viability and metastatic properties with minimal adverse effects on normal prostate epithelial cells. In addition, the combination of fisetin with cabazitaxel was associated with inhibition of proliferation and enhancement of apoptosis. Furthermore, combination treatment resulted in the inhibition of tumor growth, invasion, and metastasis when assessed in two in vivo xenograft mouse models. These results provide evidence that fisetin may have therapeutic benefit for patients with advanced prostate cancer through enhancing the efficacy of cabazitaxel under both androgen-dependent and androgen-independent conditions. This study underscores the benefit of the combination of fisetin with cabazitaxel for the treatment of advanced and resistant prostate cancer and possibly other cancer types. Mol Cancer Ther; 15(12); 2863-74. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Enhancer alterations in cancer: a source for a cell identity crisis.

    Science.gov (United States)

    Kron, Ken J; Bailey, Swneke D; Lupien, Mathieu

    2014-01-01

    Enhancers are selectively utilized to orchestrate gene expression programs that first govern pluripotency and then proceed to highly specialized programs required for the process of cellular differentiation. Whereas gene-proximal promoters are typically active across numerous cell types, distal enhancer activation is cell-type-specific and central to cell fate determination, thereby accounting for cell identity. Recent studies have highlighted the diversity of enhancer usage, cataloguing millions of such elements in the human genome. The disruption of enhancer activity, through genetic or epigenetic alterations, can impact cell-type-specific functions, resulting in a wide range of pathologies. In cancer, these alterations can promote a 'cell identity crisis', in which enhancers associated with oncogenes and multipotentiality are activated, while those promoting cell fate commitment are inactivated. Overall, these alterations favor an undifferentiated cellular phenotype. Here, we review the current knowledge regarding the role of enhancers in normal cell function, and discuss how genetic and epigenetic changes in enhancer elements potentiate oncogenesis. In addition, we discuss how understanding the mechanisms regulating enhancer activity can inform therapeutic opportunities in cancer cells and highlight key challenges that remain in understanding enhancer biology as it relates to oncology.

  19. Association of Enhancer of Zeste 2 (EZH2) Genotypes with Bladder Cancer Risk in Taiwan.

    Science.gov (United States)

    Chang, Wen-Shin; Liao, Cheng-Hsi; Tsai, Chia-Wen; Hu, Pei-Shin; Wu, Hsi-Chin; Hsu, Shih-Wei; Hsiao, Chieh-Lun; Hsu, Chang-Hsien; Hung, Yi-Wen; Bau, DA-Tian

    2016-09-01

    Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in many developed regions including southwestern Taiwan. However, the genetic contribution to the etiology of bladder cancer is not well-understood. The aim of this study was to evaluate the association of the enhancer of zeste homolog 2 (EZH2) genotypes with Taiwan bladder cancer risk. Three polymorphic variants of EZH2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same number of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method. Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146). Individuals with the EZH2 rs887569 TT genotypes were associated with decreased cancer risk than those with wild-type CC genotype. The stratified analyses showed that EZH2 rs887569 TT genotypes had protective effects on non-smokers but obviously not on smokers. Our findings provide evidence that the T allele of EZH2 rs887569 may be associated with the lower risk of bladder cancer development, especially among non-smokers. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Background parenchymal enhancement in breast MRIs of breast cancer patients: impact on tumor size estimation.

    Science.gov (United States)

    Baek, Ji Eun; Kim, Sung Hun; Lee, Ah Won

    2014-08-01

    To evaluate whether the degree of background parenchymal enhancement affects the accuracy of tumor size estimation based on breast MRI. Three hundred and twenty-two patients who had known breast cancer and underwent breast MRIs were recruited in our study. The total number of breast cancer cases was 339. All images were assessed retrospectively for the level of background parenchymal enhancement based on the BI-RADS criteria. Maximal lesion diameters were measured on the MRIs, and tumor types (mass vs. non-mass) were assessed. Tumor size differences between the MRI-based estimates and estimates based on pathological examinations were analyzed. The relationship between accuracy and tumor types and clinicopathologic features were also evaluated. The cases included minimal (47.5%), mild (28.9%), moderate (12.4%) and marked background parenchymal enhancement (11.2%). The tumors of patients with minimal or mild background parenchymal enhancement were more accurately estimated than those of patients with moderate or marked enhancement (72.1% vs. 56.8%; p=0.003). The tumors of women with mass type lesions were significantly more accurately estimated than those of the women with non-mass type lesions (81.6% vs. 28.6%; penhancement is related to the inaccurate estimation of tumor size based on MRI. Non-mass type breast cancer and HER2-positive breast cancer are other factors that may cause inaccurate assessment of tumor size. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Enhancing knowledge discovery from cancer genomics data with Galaxy

    Science.gov (United States)

    Albuquerque, Marco A.; Grande, Bruno M.; Ritch, Elie J.; Pararajalingam, Prasath; Jessa, Selin; Krzywinski, Martin; Grewal, Jasleen K.; Shah, Sohrab P.; Boutros, Paul C.

    2017-01-01

    Abstract The field of cancer genomics has demonstrated the power of massively parallel sequencing techniques to inform on the genes and specific alterations that drive tumor onset and progression. Although large comprehensive sequence data sets continue to be made increasingly available, data analysis remains an ongoing challenge, particularly for laboratories lacking dedicated resources and bioinformatics expertise. To address this, we have produced a collection of Galaxy tools that represent many popular algorithms for detecting somatic genetic alterations from cancer genome and exome data. We developed new methods for parallelization of these tools within Galaxy to accelerate runtime and have demonstrated their usability and summarized their runtimes on multiple cloud service providers. Some tools represent extensions or refinement of existing toolkits to yield visualizations suited to cohort-wide cancer genomic analysis. For example, we present Oncocircos and Oncoprintplus, which generate data-rich summaries of exome-derived somatic mutation. Workflows that integrate these to achieve data integration and visualizations are demonstrated on a cohort of 96 diffuse large B-cell lymphomas and enabled the discovery of multiple candidate lymphoma-related genes. Our toolkit is available from our GitHub repository as Galaxy tool and dependency definitions and has been deployed using virtualization on multiple platforms including Docker. PMID:28327945

  2. Enhancing knowledge discovery from cancer genomics data with Galaxy.

    Science.gov (United States)

    Albuquerque, Marco A; Grande, Bruno M; Ritch, Elie J; Pararajalingam, Prasath; Jessa, Selin; Krzywinski, Martin; Grewal, Jasleen K; Shah, Sohrab P; Boutros, Paul C; Morin, Ryan D

    2017-05-01

    The field of cancer genomics has demonstrated the power of massively parallel sequencing techniques to inform on the genes and specific alterations that drive tumor onset and progression. Although large comprehensive sequence data sets continue to be made increasingly available, data analysis remains an ongoing challenge, particularly for laboratories lacking dedicated resources and bioinformatics expertise. To address this, we have produced a collection of Galaxy tools that represent many popular algorithms for detecting somatic genetic alterations from cancer genome and exome data. We developed new methods for parallelization of these tools within Galaxy to accelerate runtime and have demonstrated their usability and summarized their runtimes on multiple cloud service providers. Some tools represent extensions or refinement of existing toolkits to yield visualizations suited to cohort-wide cancer genomic analysis. For example, we present Oncocircos and Oncoprintplus, which generate data-rich summaries of exome-derived somatic mutation. Workflows that integrate these to achieve data integration and visualizations are demonstrated on a cohort of 96 diffuse large B-cell lymphomas and enabled the discovery of multiple candidate lymphoma-related genes. Our toolkit is available from our GitHub repository as Galaxy tool and dependency definitions and has been deployed using virtualization on multiple platforms including Docker. © The Author 2017. Published by Oxford University Press.

  3. Diagnostic and prognostic values of contrast-enhanced ultrasound in breast cancer: a retrospective study

    Directory of Open Access Journals (Sweden)

    Zhao YX

    2017-02-01

    Full Text Available Yi-Xuan Zhao, Shuang Liu, Yan-Bing Hu, Yan-Yan Ge, Dong-Mei Lv Department of Ultrasound, Second Hospital, Jilin University, Changchun, People’s Republic of China Abstract: This study aimed to explore the diagnostic and prognostic values of contrast-enhanced ultrasound (CEUS in breast cancer. Between September 2009 and October 2011, a total of 143 breast cancer patients and 161 healthy people were selected as case group and control group, respectively. After the identification of lesions by conventional ultrasound, all patients underwent CEUS. The CEUS images were analyzed, and time–intensity curves (TICs were obtained. Hematoxylin–eosin and immunohistochemistry staining was performed on tissue specimens, according to which the expressions of estrogen receptor (ER, c-erb-B2, p53, and Ki-67 were measured. Multivariate logistic regression analysis was used to compare CEUS and TIC parameters between the two groups. Compared with the control group, cancer patients showed high enhancement, heterogeneous enhancement or defects in the central region, expansion of lesion diameter after enhancement and crab-like blur lesion edges. The peak intensity (PI, relative start time of enhancement, relative PI, and relative area under the curve in the case group were significantly higher than those in the control group. Logistic analysis showed that the uniformity of enhancement, expansion of lesion diameter, and relative PI were significant diagnostic parameters of breast cancer, with area under the curve being 0.798, 0.776, and 0.919, respectively. There were strong associations between CEUS characteristics and expressions of prognostic factors in breast cancer: the heterogeneous enhancement was common in c-erb-B2-positive tumors; the centripetal enhancement occurred more in ER-negative tumors; perforator vessels were often seen in tumors at high histological grade; perfusion defects were common in ER-negative, c-erb-B2-positive, and Ki-67-positive tumors

  4. XPO1 Inhibition Enhances Radiation Response in Preclinical Models of Rectal Cancer.

    Science.gov (United States)

    Ferreiro-Neira, Isabel; Torres, Nancy E; Liesenfeld, Lukas F; Chan, Carlos H F; Penson, Tristan; Landesman, Yosef; Senapedis, William; Shacham, Sharon; Hong, Theodore S; Cusack, James C

    2016-04-01

    Combination of radiation with radiosensitizing chemotherapeutic agents improves outcomes for locally advanced rectal cancer. Current treatment includes 5-fluorouracil-based chemoradiation prior to surgical resection; however pathologic complete response varies from 15% to 20%, prompting the need to identify new radiosensitizers. Exportin 1 (XPO1, also known as chromosome region 1, CRM1) mediates the nuclear export of critical proteins required for rectal cancer proliferation and treatment resistance. We hypothesize that inhibition of XPO1 may radiosensitize cancer cells by altering the function of these critical proteins resulting in decreased radiation resistance and enhanced antitumoral effects. To test our hypothesis, we used the selective XPO1 inhibitor, selinexor, to inhibit nuclear export in combination with radiation fractions similar to that given in clinical practice for rectal cancer: hypofractionated short-course radiation dosage of 5 Gy per fraction or the conventional long-course radiation dosage of 1 Gy fractions. Single and combination treatments were tested in colorectal cancer cell lines and xenograft tumor models. Combination treatment of radiotherapy and selinexor resulted in an increase of apoptosis and decrease of proliferation compared with single treatment, which correlated with reduced tumor size. We found that the combination promoted nuclear survivin accumulation and subsequent depletion, resulting in increased apoptosis and enhanced radiation antitumoral effects. Our findings suggest a novel therapeutic option for improving radiation sensitivity in the setting of rectal cancer and provide the scientific rationale to evaluate this combination strategy for clinical trials. ©2015 American Association for Cancer Research.

  5. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Kindness Interventions in Enhancing Well-Being in Breast Cancer Survivors

    Science.gov (United States)

    2017-12-05

    Cancer Survivor; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  7. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    2014-01-27

    Jan 27, 2014 ... human breast cancer cell line MCF10A (Straight et al. 2004). PALS1, human homologue of Drosophila Sdt, was identified as an essential component of crumbs complex during establishment of tight junction in human cell lines through interaction with human CRB homologues (Roh et al. 2003, 2002 ...

  8. Association between Parenchymal Enhancement of the Contralateral Breast in Dynamic Contrast-enhanced MR Imaging and Outcome of Patients with Unilateral Invasive Breast Cancer.

    Science.gov (United States)

    van der Velden, Bas H M; Dmitriev, Ivan; Loo, Claudette E; Pijnappel, Ruud M; Gilhuijs, Kenneth G A

    2015-09-01

    To retrospectively investigate whether parenchymal enhancement in dynamic contrast material-enhanced magnetic resonance (MR) imaging of the contralateral breast in patients with unilateral invasive breast cancer is associated with therapy outcome. After obtaining approval of the institutional review board and patients' written informed consent, 531 women with unilateral invasive breast cancer underwent dynamic contrast-enhanced MR imaging between 2000 and 2008. The contralateral parenchyma was segmented automatically, in which the mean of the top 10% late enhancement was calculated. Cox regression was used to test associations between parenchymal enhancement, patient and tumor characteristics, and overall survival and invasive disease-free survival. Subset analyses were performed and stratified according to immunohistochemical subtypes and type of adjuvant treatment received. Median follow-up was 86 months. Age (P breast cancer (n = 398), age (P images (P = .049), and parenchymal enhancement (P = .011) were significant. In patients who underwent endocrine therapy (n = 174), parenchymal enhancement was the only significant covariate for overall survival and invasive disease-free survival (P enhancement in the contralateral breast of patients with invasive unilateral breast cancer is significantly associated with long-term outcome, particularly in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Lower value of the mean top 10% enhancement of the parenchyma shows potential as a predictive biomarker for relatively poor outcome in patients who undergo endocrine therapy. These results should, however, be validated in a larger study.

  9. Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xuemei [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Wu, Xinchao [Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Zhang, Xiao; Hua, Wenjuan; Zhang, Yajing [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Maimaiti, Yusufu [Department of Thyroid and Breast Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Gao, Zairong, E-mail: gaobonn@163.com [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China); Zhang, Yongxue [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province (China); Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province (China)

    2016-01-15

    Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.

  10. Slug expression enhances tumor formation in a noninvasive rectal cancer model.

    Science.gov (United States)

    Camp, E Ramsay; Findlay, Victoria J; Vaena, Silvia G; Walsh, Jarret; Lewin, David N; Turner, David P; Watson, Dennis K

    2011-09-01

    Epithelial-to-mesenchymal transition (EMT) is a series of molecular changes allowing epithelial cancer cells to acquire properties of mesenchymal cells: increased motility, invasion, and protection from apoptosis. Transcriptional regulators such as Slug mediate EMT, working in part to repress E-cadherin transcription. We report a novel, noninvasive in vivo rectal cancer model to explore the role of Slug in colorectal cancer (CRC) tumor development. For the generation of DLD-1 cells overexpressing Slug (Slug DLD-1), a Slug or empty (Empty DLD-1) pCMV-3Tag-1 (kanamycin-resistant) vector was used for transfection. Cells were evaluated for Slug and E-cadherin expression, and cell migration and invasion. For the in vivo study, colon cancer cells (parental DLD-1, Slug DLD-1, empty DLD-1, and HCT-116) were submucosally injected into the posterior rectum of nude mice using endoscopic guidance. After 28 d, tumors were harvested and tissue was analyzed. Slug expression in our panel of colon cancer cell lines was inversely correlated with E-cadherin expression and enhanced migration/invasion. Slug DLD-1 cells demonstrated a 21-fold increased Slug and 19-fold decreased E-cadherin expression compared with empty DLD-1. Similarly, the Slug DLD-1 cells had significantly enhanced cellular migration and invasion. In the orthotopic rectal cancer model, Slug DLD-1 cells formed rectal tumors in 9/10 (90%) of the mice (mean volume = 458 mm(3)) compared with only 1/10 (10%) with empty DLD-1 cells. Slug mediates EMT with enhanced in vivo rectal tumor formation. Our noninvasive in vivo model enables researchers to explore the molecular consequences of altered genes in a clinically relevant rectal cancer in an effort to develop novel therapeutic approaches for patients with rectal cancer. Published by Elsevier Inc.

  11. Integrative analysis to identify oncogenic gene expression changes associated with copy number variations of enhancer in ovarian cancer.

    Science.gov (United States)

    Li, Xiaoyan; Liu, Yining; Lu, Jiachun; Zhao, Min

    2017-10-31

    Enhancers are short regulatory regions (50-1500 bp) of DNA that control the tissue-specific activation of gene expression by long distance interaction with targeting gene regions. Recently, genome-wide identification of enhancers in diverse tissues and cell lines was achieved using high-throughput sequencing. Enhancers have been associated with malfunctions in cancer development resulting from point mutations in regulatory regions. However, the potential impact of copy number variations (CNVs) on enhancer regions is unknown. To learn more about the relationship between enhancers and cancer, we integrated the CNVs data on enhancers and explored their targeting gene expression pattern in high-grade ovarian cancer. Using human enhancer-gene interaction data with 13,691 interaction pairs between 7,905 enhancers and 5,297 targeting genes, we found that the 2,910 copy number gain events of enhancer are significantly correlated with the up-regulation of targeting genes. We further identified that a number of highly mutated super-enhancers, with concordant gene expression change on their targeting genes. We also identified 18 targeting genes by super-enhancers with prognostic significance for ovarian cancer, such as the tumour suppressor CDKN1B. We are the first to report that abundant copy number variations on enhancers could change the expression of their targeting genes which would be valuable for the design of enhancer-based cancer treatment strategy.

  12. Neurobiological correlates of inhibition of the right Broca homologue during new-word learning

    Directory of Open Access Journals (Sweden)

    Pierre Nicolo

    2016-07-01

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS has demonstrated beneficial effects on motor learning. It would be important to obtain a similar enhancement for verbal learning. However, previous studies have mostly assessed short-term effects of rTMS on language performance and the effect on learning is largely unknown. This study examined whether an inhibition of the right Broca homologue has long-term impact on neural processes underlying the acquisition of new words in healthy individuals. Sixteen young participants trained a new-word learning paradigm with rare, mostly unknown objects and their corresponding words immediately after continuous theta burst stimulation (cTBS or sham stimulation of right inferior frontal gyrus (IFG in a cross-over design. Neural effects were assessed with electroencephalography (EEG source power analyses during the naming task as well as coherence analyses at rest one day before and after training.Inhibition of the right Broca homologue did not affect new word learning performance at the group level. Behavioral and neural responses to cTBS were variable across participants and were associated with the magnitude of resting-state alpha-band coherence between the stimulated area and the rest of the brain before stimulation. Only participants with high intrinsic alpha-band coherence between the stimulated area and the rest of the brain before stimulation showed the expected inhibition during naming and greater learning performance. In conclusion, our study confirms that cTBS can induce lasting modulations of neural processes which are associated with learning, but the effect depends on the individual network state.

  13. Potential of cancer screening with serum surface-enhanced Raman spectroscopy and a support vector machine

    Science.gov (United States)

    Li, S. X.; Zhang, Y. J.; Zeng, Q. Y.; Li, L. F.; Guo, Z. Y.; Liu, Z. M.; Xiong, H. L.; Liu, S. H.

    2014-06-01

    Cancer is the most common disease to threaten human health. The ability to screen individuals with malignant tumours with only a blood sample would be greatly advantageous to early diagnosis and intervention. This study explores the possibility of discriminating between cancer patients and normal subjects with serum surface-enhanced Raman spectroscopy (SERS) and a support vector machine (SVM) through a peripheral blood sample. A total of 130 blood samples were obtained from patients with liver cancer, colonic cancer, esophageal cancer, nasopharyngeal cancer, gastric cancer, as well as 113 blood samples from normal volunteers. Several diagnostic models were built with the serum SERS spectra using SVM and principal component analysis (PCA) techniques. The results show that a diagnostic accuracy of 85.5% is acquired with a PCA algorithm, while a diagnostic accuracy of 95.8% is obtained using radial basis function (RBF), PCA-SVM methods. The results prove that a RBF kernel PCA-SVM technique is superior to PCA and conventional SVM (C-SVM) algorithms in classification serum SERS spectra. The study demonstrates that serum SERS, in combination with SVM techniques, has great potential for screening cancerous patients with any solid malignant tumour through a peripheral blood sample.

  14. A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

    Science.gov (United States)

    Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

    2017-04-01

    Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

  15. Reduction of decoy receptor 3 enhances TRAIL-mediated apoptosis in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Wei Wang

    Full Text Available Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy.

  16. SHP2 overexpression enhances the invasion and metastasis of ovarian cancer in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Hu ZQ

    2017-08-01

    Full Text Available ZhongQian Hu,1,* Jia Li,2,* Qi Gao,2,* Shuping Wei,1 Bin Yang1 1Department of Ultrasound, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China; 2Department of Ultrasound, Zhongda Hospital, Southeast University, Nanjing, China *These authors contributed equally to this work Purpose: SHP2 has roles in a variety of signal transduction pathways and in many important cellular processes, including proliferation, differentiation, movement regulation, and apoptosis. In addition, SHP2 expression is closely associated with multiple types of malignancies. In this study, we examined the role of SHP2 in epithelial ovarian cancer.Patients and methods: SHP2 expression in cancer and normal ovarian tissue specimens was evaluated by immunohistochemical staining and Western blot analyses. The correlation between the SHP2 expression level and clinicopathological features was analyzed. The role of SHP2 in epithelial ovarian cancer was evaluated by assessing SHP2 expression patterns in vitro and in vivo, and activation of the PI3K/AKT pathway was examined.Results: SHP2 is expressed at higher levels in ovarian cancer tissues than in normal ovarian tissues and in an ovarian cancer cell line than in a normal ovarian cell line. On the basis of these findings, SHP2 is overexpressed in ovarian cancer both in vitro and in vivo. In addition, SHP2 overexpression is associated with tumor stage and differentiation, enhanced cell proliferation and invasion, and tumorigenesis and metastasis.Conclusion: SHP2 overexpression enhances ovarian tumor proliferation and invasion by activating the PI3K-AKT axis, indicating that SHP2 potentially plays a direct role in the pathogenesis of ovarian epithelial cell cancer. These novel findings provide key insights that are applicable to basic cancer research and to the prevention and treatment of cancer. Keywords: ovarian tumor, SHP2, overexpression, proliferation, invasion, metastasis

  17. Enhanced Efficacy of Bleomycin in Bladder Cancer Cells by Photochemical Internalization

    Directory of Open Access Journals (Sweden)

    Yan Baglo

    2014-01-01

    Full Text Available Bleomycin is a cytotoxic chemotherapeutic agent widely used in cancer treatment. However, its efficacy in different cancers is low, possibly due to limited cellular internalization. In this study, a novel approach known as photochemical internalization (PCI was explored to enhance bleomycin delivery in bladder cancer cells (human T24 and rat AY-27, as bladder cancer is a potential indication for use of PCI with bleomycin. The PCI technique was mediated by the amphiphilic photosensitizer disulfonated tetraphenyl chlorin (TPCS2a and blue light (435 nm. Two additional strategies were explored to further enhance the cytotoxicity of bleomycin; a novel peptide drug ATX-101 which is known to impair DNA damage responses, and the protease inhibitor E-64 which may reduce bleomycin degradation by inhibition of bleomycin hydrolase. Our results demonstrate that the PCI technique enhances the bleomycin effect under appropriate conditions, and importantly we show that PCI-bleomycin treatment leads to increased levels of DNA damage supporting that the observed effect is due to increased bleomycin uptake. Impairing the DNA damage responses by ATX-101 further enhances the efficacy of the PCI-bleomycin treatment, while inhibiting the bleomycin hydrolase does not.

  18. Illustrations enhance older colorectal cancer patients’ website satisfaction and recall of online cancer information

    NARCIS (Netherlands)

    Bol, N.; Smets, E.M.A.; Eddes, E.H.; de Haes, J.C.J.M.; Loos, E.F.; van Weert, J.C.M.

    2015-01-01

    This study aims to investigate the effects of illustrations in online cancer information on older cancer patients' website satisfaction (i.e. satisfaction with the attractiveness, comprehensibility and emotional support from the website) and recall of information. In an online experiment, 174

  19. Illustrations enhance older colorectal cancer patients' website satisfaction and recall of online cancer information

    NARCIS (Netherlands)

    Bol, N.; Smets, E. M A; Eddes, E. H.; de Haes, J. C J M; Loos, E. F.|info:eu-repo/dai/nl/078758475; van Weert, J. C M

    2015-01-01

    This study aims to investigate the effects of illustrations in online cancer information on older cancer patients' website satisfaction (i.e. satisfaction with the attractiveness, comprehensibility and emotional support from the website) and recall of information. In an online experiment, 174

  20. TRIB3 downregulation enhances doxorubicin-induced cytotoxicity in gastric cancer cells.

    Science.gov (United States)

    Wu, I-Jung; Lin, Rong-Jaan; Wang, Hsin-Chiao; Yuan, Tein-Ming; Chuang, Show-Mei

    2017-05-15

    TRIB3, which is a pseudokinase known to regulate multiple pro-survival pathways, appears to be a potential therapeutic target for the treatment of human tumors. However, its precise role in cancer is controversial, as TRIB3 protein levels have been associated with both good and poor prognosis in cancer patients. Here, we investigated the significance of TRIB3 expression in the survival of gastric cancer cells exposed to anticancer drugs. We found that the tested anticancer drug, doxorubicin, induced cytotoxicity by decreasing TRIB3 transcription, which was followed by apoptotic cell death. Moreover, TRIB3 siRNA knockdown appeared to enhance doxorubicin-induced apoptosis in gastric cancer cells, concurrently with altering the expression of downstream apoptotic factors. Conversely, overexpression of TRIB3 significantly protected cells against doxorubicin-induced apoptosis. Our results indicate that downregulation of TRIB3 appears to promote cell death and enhance doxorubicin-induced apoptosis, supporting the anti-apoptotic role of TRIB3. The inductions of three classes of MAPKs failed to affect doxorubicin-mediated TRIB3 downregulation, while TRIB3 overexpression did not affect doxorubicin-induced MAPK activation. In sum, our findings indicate that TRIB3 plays an anti-apoptotic role in doxorubicin-treated gastric cancer cell lines, perhaps indicating that the status of TRIB3 expression in response to anticancer drugs, such as doxorubicin, irinotecan or oxaliplatin, may reflect the efficiency for cancer therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cancer imaging using Surface-Enhanced Resonance Raman Scattering (SERRS) nanoparticles

    Science.gov (United States)

    Harmsen, Stefan; Wall, Matthew A.; Huang, Ruimin

    2017-01-01

    The unique spectral signatures and biologically inert compositions of surface-enhanced (resonance) Raman scattering (SE(R)RS) nanoparticles make them promising contrast agents for in vivo cancer imaging. Subtle aspects of their preparation can shift their limit of detection by orders of magnitude. In this protocol, we present the optimized, step-by-step procedure for generating reproducible SERRS nanoparticles with femtomolar (10−15 M) limits of detection. We introduce several applications of these nanoprobes for biomedical research, with a focus on intraoperative cancer imaging via Raman imaging. A detailed account is provided for successful intravenous administration of SERRS nanoparticles such that delineation of cancerous lesions may be achieved without the need for specific biomarker targeting. The time estimate for this straightforward, yet comprehensive protocol from initial de novo gold nanoparticle synthesis to SE(R)RS nanoparticle contrast-enhanced preclinical Raman imaging in animal models is ~96 h. PMID:28686581

  2. Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells

    Science.gov (United States)

    Srivastava, Amit Kumar; Han, Chunhua; Zhao, Ran; Cui, Tiantian; Dai, Yuntao; Mao, Charlene; Zhao, Weiqiang; Zhang, Xiaoli; Yu, Jianhua; Wang, Qi-En

    2015-01-01

    Cancer stem cells (CSCs) with enhanced tumorigenicity and chemoresistance are believed to be responsible for treatment failure and tumor relapse in ovarian cancer patients. However, it is still unclear how CSCs survive DNA-damaging agent treatment. Here, we report an elevated expression of DNA polymerase η (Pol η) in ovarian CSCs isolated from both ovarian cancer cell lines and primary tumors, indicating that CSCs may have intrinsically enhanced translesion DNA synthesis (TLS). Down-regulation of Pol η blocked cisplatin-induced CSC enrichment both in vitro and in vivo through the enhancement of cisplatin-induced apoptosis in CSCs, indicating that Pol η-mediated TLS contributes to the survival of CSCs upon cisplatin treatment. Furthermore, our data demonstrated a depletion of miR-93 in ovarian CSCs. Enforced expression of miR-93 in ovarian CSCs reduced Pol η expression and increased their sensitivity to cisplatin. Taken together, our data suggest that ovarian CSCs have intrinsically enhanced Pol η-mediated TLS, allowing CSCs to survive cisplatin treatment, leading to tumor relapse. Targeting Pol η, probably through enhancement of miR-93 expression, might be exploited as a strategy to increase the efficacy of cisplatin treatment. PMID:25831546

  3. Incidence of venous thromboembolic events in enhanced recovery after surgery for colon cancer

    DEFF Research Database (Denmark)

    Vendler, M M I; Haidari, T A; Waage, J E

    2017-01-01

    AIM: Both the Danish and the National Institute of Clinical Excellence (NICE) guidelines recommend prolonged thromboprophylaxis (PT) with low-molecular-weight heparin (LMWH) for 28 days postoperatively after elective surgery for colon cancer. The evidence relies on data from two randomized clinical...... trials (RCTs) that included not only colon cancers but also other abdominal cancers or benign colorectal diseases. Neither of those studies investigated the risk of venous thromboembolism (VTE) under enhanced recovery after surgery (ERAS). We aim to describe the risk of VTE and estimate the cost...... of preventing one case of VTE by PT under ERAS. METHOD: This was a retrospective study of 2230 patients undergoing elective surgery for colon cancer Stage I-III in the Capital Region of Denmark, 1 June 2008 to 31 December 2013. Patients who were discharged on postoperative day 28 or later, died during admission...

  4. Functional Promiscuity of Homologues of the Bacterial ArsA ATPases

    Directory of Open Access Journals (Sweden)

    Rostislav Castillo

    2010-01-01

    Full Text Available The ArsA ATPase of E. coli plays an essential role in arsenic detoxification. Published evidence implicates ArsA in the energization of As(III efflux via the formation of an oxyanion-translocating complex with ArsB. In addition, eukaryotic ArsA homologues have several recognized functions unrelated to arsenic resistance. By aligning ArsA homologues, constructing phylogenetic trees, examining ArsA encoding operons, and estimating the probable coevolution of these homologues with putative transporters and auxiliary proteins unrelated to ArsB, we provide evidence for new functions for ArsA homologues. They may play roles in carbon starvation, gas vesicle biogenesis, and arsenic resistance. The results lead to the proposal that ArsA homologues energize four distinct and nonhomologous transporters, ArsB, ArsP, CstA, and Acr3.

  5. Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

    Science.gov (United States)

    Trott, Josephine F; Kim, Jeffrey; Abu Aboud, Omran; Wettersten, Hiromi; Stewart, Benjamin; Berryhill, Grace; Uzal, Francisco; Hovey, Russell C; Chen, Ching-Hsien; Anderson, Katie; Graef, Ashley; Sarver, Aaron L; Modiano, Jaime F; Weiss, Robert H

    2016-10-11

    Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC.

  6. Background parenchymal enhancement in breast MRIs of breast cancer patients: Impact on tumor size estimation

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    Baek, Ji Eun [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea (Korea, Republic of); Kim, Sung Hun, E-mail: rad-ksh@catholic.ac.kr [Department of Radiology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea (Korea, Republic of); Lee, Ah Won [Department of Hospital Pathology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea (Korea, Republic of)

    2014-08-15

    Objective: To evaluate whether the degree of background parenchymal enhancement affects the accuracy of tumor size estimation based on breast MRI. Methods: Three hundred and twenty-two patients who had known breast cancer and underwent breast MRIs were recruited in our study. The total number of breast cancer cases was 339. All images were assessed retrospectively for the level of background parenchymal enhancement based on the BI-RADS criteria. Maximal lesion diameters were measured on the MRIs, and tumor types (mass vs. non-mass) were assessed. Tumor size differences between the MRI-based estimates and estimates based on pathological examinations were analyzed. The relationship between accuracy and tumor types and clinicopathologic features were also evaluated. Results: The cases included minimal (47.5%), mild (28.9%), moderate (12.4%) and marked background parenchymal enhancement (11.2%). The tumors of patients with minimal or mild background parenchymal enhancement were more accurately estimated than those of patients with moderate or marked enhancement (72.1% vs. 56.8%; p = 0.003). The tumors of women with mass type lesions were significantly more accurately estimated than those of the women with non-mass type lesions (81.6% vs. 28.6%; p < 0.001). The tumor of women negative for HER2 was more accurately estimated than those of women positive for HER2 (72.2% vs. 51.6%; p = 0.047). Conclusion: Moderate and marked background parenchymal enhancement is related to the inaccurate estimation of tumor size based on MRI. Non-mass type breast cancer and HER2-positive breast cancer are other factors that may cause inaccurate assessment of tumor size.

  7. Maintaining cell identity: PRC2-mediated regulation of transcription and cancer.

    Science.gov (United States)

    Comet, Itys; Riising, Eva M; Leblanc, Benjamin; Helin, Kristian

    2016-12-01

    Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb repressive complex 2 (PRC2), has attracted broad research attention in the past few years because of its involvement in the development and maintenance of many types of cancer and the use of specific EZH2 inhibitors in clinical trials. Several observations show that PRC2 can have both oncogenic and tumour-suppressive functions. We propose that these apparently opposing roles of PRC2 in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state of its several thousand target genes.

  8. Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer.

    Science.gov (United States)

    Warrick, Joshua I; Raman, Jay D; Kaag, Matthew; Bruggeman, Trey; Cates, Justin; Clark, Peter; DeGraff, David J

    2016-06-01

    Studies evaluating enhancer of zeste homolog 2 (EZH2) expression and oncologic outcomes in bladder cancer have been discrepant. EZH2 expression in noninvasive bladder cancer is not well studied. We thus set out to address the discrepancy in previous reports, and to study expression of EZH2 in noninvasive bladder cancer and its associations, in a large cystectomy cohort. EZH2 expression was evaluated in tissue microarray material (invasive and noninvasive cancer). Associations between EZH2 expression and oncologic outcomes, tumor stage, and disease type were determined. Receiver operating characteristic analysis was performed for EZH2 expression in the diagnosis of invasive carcinoma and flat carcinoma in situ (CIS) compared to benign urothelium. EZH2 expression was most common in CIS, followed by invasive carcinoma, noninvasive papillary urothelial carcinoma, and benign urothelium, in decreasing order (PEZH2 expression was not associated with oncologic outcomes, including recurrence-free survival and death from bladder cancer. The EZH2 expression status (positive or negative) of noninvasive and invasive carcinomas taken from the same bladder correlated (P = 0.05, Fisher exact). That EZH2 status of noninvasive and invasive cancer correlated in individual patients suggests that EZH2 may be a marker of lineage. EZH2 may offer diagnostic utility, particularly in flat urothelial CIS vs. benign urothelium. The present study supports that EZH2 expression in bladder cancer is not predictive of oncologic outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Emodin enhances the chemosensitivity of endometrial cancer by inhibiting ROS-mediated Cisplatin-resistance.

    Science.gov (United States)

    Ding, Ning; Zhang, Hong; Su, Shan; Ding, Yumei; Yu, Xiaohui; Tang, Yujie; Wang, Qingfang; Liu, Peishu

    2017-12-18

    Background Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drug-resistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Selective transfection with osmotically active sorbitol modified PEI nanoparticles for enhanced anti-cancer gene therapy.

    Science.gov (United States)

    Nguyen, Kim Cuc Thi; Muthiah, Muthunarayanan; Islam, Mohammad Ariful; Kalash, R Santhosh; Cho, Chong-Su; Park, Hansoo; Lee, Il-Kwon; Kim, Hyeoung-Joon; Park, In-Kyu; Cho, Kyung A

    2014-07-01

    Polysorbitol-mediated transporter (PSMT) has been previously shown to achieve high transfection efficiency with minimal cytotoxicity. Polysorbitol backbone possesses osmotic properties and leads to enhanced cellular uptake. The PSMT/pDNA nanoparticles were prepared and the particle size, surface charge of the nanoparticles was determined for the study. PSMT delivers genes into cells by the caveolae mediated endocytic pathway. Caveolae expression is usually altered in transformed cancer cells. Transfection through the caveolae may help PSMT to selectively transfect cancer cells rather than normal cells. Transfection of the luciferase gene by PSMT was tested in various cell types including cancer cell lines, primary cells, and immortalized cells. Luciferase transgene expression mediated by PSMT was remarkably increased in HeLa cells compared to expression using the control carrier Lipofectamine. Moreover, the toxicity of PSMT was comparable to the control carrier (Lipofectamine) in the same cells. Selective transfection of cancer cells using PSMT was further confirmed by co-culture of cancer and normal cells, which showed that transgene expression was pre-dominantly achieved in cancer cells. A functional p53 gene was also delivered into HeLa cells using PSMT and the selective transgene expression of p53 protein in cancer cells was analyzed through western blotting and confocal microscopy. HeLa cells transfected with PSMT/p53 plasmid nanoparticles showed cellular damage and apoptosis, which was confirmed through propidium iodide staining. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy.

    Science.gov (United States)

    Chao, Xu; Zhang, Zhuoli; Guo, Lili; Zhu, Jingjing; Peng, Mingli; Vermorken, Alphonsus J M; Van de Ven, Wim J M; Chen, Chao; Cui, Yali

    2012-01-01

    Magnetic nanoparticles (NPs) loaded with antitumor drugs in combination with an external magnetic field (EMF)-guided delivery can improve the efficacy of treatment and may decrease serious side effects. The purpose of this study was 1) to investigate application of PEG modified GMNPs (PGMNPs) as a drug carrier of the chemotherapy compound doxorubicin (DOX) in vitro; 2) to evaluate the therapeutic efficiency of DOX-conjugated PGMNPs (DOX-PGMNPs) using an EMF-guided delivery in vivo. First, DOX-PGMNPs were synthesized and the cytotoxicity of DOX-PGMNPs was assessed in vitro. Second, upon intravenous administration of DOX-PMGPNs to H22 hepatoma cell tumor-bearing mice, the DOX biodistribution in different organs (tissues) was measured. The antitumor activity was evaluated using different treatment strategies such as DOX-PMGPNs or DOX-PMGPNs with an EMF-guided delivery (DOX-PGMNPs-M). The relative tumor volumes in DOX-PGMNPs-M, DOX-PGMNPs, and DOX groups were 5.46±1.48, 9.22±1.51, and 14.8±1.64, respectively (each pchemotherapy for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers in the near future.

  12. Enhancing Tumor Detection in IR-UWB Breast Cancer System

    Science.gov (United States)

    Ghoname, Reda; Elmahdy, Abd Elmonem; Zekry, Abd Elhalim

    2017-01-01

    An ultra-wideband (UWB) microwave system for breast cancer detection is presented. The proposed system includes monocycle pulse generator, antipodal Vivaldi antenna, breast model, and calibration algorithm for tumor detection. Firstly, our pulse generator employs transmission gate in glitch generator to achieve several advantages such as low power consumption and low ringing level. Secondly, the antipodal Vivaldi antenna is designed assuming FR4 dielectric substrate material, and developed antenna element (80 × 80 mm2) features a −10 dB return loss and bandwidth ranges from 2.3 GHz to more than 11 GHz. Thirdly, the phantom breast can be modeled as a layer of skin, fat, and then tumor is inserted in this layer. Finally, subtract and add algorithm (SAD) is used as a calibration algorithm in tumor detection system. The proposed system suggested that horizontal antenna position with 90° between transmitting and receiving antennas is localized as a suitable antenna position with different rotating location and a 0.5 cm near to phantom. The mean advantages of this localization and tracking position around breast is a high received power signal approximately around mv as a higher recognized signal in tumor detection. Using our proposed system we can detect tumor in 5 mm diameter. PMID:28421208

  13. Enhancing Tumor Detection in IR-UWB Breast Cancer System

    Directory of Open Access Journals (Sweden)

    Sara Fouad

    2017-01-01

    Full Text Available An ultra-wideband (UWB microwave system for breast cancer detection is presented. The proposed system includes monocycle pulse generator, antipodal Vivaldi antenna, breast model, and calibration algorithm for tumor detection. Firstly, our pulse generator employs transmission gate in glitch generator to achieve several advantages such as low power consumption and low ringing level. Secondly, the antipodal Vivaldi antenna is designed assuming FR4 dielectric substrate material, and developed antenna element (80×80 mm2 features a −10 dB return loss and bandwidth ranges from 2.3 GHz to more than 11 GHz. Thirdly, the phantom breast can be modeled as a layer of skin, fat, and then tumor is inserted in this layer. Finally, subtract and add algorithm (SAD is used as a calibration algorithm in tumor detection system. The proposed system suggested that horizontal antenna position with 90° between transmitting and receiving antennas is localized as a suitable antenna position with different rotating location and a 0.5 cm near to phantom. The mean advantages of this localization and tracking position around breast is a high received power signal approximately around mv as a higher recognized signal in tumor detection. Using our proposed system we can detect tumor in 5 mm diameter.

  14. Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation

    Science.gov (United States)

    Szalayova, Gabriela; Ogrodnik, Aleksandra; Spencer, Brianna; Wade, Jacqueline; Bunn, Janice; Ambaye, Abiy; James, Ted; Rincon, Mercedes

    2016-01-01

    Background Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to 1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, 2) characterize the type of inflammatory response present, and 3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. Methods The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e. immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. Results We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Conclusions Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human

  15. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells.

    Science.gov (United States)

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-05-10

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment.

  16. Sulindac enhances the killing of cancer cells exposed to oxidative stress.

    Directory of Open Access Journals (Sweden)

    Maria Marchetti

    2009-06-01

    Full Text Available Sulindac is an FDA-approved non-steroidal anti-inflammatory drug (NSAID that affects prostaglandin production by inhibiting cyclooxygenases (COX 1 and 2. Sulindac has also been of interest for more than decade as a chemopreventive for adenomatous colorectal polyps and colon cancer.Pretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP or hydrogen peroxide. This effect does not involve cyclooxygenase (COX inhibition. However, under the conditions used, there is a significant increase in reactive oxygen species (ROS within the cancer cells and a loss of mitochondrial membrane potential, suggesting that cell death is due to apoptosis, which was confirmed by Tunel assay. In contrast, this enhanced killing was not observed with normal lung or colon cells.These results indicate that normal and cancer cells handle oxidative stress in different ways and sulindac can enhance this difference. The combination of sulindac and an oxidizing agent could have therapeutic value.

  17. Trichostatin A enhances estrogen receptor-alpha repression in MCF-7 breast cancer cells under hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Hyunggyun; Park, Joonwoo; Shim, Myeongguk; Lee, YoungJoo, E-mail: yjlee@sejong.ac.kr

    2016-02-12

    Estrogen receptor (ER) is a crucial determinant of resistance to endocrine therapy, which may change during the progression of breast cancer. We previously showed that hypoxia induces ESR1 gene repression and ERα protein degradation via proteasome-mediated pathway in breast cancer cells. HDAC plays important roles in the regulation of histone and non-histone protein post-translational modification. HDAC inhibitors can induce epigenetic changes and have therapeutic potential for targeting various cancers. Trichostatin A exerts potent antitumor activities against breast cancer cells in vitro and in vivo. In this report, we show that TSA augments ESR1 gene repression at the transcriptional level and downregulates ERα protein expression under hypoxic conditions through a proteasome-mediated pathway. TSA-induced estrogen response element-driven reporter activity in the absence of estrogen was synergistically enhanced under hypoxia; however, TSA inhibited cell proliferation under both normoxia and hypoxia. Our data show that the hypoxia-induced repression of ESR1 and degradation of ERα are enhanced by concomitant treatment with TSA. These findings expand our understanding of hormone responsiveness in the tumor microenvironment; however, additional in-depth studies are required to elucidate the detailed mechanisms of TSA-induced ERα regulation under hypoxia. - Highlights: • TSA augments ESR1 gene repression at the transcriptional level under hypoxia. • TSA downregulates ERα protein expression under hypoxia. • TSA-induced ERα regulation under hypoxia is essential for understanding the behavior and progression of breast cancer.

  18. A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy.

    Directory of Open Access Journals (Sweden)

    Xu Chao

    Full Text Available BACKGROUND: Magnetic nanoparticles (NPs loaded with antitumor drugs in combination with an external magnetic field (EMF-guided delivery can improve the efficacy of treatment and may decrease serious side effects. The purpose of this study was 1 to investigate application of PEG modified GMNPs (PGMNPs as a drug carrier of the chemotherapy compound doxorubicin (DOX in vitro; 2 to evaluate the therapeutic efficiency of DOX-conjugated PGMNPs (DOX-PGMNPs using an EMF-guided delivery in vivo. METHODS: First, DOX-PGMNPs were synthesized and the cytotoxicity of DOX-PGMNPs was assessed in vitro. Second, upon intravenous administration of DOX-PMGPNs to H22 hepatoma cell tumor-bearing mice, the DOX biodistribution in different organs (tissues was measured. The antitumor activity was evaluated using different treatment strategies such as DOX-PMGPNs or DOX-PMGPNs with an EMF-guided delivery (DOX-PGMNPs-M. RESULTS: The relative tumor volumes in DOX-PGMNPs-M, DOX-PGMNPs, and DOX groups were 5.46±1.48, 9.22±1.51, and 14.8±1.64, respectively (each p<0.05, following treatment for 33 days. The life span of tumor-bearing mice treated with DOX-PGMNPs-M, DOX-PGMNPs, and DOX were 74.8±9.95, 66.1±13.5, and 31.3±3.31 days, respectively (each p<0.05. CONCLUSION: This simple and adaptive nanoparticle design may accommodate chemotherapy for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers in the near future.

  19. Enhancement of radiation cytotoxicity by gold nanoparticles in MCF-7 breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul [School of Physics, Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Aziz, Azlan Abdul [School of Physics, Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Nano-Biotechnology Research and Innovation (NanoBRI), Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Shamsuddin, Shaharum [Nano-Biotechnology Research and Innovation (NanoBRI), Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia)

    2015-04-24

    Therapy combined with metallic nanoparticles is a new way to treat cancer, in which gold nanoparticles (AuNPs) are injected through intravenous administration and bound to tumor sites. Radiotherapy aims to deliver a high therapeutic dose of ionizing radiation to the tumor without exceeding normal tissue tolerance. The use of AuNPs which is a high-atomic-number (Z) material in radiotherapy will provide a high probability for photon interaction by photoelectric effect. These provide advantages in terms of radiation dose enhancement. The high linear energy transfer and short range of photoelectric interaction products (photoelectrons, characteristic x-rays, Auger electrons) produce localized dose enhancement of the tumor. In this work, breast cancer cell lines (MCF-7) are seeded in the 96-well plate and were treated with 13 nm AuNPs before they were irradiated with 6 MV and 10 MV photon beam from a medical linear accelerator at various radiation doses. To validate the enhanced killing effect, both with and without AuNPs MCF-7 cells is irradiated simultaneously. By comparison, the results show that AuNPs significantly enhance cancer killing.

  20. Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jennifer Clark

    2012-01-01

    Full Text Available RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.

  1. Quality of Life among Immigrant Latina Breast Cancer Survivors: Realities of Culture and Enhancing Cancer Care

    Science.gov (United States)

    Lopez-Class, Maria; Perret-Gentil, Monique; Kreling, Barbara; Caicedo, Larisa; Mandelblatt, Jeanne; Graves, Kristi D.

    2012-01-01

    Objectives Breast cancer is the most common cancer among Latinas. This study examined social, cultural, and health care system factors that impact quality of life and survivorship experiences of Latina immigrant breast cancer survivors. Design We interviewed Latina breast cancer survivors (n=19) and, based on the interview findings, conducted two focus groups (n=9). Research staff translated transcripts from Spanish into English. Two trained raters reviewed the content and identified themes. Thematic content analysis was used to categorize and organize data. Results Participants were largely mono-lingual in Spanish, predominantly from Central and South America and most (68%) had lived in the U.S. for 10 or more years. All women were diagnosed and treated in the U.S. and were an average of 3.1 years from diagnosis. Women’s survivorship experiences appeared to be shaped by cultural beliefs and experiences as immigrants such as secrecy/shame about a breast cancer diagnosis, feelings of isolation, importance of family support (familism), challenges with developing social relationships in the U.S. (less personalismo), and, for some, their partner’s difficulty with showing emotional support (machismo). Navigating the U.S. medical system and language barriers were additional challenges in participants’ health care interactions. Conclusion Latina breast cancer survivors adhere to certain cultural values and face unique issues as immigrants, potentially influencing overall quality of life and doctor-patient communication. Efforts to improve Latina immigrant breast cancer survivors’ quality of life could include increased assessment of psychosocial functioning and referral to social support services, culturally-sensitive navigation programs and consistent use of appropriately trained interpreters. PMID:21706194

  2. Quality of life among immigrant Latina breast cancer survivors: realities of culture and enhancing cancer care.

    Science.gov (United States)

    Lopez-Class, Maria; Perret-Gentil, Monique; Kreling, Barbara; Caicedo, Larisa; Mandelblatt, Jeanne; Graves, Kristi D

    2011-12-01

    Breast cancer is the most common cancer among Latinas. This study examined social, cultural, and health care system factors that impact the quality of life and survivorship experiences of Latina immigrant breast cancer survivors. We interviewed Latina breast cancer survivors (n = 19) and, based on the interview findings, conducted two focus groups (n = 9). Research staff translated transcripts from Spanish into English. Two trained raters reviewed the content and identified themes. Thematic content analysis was used to categorize and organize data. Participants were largely monolingual in Spanish, predominantly from Central and South America and most (68%) had lived in the U.S. for ten or more years. All women were diagnosed and treated in the U.S. and were an average of 3.1 years from diagnosis. Women's survivorship experiences appeared to be shaped by cultural beliefs and experiences as immigrants such as secrecy/shame about a breast cancer diagnosis, feelings of isolation, importance of family support (familism), challenges with developing social relationships in the U.S. (less personalismo), and, for some, their partner's difficulty with showing emotional support (machismo). Navigating the U.S. medical system and language barriers were additional challenges in the participants' health care interactions. Latina breast cancer survivors adhere to certain cultural values and face unique issues as immigrants, potentially influencing overall quality of life and doctor-patient communication. Efforts to improve Latina immigrant breast cancer survivors' quality of life could include increased assessment of psychosocial functioning and referral to social support services, culturally sensitive navigation programs, and consistent use of appropriately trained interpreters.

  3. Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.

    Science.gov (United States)

    Zhu, Hai-Xing; Shi, Lin; Zhang, Yong; Zhu, Yi-Chun; Bai, Chun-Xue; Wang, Xiang-Dong; Zhou, Jie-Bai

    2017-03-24

    Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis. Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement. Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.

  4. Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.

    Science.gov (United States)

    Huo, Zhi-Jun; Wang, Shi-Jiang; Wang, Zhi-Qi; Zuo, Wen-Shu; Liu, Ping; Pang, Bo; Liu, Kai

    2015-10-01

    The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  5. Enhanced Tumor Accumulation of Sub-2 nm Gold Nanoclusters for Cancer Radiation Therapy

    CERN Document Server

    Zhang, Xiao-Dong; Luo, Zhentao; Wu, Di; Shen, Xiu; Song, Sha-Sha; Sun, Yuan-Ming; Liu, Pei-Xun; Zhao, Jing; Huo, Shuaidong; Fan, Saijun; Fan, Feiyue; Liang, Xing-Jie; Xie, Jianping

    2013-01-01

    A new type of metabolizable and efficient radiosensitizer for cancer radiotherapy is presented in this study by combining ultrasmall Au nanoclusters (NCs, <2 nm) with biocompatible coating ligands (glutathione, GSH). The new nano-construct (GSH-coated Au25 NCs) inherits attractive features of both the Au core (strong radiosensitizing effect) and GSH shell (good biocompatibility). It can preferentially accumulate in tumor via the improved EPR effect, which leads to strong enhancement for cancer radiotherapy. After the treatment, the small-sized GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential side effects due to the accumulation of Au25 NCs in the body.

  6. Enhancing the efficacy of cisplatin in ovarian cancer treatment – could arsenic have a role

    Directory of Open Access Journals (Sweden)

    Helm C William

    2009-01-01

    Full Text Available Abstract Ovarian cancer affects more than 200,000 women each year around the world. Most women are not diagnosed until the disease has already metastasized from the ovaries with a resultant poor prognosis. Ovarian cancer is associated with an overall 5 year survival of little more than 50%. The mainstay of front-line therapy is cytoreductive surgery followed by chemotherapy. Traditionally, this has been by the intravenous route only but there is more interest in the delivery of intraperitoneal chemotherapy utilizing the pharmaco-therapeutic advantage of the peritoneal barrier. Despite three large, randomized clinical trials comparing intravenous with intraperitoneal chemotherapy showing improved outcomes for those receiving at least part of their chemotherapy by the intraperitoneal route. Cisplatin has been the most active drug for the treatment of ovarian cancer for the last 4 decades and the prognosis for women with ovarian cancer can be defined by the tumor response to cisplatin. Those whose tumors are innately platinum-resistant at the time of initial treatment have a very poor prognosis. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin and will ultimately succumb to the disease. Improving the efficacy of cisplatin could have a major impact in the fight against this disease. Arsenite is an exciting agent that not only has inherent single-agent tumoricidal activity against ovarian cancer cell lines but also multiple biochemical interactions that may enhance the cytotoxicity of cisplatin including inhibition of deoxyribose nucleic acid (DNA repair. In vitro studies suggest that arsenite may enhance the activity of cisplatin in other cell types. Arsenic trioxide is already used clinically to treat acute promyelocytic leukemia demonstrating its safety profile. Further research in ovarian cancer is warranted to define

  7. A pilot intervention to enhance psychosexual development in adolescents and young adults with cancer.

    Science.gov (United States)

    Canada, Andrea L; Schover, Leslie R; Li, Yisheng

    2007-11-01

    Evidence suggests that cancer diagnosed during adolescence and young adulthood may present considerable challenges to what would otherwise be a relatively smooth developmental trajectory, particularly in areas related to reproductive health. We created and pilot tested a two-session, individually-delivered, counseling intervention to enhance psychosexual development in this unique population. A total of 21 patients, aged 15 to 25 years and treated for cancer within the past 5 years, completed the counseling intervention. Patients were adaptively randomized to begin the intervention immediately, or to be placed on a 3-month waitlist, after which time, they were reassessed and began the intervention. The content of the intervention included education, dialog, and support regarding cancer and such issues as sexual development and function, body image, fertility, prevention of sexually transmitted disease and unwanted pregnancy, and romantic relationships (e.g., dating, sexual communication). A 1-month follow-up booster call followed the intervention. Questionnaires were completed at baseline, post-waitlist (for half the sample), post-treatment, and at 3-month follow-up. Participation in the intervention increased cancer-specific knowledge regarding sexual issues; improved body image; lessened anxiety about sexual and romantic relationships; and decreased overall level of psychological distress. Gains were maintained through the 3-month follow-up. Addressing issues of reproductive health in the adolescent/young adult with cancer can and should be offered as a part of comprehensive pediatric cancer care. (c) 2007 Wiley-Liss, Inc.

  8. Targeting Enhancer of Zeste Homolog 2 as a promising strategy for cancer treatment.

    Science.gov (United States)

    Marchesi, Irene; Bagella, Luigi

    2016-04-10

    Polycomb group proteins represent a global silencing system involved in development regulation. In specific, they regulate the transition from proliferation to differentiation, contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs. Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2, which induces transcriptional inhibition through the tri-methylation of histone H3, an epigenetic change associated with gene silencing. EZH2 expression is high in precursor cells while its level decreases in differentiated cells. EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis. Indeed, aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes, resulting in an uncontrolled proliferation and tumor formation. This editorial explores the role of Polycomb repressive complex 2 in cancer, focusing in particular on EZH2. The canonical function of EZH2 in gene silencing, the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation, were summarized. Moreover, mutations of EZH2, responsible for an increased methyltransferase activity in cancer, were recapitulated. Finally, various drugs able to inhibit EZH2 with different mechanism were described, specifically underscoring the effects in several cancers, in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.

  9. Visual perception enhancement for detection of cancerous oral tissue by multi-spectral imaging

    Science.gov (United States)

    Wang, Hsiang-Chen; Tsai, Meng-Tsan; Chiang, Chun-Ping

    2013-05-01

    Color reproduction systems based on the multi-spectral imaging technique (MSI) for both directly estimating reflection spectra and direct visualization of oral tissues using various light sources are proposed. Images from three oral cancer patients were taken as the experimental samples, and spectral differences between pre-cancerous and normal oral mucosal tissues were calculated at three time points during 5-aminolevulinic acid photodynamic therapy (ALA-PDT) to analyze whether they were consistent with disease processes. To check the successful treatment of oral cancer with ALA-PDT, oral cavity images by swept source optical coherence tomography (SS-OCT) are demonstrated. This system can also reproduce images under different light sources. For pre-cancerous detection, the oral images after the second ALA-PDT are assigned as the target samples. By using RGB LEDs with various correlated color temperatures (CCTs) for color difference comparison, the light source with a CCT of about 4500 K was found to have the best ability to enhance the color difference between pre-cancerous and normal oral mucosal tissues in the oral cavity. Compared with the fluorescent lighting commonly used today, the color difference can be improved by 39.2% from 16.5270 to 23.0023. Hence, this light source and spectral analysis increase the efficiency of the medical diagnosis of oral cancer and aid patients in receiving early treatment.

  10. Distinction of gastric cancer tissue based on surface-enhanced Raman spectroscopy

    Science.gov (United States)

    Ma, Jun; Zhou, Hanjing; Gong, Longjing; Liu, Shu; Zhou, Zhenghua; Mao, Weizheng; Zheng, Rong-er

    2012-12-01

    Gastric cancer is one of the most common malignant tumors with high recurrence rate and mortality rate in China. This study aimed to evaluate the diagnostic capability of Surface-enhanced Raman spectroscopy (SERS) based on gold colloids for distinguishing gastric tissues. Gold colloids were directly mixed with the supernatant of homogenized tissues to heighten the Raman signal of various biomolecule. A total of 56 samples were collected from normal (30) and cancer (26). Raman spectra were obtained with a 785nm excitation in the range of 600-1800 cm-1. Significant spectral differences in SERS mainly belong to nucleic acid, proteins and lipids, particularly in the range of 653, 726, 828, 963, 1004, 1032, 1088, 1130, 1243, 1369, 1474, 1596, 1723 cm-1. PCA-LDA algorithms with leave-one-patient-out cross validation yielded diagnostic sensitivities of 90% (27/30), specificities of 88.5% (23/26), and accuracy of 89.3% (50/56), for classification of normal and cancer tissues. The receiver operating characteristic (ROC) surface is 0.917, illustrating the diagnostic utility of SERS together with PCA-LDA to identify gastric cancer from normal tissue. This work demonstrated the SERS techniques can be useful for gastric cancer detection, and it is also a potential technique for accurately identifying cancerous tumor, which is of considerable clinical importance to real-time diagnosis.

  11. Homologue Pairing in Flies and Mammals: Gene Regulation When Two Are Involved

    Directory of Open Access Journals (Sweden)

    Manasi S. Apte

    2012-01-01

    Full Text Available Chromosome pairing is usually discussed in the context of meiosis. Association of homologues in germ cells enables chromosome segregation and is necessary for fertility. A few organisms, such as flies, also pair their entire genomes in somatic cells. Most others, including mammals, display little homologue pairing outside of the germline. Experimental evidence from both flies and mammals suggests that communication between homologues contributes to normal genome regulation. This paper will contrast the role of pairing in transmitting information between homologues in flies and mammals. In mammals, somatic homologue pairing is tightly regulated, occurring at specific loci and in a developmentally regulated fashion. Inappropriate pairing, or loss of normal pairing, is associated with gene misregulation in some disease states. While homologue pairing in flies is capable of influencing gene expression, the significance of this for normal expression remains unknown. The sex chromosomes pose a particularly interesting situation, as females are able to pair X chromosomes, but males cannot. The contribution of homologue pairing to the biology of the X chromosome will also be discussed.

  12. Contrast-enhanced dual-energy mammography: a promising new imaging tool in breast cancer detection.

    Science.gov (United States)

    Lalji, Ulrich; Lobbes, Marc

    2014-05-01

    Contrast-enhanced dual-energy mammography (CEDM) is a promising new breast imaging tool for breast cancer detection. In CEDM, an iodine-based contrast agent is intravenously administered and subsequently, dual-energy mammography is performed. This results in a set of images containing both a regular mammogram and an image that contains contrast enhancement information. Preliminary studies have indicated that CEDM is superior to conventional mammography and might even match the diagnostic performance of breast MRI. In this review, the imaging technique, protocol and patient handling of CEDM is presented. Furthermore, an overview of current results on CEDM and potential future indications are outlined.

  13. Contrast-enhanced ultrasound for diagnosis of prostate cancer and kidney lesions

    Energy Technology Data Exchange (ETDEWEB)

    Mitterberger, Michael [Department of Urology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)], E-mail: michael.mitterberger@uibk.ac.at; Pelzer, Alexandre; Colleselli, Daniela; Bartsch, Georg; Strasser, Hannes [Department of Urology, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Pallwein, Leo; Aigner, Friedrich; Gradl, Johann; Frauscher, Ferdinand [Department of Radiology II, University of Innsbruck, Innsbruck (Austria)

    2007-11-15

    Purpose of review: Conventional ultrasonography of both, kidney and prostate, is limited due to the poor contrast of B-mode imaging for parenchymal disease and limited sensitivity of colour Doppler for the detection of capillaries and deep pedicular vessels. Contrast-enhanced ultrasound (CEUS) overcomes these limitations. Recent findings: CEUS investigates the blood flow of the prostate, allows for prostate cancer visualization and for targeted biopsies. Comparisons between systematic and CEUS-targeted biopsies have shown that the targeted approach detects more cancers with a lower number of biopsy cores and with higher Gleason scores compared with the systematic approach. Also the kidney offers promising applications as CEUS improves the detection of abnormal microvascular and macrovascular disorders. Summary: In recent literature CEUS has shown its value for diagnosis of both, prostate cancer and kidney lesions. This paper describes recent improvements and future perspectives of CEUS.

  14. Long non-coding RNA HOTAIR enhances radioresistance in MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Zhou, Yun; Wang, Chaoqun; Liu, Xia; Wu, Chengjun; Yin, Haitao

    2017-03-01

    The aim of the present study was to investigate the radiosensitizing effects of homeobox (HOX) transcript antisense RNA (HOTAIR) long non-coding RNA on breast cancer tumor cells and examine the underlying mechanisms. Recombinant plasmid vectors containing HOTAIR gene were constructed and MDA-MB231 cells were transfected with these plasmids using liposomes. The cells were treated with radiation and cell apoptosis, proliferation, and double-stranded DNA breaks were examined. HOXD10, phosphorylated AKT (p-AKT) and p-BAD expression levels were measured using western blot analysis. The results showed a higher expression of HOTAIR in advanced tumor cells. HOTAIR efficiently enhanced radioresistance in MDA-MB231 breast cancer cells and accelerated proliferation through the Akt pathway by targeting HOXD10. In conclusion, the findings demonstrated that HOTAIR gene is a valid therapeutic target for the reversal of radiotherapy resistance in breast cancer.

  15. Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Koen M.A. Dreijerink

    2017-03-01

    Full Text Available While the multiple endocrine neoplasia type 1 (MEN1 gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER+ cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer.

  16. Co-administration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs

    Science.gov (United States)

    Sugahara, Kazuki N.; Teesalu, Tambet; Karmali, Priya Prakash; Kotamraju, Venkata Ramana; Agemy, Lilach; Greenwald, Daniel R.; Ruoslahti, Erkki

    2010-01-01

    Poor penetration of anti-cancer drugs into tumors can be an important factor limiting their efficacy. Studying mouse tumor models, we show that a previously characterized tumor-penetrating peptide, iRGD (CRGDK/RGPD/EC), increased vascular and tissue permeability in a tumor-specific and neuropilin-1-dependent manner, allowing co-administered drugs to penetrate into extravascular tumor tissue. Importantly, this effect did not require the drugs to be chemically conjugated to the peptide. Systemic injection with iRGD improved the therapeutic index of drugs of various compositions including a small molecule (doxorubicin), nanoparticles (nab-paclitaxel and doxorubicin liposomes), and a monoclonal antibody (trastuzumab). Thus, co-administration of iRGD may be a valuable way to enhance the efficacy of anti-cancer drugs while reducing their side effects, a primary goal of cancer therapy research. PMID:20378772

  17. Enhancement of Radiation Therapy in Prostate Cancer by DNA-PKcs Inhibitor

    Science.gov (United States)

    2014-09-01

    EZH2 in- tensity levels.Reprint requests to: D. W. Nathan Kim, MD Southwestern Medical Center, Department of Forest Park Rd, Dallas, TX 75390. Tel: (214... Biomed Mater Res A 2012;100(8):1998-2005. 23. Jia Y, Yuan M, Yuan H, Huang X, Sui X, Cui X, Tang F, Peng J, Chen J, Lu S and others. Co...Multifunctionality of indocyanine green-loaded biodegradable nanoparticles for enhanced optical imaging and hyperthermia intervention of cancer. J Biomed Opt

  18. A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

    OpenAIRE

    Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

    2017-01-01

    Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission elect...

  19. Respiratory Challenges in Breast Cancer: Potential for Enhanced Diagnostics and Therapy

    Science.gov (United States)

    2009-07-31

    and Briers J D 1981 Flow Visualization by Means of Single-Exposure Speckle Photography Optics Communications 37 326-30 Ferguson R D, Hammer D X...their selective toxicities toward oxygenated and hypoxic tumor cells Cancer Res 41 73-81 Vaupel P, Hockel, M. 2002 Tumor hypoxia and therapeutic ...multi- site EPR oximetry as a prognostic marker for enhanced therapeutic efficacy of fractionated radiotherapy,” Radiotherapy and Oncology (2008

  20. MiR-525-3p Enhances the Migration and Invasion of Liver Cancer Cells by Downregulating ZNF395

    Science.gov (United States)

    Pang, Fei; Zha, Ruopeng; Zhao, Yingjun; Wang, Qifeng; Chen, Di; Zhang, Zhenfeng; Chen, Taoyang; Yao, Ming; Gu, Jianren; He, Xianghuo

    2014-01-01

    Liver cancer is one of leading causes of cancer-related deaths. A deeper mechanistic understanding of liver cancer could lead to the development of more effective therapeutic strategies. In our previous work, we screened 646 miRNAs and identified 11 that regulate liver cancer cell migration. The current study shows that miR-525-3p is frequently up-regulated in liver cancer tissues, and enhanced expression of miR-525-3p can promote liver cancer cell migration and invasion. Zinc finger protein 395 (ZNF395) is the direct functional target gene for miR-525-3p, and it is frequently down-regulated in liver cancer tissues. High expression of ZNF395 can significantly inhibit while knockdown of ZNF395 expression can markedly enhance the migration and invasion of liver cancer cells, suggesting that ZNF395 suppresses metastasis in liver cancer. Down-regulation of ZNF395 can mediate miR-525-3p induced liver cancer cell migration and invasion. In conclusion, miR-525-3p promotes liver cancer cell migration and invasion by directly targeting ZNF395, and the fact that miR-525-3p and ZNF395 both play important roles in liver cancer progression makes them potential therapeutic targets. PMID:24599008

  1. Genetic alterations of RD(INK4/ARF) enhancer in human cancer cells.

    Science.gov (United States)

    Li, Junan; Knobloch, Thomas J; Poi, Ming J; Zhang, Zhaoxia; Davis, Andrew T; Muscarella, Peter; Weghorst, Christopher M

    2014-03-01

    Recent identification of an enhancer element, RD(INK4/ARF) (RD), in the prominent INK4/ARF locus provides a novel mechanism to simultaneously regulate the transcription of p15(INK4B) (p15), p14(ARF) , and p16(INK4A) (p16) tumor suppressor genes. While genetic inactivation of p15, p14(ARF) , and p16 in human tumors has been extensively studied, little is known about genetic alterations of RD and its impact on p15, p14(ARF) , and p16 in human cancer. The purpose of this study was to investigate the potential existence of genetic alterations of RD in human cancer cells. DNAs extracted from 17 different cancer cell lines and 31 primary pheochromocytoma tumors were analyzed for deletion and mutation of RD using real-time PCR and direct DNA sequencing. We found that RD was deleted in human cancer cell lines and pheochromocytoma tumors at frequencies of 41.2% (7/17) and 13.0% (4/31), respectively. While some of these RD deletion events occurred along with deletions of the entire INK4/ARF locus, other RD deletion events were independent of genetic alterations in p15, p14(ARF) , and p16. Furthermore, the status of RD was poorly associated with the expression of p15, p14(ARF) , and p16 in tested cancer cell lines and tumors. This study demonstrates for the first time that deletion of the RD enhancer is a prevalent event in human cancer cells. Its implication in carcinogenesis remains to be further explored. © 2013 Wiley Periodicals, Inc.

  2. Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals

    Science.gov (United States)

    Chuan, Li; Jia, Zhang; Yu-Jiao, Zu; Shu-Fang, Nie; Jun, Cao; Qian, Wang; Shao-Ping, Nie; Ze-Yuan, Deng; Ming-Yong, Xie; Shu, Wang

    2017-01-01

    Many phytochemicals show promise in cancer prevention and treatment, but their low aqueous solubility, poor stability, unfavorable bioavailability, and low target specificity make administering them at therapeutic doses unrealistic. This is particularly true for (–)-epigallocatechin gallate, curcumin, quercetin, resveratrol, and genistein. There is an increasing interest in developing novel delivery strategies for these natural products. Liposomes, micelles, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers and poly (lactide-co-glycolide) nanoparticles are biocompatible and biodegradable nanoparticles. Those nanoparticles can increase the stability and solubility of phytochemicals, exhibit a sustained release property, enhance their absorption and bioavailability, protect them from premature enzymatic degradation or metabolism, prolong their circulation time, improve their target specificity to cancer cells or tumors via passive or targeted delivery, lower toxicity or side-effects to normal cells or tissues through preventing them from prematurely interacting with the biological environment, and enhance anti-cancer activities. Nanotechnology opens a door for developing phytochemical-loaded nanoparticles for prevention and treatment of cancer. PMID:26412423

  3. Crystal structure of myotoxin-II: a myotoxic phospholipase A{sub 2} - homologue from Bothrops moojeni venom

    Energy Technology Data Exchange (ETDEWEB)

    Azevedo, W.F.; Ward, R.J.; Lombardi, F.R.; Arni, R.K. [UNESP, Sao Jose do Rio Preto, SP (Brazil). Inst. de Biociencias, Letras e Ciencias Exatas; Soares, A.M.; Giglio, J.R. [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Escola de Medicina; Fontes, M.R.M. [UNESP, Botucatu, SP (Brazil). Inst. Biofisica

    1997-12-31

    Full text. Phospho lipases A2 (PLA{sub 2}; E C 3.1.1.4, phosphatides s n-2 acyl hydrolases) hydrolysis the s n-2 ester bond of phospholipids showing enhanced activity at lamellar or membrane surfaces. Intracellular PLA{sub 2} s are involved at phospholipid metabolism and signal transduction, whereas extracellular PLA{sub 2} s are found in mammalian pancreatic juices, the venoms of snakes, lizards and insects. Based on their high primary sequence similarity, extracellular PLA{sub 2} s are separated into Classes I, II and III. Class II PLA{sub 2} s are found in snake venoms of Crotalidae an Viperidae species, and include the sub-family of Lys PLA{sub 2} s homologue. he coordination of the Ca{sup 2+} ion in the PLA{sub 2} calcium-binding loop includes and aspartate at position 49. In the catalytically active PLA{sub 2} s, this calcium ion plays a critical role in the stabilization of the tetrahedral transition state intermediate in the catalytic mechanism. The conservative substitution Asp49-Lys results in a decreased calcium affinity with a concomitant loss of catalytic activity, and naturally occurring PLA{sub 2} s-homologues showing the same substitution are catalytically inactive. However, the Lys PLA{sub 2} s possess cytolytic and myotoxic activities and furthermore retain the ability to disrupt the integrity of both plasma membranes and model lipid layers by a ca{sup 2+}-independent mechanism for which there is no evidence of lipid hydrolysis. Lys 49 PLA{sub 2} homologues have been isolated from several Bothrops spp. venoms including B. moojeni. Therefore, in order to improve our understanding of the molecular basis of the myotoxic and Ca{sup 2+} independent membrane damaging activities we have determined the crystal structure of MjTX-II, a Lys 49 homologue from the venom of B. moojeni. The model presented has been determined at 2.0 A resolution and refined to a crystallographic residual of 19.7% (R{sub f}ree=28.1%). (author)

  4. Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells.

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M; Vadgama, Jaydutt V

    2015-02-01

    We investigated whether a combination of two promising chemopreventive agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of Arc and Q alone or in combination for 48 h. The antiproliferative activity of Arc was 10- to 20-fold stronger than Q in both cell lines. Their combination synergistically enhanced the antiproliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  6. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chih-Hao [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Neurosurgery, Department of Surgery, Kaohsiung Veterans General Hospital, Taiwan, ROC (China); Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Kuo, Shyh Ming [Department of Biomedical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Guei-Sheung [Centre for Eye Research Australia, University of Melbourne (Australia); Chen, Wan-Nan U. [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China); Chuang, Chin-Wen [Department of Electrical Engineering, I-Shou University, Taiwan, ROC (China); Liu, Li-Feng, E-mail: liulf@isu.edu.tw [Department of Biological Science and Technology, I-Shou University, Taiwan, ROC (China)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. Black-Right-Pointing-Pointer Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. Black-Right-Pointing-Pointer 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 {mu}m porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  7. Aromaticity in Group 14 homologues of the cyclopropenylium cation.

    Science.gov (United States)

    Fernández, Israel; Duvall, Matthew; I-Chia Wu, Judy; Schleyer, Paul von Ragué; Frenking, Gernot

    2011-02-11

    The nature of the bonding and the aromaticity of the heavy Group 14 homologues of cyclopropenylium cations E3H3+ and E2H2E'H+ (E, E' = C-Pb) have been investigated systematically at the BP86/TZ2P DFT level by using several methods. Aromatic stabilization energies (ASE) were evaluated from the values obtained from energy decomposition analysis (EDA) of charged acyclic reference molecules. The EDA-ASE results compare well with the extra cyclic resonance energy (ECRE) values given by the block localized wavefunction (BLW) method. Although all compounds investigated are Hückel 4n+2 π electron species, their ASEs indicate that the inclusion of Group 14 elements heavier than carbon reduces the aromaticity; the parent C3H3+ ion and Si2H2CH+ are the most aromatic, and Pb3H3+ is the least so. The higher energies for the cyclopropenium analogues reported in 1995 employed an isodesmic scheme, and are reinterpreted by using the BLW method. The decrease in the strength of both the π cyclic conjugation and the aromaticity in the order C ≫ Si>Ge>Sn>Pb agrees reasonably well with the trends given by the refined nucleus-independent chemical shift NICS(0)πzz index.

  8. Pollen allergen homologues in barley and other crop species.

    Science.gov (United States)

    Astwood, J D; Mohapatra, S S; Ni, H; Hill, R D

    1995-01-01

    Pollen from 10 agricultural plant species was surveyed for the presence of proteins crossreactive with group I, group IV and group IX allergens. Barley (Hordeum vulgare), maize (Zea mays), rye (Secale cerale), triticale (xTriticosecale cereale), oats (Avena sativa), Canola (Brassica napus) and sunflower (Helianthus annus) pollens contained numerous allergen cognate proteins. Northern blot analysis of barley pollen RNA revealed the presence of group I and group IX allergen transcripts. The barley pollen cDNA hvp9742, and three other cloned allergens: phlenum protense (Phl p) V, Phl p Va and Lolium perenne (Lol p) 1b, were demonstrated to have extensive nucleotide and amino acid sequence similarity to the Poa p IX isoallergens. It was concluded that hvp9742 represents a Poa p IX isoallergen homologue expressed by barley pollen, and was therefore designated Hor v IX. It is further shown that the most highly conserved domains of all seven proteins, including Hor v IX, map to previously defined Poa p IX antibody binding epitopes.

  9. Plant retinoblastoma homologues control nuclear proliferation in the female gametophyte.

    Science.gov (United States)

    Ebel, Chantal; Mariconti, Luisa; Gruissem, Wilhelm

    2004-06-17

    Haploid spores of plants divide mitotically to form multicellular gametophytes. The female spore (megaspore) of most flowering plants develops by means of a well-defined programme into the mature megagametophyte consisting of the egg apparatus and a central cell. We investigated the role of the Arabidopsis retinoblastoma protein homologue and its function as a negative regulator of cell proliferation during megagametophyte development. Here we show that three mutant alleles of the gene for the Arabidopsis retinoblastoma-related protein, RBR1 (ref. 4), are gametophytic lethal. In heterozygous plants 50% of the ovules are aborted when the mutant allele is maternally inherited. The mature unfertilized mutant megagametophyte fails to arrest mitosis and undergoes excessive nuclear proliferation in the embryo sac. Supernumerary nuclei are present at the micropylar end of the megagametophyte, which develops into the egg apparatus and central cell. The central cell nucleus, which gives rise to the endosperm after fertilization, initiates autonomous endosperm development reminiscent of fertilization-independent seed (fis) mutants. Thus, RBR1 has a novel and previously unrecognized function in cell cycle control during gametogenesis and in the repression of autonomous endosperm development.

  10. Dynamic Contrast-Enhanced MRI of Cervical Cancers: Temporal Percentile Screening of Contrast Enhancement Identifies Parameters for Prediction of Chemoradioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Erlend K.F. [Department of Medical Physics, Oslo University Hospital, Oslo (Norway); Hole, Knut Hakon; Lund, Kjersti V. [Department of Radiology, Oslo University Hospital, Oslo (Norway); Sundfor, Kolbein [Department of Gynaecological Oncology, Oslo University Hospital, Oslo (Norway); Kristensen, Gunnar B. [Department of Gynaecological Oncology, Oslo University Hospital, Oslo (Norway); Institute for Medical Informatics, Oslo University Hospital, Oslo (Norway); Lyng, Heidi [Department of Radiation Biology, Oslo University Hospital, Oslo (Norway); Malinen, Eirik, E-mail: eirik.malinen@fys.uio.no [Department of Medical Physics, Oslo University Hospital, Oslo (Norway); Department of Physics, University of Oslo, Oslo (Norway)

    2012-03-01

    Purpose: To systematically screen the tumor contrast enhancement of locally advanced cervical cancers to assess the prognostic value of two descriptive parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods and Materials: This study included a prospectively collected cohort of 81 patients who underwent DCE-MRI with gadopentetate dimeglumine before chemoradiotherapy. The following descriptive DCE-MRI parameters were extracted voxel by voxel and presented as histograms for each time point in the dynamic series: normalized relative signal increase (nRSI) and normalized area under the curve (nAUC). The first to 100th percentiles of the histograms were included in a log-rank survival test, resulting in p value and relative risk maps of all percentile-time intervals for each DCE-MRI parameter. The maps were used to evaluate the robustness of the individual percentile-time pairs and to construct prognostic parameters. Clinical endpoints were locoregional control and progression-free survival. The study was approved by the institutional ethics committee. Results: The p value maps of nRSI and nAUC showed a large continuous region of percentile-time pairs that were significantly associated with locoregional control (p < 0.05). These parameters had prognostic impact independent of tumor stage, volume, and lymph node status on multivariate analysis. Only a small percentile-time interval of nRSI was associated with progression-free survival. Conclusions: The percentile-time screening identified DCE-MRI parameters that predict long-term locoregional control after chemoradiotherapy of cervical cancer.

  11. Noninvasive enhanced mid-IR imaging of breast cancer development in vivo

    Science.gov (United States)

    Case, Jason R.; Young, Madison A.; Dréau, D.; Trammell, Susan R.

    2015-11-01

    Lumpectomy coupled with radiation therapy and/or chemotherapy is commonly used to treat breast cancer patients. We are developing an enhanced thermal IR imaging technique that has the potential to provide real-time imaging to guide tissue excision during a lumpectomy by delineating tumor margins. This enhanced thermal imaging method is a combination of IR imaging (8 to 10 μm) and selective heating of blood (˜0.5°C) relative to surrounding water-rich tissue using LED sources at low powers. Postacquisition processing of these images highlights temporal changes in temperature and the presence of vascular structures. In this study, fluorescent, standard thermal, and enhanced thermal imaging modalities, as well as physical caliper measurements, were used to monitor breast cancer tumor volumes over a 30-day study period in 19 mice implanted with 4T1-RFP tumor cells. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after day 22. The tumor volumes estimated from enhanced thermal imaging, standard thermal imaging, and caliper measurements all show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging, standard IR imaging, and caliper measurements with enhanced thermal imaging, indicating that enhanced thermal imaging monitors tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses associated with the tumor margin. In the future, this IR technique might be used to estimate tumor margins in real time during surgical procedures.

  12. Noninvasive enhanced mid-IR imaging of breast cancer development in vivo.

    Science.gov (United States)

    Case, Jason R; Young, Madison A; Dréau, D; Trammell, Susan R

    2015-11-01

    Lumpectomy coupled with radiation therapy and/or chemotherapy is commonly used to treat breast cancer patients. We are developing an enhanced thermal IR imaging technique that has the potential to provide real-time imaging to guide tissue excision during a lumpectomy by delineating tumor margins. This enhanced thermal imaging method is a combination of IR imaging (8 to 10  μm ) and selective heating of blood (∼0.5°C ) relative to surrounding water-rich tissue using LED sources at low powers. Postacquisition processing of these images highlights temporal changes in temperature and the presence of vascular structures. In this study, fluorescent, standard thermal, and enhanced thermal imaging modalities, as well as physical caliper measurements, were used to monitor breast cancer tumor volumes over a 30-day study period in 19 mice implanted with 4T1-RFP tumor cells. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after day 22. The tumor volumes estimated from enhanced thermal imaging, standard thermal imaging, and caliper measurements all show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging, standard IR imaging, and caliper measurements with enhanced thermal imaging, indicating that enhanced thermal imaging monitors tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses associated with the tumor margin. In the future, this IR technique might be used to estimate tumor margins in real time during surgical procedures.

  13. Rosiglitazone enhances the radiosensitivity of p53-mutant HT-29 human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Shu-Jun, E-mail: chiusj@mail.tcu.edu.tw [Department of Life Science, Tzu Chi University, Hualien, Taiwan (China); Institute of Radiation Sciences, Tzu Chi Technology College, Hualien, Taiwan (China); Hsaio, Ching-Hui; Tseng, Ho-Hsing; Su, Yu-Han [Department of Life Science, Tzu Chi University, Hualien, Taiwan (China); Shih, Wen-Ling [Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung, Taiwan (China); Lee, Jeng-Woei; Chuah, Jennifer Qiu-Yu [Department of Life Science, Tzu Chi University, Hualien, Taiwan (China)

    2010-04-09

    Combined-modality treatment has improved the outcome in cases of various solid tumors, and radiosensitizers are used to enhance the radiotherapeutic efficiency. Rosiglitazone, a synthetic ligand of peroxisome proliferator-activated receptors {gamma} used in the treatment of type-2 diabetes, has been shown to reduce tumor growth and metastasis in human cancer cells, and may have the potential to be used as a radiosensitizer in radiotherapy for human colorectal cancer cells. In this study, rosiglitazone treatment significantly reduced the cell viability of p53-wild type HCT116 cells but not p53-mutant HT-29 cells. Interestingly, rosiglitazone pretreatment enhanced radiosensitivity in p53-mutant HT-29 cells but not HCT116 cells, and prolonged radiation-induced G{sub 2}/M arrest and enhanced radiation-induced cell growth inhibition in HT-29 cells. Pretreatment with rosiglitazone also suppressed radiation-induced H2AX phosphorylation in response to DNA damage and AKT activation for cell survival; on the contrary, rosiglitazone pretreatment enhanced radiation-induced caspase-8, -9, and -3 activation and PARP cleavage in HT-29 cells. In addition, pretreatment with a pan-caspase inhibitor, zVAD-fmk, attenuated the levels of caspase-3 activation and PARP cleavage in radiation-exposed cancer cells in combination with rosiglitazone pretreatment. Our results provide proof for the first time that rosiglitazone suppresses radiation-induced survival signals and DNA damage response, and enhances the radiation-induced apoptosis signaling cascade. These findings can assist in the development of rosiglitazone as a novel radiosensitizer.

  14. Resveratrol enhances antitumor activity of TRAIL in prostate cancer xenografts through activation of FOXO transcription factor.

    Directory of Open Access Journals (Sweden)

    Suthakar Ganapathy

    Full Text Available BACKGROUND: Resveratrol (3, 4', 5 tri-hydroxystilbene, a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining and inducing apoptosis (TUNEL staining. The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27(/KIP1, and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells and markers of metastasis (MMP-2 and MMP-9. The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity. CONCLUSIONS/SIGNIFICANCE: These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer.

  15. Comparison of gadobenate dimeglumine-enhanced breast MRI and gadopentetate dimeglumine-enhanced breast MRI with mammography and ultrasound for the detection of breast cancer.

    Science.gov (United States)

    Gilbert, Fiona J; van den Bosch, Harrie C M; Petrillo, Antonella; Siegmann, Katja; Heverhagen, Johannes T; Panizza, Pietro; Gehl, Hans-Björn; Pediconi, Federica; Diekmann, Felix; Peng, Wei-Jun; Ma, Lin; Sardanelli, Francesco; Belli, Paolo; Corcione, Stefano; Zechmann, Christian M; Faivre-Pierret, Matthieu; Martincich, Laura

    2014-05-01

    To compare gadobenate dimeglumine-enhanced magnetic resonance imaging (MRI) with gadopentetate dimeglumine-enhanced MRI, mammography, and ultrasound for breast cancer detection across different malignant lesion types and across different densities of breast tissue. In all, 153 women with Breast Imaging Reporting and Data System (BI-RADS) 3–5 findings on mammography and/or ultrasound underwent identical breast MRI exams at 1.5T with gadobenate dimeglumine and gadopentetate dimeglumine. Images were evaluated by three independent blinded radiologists. Mammography, ultrasound, and combined mammography and/or ultrasound findings were available for 108, 109, and 131 women. Imaging findings were matched with histology data by a fourth, independent, blinded radiologist. Malignant lesion detection rates and diagnostic performance were compared. In all, 120, 120, and 140 confirmed malignant lesions were present in patients undergoing MRI+mammography, MRI+ultrasound, and MRI+mammography and/or ultrasound, respectively. Significantly greater cancer detection rates were noted by all three readers for comparisons of gadobenate dimeglumine-enhanced MRI with mammography (Δ15.8–17.5%; P gadopentetate dimeglumine-enhanced MRI with conventional techniques (P > 0.05). The false-positive detection rates were lower on gadobenate dimeglumine-enhanced MRI than on conventional imaging (4.0–5.5% vs. 11.1% at mammography; 6.3–8.4% vs. 15.5% at ultrasound). Significantly improved cancer detection on MRI was noted in heterogeneously dense breast (91.2–97.3% on gadobenate dimeglumine-enhanced MRI vs. 77.2–84.9% on gadopentetate dimeglumine-enhanced MRI vs. 71.9-84.9% with conventional techniques) and for invasive cancers (93.2–96.2% for invasive ductal carcinoma [IDC] on gadobenate dimeglumine-enhanced MRI vs. 79.7–88.5% on gadopentetate dimeglumine-enhanced MRI vs. 77.0–84.4% with conventional techniques). Overall diagnostic performance for the detection of cancer was

  16. Reconfiguration of nucleosome-depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancer

    National Research Council Canada - National Science Library

    Taberlay, Phillippa C; Statham, Aaron L; Kelly, Theresa K; Clark, Susan J; Jones, Peter A

    2014-01-01

    .... Here, we evaluate the scope of global epigenetic alterations at enhancers and insulator elements in prostate and breast cancer cells using simultaneous genome-wide mapping of DNA methylation and nucleosome occupancy (NOMe-seq...

  17. A randomized clinical trial with oral Immunonutrition (omega3-enhanced formula vs. arginine-enhanced formula) in ambulatory head and neck cancer patients.

    Science.gov (United States)

    de Luis, D A; Izaola, O; Aller, R; Cuellar, L; Terroba, M C

    2005-01-01

    The aim of our study was to investigate whether oral ambulatory nutrition of head and neck cancer patients, using an omega3 fatty acid-enhanced diet (low ratio omega6/omega3 fatty acids) versus an arginine-enhanced diet, could improve nutritional variables as well as clinical outcome, postoperative infectious and wound complications. A population of 73 ambulatory postsurgical patients with oral and laryngeal cancer were enrolled. At discharge from hospital the postsurgical head and neck cancer patients were asked to consume two units per day of either a specially designed omega3 fatty acid-enhanced supplement (group 1) or an arginine-enhanced supplement (group 2) for a 12-week period. No significant intergroup differences in the trend of the three serum proteins and lymphocytes were detected. Differences were detected in weight (group 1: 65.5 +/- 11.5 kg vs. 70.4 +/- 11.1 kg; p cancer patients. The arginine-enhanced formula improved proteins. Further studies are required to examine the potential role of immune-enhanced supplements. Copyright (c) 2005 S. Karger AG, Basel.

  18. IκB kinases increase Myc protein stability and enhance progression of breast cancer cells

    Directory of Open Access Journals (Sweden)

    Ou Da-Liang

    2011-05-01

    Full Text Available Abstract Background Both IκB kinase (IKK complex and oncgenic protein Myc play important roles in cancer progression, including cancer cell invasiveness and metastasis. The levels of Myc is regulated by the phosphorylation of Myc at Thr58 and Ser62. Results In this study, we show that the expression of Myc is associated with IKKα and IKKβ in breast cancers and that Myc is an IKKs substrate. Suppression of IKK activity by either chemical inhibitor or transfection of kinase-dead mutants decreases the phosphorylation of Myc at Ser62 and enhances the degradation of Myc. Consequently, these treatments decrease the tumorigenic and invasive ability of breast cancer cells. Furthermore, doxorubicin, a frequently used anticancer drug in breast cancer, activates IKKs and Myc, thereby increasing invasiveness and tumorigenesis of breast carcinoma MCF7 cells. Inhibition of IKKs prevents these doxorubicin-induced effects. Conclusions Our study indicates that IKKs tightly regulate Myc expression through prolonging protein stability, and suggests that IKKs are potentially therapeutic targets and that suppression of IKKs may be used following chemotherapy to reduce the risk of treatment-induced tumor progression.

  19. Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer

    Directory of Open Access Journals (Sweden)

    Joshua Runtuwene

    2015-04-01

    Full Text Available Oxidative stress is involved in cancer development. Hydrogen (H2 is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 incombination with 5-fluorouracil (5-FU in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan–Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK, Apoptosis-inducing factor (AIF and Caspase 3 were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with spect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger antioxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.

  20. C60(Nd) nanoparticles enhance chemotherapeutic susceptibility of cancer cells by modulation of autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Wei Pengfei; Zhang Li; Man Na; Wen Longping [Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui (China); Lu Yang, E-mail: lpwen@ustc.edu.cn [Division of Nanomaterials and Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui (China)

    2010-12-10

    Autophagy, an evolutionally conserved intracellular process degrading cytoplasmic proteins and organelles for recycling, has become one of the most remarkable strategies applied in cancer research. The fullerene C60 nanoparticle (nC60) has been shown to induce autophagy and sensitize chemotherapeutic killing of cancer cells, but the details still remain unknown. Here we show that a water-dispersed nanoparticle solution of derivatized fullerene C60, C60(Nd) nanoparticles (nC60(Nd)), has greater potential in inducing autophagy and sensitizing chemotherapeutic killing of both normal and drug-resistant cancer cells than nC60 does in an autophagy-dependent fashion. Additionally we further demonstrated that autophagy induced by nC60/C60(Nd) and Rapamycin had completely different roles in cancer chemotherapy. Our results, for the first time, revealed a novel and more potent derivative of the C60 nanoparticle in enhancing the cytotoxicity of chemotherapeutic agents and reducing drug resistance through autophagy modulation, which may ultimately lead to novel therapeutic strategies in cancer therapy.

  1. From patient to participant: enhancing the validity and ethics of cancer research through participatory research.

    Science.gov (United States)

    Chiu, Connie G; Mitchell, Terry L; Fitch, Margaret I

    2013-06-01

    Participatory health research involves a wide spectrum of participation from the population of study. We describe the participatory research processes of a large mixed method study on the psychosocial impact of dragon boating in individuals with breast cancer. In particular, we discuss the involvement of a Community Advisory Group (consisting of five breast cancer patients/survivors) in the development of the research study, data collection and analysis, and dissemination of the study results. We also outline the elements of a research workshop, in which 13 breast cancer patients/survivors were involved in the development of a provincial survey for the study. The purpose of this article is to share our experience of engaging cancer patients/survivors in a participatory research study. We discuss the value-based elements of participatory research (power sharing, voice and respect, reciprocity, and mutual benefit), and provide a case-based example of how these participatory elements were employed to potentially increase the validity of the survey instrument, to enhance the ethics of working with a cancer population, and ultimately contributed to a high survey response rate.

  2. Enhanced antitumor activity of doxorubicin in breast cancer through the use of poly(butylcyanoacrylate) nanoparticles.

    Science.gov (United States)

    Cabeza, Laura; Ortiz, Raúl; Arias, José L; Prados, Jose; Ruiz Martínez, Maria Adolfina; Entrena, José M; Luque, Raquel; Melguizo, Consolación

    2015-01-01

    The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers.

  3. Contrast-enhanced spectral mammography in patients referred from the breast cancer screening programme.

    Science.gov (United States)

    Lobbes, Marc B I; Lalji, Ulrich; Houwers, Janneke; Nijssen, Estelle C; Nelemans, Patty J; van Roozendaal, Lori; Smidt, Marjolein L; Heuts, Esther; Wildberger, Joachim E

    2014-07-01

    Feasibility studies have shown that contrast-enhanced spectral mammography (CESM) increases diagnostic accuracy of mammography. We studied diagnostic accuracy of CESM in patients referred from the breast cancer screening programme, who have a lower disease prevalence than previously published papers on CESM. During 6 months, all women referred to our hospital were eligible for CESM. Two radiologists blinded to the final diagnosis provided BI-RADS classifications for conventional mammography and CESM. Statistical significance of differences between mammography and CESM was calculated using McNemar's test. Receiver operating characteristic (ROC) curves were constructed for both imaging modalities. Of the 116 eligible women, 113 underwent CESM. CESM increased sensitivity to 100.0% (+3.1%), specificity to 87.7% (+45.7%), PPV to 76.2% (+36.5%) and NPV to 100.0% (+2.9%) as compared to mammography. Differences between conventional mammography and CESM were statistically significant (p mammography, AUC was 0.779. With CESM, AUC increased to 0.976 (p mammography, even in lower prevalence patient populations such as referrals from breast cancer screening. • CESM is feasible in the workflow of referrals from routine breast screening. • CESM is superior to mammography, even in low disease prevalence populations. • CESM has an extremely high negative predictive value for breast cancer. • CESM is comparable to MRI in assessment of breast cancer extent. • CESM is comparable to histopathology in assessment of breast cancer extent.

  4. Long Noncoding RNA MALAT-1 Enhances Stem Cell-Like Phenotypes in Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Feng Jiao

    2015-03-01

    Full Text Available Cancer stem cells (CSCs play a vital role in tumor initiation, progression, metastasis, chemoresistance, and recurrence. The mechanisms that maintain the stemness of these cells remain largely unknown. Our previous study indicated that MALAT-1 may serve as an oncogenic long noncoding RNA in pancreatic cancer by promoting epithelial-mesenchymal transition (EMT and regulating CSCs markers expression. More significantly, there is emerging evidence that the EMT process may give rise to CSCs, or at least cells with stem cell-like properties. Therefore, we hypothesized that MALAT-1 might enhance stem cell-like phenotypes in pancreatic cancer cells. In this study, our data showed that MALAT-1 could increase the proportion of pancreatic CSCs, maintain self-renewing capacity, decrease the chemosensitivity to anticancer drugs, and accelerate tumor angiogenesis in vitro. In addition, subcutaneous nude mouse xenografts revealed that MALAT-1 could promote tumorigenicity of pancreatic cancer cells in vivo. The underlying mechanisms may involve in increased expression of self-renewal related factors Sox2. Collectively, we for the first time found the potential effects of MALAT-1 on the stem cell-like phenotypes in pancreatic cancer cells, suggesting a novel role of MALAT-1 in tumor stemness, which remains to be fully elucidated.

  5. Saliva surface-enhanced Raman spectroscopy for noninvasive optical detection of nasopharyngeal cancer

    Science.gov (United States)

    Lin, Xueliang; Ge, Xiaosong; Xu, Zhihong; Zheng, Zuci; Huang, Wei; Hong, Quanxing; Lin, Duo

    2016-10-01

    The early cancer detection is of great significance to increase the patient's survival rate and reduce the risk of cancer development. Surface enhanced Raman spectroscopy (SERS) technique, a rapid, convenient, nondestructive optical detection method, can provide a characteristic "fingerprint" information of target substances, even achieving single molecule detection. Its ultra-high detection sensitivity has made it become one of the most potential biochemical detection methods. Saliva, a multi-constituent oral fluid, contains the bio-markers which is capable of reflecting the systemic health condition of human, showing promising potential as an effect medium for disease monitoring. Compared with the serum samples, the collection and processing of saliva is safer, more convenient and noninvasive. Thus, saliva test is becoming the hotspot issues of the noninvasive cancer research field. This review highlights and analyzes current application progress within the field of SERS saliva test in cancer detection. Meanwhile, the primary research results of SERS saliva for the noninvasive differentiation of nasopharyngeal cancer, normal and rhinitis obtained by our group are shown.

  6. Enhanced Recovery After Surgery for Advanced Ovarian Cancer: A Systematic Review of Interventions Trialed.

    Science.gov (United States)

    Lindemann, Kristina; Kok, Peey-Sei; Stockler, Martin; Jaaback, Ken; Brand, Alison

    2017-07-01

    We sought to summarize the evidence for interventions aiming at enhanced recovery after surgery (ERAS) in ovarian cancer through a systematic review. We searched MEDLINE, EMBASE, and The Cochrane Library for studies testing ERAS interventions in patients undergoing surgery for ovarian cancer. Study selection and data extraction were done independently by 2 reviewers with disagreements resolved by discussion with a senior, third reviewer. We identified 25 studies including 1648 participants with ovarian cancer. Nine observational studies addressed ERAS protocols. Four of them were prospective, and 3 included historical controls. The other 16 studies reported single interventions, for example, early feeding, omission of pelvic drains, early orogastric tube removal, Doppler-guided fluid management, and patient-controlled epidural analgesia. Early feeding protocols were tested in 7 of the 12 randomized trials. Early feeding appeared to be safe and was associated with significantly faster recovery of bowel function. Few studies have specifically studied ERAS interventions in ovarian cancer. All studies on protocols including multiple interventions were susceptible to bias. Early feeding is the intervention that is best supported by randomized trials. Application of evidence for ERAS derived from nonovarian cancer is challenged by the differences not only in the scope of surgery but also in ovarian cancer patients' comorbidities. Postoperative morbidity is particularly high in these patients because of their poor nutritional status, perioperative fluids shifts, and long operating times. These patients may also show excessive response to surgical stress. Innovative, randomized trials are needed to reliably determine the feasibility, safety, and effectiveness of specific ERAS interventions in ovarian cancer.

  7. Enhanced therapeutic efficacy of LHRHa-targeted brucea javanica oil liposomes for ovarian cancer.

    Science.gov (United States)

    Ye, Hongxia; Liu, Xiaojuan; Sun, Jiangchuan; Zhu, Shenyin; Zhu, Yi; Chang, Shufang

    2016-10-29

    Although brucea javanica oil liposomes (BJOLs) have been used clinically to treat ovarian cancer, its clinical efficacy is often limited by systemic side effects due to non-specific distribution. Luteinizing hormone releasing hormone receptor (LHRHR) is overexpressed in most ovarian cancers but negligibly expressed in most of the other visceral organs. In this study, we aimed to develop a novel LHRHa targeted and BJO-loaded liposomes (LHRHa-BJOLs), and investigate its characteristics, targeting ability and anti-ovarian cancer efficiency both in vitro and in vivo. The LHRHa-BJOLs were prepared by film-dispersion and biotin-streptavidin linkage methods, and characterized in terms of its morphology, particle size, zeta potential, ligand conjugation, encapsulation efficiency and stability. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured human ovarian cancer A2780/DDP cells, and in vivo using ovarian cancer-bearing nude mice. The LHRHa-BJOLs were successfully synthesized, with a uniformly spherical shape, appropriate particle size and zeta potential, as well as a high encapsulation efficiency. Compared to non-targeted liposomes and BJO emulsion, the LHRHa-BJOLs could significantly increase specific intracellular uptaking rate, enhance cell inhibitory effect and induce cell apoptosis in A2780/DDP cells in vitro. Meanwhile, LHRHa-BJOLs also had a significantly stronger activity of targeting tumor tissue, inhibiting tumor growth, inducing tumor apoptosis and prolonging survival time in ovarian cancer-bearing mice in vivo. Our experiment suggests that LHRHa-BJOLs may be a useful targeted drug for the treatment of ovarian cancer.

  8. Enhanced ZAG production by subcutaneous adipose tissue is linked to weight loss in gastrointestinal cancer patients.

    Science.gov (United States)

    Mracek, T; Stephens, N A; Gao, D; Bao, Y; Ross, J A; Rydén, M; Arner, P; Trayhurn, P; Fearon, K C H; Bing, C

    2011-02-01

    Profound loss of adipose tissue is a hallmark of cancer cachexia. Zinc-α2-glycoprotein (ZAG), a recently identified adipokine, is suggested as a candidate in lipid catabolism. In the first study, eight weight-stable and 17 cachectic cancer patients (weight loss 5% in previous 6 months) were recruited. Zinc-α2-glycoprotein mRNA and protein expression were assessed in subcutaneous adipose tissue (SAT), subcutaneous adipose tissue morphology was examined and serum ZAG concentrations were quantified. In the second cohort, ZAG release by SAT was determined in 18 weight-stable and 15 cachectic cancer patients. The effect of ZAG on lipolysis was evaluated in vitro. Subcutaneous adipose tissue remodelling in cancer cachexia was evident through shrunken adipocytes with increased fibrosis. In cachectic cancer patients, ZAG mRNA was upregulated (2.7-fold, P=0.028) while leptin mRNA decreased (2.2-fold, P=0.018); serum ZAG levels were found to be unaffected. Zinc-α2-glycoprotein mRNA correlated positively with weight loss (r=0.51, P=0.01) and serum glycerol levels (r=0.57, P=0.003). Zinc-α2-glycoprotein release by SAT was also elevated in cachectic patients (1.5-fold, P=0.024) and correlated with weight loss (r=0.50, P=0.003). Recombinant ZAG stimulated lipolysis in human adipocytes. Zinc-α2-glycoprotein expression and secretion by adipose tissue is enhanced in cachectic cancer patients. Given its lipid-mobilising effect, ZAG may contribute to adipose atrophy associated with cancer cachexia in human beings.

  9. Icaritin Synergistically Enhances the Radiosensitivity of 4T1 Breast Cancer Cells

    Science.gov (United States)

    Lv, Wenlong; Zhang, Mei; Chen, Chun; Yang, Shanmin; Li, Shan; Zhang, Lurong; Han, Deping; Zhang, Weijian

    2013-01-01

    Icaritin (ICT) is a hydrolytic form of icariin isolated from plants of the genus Epimedium. This study was to investigate the radiosensitization effect of icaritin and its possible underlying mechanism using murine 4T1 breast cancer cells. The combination of Icaritin at 3 µM or 6 µM with 6 or 8 Gy of ionizing radiation (IR) in the clonogenic assay yielded an ER (enhancement ratio) of 1.18 or 1.28, CI (combination index) of 0.38 or 0.19 and DRI (dose reducing index) of 2.51 or 5.07, respectively. These strongly suggest that Icaritin exerted a synergistic killing (?) effect with radiation on the tumor cells. This effect might relate with bioactivities of ICT: 1) exert an anti-proliferative effect in a dose- and time-dependent manner, which is different from IR killing effect but likely work together with the IR effect; 2) suppress the IR-induced activation of two survival paths, ERK1/2 and AKT; 3) induce the G2/M blockage, enhancing IR killing effect; and 4) synergize with IR to enhance cell apoptosis. In addition, ICT suppressed angiogenesis in chick embryo chorioallantoic membrane (CAM) assay. Taken together, ICT is a new radiosensitizer and can enhance anti-cancer effect of IR or other therapies. PMID:23977023

  10. Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis

    OpenAIRE

    Shankar, Sharmila; Chen, Qinghe; Sarva, Krishna; Siddiqui, Imtiaz; Srivastava, Rakesh K

    2007-01-01

    Background: We have recently shown that curcumin (a diferuloylmethane) inhibits growth and induces apoptosis, and also demonstrated that TRAIL induces apoptosis by binding to specific cell surface death receptors in prostate cancer cells. The objectives of this paper were to investigate the molecular mechanisms by which curcumin enhanced the apoptosis-inducing potential of TRAIL in prostate cancer cells.Results: Curcumin enhanced the apoptosis-inducing potential of TRAIL in androgen-unrespons...

  11. Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages.

    Science.gov (United States)

    Liu, Yueying; Metzinger, Matthew N; Lewellen, Kyle A; Cripps, Stephanie N; Carey, Kyle D; Harper, Elizabeth I; Shi, Zonggao; Tarwater, Laura; Grisoli, Annie; Lee, Eric; Slusarz, Ania; Yang, Jing; Loughran, Elizabeth A; Conley, Kaitlyn; Johnson, Jeff J; Klymenko, Yuliya; Bruney, Lana; Liang, Zhong; Dovichi, Norman J; Cheatham, Bentley; Leevy, W Matthew; Stack, M Sharon

    2015-12-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intraperitoneal metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional mesomimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced intraperitoneal tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histologic analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently affects ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival. ©2015 American Association for Cancer Research.

  12. Nanoparticle-enhanced synergistic HIFU ablation and transarterial chemoembolization for efficient cancer therapy

    Science.gov (United States)

    You, Yufeng; Wang, Zhigang; Ran, Haitao; Zheng, Yuanyi; Wang, Dong; Xu, Jinshun; Wang, Zhibiao; Chen, Yu; Li, Pan

    2016-02-01

    High-intensity focused ultrasound (HIFU) is being generally explored as a non-invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high-efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment.

  13. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

    Science.gov (United States)

    Allen, Bryan G; Bhatia, Sudershan K; Buatti, John M; Brandt, Kristin E; Lindholm, Kaleigh E; Button, Anna M; Szweda, Luke I; Smith, Brian J; Spitz, Douglas R; Fath, Melissa A

    2013-07-15

    Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress. Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a ketogenic diet (KetoCal 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8-2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modified proteins as a marker of oxidative stress as well as proliferating cell nuclear antigen (PCNA) and γH2AX as indices of proliferation and DNA damage, respectively. The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (P ketogenic diet also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a ketogenic diet in combination with radiation showed increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA. These results show that a ketogenic diet enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress.

  14. Blockade of chloride ion transport enhances the cytocidal effect of hypotonic solution in gastric cancer cells.

    Science.gov (United States)

    Iitaka, Daisuke; Shiozaki, Atsushi; Ichikawa, Daisuke; Kosuga, Toshiyuki; Komatsu, Shuhei; Okamoto, Kazuma; Fujiwara, Hitoshi; Ishii, Hiromichi; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

    2012-08-01

    Cancer cells that are exfoliated into the peritoneal cavity during surgery are viable and have the potential to produce peritoneal recurrence. Although peritoneal lavage with distilled water is applied in some cancer surgeries to kill tumor cells, there is no consensus regarding the optimal methodology and its effects. Three human gastric cancer cell lines, MKN28, MKN45, and Kato-III, were exposed to distilled water, and the resultant morphologic changes were observed using a microscope. Analysis of cell volume changes was performed using a flow cytometer. To investigate the cytocidal effects of the water, re-incubation of the cells was performed after exposing them to hypotonic solution. Additionally, the effects of 5-nitro-2-3-phenylpropylamino)-benzoic acid (NPPB), a Cl(-) channel blocker, and R(+)-[(dihydroindenyl)oxy] alkanoic acid (DIOA), a blocker of the K(+)/Cl(-) co-transporter, on the cells during their exposure to hypotonic solution were analyzed. After the cells had been exposed to the distilled water, a rapid increase in cell volume occurred followed by cell rupture. In the MKN45 and Kato-III cells, treatment with NPPB increased cell volume by inhibiting regulatory volume decrease and enhanced the cytocidal effects of the hypotonic solution, whereas no such effects were observed in the MKN28 cells. On the other hand, treatment of the MKN28 cells with DIOA inhibited RVD and enhanced the cytocidal effects of hypotonic shock. These findings support the efficacy of peritoneal lavage with distilled water during surgery for gastric cancer and suggest that the regulation of Cl(-) transport enhances the cytocidal effects of hypotonic shock. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Additively Enhanced Antiproliferative Effect of Interferon Combined with Proanthocyanidin on Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrew I. Fishman, Blake Johnson, Bobby Alexander, John Won, Muhammad Choudhury, Sensuke Konno

    2012-01-01

    Full Text Available Although interferon (IFN has been often used as immunotherapy for bladder cancer, its efficacy is rather unsatisfactory, demanding further improvement. Combination therapy is one of viable options, and grape seed proanthocyanidin (GSP could be such an agent to be used with IFN because it has been shown to have anticancer activity. We thus investigated whether combination of IFN and GSP might enhance the overall antiproliferative effect on bladder cancer cells in vitro. Human bladder cancer T24 cells were employed and treated with the varying concentrations of recombinant IFN-α2b (0-100,000 IU/ml, GSP (0-100 μg/ml, or their combinations. IFN-α2b alone led to a ~50% growth reduction at 20,000 (20K IU/ml, which further declined to ~67% at ≥50K IU/ml. Similarly, GSP alone induced a ~35% and ~100% growth reduction at 25 and ≥50 μg/ml, respectively. When IFN-α2b and GSP were then combined, combination of 50K IU/ml IFN-α2b and 25 μg/ml GSP resulted in a drastic >95% growth reduction. Cell cycle analysis indicated that such an enhanced growth inhibition was accompanied by a G1 cell cycle arrest. This was further confirmed by Western blot analysis revealing that expressions of G1-specific cell cycle regulators (CDK2, CDK4, cyclin E and p27/Kip1 were distinctly modulated with such IFN-α2b/GSP treatment. Therefore, these findings support the notion that combination of IFN-α2b and GSP is capable of additively enhancing antiproliferative effect on T24 cells with a G1 cell cycle arrest, implying an adjuvant therapeutic modality for superficial bladder cancer.

  16. The WAGR syndrome gene PRRG4 is a functional homologue of the commissureless axon guidance gene.

    Science.gov (United States)

    Justice, Elizabeth D; Barnum, Sarah J; Kidd, Thomas

    2017-08-01

    WAGR syndrome is characterized by Wilm's tumor, aniridia, genitourinary abnormalities and intellectual disabilities. WAGR is caused by a chromosomal deletion that includes the PAX6, WT1 and PRRG4 genes. PRRG4 is proposed to contribute to the autistic symptoms of WAGR syndrome, but the molecular function of PRRG4 genes remains unknown. The Drosophila commissureless (comm) gene encodes a short transmembrane protein characterized by PY motifs, features that are shared by the PRRG4 protein. Comm intercepts the Robo axon guidance receptor in the ER/Golgi and targets Robo for degradation, allowing commissural axons to cross the CNS midline. Expression of human Robo1 in the fly CNS increases midline crossing and this was enhanced by co-expression of PRRG4, but not CYYR, Shisa or the yeast Rcr genes. In cell culture experiments, PRRG4 could re-localize hRobo1 from the cell surface, suggesting that PRRG4 is a functional homologue of Comm. Comm is required for axon guidance and synapse formation in the fly, so PRRG4 could contribute to the autistic symptoms of WAGR by disturbing either of these processes in the developing human brain.

  17. The WAGR syndrome gene PRRG4 is a functional homologue of the commissureless axon guidance gene.

    Directory of Open Access Journals (Sweden)

    Elizabeth D Justice

    2017-08-01

    Full Text Available WAGR syndrome is characterized by Wilm's tumor, aniridia, genitourinary abnormalities and intellectual disabilities. WAGR is caused by a chromosomal deletion that includes the PAX6, WT1 and PRRG4 genes. PRRG4 is proposed to contribute to the autistic symptoms of WAGR syndrome, but the molecular function of PRRG4 genes remains unknown. The Drosophila commissureless (comm gene encodes a short transmembrane protein characterized by PY motifs, features that are shared by the PRRG4 protein. Comm intercepts the Robo axon guidance receptor in the ER/Golgi and targets Robo for degradation, allowing commissural axons to cross the CNS midline. Expression of human Robo1 in the fly CNS increases midline crossing and this was enhanced by co-expression of PRRG4, but not CYYR, Shisa or the yeast Rcr genes. In cell culture experiments, PRRG4 could re-localize hRobo1 from the cell surface, suggesting that PRRG4 is a functional homologue of Comm. Comm is required for axon guidance and synapse formation in the fly, so PRRG4 could contribute to the autistic symptoms of WAGR by disturbing either of these processes in the developing human brain.

  18. Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor.

    Science.gov (United States)

    Babitt, Jodie L; Zhang, Ying; Samad, Tarek A; Xia, Yin; Tang, Jie; Campagna, Jason A; Schneyer, Alan L; Woolf, Clifford J; Lin, Herbert Y

    2005-08-19

    Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta (TGF-beta) superfamily of ligands, which regulate many mammalian physiologic and pathophysiologic processes. BMPs exert their effects through type I and type II serine/threonine kinase receptors and the Smad intracellular signaling pathway. Recently, the glycosylphosphatidylinositol (GPI)-anchored protein DRAGON was identified as a co-receptor for BMP signaling. Here, we investigate whether a homologue of DRAGON, repulsive guidance molecule (RGMa), is similarly involved in the BMP signaling pathway. We show that RGMa enhances BMP, but not TGF-beta, signals in a ligand-dependent manner in cell culture. The soluble extracellular domain of RGMa fused to human Fc (RGMa.Fc) forms a complex with BMP type I receptors and binds directly and selectively to radiolabeled BMP-2 and BMP-4. RGMa mediates BMP signaling through the classical BMP signaling pathway involving Smad1, 5, and 8, and it up-regulates endogenous inhibitor of differentiation (Id1) protein, an important downstream target of BMP signals. Finally, we demonstrate that BMP signaling occurs in neurons that express RGMa in vivo. These data are consistent with a role for RGMa as a BMP co-receptor.

  19. Contrast enhanced MR imaging of female pelvic cancers: Established methods and emerging applications

    Energy Technology Data Exchange (ETDEWEB)

    Punwani, Shonit, E-mail: shonit.punwani@gmail.com [Department of Academic Radiology, 2nd Floor Podium, University College London Hospital, 235 Euston Road, London NW1 2BU (United Kingdom)

    2011-04-15

    Contrast enhanced magnetic resonance imaging of female pelvic cancers has been established for over 20 years. Conventional contrast enhanced imaging involves acquiring a set of pre-contrast T1 weighted images, followed by intravenous injection of an gadolinium based contrast agent and subsequent acquisition of a second set of contrast enhanced images. Developments in MR hardware and pulse sequences over the last 10 years have made dynamic contrast enhanced (DCE) protocols possible. DCE-MRI entails imaging of the same volume repeatedly prior to, during and following contrast injection. There have also been developments in image analysis methods and tools to reflect the increased data acquired. Qualitative analysis of contrast enhanced imaging (whether a single set or temporal series) by radiologists remains the mainstay for clinical reporting. Semi-quantitative assessment of signal intensity versus time curves and full pharmacokinetic modelling methods have emerged for evaluation of DCE-MRI data. DCE-MRI has found an established role in the detection, localisation and staging of female pelvic malignancies. Emerging applications of DCE-MRI include assessment of tumour grade, histology prior to and following treatment and prediction of individual and final treatment outcome. This article reviews the biophysical basis of contrast enhancement, the technical aspects of performance and analysis of DCE-MRI studies, and the established and emerging clinical utility of DCE-MRI in female pelvic malignancies.

  20. Structure-activity studies of homologues of short chain neurotoxins from Elapid snake venoms.

    OpenAIRE

    Harvey, A. L.; Hider, R C; Hodges, S J; Joubert, F. J.

    1984-01-01

    Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata) were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer cervicis nerve-muscle preparations. All three homologues had acetylcholine receptor blocking activity, as they abolished responses to indirect stimulation, acetylcholine and carba...

  1. Radiogenomic analysis of breast cancer: luminal B molecular subtype is associated with enhancement dynamics at MR imaging.

    Science.gov (United States)

    Mazurowski, Maciej A; Zhang, Jing; Grimm, Lars J; Yoon, Sora C; Silber, James I

    2014-11-01

    To investigate associations between breast cancer molecular subtype and semiautomatically extracted magnetic resonance (MR) imaging features. Imaging and genomic data from the Cancer Genome Atlas and the Cancer Imaging Archive for 48 patients with breast cancer from four institutions in the United States were used in this institutional review board approval-exempt study. Computer vision algorithms were applied to extract 23 imaging features from lesions indicated by a breast radiologist on MR images. Morphologic, textural, and dynamic features were extracted. Molecular subtype was determined on the basis of genomic analysis. Associations between the imaging features and molecular subtype were evaluated by using logistic regression and likelihood ratio tests. The analysis controlled for the age of the patients, their menopausal status, and the orientation of the MR images (sagittal vs axial). There is an association (P = .0015) between the luminal B subtype and a dynamic contrast material-enhancement feature that quantifies the relationship between lesion enhancement and background parenchymal enhancement. Cancers with a higher ratio of lesion enhancement rate to background parenchymal enhancement rate are more likely to be luminal B subtype. The luminal B subtype of breast cancer is associated with MR imaging features that relate the enhancement dynamics of the tumor and the background parenchyma.

  2. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

    2008-06-02

    {beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

  3. Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model.

    Science.gov (United States)

    Li, Qi; Ma, Zhuang; Liu, Yinhua; Kan, Xiaoxi; Wang, Changjun; Su, Bingnan; Li, Yuchen; Zhang, Yingmei; Wang, Pingzhang; Luo, Yang; Na, Daxiang; Wang, Lanlan; Zhang, Guoying; Zhu, Xiaoxin; Wang, Lu

    2016-08-01

    Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. In addition to its well-known cytotoxic effects, recent studies have shown that paclitaxel has tumor-supportive activities. Importantly, paclitaxel levels are not maintained at the effective concentration through one treatment cycle; rather, the concentration decreases during the cycle as a result of drug metabolism. Therefore, a comprehensive understanding of paclitaxel's effects requires insight into the dose-specific activities of paclitaxel and their influence on cancer cells and the host microenvironment. Here we report that a low dose of paclitaxel enhances metastasis of breast cancer cells to the liver in mouse models. We used microarray analysis to investigate gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel. We also investigated the effects of low doses of paclitaxel on cell migration, invasion and metastasis in vitro and in vivo. The results showed that low doses of paclitaxel promoted inflammation and initiated the epithelial-mesenchymal transition, which enhanced tumor cell migration and invasion in vitro. These effects could be reversed by inhibiting NF-κB. Furthermore, low doses of paclitaxel promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver. Collectively, these findings reveal the paradoxical and dose-dependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment. Gene expression microarray data are available in the GEO database under accession number GSE82048. © 2016 Federation of European Biochemical Societies.

  4. Identification of rTid-1, the rat homologue of the drosophila tumor suppressor l(2)tid gene.

    Science.gov (United States)

    Fujita, Masako; Nagai, Yasuo; Sawada, Tohru; Heese, Klaus

    2004-03-01

    Active cell death ('apoptosis' or 'programmed cell death') is essential in the development and homeostasis of multicellular organisms and abnormal inhibition of apoptosis is an indicator of cancer and autoimmune diseases, whereas excessive cell death is implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Here we demonstrate new isoforms of the rat homologue of the drosophila tumor suppressor l(2)tid gene (rTid-1). Moreover, we show that rTid-1 interacts isoform-specifically with the heat-shock-cognate-glucose-regulated protein hscGRP75 and neither induces nor inhibits directly neuronal apoptosis. This finding points to a pivotal role of Tid-1 in the control of cellular survival.

  5. Health risk equations and risk assessment of airborne benzene homologues exposure to drivers and passengers in taxi cabins.

    Science.gov (United States)

    Chen, Xiaokai; Feng, Lili; Luo, Huilong; Cheng, Heming

    2016-03-01

    Interior air environment and health problems of vehicles have attracted increasing attention, and benzene homologues (BHs) including benzene, toluene, ethylbenzene, xylenes, and styrene are primary hazardous gases in vehicular cabins. The BHs impact on the health of passengers and drivers in 38 taxis is assessed, and health risk equations of in-car BHs to different drivers and passengers are induced. The health risk of in-car BHs for male drivers is the highest among all different receptors and is 1.04, 6.67, and 6.94 times more than ones for female drivers, male passengers, and female passengers, respectively. In-car BHs could not lead to the non-cancer health risk to all passengers and drivers as for the maximal value of non-cancer indices is 0.41 and is less than the unacceptable value (1.00) of non-cancer health risk from USEPA. However, in-car BHs lead to cancer health risk to drivers as for the average value of cancer indices is 1.21E-04 which is 1.21 times more than the unacceptable value (1.00E-04) of cancer health risk from USEPA. Finally, for in-car airborne benzene concentration (X, μg/m(3)) to male drivers, female drivers, male passengers, and female passengers, the cancer health risk equations are Y = 1.48E-06X, Y = 1.42E-06X, Y = 2.22E-07X, and Y = 2.13E-07X, respectively, and the non-cancer health risk equations are Y = 1.70E-03X, Y = 1.63E-03X, Y = 2.55E-04X, and Y = 2.45E-04X, respectively.

  6. Antidepressant Binding Site in a Bacterial Homologue of Neurotransmitter Transporters

    Energy Technology Data Exchange (ETDEWEB)

    Singh,S.; Yamashita, A.; Gouaux, E.

    2007-01-01

    Sodium-coupled transporters are ubiquitous pumps that harness pre-existing sodium gradients to catalyse the thermodynamically unfavourable uptake of essential nutrients, neurotransmitters and inorganic ions across the lipid bilayer. Dysfunction of these integral membrane proteins has been implicated in glucose/galactose malabsorption, congenital hypothyroidism, Bartter's syndrome, epilepsy, depression, autism and obsessive-compulsive disorder. Sodium-coupled transporters are blocked by a number of therapeutically important compounds, including diuretics, anticonvulsants and antidepressants, many of which have also become indispensable tools in biochemical experiments designed to probe antagonist binding sites and to elucidate transport mechanisms. Steady-state kinetic data have revealed that both competitive and noncompetitive modes of inhibition exist. Antagonist dissociation experiments on the serotonin transporter (SERT) have also unveiled the existence of a low-affinity allosteric site that slows the dissociation of inhibitors from a separate high-affinity site. Despite these strides, atomic-level insights into inhibitor action have remained elusive. Here we screen a panel of molecules for their ability to inhibit LeuT, a prokaryotic homologue of mammalian neurotransmitter sodium symporters, and show that the tricyclic antidepressant (TCA) clomipramine noncompetitively inhibits substrate uptake. Cocrystal structures show that clomipramine, along with two other TCAs, binds in an extracellular-facing vestibule about 11 {angstrom} above the substrate and two sodium ions, apparently stabilizing the extracellular gate in a closed conformation. Off-rate assays establish that clomipramine reduces the rate at which leucine dissociates from LeuT and reinforce our contention that this TCA inhibits LeuT by slowing substrate release. Our results represent a molecular view into noncompetitive inhibition of a sodium-coupled transporter and define principles for the

  7. Effects of an immuno-enhanced diet containing antioxidants in esophageal cancer surgery following neoadjuvant therapy.

    Science.gov (United States)

    Aiko, S; Kumano, I; Yamanaka, N; Tsujimoto, H; Takahata, R; Maehara, T

    2012-02-01

    Neoadjuvant therapy-induced immunological deterioration may be a key factor in postoperative morbidity in patients with esophageal cancer. This study aimed to determine the effects of perioperative feeding with an immuno-enhanced diet on immune competence in patients treated with neoadjuvant therapy followed by surgery. Because an immuno-enhanced diet that contained several antioxidants was used, perioperative oxidative stress and the effects of the immuno-enhanced diet on this stress were also investigated. Of 39 patients with esophageal cancer who underwent similar surgical procedures, 26 patients who received chemotherapy or chemoradiation therapy before surgery were randomly divided into two groups: group 1 (n= 14) was given an immuno-enhanced diet for 5 days before surgery, and group 2 (n= 12) received no enteral feeding products before surgery. Group 3 (n= 13) consisted of patients that did not receive neoadjuvant therapy and received no enteral feeding products before surgery. Several markers for coagulation and fibrinolysis were determined and immunological assessments were performed for each patient. To measure reactive oxygen metabolites and the total antioxidant capacity, diacron-reactive oxygen metabolites (d-ROMs) and OXY-adsorbent tests were performed using a free radical elective evaluator. Significant depression in lymphocyte numbers was observed in groups 1 and 2 before and early after surgery as compared to group 3. Numbers of B cells, CD4/CD8 ratio, and phytohemagglutinin-induced lymphocyte transformation tests were also significantly decreased in groups 1 and 2 on postoperative day 1. Fibrin and fibrinogen degradation products were significantly elevated in group 2 compared to group 1. d-ROMs and OXY-adsorbent test values were elevated before surgery and were decreased transiently early after surgery. Compared to groups 2 and 3, d-ROMs values were significantly lower in group 1 patients throughout the postoperative period, while OXY

  8. [Sodium valproate enhances doxorubicin cytotoxicity in breast cancer cells in vitro].

    Science.gov (United States)

    Tong, Xu-Hui; Zheng, Chao; Jiang, Guo-Jun; Dong, Shu-Ying

    2015-01-01

    To investigate the effect of sodium valproate, a histone deacetylase inhibitor, on the cytotoxicity of doxorubicin in breast cancer cells. Western blotting was used to assess Cx43 protein expression in breast cancer Hs578T cells exposed to doxorubicin and sodium valproate. MTT assay was used to determine the cytotoxicity of doxorubicin; annexin V/PI double staining and Hochest 33258 fluorescence staining were employed to detect doxorubicin-induced early and late apoptosis, respectively. Western blotting showed that sodium valproate significantly increased Cx43 protein expression in Hs578T cells (P/0.01). The cells exposed to both sodium valproate and doxorubicin showed significantly lowered cell viability compared with the cells exposed to doxorubicin alone (P/0.01). Exposure to both sodium valproate and doxorubicin resulted in significantly increased early and late cell apoptosis rate compared with doxorubicin treatment alone (P/0.01). sodium valproate can significantly enhance the cytotoxicity of doxorubicin and increase doxorubicin-induced apoptosis in breast cancer cells in vitro possibly by enhancing the gap junction function.

  9. Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer

    Science.gov (United States)

    Martinel Lamas, Diego J; Cortina, Jorge E; Ventura, Clara; Sterle, Helena A; Valli, Eduardo; Balestrasse, Karina B; Blanco, Horacio; Cremaschi, Graciela A; Rivera, Elena S; Medina, Vanina A

    2015-01-01

    The radioprotective potential of histamine on healthy tissue has been previously demonstrated. The aims of this work were to investigate the combinatorial effect of histamine or its receptor ligands and gamma radiation in vitro on the radiobiological response of 2 breast cancer cell lines (MDA-MB-231 and MCF-7), to explore the potential molecular mechanisms of the radiosensitizing action and to evaluate the histamine-induced radiosensitization in vivo in a triple negative breast cancer model. Results indicate that histamine significantly increased the radiosensitivity of MDA-MB-231 and MCF-7 cells. This effect was mimicked by the H1R agonist 2-(3-(trifluoromethyl)phenyl)histamine and the H4R agonists (Clobenpropit and VUF8430) in MDA-MB-231 and MCF-7 cells, respectively. Histamine and its agonists enhanced radiation-induced oxidative DNA damage, DNA double-strand breaks, apoptosis and senescence. These effects were associated with increased production of reactive oxygen species, which correlated with the inhibition of catalase, glutathione peroxidase and superoxide dismutase activities in MDA-MB-231 cells. Histamine was able also to potentiate in vivo the anti-tumoral effect of radiation, increasing the exponential tumor doubling time. We conclude that histamine increased radiation response of breast cancer cells, suggesting that it could be used as a potential adjuvant to enhance the efficacy of radiotherapy. PMID:25482934

  10. Customizable radiotherapy enhancement (CuRE) for prostate cancer using platinum based nanoparticles

    Science.gov (United States)

    Cifter, Gizem

    New approach to prostate cancer (PCa) therapy titled "Customizable Radiotherapy Enhancement (CuRE)" employs cisplatin (C), carboplatin (Ca) and oxaliplatin (O) nanoparticles (CNPs, CaNPs and ONPs) as adjuvants to brachytherapy and external beam radiation therapy (EBRT), with the CNPs/CaNPs/ONPs released in situ from either brachytherapy spacers or fudicials loaded with the nanoparticles. The chemotherapy dose from the nanoparticles released in situ from within the prostate capsule, is enhanced by the physical dose due to photon interactions with the nanoparticles. The physical dose enhancement is due to low energy photons from the brachytherapy and EBRT sources interacting with the high-Z platinum component of the nanoparticles, causing emission of short-range photoelectrons to boost dose to the tumor. By varying the nanoparticle parameters, such as size, initial concentration, functionalization, location of spacer or fiducial, and intra-tumor biodistribution, the dose enhancement can be customized to maximize dose to tumor cells while minimizing toxicity to healthy cells. The hypothesis is that the CuRE approach will be a more efficacious method for concomitant cisplatin/carboplatin/oxaliplatin and radiotherapy treatment of localized prostate cancer due to significant dose boost to the PCa cells with minimal toxicity to healthy tissue. To investigate this hypothesis, microdosimetry calculations employing the energy loss formula of Cole were used to calculate the dose enhancement to the PCa cells from the CNPs/CaNPs/OPNs. The dose enhancement ratio (DEF) representing the ratio of the overall dose in the presence of CNPs/CaNPs/ONPs to the dose without CNPs/CaNPs/ONPs was determined for a range of CNP/CaNP/OPN concentrations up to their FDA approved limits. The dose enhancement to endothelial cells with (EDEF) with single concentration of cisplatin (42.8 mg/g) was found 2.6 with Pd-103. When EBRT source was used with single concentration of cisplatin, with 10cm x 10

  11. Importance of sexuality in colorectal cancer: predictors, changes, and response to an intimacy enhancement intervention.

    Science.gov (United States)

    Reese, Jennifer Barsky; Haythornthwaite, Jennifer A

    2016-10-01

    The primary objectives were (1) to examine the importance of sexuality within the self-view and cross-sectional correlates for 120 colorectal cancer patients and (2) to determine whether the importance of sexuality changed for 46 colorectal cancer patients and partners participating in an intimacy enhancement intervention. Two newly developed items assessed importance of sexuality within the self-view (1) currently and (2) before cancer; a calculated change score assessed perceived change. In the cross-sectional sample, associations between importance of sexuality and demographic and medical factors and sexual function status were examined. Intervention participants' importance ratings before and after participation were used to calculate effect sizes. For patients, importance of sexuality before cancer was greater (M = 65.7) than current importance (M = 56.8, p = .001). Greater current importance of sexuality was associated with partnered status, non-metastatic disease, and not being in treatment. Scoring in the sexually functional range was associated with greater current importance of sexuality for men and a smaller perceived change in importance for both men and women (p values Sexual function status also significantly predicted current importance independent of covariates. Small to medium effect sizes for intervention patients (.37) and partners (.60) were found for increases in importance of sexuality. Items showed evidence of test-retest reliability and construct validity. Coping with sexual concerns is important to those affected by colorectal cancer. Findings suggest that the importance of sexuality can decrease through colorectal cancer and associated sexual problems and can increase through participating in an intimacy-focused intervention.

  12. Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway.

    Science.gov (United States)

    Yao, Xiangyang; Zhu, Fenfen; Zhao, Zhihui; Liu, Chang; Luo, Lan; Yin, Zhimin

    2011-10-01

    Arctigenin is a dibenzylbutyrolactone lignan isolated from Bardanae fructus, Arctium lappa L, Saussureamedusa, Torreya nucifera, and Ipomea cairica. It has been reported to exhibit anti-inflammatory activities, which is mainly mediated through its inhibitory effect on nuclear transcription factor-kappaB (NF-κB). But the role of arctigenin in JAK-STAT3 signaling pathways is still unclear. In present study, we investigated the effect of arctigenin on signal transducer and activator of transcription 3 (STAT3) pathway and evaluated whether suppression of STAT3 activity by arctigenin could sensitize cancer cells to a chemotherapeutic drug cisplatin. Our results show that arctigenin significantly suppressed both constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation in cancer cells. Inhibition of STAT3 tyrosine phosphorylation was found to be achieved through suppression of Src, JAK1, and JAK2, while suppression of STAT3 serine phosphorylation was mediated by inhibition of ERK activation. Pervanadate reversed the arctigenin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, arctigenin can obviously induce the expression of the PTP SHP-2. Furthermore, the constitutive activation level of STAT3 was found to be correlated to the resistance of cancer cells to cisplatin-induced apoptosis. Arctigenin dramatically promoted cisplatin-induced cell death in cancer cells, indicating that arctigenin enhanced the sensitivity of cancer cells to cisplatin mainly via STAT3 suppression. These observations suggest a novel anticancer function of arctigenin and a potential therapeutic strategy of using arctigenin in combination with chemotherapeutic agents for cancer treatment. Copyright © 2011 Wiley-Liss, Inc.

  13. Enhancing a cancer prevention and control curriculum through interactive group discussions.

    Science.gov (United States)

    Forsythe, L P; Gadalla, S M; Hamilton, J G; Heckman-Stoddard, B M; Kent, E E; Lai, G Y; Lin, S W; Luhn, P; Faupel-Badger, J M

    2012-06-01

    The Principles and Practice of Cancer Prevention and Control course (Principles course) is offered annually by the National Cancer Institute Cancer Prevention Fellowship Program. This 4-week postgraduate course covers the spectrum of cancer prevention and control research (e.g., epidemiology, laboratory, clinical, social, and behavioral sciences) and is open to attendees from medical, academic, government, and related institutions across the world. In this report, we describe a new addition to the Principles course syllabus, which was exclusively a lecture-based format for over 20 years. In 2011, cancer prevention fellows and staff designed and implemented small group discussion sessions as part of the curriculum. The goals of these sessions were to foster an interactive environment, discuss concepts presented during the Principles course, exchange ideas, and enhance networking among the course participants and provide a teaching and leadership opportunity to current cancer prevention fellows. Overall, both the participants and facilitators who returned the evaluation forms (n=61/87 and 8/10, respectively) reported a high satisfaction with the experience for providing both an opportunity to explore course concepts in a greater detail and to network with colleagues. Participants (93%) and facilitators (100%) stated that they would like to see this component remain a part of the Principles course curriculum, and both groups provided recommendations for the 2012 program. The design, implementation, and evaluation of this initial discussion group component of the Principles course are described herein. The findings in this report will not only inform future discussion group sessions in the Principles course but may also be useful to others planning to incorporate group learning into large primarily lecture-based courses.

  14. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming, E-mail: erc1080@gmail.com; Wang, Yujiong, E-mail: erc1080@gmail.com [Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Yinchuan 750021, Ningxia (China); College of Life Science, Ningxia University, Yinchuan 750021, Ningxia (China)

    2012-12-04

    In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC{sub 50}) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC{sub 50} values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs.

  15. Enhancer of zeste homolog 2 as an independent prognostic marker for cancer: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Shuling Chen

    Full Text Available Novel biomarkers are of particular interest for predicting cancer prognosis. This study aimed to explore the associations between enhancer of zeste homolog 2 (EZH2 and patient survival in various cancers.Relevant literature was retrieved from PubMed and Web of Science databases. Pooled hazard ratios (HRs, odds ratios (ORs, and 95% confidence intervals (CIs were calculated.Forty-nine studies (8,050 patients were included. High EZH2 expression was significantly associated with shorter overall (hazard ratio [HR] 1.74, 95% CI: 1.46-2.07, disease-free (HR 1.59, 95% CI: 1.27-1.99, metastasis-free (HR 2.19, 95% CI: 1.38-3.47, progression-free (HR 2.53, 95% CI: 1.52-4.21, cancer-specific (HR 3.13, 95% CI: 1.70-5.74, and disease-specific (HR 2.29, 95% CI: 1.56-3.35 survival, but not recurrence-free survival (HR 1.38, 95% CI: 0.93-2.06. Moreover, EZH2 expression significantly correlated with distant metastasis (OR 3.25, 95% CI: 1.07-9.87 in esophageal carcinoma; differentiation (OR 3.00, 95% CI: 1.37-6.55 in non-small cell lung cancer; TNM stage (OR 3.18, 95% CI: 2.49-4.08 in renal cell carcinoma; and histological grade (OR 4.50, 95% CI: 3.33-6.09, estrogen receptor status (OR 0.15, 95% CI: 0.11-0.20 and progesterone receptor status (OR 0.30, 95% CI: 0.23-0.39 in breast cancer.Our results suggested that EZH2 might be an independent prognostic factor for multiple survival measures in different cancers.

  16. Enhancing a Cancer Prevention and Control Curriculum through Interactive Group Discussions

    Science.gov (United States)

    Forsythe, L.P.; Gadalla, S.M.; Hamilton, J.G.; Heckman-Stoddard, B.M.; Kent, E.E.; Lai, G.Y.; Lin, S.W.; Luhn, P.; Faupel-Badger, J.M.

    2012-01-01

    The Principles and Practice of Cancer Prevention and Control course (Principles course) is offered annually by the National Cancer Institute Cancer Prevention Fellowship Program. This four-week post-graduate course covers the spectrum of cancer prevention and control research (e.g. epidemiology, laboratory, clinical, social, and behavioral sciences) and is open to attendees from medical, academic, government, and related institutions across the world. In this report, we describe a new addition to the Principles course syllabus, which was exclusively a lecture-based format for over 20 years. In 2011, Cancer Prevention Fellows and staff designed and implemented small group discussion sessions as part of the curriculum. The goals of these sessions were to foster an interactive environment, discuss concepts presented during the Principles course, exchange ideas, and enhance networking amongst the course participants, and provide a teaching and leadership opportunity to current Cancer Prevention Fellows. Overall, both the participants and facilitators who returned the evaluation forms (n=61/87, and 8/10, respectively), reported high satisfaction with the experience for providing both an opportunity to explore course concepts in greater detail and to network with colleagues. Participants (93%) and facilitators (100%) stated they would like to see this component remain a part of the Principles course curriculum, and both groups provided recommendations for the 2012 program. The design, implementation, and evaluation of this initial discussion group component of the Principles course are described herein. The findings in this report will not only inform future discussion group sessions in the Principles course but may also be useful to others planning to incorporate group learning into large primarily lecture-based courses. PMID:22661264

  17. Human cytomegalovirus interleukin-10 enhances matrigel invasion of MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Valle Oseguera, Cendy A; Spencer, Juliet V

    2017-01-01

    While some risk factors for breast cancer are well-known, the influence of other factors, particularly virus infection, remains unclear. Human cytomegalovirus (HCMV) is widespread in the general population, and both molecular and epidemiological evidence has indicated links between HCMV and breast cancer. The HCMV protein cmvIL-10 is a potent suppressor of immune function that has also been shown to promote proliferation and migration of breast cancer cells. In this study, the impact of cmvIL-10 on tumor cell invasion through a simulated basement membrane was investigated. MDA-MB-231 breast cancer cells exhibited invasion through a matrigel layer that was significantly enhanced in the presence of either purified cmvIL-10 or supernatants from HCMV-infected cells containing secreted cmvIL-10. Transcriptional profiling revealed that cmvIL-10 altered expression of several genes implicated in metastasis. Exposure to cmvIL-10 resulted in higher MMP-3 mRNA levels, greater protein expression, and increased enzymatic activity. Treatment with cmvIL-10 also increased expression of both urokinase plasminogen receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), which can stimulate MMP-3 activity and have previously been identified as poor prognostic markers in breast cancer patients. Finally, MDA-MB-231 cells treated with cmvIL-10 showed significant downregulation of metastasis suppressor 1 (MTSS1), a scaffolding protein that regulates cytoskeletal rearrangements and is frequently lost in metastatic tumors. HCMV, and in particular the secreted viral cytokine, cmvIL-10, can induce cellular changes that facilitate cell migration and invasion. These findings indicate that HCMV may be associated with promoting the malignant spread of breast cancer cells and suggest that antiviral treatment may be a useful complement to chemotherapy in some patients.

  18. Prostate Cancer Ambassadors: Enhancing a Theory-Informed Training Program for Informed Decision-Making.

    Science.gov (United States)

    Vines, Anissa I; Hunter, Jaimie C; Carlisle, Veronica A; Richmond, Alan N

    2017-09-01

    Despite the high burden of prostate cancer in African American communities, there is a paucity of knowledge about prostate health. This paper describes the enhancement of a curriculum for training lay health advisors, called prostate cancer ambassadors, on informed decision-making for prostate cancer screening. Adult learning theory informed the structuring of the training sessions to be interactive, self-directed, and engaging. Trainings were developed in a manner that made the material relevant to the learners and encouraged co-learning. The research team developed strategies, such as using discussions and interactive activities, to help community members weigh the pros and cons of prostate-specific antigen (PSA) screening and to make an informed decision about screening. Furthermore, activities were developed to bolster four social cognitive theory constructs: observational learning, self-efficacy for presenting information to the community and for making an informed decision themselves, collective efficacy for presenting information to the community, and outcome expectations from those presentations. Games, discussions, and debates were included to make learning fun and encourage discovery. Practice sessions and team-building activities were designed to build self-efficacy for sharing information about informed decision-making. Topics added to the original curriculum included updates on prostate cancer screening, informed decision-making for screening, skills for being a lay health advisor, and ethics. This dynamic model and approach to lay health advisor (ambassador) training is flexible: while it was tailored for use with prostate cancer education, it can be adjusted for use with other types of cancer and even other diseases.

  19. Enhanced Quitline Intervention in Smoking Cessation for Patients With Non-Metastatic Lung Cancer

    Science.gov (United States)

    2017-05-25

    Limited Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Tobacco Use Disorder

  20. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms.

    Science.gov (United States)

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-05-07

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm(-1) related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

  1. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer

    Science.gov (United States)

    Bhola, Neil E.; Balko, Justin M.; Dugger, Teresa C.; Kuba, María Gabriela; Sánchez, Violeta; Sanders, Melinda; Stanford, Jamie; Cook, Rebecca S.; Arteaga, Carlos L.

    2013-01-01

    After an initial response to chemotherapy, many patients with triple-negative breast cancer (TNBC) have recurrence of drug-resistant metastatic disease. Studies with TNBC cells suggest that chemotherapy-resistant populations of cancer stem-like cells (CSCs) with self-renewing and tumor-initiating capacities are responsible for these relapses. TGF-β has been shown to increase stem-like properties in human breast cancer cells. We analyzed RNA expression in matched pairs of primary breast cancer biopsies before and after chemotherapy. Biopsies after chemotherapy displayed increased RNA transcripts of genes associated with CSCs and TGF-β signaling. In TNBC cell lines and mouse xenografts, the chemotherapeutic drug paclitaxel increased autocrine TGF-β signaling and IL-8 expression and enriched for CSCs, as indicated by mammosphere formation and CSC markers. The TGF-β type I receptor kinase inhibitor LY2157299, a neutralizing TGF-β type II receptor antibody, and SMAD4 siRNA all blocked paclitaxel-induced IL8 transcription and CSC expansion. Moreover, treatment of TNBC xenografts with LY2157299 prevented reestablishment of tumors after paclitaxel treatment. These data suggest that chemotherapy-induced TGF-β signaling enhances tumor recurrence through IL-8–dependent expansion of CSCs and that TGF-β pathway inhibitors prevent the development of drug-resistant CSCs. These findings support testing a combination of TGF-β inhibitors and anticancer chemotherapy in patients with TNBC. PMID:23391723

  2. Nanotechnology-Enhanced No-Wash Biosensors for in Vitro Diagnostics of Cancer.

    Science.gov (United States)

    Huang, Xiaolin; Liu, Yijing; Yung, Bryant; Xiong, Yonghua; Chen, Xiaoyuan

    2017-06-27

    In vitro biosensors have been an integral component for early diagnosis of cancer in the clinic. Among them, no-wash biosensors, which only depend on the simple mixing of the signal generating probes and the sample solution without additional washing and separation steps, have been found to be particularly attractive. The outstanding advantages of facile, convenient, and rapid response of no-wash biosensors are especially suitable for point-of-care testing (POCT). One fast-growing field of no-wash biosensor design involves the usage of nanomaterials as signal amplification carriers or direct signal generating elements. The analytical capacity of no-wash biosensors with respect to sensitivity or limit of detection, specificity, stability, and multiplexing detection capacity is largely improved because of their large surface area, excellent optical, electrical, catalytic, and magnetic properties. This review provides a comprehensive overview of various nanomaterial-enhanced no-wash biosensing technologies and focuses on the analysis of the underlying mechanism of these technologies applied for the early detection of cancer biomarkers ranging from small molecules to proteins, and even whole cancerous cells. Representative examples are selected to demonstrate the proof-of-concept with promising applications for in vitro diagnostics of cancer. Finally, a brief discussion of common unresolved issues and a perspective outlook on the field are provided.

  3. Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide.

    Science.gov (United States)

    Agrawal, Siddarth; Łuc, Mateusz; Ziółkowski, Piotr; Agrawal, Anil Kumar; Pielka, Ewa; Walaszek, Kinga; Zduniak, Krzysztof; Woźniak, Marta

    2017-06-01

    The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.

  4. Enhancement of radiation effect on cancer cells by gold-pHLIP

    Science.gov (United States)

    Antosh, Michael P.; Wijesinghe, Dayanjali D.; Shrestha, Samana; Lanou, Robert; Huang, Yun Hu; Hasselbacher, Thomas; Fox, David; Neretti, Nicola; Sun, Shouheng; Katenka, Natallia; Cooper, Leon N; Andreev, Oleg A.; Reshetnyak, Yana K.

    2015-01-01

    Previous research has shown that gold nanoparticles can increase the effectiveness of radiation on cancer cells. Improved radiation effectiveness would allow lower radiation doses given to patients, reducing adverse effects; alternatively, it would provide more cancer killing at current radiation doses. Damage from radiation and gold nanoparticles depends in part on the Auger effect, which is very localized; thus, it is important to place the gold nanoparticles on or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to cancer cells. We find that the conjugation of pHLIP to gold nanoparticles increases gold uptake in cells compared with gold nanoparticles without pHLIP, with the nanoparticles distributed mostly on the cellular membranes. We further find that gold nanoparticles conjugated to pHLIP produce a statistically significant decrease in cell survival with radiation compared with cells without gold nanoparticles and cells with gold alone. In the context of our previous findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to tumors, the obtained results serve as a foundation for further preclinical evaluation of dose enhancement. PMID:25870296

  5. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

    Science.gov (United States)

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-05-01

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm-1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

  6. Intervention to enhance empowerment in breast cancer self-help groups.

    Science.gov (United States)

    Stang, Ingun; Mittelmark, Maurice B

    2010-03-01

    As arduous psychological reactions and loss of control almost inevitably represent a challenge for women diagnosed and treated for breast cancer, a participatory intervention study was initiated that aimed to enhance empowerment in breast cancer self-help groups. Women newly diagnosed with breast cancer were invited to participate. The intervention encompassed three professionally led self-help groups running sequentially, each group for approximately 4 months. Each group of five to seven participants met weekly. Several empowerment strategies were initiated by two professional facilitators, aiming to promote empowerment processes and to manage stress. The participants experienced group participation as both empowering and as a valuable source of support, and although the group processes developed very differently, a strong sense of fellowship developed in all three groups. The discussion highlights the findings in relation to several theoretical perspectives including social capital, social cohesion, risky agreements, helper-therapy and power/empowerment. We conclude that empowerment strategies that are implemented in professionally led breast cancer self-help groups can contribute to participant empowerment and function as an important source of re-discovery and confirmation of the participants' strengths and abilities.

  7. [Application of dynamic contrast enhancement MRI and post-processing technique for diagnosis of breast cancer].

    Science.gov (United States)

    Peng, Kang-Qiang; Huang, Zi-Lin; Xie, Chuan-Miao; Chen, Lin; Ouyang, Yi; Zheng, Qing-Sheng; Zhang, Yan; He, Hao-Qiang; Wu, Pei-Hong

    2009-05-01

    Magnetic resonance imaging (MRI), an advanced non-invasive technique, is regarded as one of the potential modalities in the diagnosis of breast cancer. This study was to investigate the application of dynamic contrast enhancement MRI and 3D reconstruction images in diagnosing breast tumors. From May 2006 to September 2007, 30 patients with breast diseases were scanned with MRI in Sun Yat-sen University Cancer Center. MR plain scans, dynamic contrast enhancement scans were performed, and 3D reconstruction images were obtained. The normal breast tissue was used as control, and the maximum slope ratio was calculated. Forty-nine lesions were found in 30 patients, with an accuracy rate of 93.3%. MRI scan is an effective and specific modality for the diagnosis of breast diseases with high sensitivity and accuracy. Dynamic contrast enhancement MRI, image subtraction, time-signal intensity curve, 3D reconstruction images and the maximum slope ratio are helpful to make the correct diagnosis of breast lesions.

  8. CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells

    Directory of Open Access Journals (Sweden)

    Chen Ying-Chun

    2008-07-01

    Full Text Available Abstract Background The cellular apoptosis susceptibility (CAS protein is regarded as a proliferation-associated protein that associates with tumour proliferation as it associates with microtubule and functions in the mitotic spindle checkpoint. However, there is no any actual experimental study showing CAS (or CSE1 and CSE1L can increase the proliferation of cancer cells. Previous pathological study has reported that CAS was strongly positive stained in all of the metastasis melanoma that be examined. Thus, CAS may regulate the invasion and metastasis of cancers. CAS is highly expressed in cancers; if CAS is associated with cancer proliferation, then increased CAS expression should be able to increase the proliferation of cancer cells. We studied whether increased CAS expression can increase cancer cell proliferation and whether CAS regulates the invasion of cancer cells. Methods We enhanced or reduced CAS expression by transfecting CAS or anti-CAS expression vectors into human MCF-7 breast cancer cells. The proliferations of cells were determined by trypan blue exclusion assay and flow cytometry analysis. Invasion of cancer cells were determined by matrigel-based invasion assay. Results Our studies showed that increased CAS expression was unable to enhance cancer cell proliferation. Immunofluorescence showed CAS was distributed in cytoplasm areas near cell membrane and cell protrusions. CAS was localized in cytoplasmic vesicle and immunogold electronmicroscopy showed CAS was located in vesicle membrane. CAS overexpression enhanced matrix metalloproteinase-2 (MMP-2 secretion and cancer cell invasion. Animal experiments showed CAS reduction inhibited the metastasis of B16-F10 melanoma cells by 56% in C57BL/6 mice. Conclusion Our results indicate that CAS increases the invasion but not the proliferation of cancer cells. Thus, CAS plus ECM-degradation proteinases may be used as the markers for predicting the advance of tumour metastasis.

  9. All-trans retinoic acid enhances bystander effect of suicide gene therapy in the treatment of breast cancer.

    Science.gov (United States)

    Kong, Heng; Liu, Xia; Yang, Liucheng; Qi, Ke; Zhang, Haoyun; Zhang, Jingwen; Huang, Zonghai; Wang, Hongxian

    2016-03-01

    All-trans retinoic acid (ATRA) has been shown to enhance the expression of connexin 43 (Cx43) and the bystander effect (BSE) in suicide gene therapy. These in turn improve effects of suicide gene therapies for several tumor types. However, whether ATRA can improve BSE remains unclear in suicide gene therapy for breast cancer. In the present study, MCF-7, human breast cancer cells were treated with ATRA in combination with a VEGFP-TK/CD gene suicide system developed by our group. We found that this combination enhances the efficiency of cell killing and apoptosis of breast cancer by strengthening the BSE in vitro. ATRA also promotes gap junction intercellular communication (GJIC) in MCF-7 cells by upregulation of the connexin 43 mRNA and protein in MCF-7 cells. These results indicate that enhancement of GJIC by ATRA in suicide gene system might serve as an attractive and cost-effective strategy of therapy for breast cancer cells.

  10. Staging accuracy of pancreatic cancer: Comparison between non-contrast-enhanced and contrast-enhanced PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Yoneyama, Tomohiro [Department of Radiology, Yokohama City University, Graduate School of Medicine, Yokohama (Japan); Tateishi, Ukihide, E-mail: utateish@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University, Graduate School of Medicine, Yokohama (Japan); Endo, Itaru [Department of Surgery, Yokohama City University, Graduate School of Medicine, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University, Graduate School of Medicine, Yokohama (Japan)

    2014-10-15

    Purpose: Our aim was to clarify the diagnostic impact of contrast-enhanced (CE) {sup 18}F-fluorodeoxyglucose (FDG)–positron emission tomography (PET)/computed tomography (CT) for staging of pancreatic cancer compared to non-CE PET/CT. Method and materials: Between April 2006 and November 2009, a total of 95 patients (age range, 36–83 years [mean age, 67]) with primary pancreatic cancer underwent {sup 18}F-FDG PET/CT examinations. Diagnostic accuracy was compared between non-CE PET/CT and CE PET/CT. Images were analyzed visually and quantitatively by two blinded reviewers. Reference standard was histological examination in 48 patients (51%) and/or confirmation of an obvious progression in number and/or size of the lesions on follow-up CT examinations in 47 patients (49%). Results: For T-staging, invasion of duodenum (n = 20, 21%), mesentery (n = 12, 13%), and retroperitoneum (n = 13, 14%) was correctly diagnosed by both modalities. The ROC analyses revealed that the Az values of celiac artery (CA), common hepatic artery (CHA), splenic artery (SV), and superior mesenteric vein (SMV) invasion were significantly higher in the CE PET/CT group for both readers. Nodal metastasis was correctly diagnosed by CE PET/CT in 38 patients (88%) and by non-CE PET/CT in 45 patients (87%). Diagnostic accuracies of nodal metastasis in two modalities were similar. Using CE PET/CT, distant metastasis, scalene node metastasis, and peritoneal dissemination were correctly assigned in 39 patients (91%), while interpretation based on non-CE PET/CT revealed distant metastasis, scalene node metastasis, and peritoneal dissemination in 42 patients (81%). Diagnostic accuracy of distant metastasis, scalene node metastasis, and peritoneal dissemination with CE PET/CT was significantly higher than that of non-CE PET/CT (p < 0.05). Conclusion: CE PET/CT allows a more precise assessment of distant metastasis, scalene node metastasis, and peritoneal dissemination in patients with pancreatic cancer.

  11. EGCG/gelatin-doxorubicin gold nanoparticles enhance therapeutic efficacy of doxorubicin for prostate cancer treatment.

    Science.gov (United States)

    Tsai, Li-Chu; Hsieh, Hao-Ying; Lu, Kun-Ying; Wang, Sin-Yu; Mi, Fwu-Long

    2016-01-01

    Development of epigallocatechin gallate (EGCG) and gelatin-doxorubicin conjugate (GLT-DOX)-coated gold nanoparticles (DOX-GLT/EGCG AuNPs) for fluorescence imaging and inhibition of prostate cancer cell growth. AuNPs alternatively coated with EGCG and DOX-GLT conjugates were prepared by a layer-by-layer assembly method. The physicochemical properties of the AuNPs and the effect of Laminin 67R receptor-mediated endocytosis on the anticancer efficacy of the AuNPs were examined. The AuNPs significantly inhibit the proliferation of PC-3 cancer cell and the enzyme-responsive intracellular release of DOX could be tracked by monitoring the recovery of the fluorescence signal of DOX. Laminin 67R receptor-mediated delivery of DOX using the AuNPs enhanced cellular uptake of DOX and improved apoptosis of PC-3 cells.

  12. Identifying Triple-Negative Breast Cancer Using Background Parenchymal Enhancement Heterogeneity on Dynamic Contrast-Enhanced MRI: A Pilot Radiomics Study.

    Directory of Open Access Journals (Sweden)

    Jeff Wang

    Full Text Available To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE MRI at 3.0 Tesla in identifying "triple-negative" breast cancers.In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC using cross-validation.Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (p<0.01. Similar improvements were seen in nearly all subtype classification tasks undertaken. Notably, amongst the most discriminating features for predicting triple-negative cancers were textures of background parenchymal enhancement.Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype

  13. Protopanaxadiol, an Active Ginseng Metabolite, Significantly Enhances the Effects of Fluorouracil on Colon Cancer

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    Chong-Zhi Wang

    2015-01-01

    Full Text Available In this study, we evaluated the effects of protopanaxadiol (PPD, a gut microbiome induced ginseng metabolite, in increasing the anticancer effects of a chemotherapeutic agent fluorouracil (5-FU on colorectal cancer. An in vitro HCT-116 colorectal cancer cell proliferation test was conducted to observe the effects of PPD, 5-FU and their co-administration and the related mechanisms of action. Then, an in vivo xenografted athymic mouse model was used to confirm the in vitro data. Our results showed that the human gut microbiome converted ginsenoside compound K to PPD as a metabolite. PPD and 5-FU significantly inhibited HCT-116 cell proliferation in a concentration-dependent manner (both p < 0.01, and the effects of 5-FU were very significantly enhanced by combined treatment with PPD (p < 0.01. Cell cycle evaluation demonstrated that 5-FU markedly induced the cancer cell S phase arrest, while PPD increased arrest in G1 phase. Compared to the control, 5-FU and PPD increased apoptosis, and their co-administration significantly increased the number of apoptotic cells (p < 0.01. Using bioluminescence imaging, in vivo data revealed that 5-FU significantly reduced the tumor growth up to Day 20 (p < 0.05. PPD and 5-FU co-administration very significantly reduced the tumor size in a dose-related manner (p < 0.01 compared to the 5-FU alone. The quantification of the tumor size and weight changes for 43 days supported the in vivo imaging data. Our results demonstrated that the co-administration of PPD and 5-FU significantly inhibited the tumor growth, indicating that PPD significantly enhanced the anticancer action of 5-FU, a commonly used chemotherapeutic agent. PPD may have a clinical value in 5-FU’s cancer therapeutics.

  14. Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

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    Kenji Ikemura

    2017-12-01

    Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

  15. Sequential gemcitabine and tamoxifen treatment enhances apoptosis and blocks transformation in bladder cancer cells.

    Science.gov (United States)

    Takeuchi, Hisashi; Mmeje, Chinedu O; Jinesh, Goodwin G; Taoka, Rikiya; Kamat, Ashish M

    2015-11-01

    Bladder cancer is a common malignancy for which regional or metastatic disease is identified at diagnosis. The aim of this study was to determine whether tamoxifen (Tam), an estrogen receptor (ER) antagonist, can sensitize bladder cancer cell lines to gemcitabine (Gem) chemotherapy. ERα and ERβ protein levels were determined in each cell line using western blot analysis. The TCC-Sup, 5637, and RT4 bladder cancer cells were exposed to various concentrations and regimens of Tam or Gem alone or in combination. Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide followed by flow cytometry. Apoptosis was then evaluated by western blot analysis. Treated TCC-Sup cells were subjected to soft agar colony formation assay to determine the cellular transformation. Western blot analysis results revealed ER expression in the three cell lines. TCC-Sup and 5637 cells treated with a combination of Tam and Gem had lower cell viabilities than those treated with Tam or Gem alone for 72 h in TCC-Sup and 5637. Compared with the other treatments, sequential Gem followed by Tam (Gem→Tam) treatment caused the largest increase in DNA fragmentation at 72 h in TCC-Sup cells. Western blot analysis results revealed that this sequential Gem→Tam treatment increased poly(ADP-ribose) polymerase cleavage in TCC-Sup cells. Sequential Gem→Tam inhibited the cell transformation in TCC-Sup cells. In conclusion, sequential Gem→Tam enhanced the cytotoxicity of Gem in vitro. This regimen be useful to enhance the efficacy of Gem in bladder cancer. However, future in vivo studies are required to verify the results.

  16. Neurophysiological evidence that musical training influences the recruitment of right hemispheric homologues for speech perception.

    Science.gov (United States)

    Jantzen, McNeel G; Howe, Bradley M; Jantzen, Kelly J

    2014-01-01

    Musicians have a more accurate temporal and tonal representation of auditory stimuli than their non-musician counterparts (Musacchia et al., 2007; Parbery-Clark et al., 2009a; Zendel and Alain, 2009; Kraus and Chandrasekaran, 2010). Musicians who are adept at the production and perception of music are also more sensitive to key acoustic features of speech such as voice onset timing and pitch. Together, these data suggest that musical training may enhance the processing of acoustic information for speech sounds. In the current study, we sought to provide neural evidence that musicians process speech and music in a similar way. We hypothesized that for musicians, right hemisphere areas traditionally associated with music are also engaged for the processing of speech sounds. In contrast we predicted that in non-musicians processing of speech sounds would be localized to traditional left hemisphere language areas. Speech stimuli differing in voice onset time was presented using a dichotic listening paradigm. Subjects either indicated aural location for a specified speech sound or identified a specific speech sound from a directed aural location. Musical training effects and organization of acoustic features were reflected by activity in source generators of the P50. This included greater activation of right middle temporal gyrus and superior temporal gyrus in musicians. The findings demonstrate recruitment of right hemisphere in musicians for discriminating speech sounds and a putative broadening of their language network. Musicians appear to have an increased sensitivity to acoustic features and enhanced selective attention to temporal features of speech that is facilitated by musical training and supported, in part, by right hemisphere homologues of established speech processing regions of the brain.

  17. Neurophysiological Evidence That Musical Training Influences the Recruitment of Right Hemispheric Homologues for Speech Perception

    Directory of Open Access Journals (Sweden)

    McNeel Gordon Jantzen

    2014-03-01

    Full Text Available Musicians have a more accurate temporal and tonal representation of auditory stimuli than their non-musician counterparts (Kraus & Chandrasekaran, 2010; Parbery-Clark, Skoe, & Kraus, 2009; Zendel & Alain, 2008; Musacchia, Sams, Skoe, & Kraus, 2007. Musicians who are adept at the production and perception of music are also more sensitive to key acoustic features of speech such as voice onset timing and pitch. Together, these data suggest that musical training may enhance the processing of acoustic information for speech sounds. In the current study, we sought to provide neural evidence that musicians process speech and music in a similar way. We hypothesized that for musicians, right hemisphere areas traditionally associated with music are also engaged for the processing of speech sounds. In contrast we predicted that in non-musicians processing of speech sounds would be localized to traditional left hemisphere language areas. Speech stimuli differing in voice onset time was presented using a dichotic listening paradigm. Subjects either indicated aural location for a specified speech sound or identified a specific speech sound from a directed aural location. Musical training effects and organization of acoustic features were reflected by activity in source generators of the P50. This included greater activation of right middle temporal gyrus (MTG and superior temporal gyrus (STG in musicians. The findings demonstrate recruitment of right hemisphere in musicians for discriminating speech sounds and a putative broadening of their language network. Musicians appear to have an increased sensitivity to acoustic features and enhanced selective attention to temporal features of speech that is facilitated by musical training and supported, in part, by right hemisphere homologues of established speech processing regions of the brain.

  18. Autophagy inhibition enhances RAD001-induced cytotoxicity in human bladder cancer cells.

    Science.gov (United States)

    Lin, Ji-Fan; Lin, Yi-Chia; Yang, Shan-Che; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Hwang, Thomas I-Sheng

    2016-01-01

    Mammalian target of rapamycin (mTOR), involved in PI3K/AKT/mTOR pathway, is known to play a central role in regulating the growth of cancer cells. The PI3K/AKT/mTOR pathway enhances tumor survival and proliferation through suppressing autophagy, which sustains energy homeostasis by collecting and recycling cellular components under stress conditions. Conversely, inhibitors of the mTOR pathway such as RAD001 induce autophagy, leading to promotion of tumor survival and limited antitumor efficacy. We thus hypothesized that the use of autophagy inhibitor in combination with mTOR inhibition improves the cytotoxicity of mTOR inhibitors in bladder cancer. The cytotoxicity of RT4, 5637, HT1376, and T24 human bladder cancer cells treated with RAD001 alone or combined with autophagy inhibitors (3-methyladenine (3-MA), bafilomycin A1 (Baf A1), chloroquine, or hydroxychloroquine) was assessed using the WST-8 cell viability kit. The autophagy status in cells was analyzed by the detection of microtubule-associated light chain 3 form II (LC3-II), using immunofluorescent staining and Western blot. Acidic vesicular organelle (AVO) formation in treated cells was determined by acridine orange vital staining. Inhibition of mTOR pathway by RAD001 was monitored by using a homemade quantitative polymerase chain reaction gene array, while phospho-mTOR was detected using Western blot. Induced apoptosis was determined by measurement of caspase 3/7 activity and DNA fragmentation in cells after treatment. Advanced bladder cancer cells (5637, HT1376, and T24) were more resistant to RAD001 than RT4. Autophagy flux detected by the expression of LC3-II showed RAD001-induced autophagy. AVO formation was detected in cells treated with RAD001 and was inhibited by the addition of 3-MA or Baf A1. Cotreatment of RAD001 with autophagy inhibitors further reduced cell viability and induced apoptosis in bladder cancer cells. Our results indicate that simultaneous inhibition of the mTOR and autophagy

  19. Investigation of evaporation characteristics of polonium and its lighter homologues selenium and tellurium from liquid Pb-Bi-eutecticum

    CERN Document Server

    Neuhausen, J; Eichler, B

    2004-01-01

    The evaporation behaviour of polonium and its lighter homologues selenium and tellurium dissolved in liquid Pb-Bi-eutecticum (LBE) has been studied at various temperatures in the range from 482 K up to 1330 K under Ar/H2 and Ar/H2O-atmospheres using γ-ray spectroscopy. Polonium release in the temperature range of interest for technical applications is slow. Within short term (1h) experiments measurable amounts of polonium are evaporated only at temperatures above 973 K. Long term experiments reveal that a slow evaporation of polonium occurs at temperatures around 873 K resulting in a fractional polonium loss of the melt around 1% per day. Evaporation rates of selenium and tellurium are smaller than those of polonium. The presence of H2O does not enhance the evaporation within the error limits of our experiments. The thermodynamics and possible reaction pathways involved in polonium release from LBE are discussed.

  20. The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer.

    Science.gov (United States)

    Xiang, Zhiming; Liang, Qianwen; Liang, Changhong; Zhong, Guimian

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P 0.05). However, the quantitative parameter of them were significantly positively correlated (P liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

  1. Background enhancement of mammary glandular tissue on breast dynamic MRI: imaging features and effect on assessment of breast cancer extent.

    Science.gov (United States)

    Uematsu, Takayoshi; Kasami, Masako; Watanabe, Junichiro

    2012-07-01

    Just as mammographic breast density influences mammographic sensitivity, the degree of background enhancement in breast magnetic resonance imaging (MRI) may influence the sensitivity of breast MRI. The purpose of this study is to assess the influence of background enhancement on the accuracy of breast cancer extent assessment using MRI and to assess the correlation between the accuracy of breast cancer extent assessment and the kinetic analysis of background enhancement in dynamic contrast-enhanced MRI. Seventy bilateral breast MRI examinations were evaluated to assess the extent of a known primary tumor. Background enhancement was classified into four categories by visual assessment: minimal, mild, moderate, and marked, in the early dynamic phase and in the late dynamic phase. The correlation of the results with histological findings was examined. Background enhancement grade showed a significant tendency to increase during dynamic contrast-enhanced MRI. When classifying background enhancement at early dynamic phase, the accuracy of tumor extent assessment by MRI with moderate/marked background enhancement was 60%, which was lower than the 78% accuracy with minimal/mild background enhancement, but not significantly so (p = 0.153). When classifying background enhancement at late dynamic phase, the accuracy with moderate/marked background enhancement was 61%, which was significantly lower than the 83% accuracy with minimal/mild background enhancement (p = 0.034). There was no tumor-size-related bias between the groups (p = 0.089). The degree of background enhancement on breast MRI affects the accuracy of breast cancer extent assessment, especially at late dynamic phase.

  2. Curcumin enhances the anticancer effects of trichostatin a in breast cancer cells.

    Science.gov (United States)

    Yan, Guang; Graham, Kimmer; Lanza-Jacoby, Susan

    2013-05-01

    Breast cancer patients with HER-2 positive or estrogen receptor negative tumors have a poor prognosis because these tumors are aggressive and respond poorly to standard therapies. Histone deacetylase (HDAC) inhibitors have been shown to decreased cell survival, which suggests that HDAC inhibitors may be developed for preventing and treating breast cancer. Curcumin has anti-inflammatory and proapoptotic effects in cancer cells. We determined whether the HDAC inhibitor, Tricostatin A (TSA) in combination with curcumin would produce greater antiproliferative and apoptotic effects than either agent alone. Increasing the concentration of curcumin from 10 to 20 µM enhanced the growth inhibitory effects of the combination in SkBr3 and 435eB breast cancer cells, which was accompanied by decreased viability along with decreased phosphorylation of ERK and Akt. The decreased cell viability observed in SkBr3 cells when curcumin was combined with TSA led to a G0/G1 cell cycle arrest and increased p21 and p27, and decreased Cyclin D1 protein expression. The combination induced cleavage of caspase 3 and poly(ADP-ribose) polymerase-1, suggesting that cell death occurred by apoptosis. There were no changes in protein expression of Bcl2, Bax, or Bcl-xL and decreased expression of p53. The combination increased protein expression of phosphorylated JNK and phosphorylated p38. Pharmacological inhibition of JNK, but not p38, attenuated the decreased viability induced by the curcumin and TSA combination. We conclude that p53 independent apoptosis induced by combining curcumin and TSA involves JNK activation. These findings provide a rationale for exploring the potential benefits of the combination of curcumin with TSA for treatment of breast cancer. Copyright © 2012 Wiley Periodicals, Inc.

  3. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

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    Song, Kai [Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Shandong Province (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Song, Yong [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Department of Stomatology, Liu Zhou People' s Hospital, Guangxi (China); Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-lin [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Liu, Ke, E-mail: liuke.1999@aliyun.com [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Shang, Zheng-jun, E-mail: shangzhengjun@hotmail.com [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China)

    2014-10-15

    Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo.

  4. Epothilone B enhances surface EpCAM expression in ovarian cancer Hey cells.

    Science.gov (United States)

    Shahabi, Shohreh; Yang, Chia-Ping Huang; Goldberg, Gary L; Horwitz, Susan Band

    2010-11-01

    Epothilone B (EpoB), like Taxol, stabilizes microtubules resulting in an inhibition of microtubule dynamic instability. The drug is being evaluated in phase III clinical trials. An EpoB analog, Ixabepilone, was approved by the FDA for the treatment of taxane-resistant metastatic breast cancer. Epithelial cell adhesion antigen (EpCAM) expression is significantly higher in epithelial ovarian cancer cells compared to normal cells. The effects of EpoB and other microtubule-interacting agents on surface EpCAM expression were studied. Biochemical methods, immunofluorescence and flow cytometry were used to identify EpCAM expression on the surface of the ovarian cancer cell line, Hey, after exposure to EpoB. The relationship between EpoB-mediated surface EpCAM expression and EpoB-induced α-tubulin acetylation, a surrogate marker for stable microtubules, in Hey cells also was investigated. Nanomolar concentrations of EpoB, Taxol, discodermolide or vinblastine caused a marked increase in surface EpCAM expression in Hey cells. Alpha-tubulin acetylation was increased following treatment with Taxol, EpoB and discodermolide, but not with vinblastine, indicating that drug-enhanced surface EpCAM expression does not correlate with tubulin acetylation or stabilization. Unexpectedly, EpoB did not have a significant effect on EpCAM mRNA expression, nor did it alter the level of total cellular EpCAM in Hey cells. The results indicate that disruption of the microtubule cytoskeleton is associated with the redistribution of cell surface antigens in ovarian cancer cells. The increase in cell surface EpCAM antigen density may facilitate the antibody targeting of EpCAM-positive ovarian cancer cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential.

    Science.gov (United States)

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-Lin; Liu, Ke; Shang, Zheng-Jun

    2014-10-15

    Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells.

    Science.gov (United States)

    Wang, Yanli; Kong, Hui; Zeng, Xiaoning; Liu, Wenrui; Wang, Zailiang; Yan, Xiaopei; Wang, Hong; Xie, Weiping

    2016-04-01

    Lung cancer is the leading cause of cancer death, and it is widely accepted that chronic inflammation is an important risk for the development of lung cancer. Now, it is recognized that the nucleotide-binding and oligomerization domain (NOD) like receptors (NLRs)-containing inflammasomes are involved in cancer-related inflammation. This study was designed to investigate the effects of NLR family pyrin domain containing protein 3 (NLRP3) inflammasome on the proliferation and migration of lung adenocarcinoma cell line A549. Using 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, scratch assay, and Transwell migration assay, we showed that activation of the NLRP3 inflammasome by LPS+ATP enhanced the proliferation and migration of A549 cells. Western blot analysis showed that activation of phosphorylation of Akt, ERK1/2, CREB and the expression of Snail increased, while the expression of E-cadherin decreased after the activation of NLRP3 inflammasome. Moreover, these effects were inhibited by the following treatments: i) downregulating the expression of NLRP3 by short hairpin RNA (shRNA) interference, ii) inhibiting the activation of NLRP3 inflammasome with a caspase-1 inhibitor, iii) blocking the interleukin-1β (IL-1β) and IL-18 signal transduction with IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP). Collectively, these results indicate that NLRP3 inflammasome plays a vital role in regulating the proliferation and migration of A549 cells and it might be a potential target for the treatment of lung cancer.

  7. Silencing the livin gene enhances the cytotoxic effects of anticancer drugs on colon cancer cells.

    Science.gov (United States)

    Oh, Bo Young; Kim, Kwang Ho; Chung, Soon Sup; Lee, Ryung-Ah

    2016-12-01

    Livin is associated with drug response in several cancers. The aim of this study was to investigate the effect of silencing the livin gene expression on anticancer drug response in colorectal cancer. siRNA was transfected at different concentrations (0, 10, and 30nM) into HCT116 cells, then cells were treated with either 5-fluorouracil (FU)/leucovorin (LV) or oxaliplatin (L-OHP)/5-FU/LV. Cellular viability and apoptosis were evaluated following silencing of livin gene expression combined with treatment with anticancer drugs. Livin gene expression was effectively suppressed by 30nM siRNA compared with control and 10nM siRNA. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that proliferation was effectively inhibited in cells treated with a combination of both siRNA and an anticancer drug, compared to cells treated with siRNA-Livin or anticancer drug alone. In particular, the combination of 30nM siRNA and L-OHP/5-FU/LV resulted in a 93.8% and 91.4% decrease, compared to untreated control or L-OHP/5-FU/LV alone, respectively. Cellular proliferation was most effectively suppressed by a combination of 30nM of siRNA and L-OHP/5-FU/LV compared to other combinations. siRNA-mediated down-regulation of livin gene expression could significantly suppress colon cancer growth and enhance the cytotoxic effects of anticancer drugs such as 5-FU and L-OHP. The results of this study suggest that silencing livin gene expression in combination with treatment with anticancer drugs might be a novel cancer therapy for colorectal cancer.

  8. Benign mammary epithelial cells enhance the transformed phenotype of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Schedin Pepper J

    2010-07-01

    Full Text Available Abstract Background Recent research has yielded a wealth of data underscoring the key role of the cancer microenvironment, especially immune and stromal cells, in the progression of cancer and the development of metastases. However, the role of adjacent benign epithelial cells, which provide initial cell-cell contacts with cancer cells, in tumor progression has not been thoroughly examined. In this report we addressed the question whether benign MECs alter the transformed phenotype of human breast cancer cells. Methods We used both in vitro and in vivo co-cultivation approaches, whereby we mixed GFP-tagged MCF-10A cells (G2B-10A, as a model of benign mammary epithelial cells (MECs, and RFP-tagged MDA-MB-231-TIAS cells (R2-T1AS, as a model of breast cancer cells. Results The in vitro studies showed that G2B-10A cells increase the colony formation of R2-T1AS cells in both soft agar and clonogenicity assays. Conditioned media derived from G2B-10A cells enhanced colony formation of R2-T1AS cells, whereas prior paraformaldehyde (PFA fixation of G2B-10A cells abrogated this enhancement effect. Moreover, two other models of benign MECs, MCF-12A and HuMECs, also enhanced R2-T1AS colony growth in soft agar and clonogenicity assays. These data reveal that factors secreted by benign MECs are responsible for the observed enhancement of the R2-T1AS transformed phenotype. To determine whether G2B-10A cells enhance the tumorigenic growth of co-injected R2-T1AS cells in vivo, we used the nude mouse xenograft assay. Co-injecting R2-T1AS cells with G2B-10A cells ± PFA-fixation, revealed that G2B-10A cells promoted a ~3-fold increase in tumor growth, irrespective of PFA pre-treatment. These results indicate that soluble factors secreted by G2B-10A cells play a less important role in promoting R2-T1AS tumorigenesis in vivo, and that additional components are operative in the nude mouse xenograft assay. Finally, using array analysis, we found that both live and PFA

  9. Silencing the expression of Cbl-b enhances the immune activation of T lymphocytes against RM-1 prostate cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Shu-Kui Zhou

    2014-12-01

    Conclusion: Silencing Cbl-b significantly enhanced T lymphocyte function and T lymphocyte cytotoxicity activity against a model prostate cancer cell line in vitro. This study suggests a potentially novel immunotherapeutic strategy against prostate cancer.

  10. Quantitative assessment of background parenchymal enhancement in breast magnetic resonance images predicts the risk of breast cancer.

    Science.gov (United States)

    Hu, Xiaoxin; Jiang, Luan; Li, Qiang; Gu, Yajia

    2017-02-07

    The objective of this study was to evaluate the association betweenthe quantitative assessment of background parenchymal enhancement rate (BPER) and breast cancer. From 14,033 consecutive patients who underwent breast MRI in our center, we randomly selected 101 normal controls. Then, we selected 101 women with benign breast lesions and 101 women with breast cancer who were matched for age and menstruation status. We evaluated BPER at early (2 minutes), medium (4 minutes) and late (6 minutes) enhanced time phases of breast MRI for quantitative assessment. Odds ratios (ORs) for risk of breast cancer were calculated using the receiver operating curve. The BPER increased in a time-dependent manner after enhancement in both premenopausal and postmenopausal women. Premenopausal women had higher BPER than postmenopausal women at early, medium and late enhanced phases. In the normal population, the OR for probability of breast cancer for premenopausal women with high BPER was 4.1 (95% CI: 1.7-9.7) and 4.6 (95% CI: 1.7-12.0) for postmenopausal women. The OR of breast cancer morbidity in premenopausal women with high BPER was 2.6 (95% CI: 1.1-6.4) and 2.8 (95% CI: 1.2-6.1) for postmenopausal women. The BPER was found to be a predictive factor of breast cancer morbidity. Different time phases should be used to assess BPER in premenopausal and postmenopausal women.

  11. EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer.

    Directory of Open Access Journals (Sweden)

    Xuemin Wang

    Full Text Available Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1, a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP. The present study demonstrates for the first time that (--epigallocatechin-3-gallate (EGCG, a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.

  12. SG2NA enhances cancer cell survival by stabilizing DJ-1 and thus activating Akt

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    Tanti, Goutam Kumar, E-mail: goutamjnu@hotmail.com; Pandey, Shweta; Goswami, Shyamal K.

    2015-08-07

    SG2NA in association with striatin and zinedin forms a striatin family of WD-40 repeat proteins. This family of proteins functions as scaffold in different signal transduction pathways. They also act as a regulatory subunit of protein phosphatase 2A. We have shown that SG2NA which evolved first in the metazoan evolution among the striatin family members expresses different isoforms generated out of alternative splicing. We have also shown that SG2NA protects cells from oxidative stress by recruiting DJ-1 and Akt to mitochondria and membrane in the post-mitotic neuronal cells. DJ-1 is both cancer and Parkinson's disease related protein. In the present study we have shown that SG2NA protects DJ-1 from proteasomal degradation in cancer cells. Hence, downregulation of SG2NA reduces DJ-1/Akt colocalization in cancer cells resulting in the reduction of anchorage dependent and independent growth. Thus SG2NA enhances cancer cell survival. Reactive oxygen species enhances SG2NA, DJ-1 and Akt trimerization. Removal of the reactive oxygen species by N-acetyl-cysteine thus reduces cancer cell growth. - Highlights: • Reactive oxygen species (ROS) play potential role in cancer cell proliferation. • It enhances the association between DJ-1 and Akt mediated by SG2NA. • In cancer cells SG2NA stabilizes DJ-1 by inhibiting it from proteosomal degradation. • DJ-1 then activates Akt and cancer cells get their property of enhanced proliferation by sustained activation of Akt. • Further study on this field could lead to new target for cancer therapy.

  13. Separation of bacteriochlorophyll homologues from green photosynthetic sulfur bacteria by reversed-phase HPLC.

    Science.gov (United States)

    Borrego, C M; Garcia-Gil, L J

    1994-07-01

    A reversed-phase High Performance Liquid Cromatography (HPLC) method has been developed to accurately separate bacteriochlorophyllsc, d ande homologues in a reasonably short run time of 60 minutes. By using this method, two well-defined groups of bacteriochlorophyll homologue peaks can be discriminated. The first one consists of 4 peaks (min 24 to 30), which corresponds to the four main farnesyl homologues. The second peak subset is formed by a cluster of up to 10 minor peaks (min 33 to 40). These peaks can be related with series of several alcohol esters of the different chlorosome chlorophylls. The number of homologues was, however, quite variable depending on both, the bacteriochlorophyll and the bacterial species. The method hereby described, also provides a good separation of other photosynthetic pigments, either bacterial (Bacteriochlorophylla, chlorobactene, isorenieratene and okenone) or algal ones (Chlorophylla, Pheophytina and β-carotene). A preliminary screening of the homologue composition of several green photosynthetic bacterial species and isolates, has revealed different relative quantitative patterns. These differences seem to be related to physiological aspects rather than to taxonomic ones. The application of the method to the study of natural populations avoids the typical drawbacks on the pigment identification of overlapping eukaryotic and prokaryotic phototrophic microorganisms, giving further information about their physiological status.

  14. Functional enhancers at the gene-poor 8q24 cancer-linked locus.

    Directory of Open Access Journals (Sweden)

    Li Jia

    2009-08-01

    Full Text Available Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their biological activities have been unknown. Here we profiled a 5-megabase chromatin segment encompassing all the risk regions for RNA expression, histone modifications, and locations occupied by RNA polymerase II and androgen receptor (AR. This led to the identification of several transcriptional enhancers, which were verified using reporter assays. Two enhancers in one risk region were occupied by AR and responded to androgen treatment; one contained a single nucleotide polymorphism (rs11986220 that resides within a FoxA1 binding site, with the prostate cancer risk allele facilitating both stronger FoxA1 binding and stronger androgen responsiveness. The study reported here exemplifies an approach that may be applied to any risk-associated allele in non-protein coding regions as it emerges from genome-wide association studies to better understand the genetic predisposition of complex diseases.

  15. Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

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    Jung, Joohee [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of); Park, Sung-Jin [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium (Singapore); Chung, Hye Kyung [Center for Development and Commercialization of Anti-cancer Therapeutics, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kang, Hye-Won; Lee, Sa-Won; Seo, Min Hyo [Department of Parenteral Delivery Program, Samyang Pharmaceuticals R and D, Daejeon (Korea, Republic of); Park, Heon Joo [Department of Microbiology, College of Medicine, Inha University, Inchon (Korea, Republic of); Song, Si Yeol [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jeong, Seong-Yun, E-mail: syj@amc.seoul.kr [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Kyung, E-mail: ekchoi@amc.seoul.kr [Institute for Innovative Cancer Research, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Radiation Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of)

    2012-09-01

    Purpose: To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. Methods and Materials: The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR). Results: The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice. Conclusions: We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.

  16. Nanotextured polymer substrates show enhanced cancer cell isolation and cell culture

    Science.gov (United States)

    Islam, Muhymin; Sajid, Adeel; Arif Iftakher Mahmood, M.; Motasim Bellah, Mohammad; Allen, Peter B.; Kim, Young-Tae; Iqbal, Samir M.

    2015-06-01

    Detection of circulating tumor cells (CTCs) in the early stages of cancer is a great challenge because of their exceedingly small concentration. There are only a few approaches sensitive enough to differentiate tumor cells from the plethora of other cells in a sample like blood. In order to detect CTCs, several antibodies and aptamers have already shown high affinity. Nanotexture can be used to mimic basement membrane to further enhance this affinity. This article reports an approach to fabricate nanotextured polydimethylsiloxane (PDMS) substrates using micro reactive ion etching (micro-RIE). Three recipes were used to prepare nanotextured PDMS using oxygen and carbon tetrafluoride. Micro-RIE provided better control on surface properties. Nanotexturing improved the affinity of PDMS surfaces to capture cancer cells using surface immobilized aptamers against cell membrane overexpressed with epidermal growth factor receptors. In all cases, nanotexture of PDMS increased the effective surface area by creating nanoscale roughness on the surface. Nanotexture also enhanced the growth rate of cultured cells compared to plain surfaces. A comparison among the three nanotextured surfaces demonstrated an almost linear relationship between the surface roughness and density of captured tumor cells. The nanotextured PDMS mimicked biophysical environments for cells to grow faster. This can have many implications in microfluidic platforms used for cell handling.

  17. Herceptin-functionalized pure paclitaxel nanocrystals for enhanced delivery to HER2-postive breast cancer cells.

    Science.gov (United States)

    Noh, Jin-Ki; Naeem, Muhammad; Cao, Jiafu; Lee, Eun Hee; Kim, Min-Soo; Jung, Yunjin; Yoo, Jin-Wook

    2016-11-20

    The objective of this study was to prepare Herceptin (HCT)-functionalized paclitaxel nanocrystals and evaluated their cell-specific interactions, cellular accumulation, and growth inhibition in HER2-positve breast cancer cells as a tumor-targeted delivery module. Paclitaxel (PTX) was fabricated in the form of nanocrystals (PNCs) by a sono-precipitation method, and HCT were coated using a facile non-covalent method (PNCs-HCT). Our results showed that the PNCs-HCT were stable for at least 1month at 4°C with no noticeable desorption of HCT. The release test showed that PNCs-HCT exhibited sustained drug release similar to only PNCs but with a higher release rate than only PTX powder. Cellular uptake, cytotoxicity, and cell cycle arrest studies revealed that PNCs-HCT exhibit greater binding affinity and higher cell-specific internalization to HER2-positive breast cancer cell lines as compared to PNCs, followed by enhanced cell growth inhibition. HCT-functionalized PNCs presented in this study offer a promising strategy for targeted pure drug nanocrystal delivery and enhancing the efficiency of anticancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. [Effect of PLISSIT model sexual health enhancement program for women with gynecologic cancer and their husbands].

    Science.gov (United States)

    Nho, Ju-Hee

    2013-10-01

    The purpose of this study was to examine effects of the Permission, Limited Information, Specific Suggestions, Intensive Therapy (PLISSIT) model sexual health enhancement program on, and development in, sexual function, sexual distress, marital intimacy, and subjective happiness of women with gynecologic cancer and their husbands. The comprehensive program (4 session, 90 minutes per session) was developed based on the PLISSIT model. Participants were 43 couples, 21 assigned to the experimental group who attended the 4-week program, and 22 to the control group. Sexual function, sexual distress, marital intimacy, subjective happiness of the women, marital intimacy, subjective happiness of husbands were determined by a questionnaire that was completed by the participants before and after the program. The control group received the intervention post experiment. Chi-square test, t-test, Fisher's exact test were used to test the effectiveness of the program. Post intervention results showed significant differences between the groups for sexual function, sexual distress, and marital intimacy in the women and for subjective happiness in the husbands. Results indicate that the sexual health enhancement program is effective in improving sexual function, lowering sexual distress, increasing marital intimacy, and subjective happiness in women with gynecologic cancer and their husbands.

  19. Identifying Triple-Negative Breast Cancer Using Background Parenchymal Enhancement Heterogeneity on Dynamic Contrast-Enhanced MRI: A Pilot Radiomics Study

    Science.gov (United States)

    Wang, Jeff; Kato, Fumi; Oyama-Manabe, Noriko; Li, Ruijiang; Cui, Yi; Tha, Khin Khin; Yamashita, Hiroko; Kudo, Kohsuke; Shirato, Hiroki

    2015-01-01

    Objectives To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE) MRI at 3.0 Tesla in identifying “triple-negative" breast cancers. Materials and Methods In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC) using cross-validation. Results Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (pcancers were textures of background parenchymal enhancement. Conclusions Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype. Prospective validation studies are warranted to confirm these findings and determine potential implications. PMID:26600392

  20. Rationale for a multimodality strategy to enhance the efficacy of dendritic cell-based cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Jashodeep eDatta

    2015-06-01

    Full Text Available Dendritic cells (DC, master antigen-presenting cells that orchestrate interactions between the adaptive and innate immune arms, are increasingly utilized in cancer immunotherapy. Despite remarkable progress in our understanding of DC immunobiology, as well as several encouraging clinical applications — such as DC-based sipuleucel-T for metastatic castration-resistant prostate cancer — clinically effective DC-based immunotherapy as monotherapy for a majority of tumors remains a distant goal. The complex interplay between diverse molecular and immune processes that govern resistance to DC-based vaccination compels a multimodality approach, encompassing a growing arsenal of antitumor agents which target these distinct processes and synergistically enhance DC function. These include antibody-based targeted molecular therapies, immune checkpoint inhibitors, therapies that inhibit immunosuppressive cellular elements, conventional cytotoxic modalities, and immune potentiating adjuvants. It is likely that in the emerging era of precision cancer therapeutics, tangible clinical benefits will only be realized with a multifaceted—and personalized—approach combining DC-based vaccination with adjunctive strategies.

  1. Breast Cancer Preoperative Staging: Does Contrast-Enhanced Magnetic Resonance Mammography Modify Surgery?

    Directory of Open Access Journals (Sweden)

    Chiara Perono Biacchiardi

    2011-01-01

    Full Text Available Women with newly diagnosed breast cancer may have lesions undetected by conventional imaging. Recently contrast-enhanced magnetic resonance mammography (CE-MRM showed higher sensitivity in breast lesions detection. The present analysis was aimed at evaluating the benefit of preoperative CE-MRM in the surgical planning. From 2005 to 2009, 525 consecutive women (25–75 years with breast cancer, newly diagnosed by mammography, ultrasound, and needle-biopsy, underwent CE-MRM. The median invasive tumour size was 19 mm. In 144 patients, CE-MRM identified additional lesions. After secondlook, 119 patients underwent additional biopsy. CE-MRM altered surgery in 118 patients: 57 received double lumpectomy or wider excision (41 beneficial, 41 required mastectomy (40 beneficial, and 20 underwent contra lateral surgery (18 beneficial. The overall false-positive rate was 27.1% (39/144. CE-MRM contributed significantly to the management of breast cancer, suggesting more extensive disease in 144/525 (27.4% patients and changing the surgical plan in 118/525 (22.5% patients (99/525, 18.8% beneficial.

  2. Partnership with an African American sorority to enhance participation in cancer genetics research.

    Science.gov (United States)

    Olsen, Sharon J; Malvern, Kathryn T; May, Betty J; Jenkins, Issie L; Griffin, Constance A

    2008-01-01

    Reduced minority participation in clinical research challenges researchers to consider novel recruitment modalities. This study describes a formal partnership between the National Educational Foundation of the Zeta Phi Beta Sorority and the Mid-Atlantic Cancer Genetics Network. The goal was to enhance awareness about inherited breast cancer and to increase enrollment in the national Cancer Genetics Network. In this descriptive, pilot study, two recruitment strategies across four states were undertaken: an onsite educational session at four Annual State Leadership Conferences and a 2-tiered direct mail campaign to the sorority membership. Recruitment methods targeted over 1,200 well-educated African American women. Of the 279 attendees at the state conference educational sessions, only 3 women meeting the high risk eligibility requirement enrolled. Direct mail recruitment elicited 24 eligible women. Lessons learned are described. Despite low accrual, the partnership laid a foundation for broader collaboration with the Zeta Phi Beta Sorority. In the future, collaboration with minority sororities and fraternities as part of standard registry recruitment should be explored. Copyright 2008 S. Karger AG, Basel.

  3. [Bortezomib enhances the sensitivity of prostate cancer cells to natural killer cell-mediated cytotoxicity].

    Science.gov (United States)

    Hu, Wei; Gao, Zhen-Yu; Wang, Wei

    2014-03-01

    To investigate whether bortezomib can enhance the sensitivity of human prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity, and whether it produces the same effect on different PCa cell lines. We treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145 cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for 24, 48 and 72 hours, and then detected the proliferation and apoptosis of the tumor cells by CCK-8 and Annexin V/PI, respectively. The proliferation rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79 +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/- 5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both significantly inhibited as compared with the control group (P cancer therapies, and it is more efficacious for androgen-independent prostate cancer.

  4. Inhibition of PARP1 activity enhances chemotherapeutic efficiency in cisplatin-resistant gastric cancer cells.

    Science.gov (United States)

    Wang, Qiang; Xiong, Jianping; Qiu, Danping; Zhao, Xue; Yan, Donglin; Xu, Wenxia; Wang, Zhangding; Chen, Qi; Panday, Sapna; Li, Aiping; Wang, Shouyu; Zhou, Jianwei

    2017-11-01

    Cisplatin (DDP) is the first line chemotherapeutic drug for several cancers, including gastric cancer (GC). Unfortunately, the rapid development of drug resistance remains a significant challenge for the clinical application of cisplatin. There is an urgent need to develop new strategies to overcome DDP resistance for cancer treatment. In this study, four types of human GC cells have been divided into naturally sensitive or naturally resistant categories according to their responses to cisplatin. PARP1 activity (poly (ADP-ribose), PAR) was found to be greatly increased in cisplatin-resistant GC cells. PARP1 inhibitors significantly enhanced cisplatin-induced DNA damage and apoptosis in the resistant GC cells via the inhibition of PAR. Mechanistically, PARP1 inhibitors suppress DNA-PKcs stability and reduce the capability of DNA double-strand break (DSB) repair via the NHEJ pathway. This was also verified in BGC823/DDP GC cells with acquired cisplatin resistance. In conclusion, we identified that PARP1 is a useful interceptive target in cisplatin-resistant GC cells. Our data provide a promising therapeutic strategy against cisplatin resistance in GC cells that has potential translational significance. Copyright © 2017. Published by Elsevier Ltd.

  5. Fusion imaging of contrast-enhanced ultrasound and contrast-enhanced CT or MRI before radiofrequency ablation for liver cancers.

    Science.gov (United States)

    Bo, Xiao-Wan; Xu, Hui-Xiong; Wang, Dan; Guo, Le-Hang; Sun, Li-Ping; Li, Xiao-Long; Zhao, Chong-Ke; He, Ya-Ping; Liu, Bo-Ji; Li, Dan-Dan; Zhang, Kun

    2016-11-01

    To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers. 45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded. On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA. Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA. Advances in knowledge: CEUS and CECT/CEMRI fusion imaging is better than both conventional ultrasound and ultrasound

  6. Re-expression of ARHI (DIRAS3 induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel

    Directory of Open Access Journals (Sweden)

    Bast Robert C

    2011-01-01

    Full Text Available Abstract Background ARHI is a Ras-related imprinted gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of breast cancers, and loss of its expression is associated with its progression from ductal carcinoma in situ (DCIS to invasive disease. In ovarian cancer, re-expression of ARHI induces autophagy and leads to autophagic death in cell culture; however, ARHI re-expression enables ovarian cancer cells to remain dormant when they are grown in mice as xenografts. The purpose of this study is to examine whether ARHI induces autophagy in breast cancer cells and to evaluate the effects of ARHI gene re-expression in combination with paclitaxel. Methods Re-expression of ARHI was achieved by transfection, by treatment with trichostatin A (TSA or by a combination of TSA and 5-aza-2'-deoxycytidine (DAC in breast cancer cell cultures and by liposomal delivery of ARHI in breast tumor xenografts. Results ARHI re-expression induces autophagy in breast cancer cells, and ARHI is essential for the induction of autophagy. When ARHI was re-expressed in breast cancer cells treated with paclitaxel, the growth inhibitory effect of paclitaxel was enhanced in both the cell culture and the xenografts. Although paclitaxel alone did not induce autophagy in breast cancer cells, it enhanced ARHI-induced autophagy. Conversely, ARHI re-expression promoted paclitaxel-induced apoptosis and G2/M cell cycle arrest. Conclusions ARHI re-expression induces autophagic cell death in breast cancer cells and enhances the inhibitory effects of paclitaxel by promoting autophagy, apoptosis, and G2/M cell cycle arrest.

  7. Low-coherence enhanced backscattering of light: characteristics and applications for colon cancer screening

    Science.gov (United States)

    Kim, Young L.; Pradhan, Prabhakar; Turzhitsky, Vladimir M.; Subramanian, Hariharan; Liu, Yang; Wali, Ramesh K.; Roy, Hemant K.; Backman, Vadim

    2007-02-01

    The phenomenon of enhanced backscattering (EBS) of light, also known as coherent backscattering (CBS) of light, is a spectacular manifestation of self-interference effects in elastic light scattering, which gives rise to an enhanced scattered intensity in the backward direction. Although EBS has been the object of intensive investigation in non-biological media over the last two decades, there have been only a few attempts to explore EBS for tissue characterization and diagnosis. We have recently made progress in the EBS measurements of biological tissue by taking advantage of lowcoherence (or partially coherent) illumination, which is referred to as low-coherence EBS (LEBS) of light. LEBS possess novel and intriguing properties such as speckle reduction, self-averaging effect, broadening of the EBS width, depth-selectivity, double scattering, and circular polarization memory effect. After we review the current state of research on LEBS, we discuss how these characteristics apply for early cancer detection, especially in colorectal cancer (CRC), which is the second leading cause of cancer mortality in the United States. Although colonoscopy remains the gold standard for CRC screening, resource constraints and potential complications make it impractical to perform colonoscopy on the entire population at risk (age > 50). Thus, identifying patients who are most likely to benefit from colonoscopy is of paramount importance. We demonstrate that LEBS measurements in easily accessible colonoscopically normal mucosa (e.g., in the rectum of the colon) can be used for predicting the risk of CRC, and thus LEBS has the potential to serve as accurate markers of the risk of neoplasia elsewhere in the colon.

  8. Morinda citrifolia edible leaf extract enhanced immune response against lung cancer.

    Science.gov (United States)

    Lim, Swee-Ling; Goh, Yong-Meng; Noordin, M Mustapha; Rahman, Heshu S; Othman, Hemn H; Abu Bakar, Nurul Ain; Mohamed, Suhaila

    2016-02-01

    Lung cancer causes 1.4 million deaths annually. In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib. Lung tumour-induced BALB/c mice were fed with 150 mg kg(-1) or 300 mg kg(-1) body weight of the leaf extract, or erlotinib (50 mg kg(-1) body-weight) for 21 days. The 300 mg kg(-1) body weight extract significantly (and dose-dependently) suppressed lung tumour growth; the extract worked more effectively than the 50 mg kg(-1) body weight erlotinib treatment. The extract significantly increased blood lymphocyte counts, and spleen tissue B cells, T cells and natural killer cells, and reduced the epidermal growth factor receptor (EGFR) which is a lung adenocarcinoma biomarker. The extract also suppressed the cyclooxygenase 2 (COX2) inflammatory markers, and enhanced the tumour suppressor gene (phosphatase and tensin homolog, PTEN). It inhibited tumour growth cellular gene (transformed mouse 3T3 cell double minute 2 (MDM2), V-raf-leukemia viral oncogene 1 (RAF1), and mechanistic target of rapamycin (MTOR)) mRNA expression in the tumours. The extract is rich in scopoletin and epicatechin, which are the main phenolic compounds. The 300 mg kg(-1)Morinda citrifolia leaf 50% ethanolic extract showed promising potential as a complementary therapeutic dietary supplement which was more effective than the 50 mg kg(-1) erlotinib in suppressing lung adenocarcinoma. Part of the mechanisms involved enhancing immune responses, suppressing proliferation and interfering with various tumour growth signalling pathways.

  9. Functionalization of nanotextured substrates for enhanced identification of metastatic breast cancer cells

    Science.gov (United States)

    Mansur, Nuzhat; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2017-09-01

    Metastasis is the major cause of low survival rates among cancer patients. Once cancer cells metastasize, it is extremely difficult to contain the disease. We report on a nanotextured platform for enhanced detection of metastatic cells. We captured metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells on anti-EGFR aptamer modified plane and nanotextured substrates. Metastatic cells were seen to change their morphology at higher rates when captured on nanotextured substrates than on plane substrates. Analysis showed statistically different morphological behaviors of metastatic cells that were very pronounced on the nanotextured substrates. Several distance matrices were calculated to quantify the dissimilarity of cell shape change. Nanotexturing increased the dissimilarity of the metastatic cells and as a result the contrast between metastatic and non-metastatic cells increased. Jaccard distance measurements found that the shape change ratio of the non-metastatic and metastatic cells was enhanced from 1:1.01 to 1:1.81, going from plane to nanotextured substrates. The shape change ratio of the non-metastatic to metastatic cells improved from 1:1.48 to 1:2.19 for the Hausdorff distance and from 1:1.87 to 1:4.69 for the Mahalanobis distance after introducing nanotexture. Distance matrix analysis showed that nanotexture increased the shape change ratios of non-metastatic and metastatic cells. Hence, the detectability of metastatic cells increased. These calculated matrices provided clear and explicit measures to discriminate single cells for their metastatic state on functional nanotextured substrates.

  10. Enhanced Detection of Cancer Biomarkers in Blood-Borne Extracellular Vesicles Using Nanodroplets and Focused Ultrasound.

    Science.gov (United States)

    Paproski, Robert J; Jovel, Juan; Wong, Gane Ka-Shu; Lewis, John D; Zemp, Roger J

    2017-01-01

    The feasibility of personalized medicine approaches will be greatly improved by the development of noninvasive methods to interrogate tumor biology. Extracellular vesicles shed by solid tumors into the bloodstream have been under recent investigation as a source of tumor-derived biomarkers such as proteins and nucleic acids. We report here an approach using submicrometer perfluorobutane nanodroplets and focused ultrasound to enhance the release of extracellular vesicles from specific locations in tumors into the blood. The released extracellular vesicles were enumerated and characterized using micro flow cytometry. Only in the presence of nanodroplets could ultrasound release appreciable levels of tumor-derived vesicles into the blood. Sonication of HT1080-GFP tumors did not increase the number of circulating tumor cells or the metastatic burden in the tumor-bearing embryos. A variety of biological molecules were successfully detected in tumor-derived extracellular vesicles, including cancer-associated proteins, mRNAs, and miRNAs. Sonication of xenograft HT1080 fibrosarcoma tumors released extracellular vesicles that contained detectable RAC1 mRNA with the highly tumorigenic N92I mutation known to exist in HT1080 cells. Deep sequencing serum samples of embryos with sonicated tumors allowed the identification of an additional 13 known heterozygous mutations in HT1080 cells. Applying ultrasound to HT1080 tumors increased tumor-derived DNA in the serum by two orders of magnitude. This work is the first demonstration of enhanced extracellular vesicle release by ultrasound stimulation and suggests that nanodroplets/ultrasound offers promise for genetic profiling of tumor phenotype and aggressiveness by stimulating the release of extracellular vesicles. Cancer Res; 77(1); 3-13. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Propofol enhances the cisplatin-induced apoptosis on cervical cancer cells via EGFR/JAK2/STAT3 pathway.

    Science.gov (United States)

    Li, Haoran; Lu, Yan; Pang, Yangyang; Li, Mengjiao; Cheng, Xi; Chen, Jiawei

    2017-02-01

    The main purpose of this study was to evaluate propofol and its combined effect with cisplatin on apoptosis of cervical cancer cells and molecular mechanisms of this phenomenon. The effects of propofol and cisplatin on cell viability and apoptosis were detected by cell counting kit-8 (CCK-8) assay, colony formation assay and flow cytometry assay. Besides, protein expression of EGFR/JAK2/STAT3 pathway was determined by western blot. STAT3 was over-expressed in cervical cancer cells by STAT3 cDNA. Expression of EGFR and STAT3 protein of human tissues was evaluated by immunohistochemistry (IHC) assay. In this study, we found that not only propofol alone could inhibit cervical cancer cells viability but also could increase the inhibitory effect of cisplatin on cervical cancer cells growth. Meanwhile, propofol sensitized cervical cancer cells to cisplatin-induced apoptosis but not affected normal cervical cells. In genetic level, propofol could enhance the anti-tumor effect of cisplatin through EGFR/JAK2/STAT3 pathway. Further studies indicated that overexpression of EGFR and STAT3 is related to poor prognoses in cervical cancer patients, which contributed to confirm the clinical role of combined application of propofol and cisplatin. Propofol enhances the cisplatin-induced cell apoptosis cervical cancer cells via EGFR/JAK2/STAT3 pathway and may be developed as a potential therapeutic agent to treat cervical cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. The value of gadoxetic acid-enhanced MRI for differentiation between hepatic microabscesses and metastases in patients with periampullary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo-Youn [Soonchunhyang University College of Medicine, Bucheon Hospital, Department of Radiology, Bucheon (Korea, Republic of); Kim, Young Kon; Cha, Dong Ik; Jeong, Woo Kyoung; Lee, Won Jae [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Min, Ji Hye [Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Seoul (Korea, Republic of); Chungnam National University Hospital, Chungnam National University College of Medicine, Department of Radiology, Daejeon (Korea, Republic of)

    2017-10-15

    We aimed to identify features that differentiate hepatic microabscess from hepatic metastasis on gadoxetic acid-enhanced MRI in patients with periampullary cancer. We included 72 patients (31 patients with 83 hepatic microabscesses and 41 patients with 71 hepatic metastases) who had a history of periampullary cancer and underwent gadoxetic acid-enhanced MRI. Image analysis was performed for margin, signal intensity, rim enhancement, perilesional hyperaemia, pattern on DWI and dynamic phases, and size discrepancy between sequences by consensus of two observers. Multivariate analysis revealed that the following significant parameters favour microabscess: a history of bile duct cancer, perilesional hyperaemia, persistent arterial rim enhancement through the transitional phase (TP), and size discrepancy between T1WI and T2WI and between T1WI and hepatobiliary phase image (HBPI). The diagnostic accuracy for microabscess was highest (90.9%) when showing a size discrepancy ≥30% between T1WI and HBPI or persistent arterial rim enhancement through the TP. When the lesion was positive for both these variables, specificity reached 100%. The combination of a size discrepancy between T1WI and HBPI and persistent arterial rim enhancement through the TP represents a reliable MRI feature for distinguishing between hepatic microabscess and metastasis in patients with periampullary cancer. (orig.)

  13. Targeting the oncogenic protein beta-catenin to enhance chemotherapy outcome against solid human cancers

    Directory of Open Access Journals (Sweden)

    Rempinski Donald R

    2010-12-01

    Full Text Available Abstract Background Beta-catenin is a multifunctional oncogenic protein that contributes fundamentally to cell development and biology. Elevation in expression and activity of β-catenin has been implicated in many cancers and associated with poor prognosis. Beta-catenin is degraded in the cytoplasm by glycogen synthase kinase 3 beta (GSK-3β through phosphorylation. Cell growth and proliferation is associated with β-catenin translocation from the cytoplasm into the nucleus. This laboratory was the first to demonstrate that selenium-containing compounds can enhance the efficacy and cytotoxicity of anticancer drugs in several preclinical xenograft models. These data provided the basis to identify mechanism of selenium action focusing on β-catenin as a target. This study was designed to: (1 determine whether pharmacological doses of methylseleninic acid (MSeA have inhibitory effects on the level and the oncogenic activity of β-catenin, (2 investigate the kinetics and the mechanism of β-catenin inhibition, and (3 confirm that inhibition of β-catenin would lead to enhanced cytotoxicity of standard chemotherapeutic drugs. Results In six human cancer cell lines, the inhibition of total and nuclear expression of β-catenin by MSeA was dose and time dependent. The involvement of GSK-3β in the degradation of β-catenin was cell type dependent (GSK-3β-dependent in HT-29, whereas GSK-3β-independent in HCT-8. However, the pronounced inhibition of β-catenin by MSeA was independent of various drug treatments and was not reversed after combination therapy. Knockout of β-catenin by ShRNA and its inhibition by MSeA yielded similar enhancement of cytotoxicity of anticancer drugs. Collectively, the generated data demonstrate that β-catenin is a target of MSeA and its inhibition resulted in enhanced cytotoxicity of chemotherapeutic drugs. Conclusions This study demonstrates that β-catenin, a molecule associated with drug resistance, is a target of

  14. Contrast-Enhanced Digital Mammography in the Surgical Management of Breast Cancer.

    Science.gov (United States)

    Ali-Mucheru, Mariam; Pockaj, Barbara; Patel, Bhavika; Pizzitola, Victor; Wasif, Nabil; Stucky, Chee-Chee; Gray, Richard

    2016-12-01

    Contrast-enhanced digital mammography (CEDM) is a new breast imaging technique. The role of CEDM in the surgical management of breast cancer has not yet been characterized. A retrospective review of prospective breast surgery and breast imaging databases for patients who underwent CEDM and had breast cancer surgery. A total of 351 patients had CEDM; 128 had malignant lesions, and 101 of these underwent surgery with 105 malignancies identified. The mean age was 62 years (range 25-85 years). The histology was 65 % invasive ductal carcinoma, 16 % invasive lobular carcinoma, 11 % ductal carcinoma-in situ, 3 % mixed invasive ductal carcinoma/invasive lobular carcinoma, and 5 % other histologies. After excluding two lesions that had been removed before the examination, CEDM identified 98 % (n = 101/103) of the index lesions. The two lesions not identified were Paget disease only and a parasternal lesion too medial to include in the field of view. CEDM led to additional biopsies in 12 % (n = 12) of patients. Of these, 67 % (n = 8) proved to be invasive carcinoma and 33 % (n = 4) were benign. CEDM changed surgical management in 20 % (n = 20) of cancer patients with a 4 % (n = 4) rate of conversion to mastectomy. Among patients undergoing surgical therapy for breast cancer, CEDM was highly sensitive, had size measurements that correlated well with histologic size, and produced a relatively low rate of false-positive additional biopsy findings. CEDM appears to be promising as an alternative to magnetic resonance imaging in the surgical planning of these patients.

  15. Knockdown of FUSE binding protein 1 enhances the sensitivity of epithelial ovarian cancer cells to carboplatin.

    Science.gov (United States)

    Zhang, Jinli; Xiong, Xifeng; Hua, Xing; Cao, Wenjuan; Qin, Shengnan; Dai, Libing; Liang, Peihong; Zhang, Huiling; Liu, Zhihe

    2017-11-01

    Epithelial ovarian cancer (EOC) affects almost 25,000 women annually and is the fifth most common malignancy in women in North America. A combination of surgery and cytotoxic chemotherapy may produce a favorable clinical response. The platinum-paclitaxel combination regimen is the chemotherapy gold-standard for advanced ovarian cancer, and carboplatin is one of the agents in this combination therapy. However, the majority of patients eventually experience a relapse due to the development of platinum resistance. FUSE binding protein 1 (FBP1) has been identified as an anti-apoptotic and pro-proliferative oncoprotein that is overexpressed in hepatocellular carcinoma. Its high expression is also associated with carboplatin resistance. In the present study, it was identified that the expression of FBP1 was significantly higher in EOC tissues than in normal epithelial ovarian or in epithelial ovarian adenoma tissue. FBP1 expression was significantly correlated with the grade of epithelial ovarian cancer. Carboplatin inhibited the expression of FBP1 in epithelial ovarian cancer cells and the knockdown of FBP1 enhanced the inhibition of cell viability and migration by carboplatin. In addition to FBP1, carboplatin also inhibited the expression of β-catenin and matrix metalloproteinase (MMP)-9. Furthermore, the expression of β-catenin and MMP-9 were lower in FBP1 knockdown cells compared with control EOC cells. FBP1 may thus serve a role in the regulation of the expression of β-catenin and MMP-9; the inhibition of β-catenin and MMP-9 by carboplatin may be mediated through the inhibition of FBP1. The inhibition of FBP1 expression by carboplatin may be a mechanism in the treatment of EOC by carboplatin.

  16. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Directory of Open Access Journals (Sweden)

    Katja Storch

    Full Text Available Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  17. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Science.gov (United States)

    Storch, Katja; Dickreuter, Ellen; Artati, Anna; Adamski, Jerzy; Cordes, Nils

    2016-01-01

    Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  18. Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate nanoparticles

    Directory of Open Access Journals (Sweden)

    Melguizo C

    2015-12-01

    Full Text Available Consolación Melguizo1,2,* Laura Cabeza,1,* Jose Prados,1,2 Raúl Ortiz,1,3 Octavio Caba,1,3 Ana R Rama,1,3 Ángel V Delgado,4 José L Arias1,2,5 1Institute of Biopathology and Regenerative Medicine (IBIMER, Biomedical Research Center, 2Biosanitary Institute of Granada (IBS Granada, SAS Universidad de Granada, Granada, 3Department of Health Science, University of Jaén, Jaén, 4Department of Applied Physics, 5Department of Pharmacy and Pharmaceutical Technology, University of Granada, Granada, Spain *These authors contributed equally to this work Abstract: Doxorubicin (Dox is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate (PBCA. The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations. Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug’s antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma. Keywords: lung cancer, cancer chemotherapy, PBCA, polymeric nanoparticles, drug carrier

  19. SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells.

    Science.gov (United States)

    Li, M-Z; Lai, D-H; Zhao, H-B; Chen, Z; Huang, Q-X; Situ, J

    2017-07-01

    JAK-STAT3 signaling pathway widely participates in cell proliferation and apoptosis. Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT3. SOCS3 downregulation is associated with drug resistance in breast cancer and leukemia. However, its role in bladder cancer drug resistance is still unclear. This study established ADM resistant bladder cancer cell model to investigate the role of SOCS3-JAK/STAT3 signaling pathway ADM resistance. ADM drug resistant cell line T24/ADM was established. SOCS3, p-JAK2, p-JAK3, and Bcl-2 expressions in T24/ADM, T24, and HBEC cells were compared. Cell proliferation and apoptosis were evaluated by flow cytometry. T24/ADM cells were divided into five groups, including control, pSicoR-blank, pSicoR-SOCS3, FLLL32, and pSicoR-SOCS3 + FLLL32 groups. Cell proliferation was determined by EdU staining. SOCS3 was reduced, while p-JAK2, p-STAT3, and Bcl-2 expressions upregulated in T24 cells compared with HBEC cells. T24/ADM cells exhibited lower SOCS3, higher p-JAK2, p-STAT3, and Bcl-2 levels than T24 cells. Cell apoptosis was higher, whereas cell proliferation was weaker in T24 cells compared with T24/ADM cells. SOCS3 overexpression and/or FLLL32 treatment significantly downregulated p-JAK2, p-STAT3, and Bcl-2 expressions, attenuated cell proliferation, and elevated sensitivity to ADM induced cell apoptosis. SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells.

  20. E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells.

    Science.gov (United States)

    Wu, Minghui; Seto, Edward; Zhang, Jingsong

    2015-05-10

    The fast proliferation of cancer cells requires reprogramming of its energy metabolism with aerobic glycolysis as a major energy source. Sirt6, a class III histone deacetylase, has been shown to down regulate glycolysis by inhibiting the expression of several key glycolytic genes. Based on the published study on the metabolic phenotype of E2F1 -/- mice and SIRT6 -/- mice, we hypothesize that E2F1 enhances glycolysis and inhibits the expression of Sirt6. Indeed, over-expressing of E2F1, but not its DNA binding deficient mutant, significantly enhanced glucose uptake and lactate production in bladder and prostate cancer cell lines. E2F1 over-expression also suppressed Sirt6 expression and function. Moreover, E2F1 directly bound to Sirt6 promoter and suppressed Sirt6 promoter activity under both normoxic and hypoxic culture conditions. E2F1 siRNA blocked the up-regulation of E2F1 under hypoxia, increased Sirt6 expression and decreased glycolysis compared to those of scrambled siRNA transected cells. Furthermore, HDAC1 deacetylated E2F1 and diminished its transcription suppression of Sirt6 promoter. Treatment with the HDAC inhibitor, trichostatin A (TSA), suppressed Sirt6 promoter activity with increased binding of acetylated E2F1 to Sirt6 promoter. Mutating the E2F1 binding site on the proximal Sirt6 promoter abolished the suppression of Sirt6 transcription by TSA. These data indicate a novel oncogenic role of E2F1, i.e. enhancing glycolysis by suppressing Sirt6 transcription.

  1. Identification and Characterisation of the Murine Homologue of the Gene Responsible for Cystinosis, Ctns

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    Poras Isabelle

    2000-12-01

    Full Text Available Abstract Background Cystinosis is an autosomal recessive disorder characterised by an intralysosomal accumulation of cystine, and affected individuals progress to end-stage renal failure before the age of ten. The causative gene, CTNS, was cloned in 1998 and the encoded protein, cystinosin, was predicted to be a lysosomal membrane protein. Results We have cloned the murine homologue of CTNS, Ctns, and the encoded amino acid sequence is 92.6% similar to cystinosin. We localised Ctns to mouse chromosome 11 in a region syntenic to human chromosome 17 containing CTNS. Ctns is widely expressed in all tissues tested with the exception of skeletal muscle, in contrast to CTNS. Conclusions We have isolated, characterised and localised Ctns, the murine homologue of CTNS underlying cystinosis. Furthermore, our work has brought to light the existence of a differential pattern of expression between the human and murine homologues, providing critical information for the generation of a mouse model for cystinosis.

  2. Expression pattern of INNER NO OUTER homologue in Nymphaea (water lily family, Nymphaeaceae).

    Science.gov (United States)

    Yamada, Toshihiro; Ito, Motomi; Kato, Masahiro

    2003-10-01

    Two homologues of INNER NO OUTER ( INO) in Nymphaea alba and N. colorata (Nymphaeaceae) were isolated and the expression pattern of the N. alba INO homologue NaINO was examined by in situ hybridization. The INO homologues obtained have a portion similar to INO in the predicted amino acid sequences between the conserved zinc finger-like and YABBY domains. In an in situ hybridization analysis, NaINO is expressed in the outer epidermis of the outer integument, inner integument, and the tip of the nucellus. The pattern observed in the outer integument is very similar to that of Arabidopsis thaliana, while the expression in the inner integument and nucellus is not observed in A. thaliana.

  3. Solid-Phase Synthesis of Amine/Carboxyl Substituted Prolines and Proline Homologues: Scope and Limitations.

    Science.gov (United States)

    Zhou, Ziniu; Scott, William L; O'Donnell, Martin J

    2016-03-15

    A solid-phase procedure is used to synthesize racemic peptidomimetics based on the fundamental peptide unit. The peptidomimetics are constructed around proline or proline homologues variably substituted at the amine and carbonyl sites. The procedure expands the diversity of substituted peptidomimetic molecules available to the Distributed Drug Discovery (D3) project. Using a BAL-based solid-phase synthetic sequence the proline or proline homologue subunit is both constructed and incorporated into the peptidomimetic by an α-alkylation, hydrolysis and intramolecular cyclization sequence. Further transformations on solid-phase provide access to a variety of piperazine derivatives representing a class of molecules known to exhibit central nervous system activity. The procedure works well with proline cores, but with larger six- and seven-membered ring homologues the nature of the carboxylic acid acylating the cyclic amine can lead to side reactions and result in poor overall yields.

  4. Quantitative assessment of background parenchymal enhancement in breast magnetic resonance images predicts the risk of breast cancer

    OpenAIRE

    Hu, Xiaoxin; Jiang, Luan; Li, Qiang; Gu, Yajia

    2016-01-01

    The objective of this study was to evaluate the association betweenthe quantitative assessment of background parenchymal enhancement rate (BPER) and breast cancer. From 14,033 consecutive patients who underwent breast MRI in our center, we randomly selected 101 normal controls. Then, we selected 101 women with benign breast lesions and 101 women with breast cancer who were matched for age and menstruation status. We evaluated BPER at early (2 minutes), medium (4 minutes) and late (6 minutes) ...

  5. A Platinum(IV) Pro-drug Preferentially Targets IDO Providing Enhanced Ovarian Cancer Immuno-Chemotherapy

    OpenAIRE

    Awuah, Samuel G.; Zheng, Yao-Rong; Bruno, Peter M.; Hemann, Michael T.; Lippard, Stephen J.

    2015-01-01

    Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a tumor immunotherapeutic target, and several IDO inhibitors are currently undergoing clinical trials. IDO inhibitors can enhance the efficacy of common cancer chemotherapeutics. Here we investigated Pt(IV) – (D)-1-methyltryptophan conjugates 1 and 2 for combined immunomodulation and DNA cross-link-triggered apoptosis for cancer ‘immuno-ch...

  6. Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

    Directory of Open Access Journals (Sweden)

    Sana Abbasi

    2012-01-01

    Full Text Available Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI- enhanced human serum albumin (HSA nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs.

  7. Sensitivity improved surface plasmon resonance biosensor for cancer biomarker detection based on plasmonic enhancement.

    Science.gov (United States)

    Law, Wing-Cheung; Yong, Ken-Tye; Baev, Alexander; Prasad, Paras N

    2011-06-28

    In this study, we report the development of a nanoparticle-enhanced biosensor by integrating both the nanoparticles and immunoassay sensing technologies into a phase interrogation surface plasmon resonance (SPR) system for detecting antigen at a concentration as low as the femtomolar range. Our work has demonstrated that the plasmonic field extension generated from the gold film to gold nanorod (GNR) has led to a drastic sensitivity enhancement. Antibody-functionalized sensing film, together with antibody-conjugated GNRs, was readily served as a plasmonic coupling partner that can be used as a powerful ultrasensitive sandwich immunoassay for cancer-related disease detection. Experimentally, it was found that the bioconjugated GNR labels enhance the tumor necrosis factor alpha (TNF-α) antigen signal with more than 40-fold increase compared to the traditional SPR biosensing technique. The underlying principle was analyzed by simulating the near-field coupling between the sensing film and the GNR. The results have shown that GNRs were readily served as promising amplification labels in SPR sensing technology.

  8. Incorporating Oxygen-Enhanced MRI into Multi-Parametric Assessment of Human Prostate Cancer.

    Science.gov (United States)

    Zhou, Heling; Hallac, Rami R; Yuan, Qing; Ding, Yao; Zhang, Zhongwei; Xie, Xian-Jin; Francis, Franto; Roehrborn, Claus G; Sims, R Douglas; Costa, Daniel N; Raj, Ganesh V; Mason, Ralph P

    2017-08-24

    Hypoxia is associated with prostate tumor aggressiveness, local recurrence, and biochemical failure. Magnetic resonance imaging (MRI) offers insight into tumor pathophysiology and recent reports have related transverse relaxation rate (R₂*) and longitudinal relaxation rate (R₁) measurements to tumor hypoxia. We have investigated the inclusion of oxygen-enhanced MRI for multi-parametric evaluation of tumor malignancy. Multi-parametric MRI sequences at 3 Tesla were evaluated in 10 patients to investigate hypoxia in prostate cancer prior to radical prostatectomy. Blood oxygen level dependent (BOLD), tissue oxygen level dependent (TOLD), dynamic contrast enhanced (DCE), and diffusion weighted imaging MRI were intercorrelated and compared with the Gleason score. The apparent diffusion coefficient (ADC) was significantly lower in tumor than normal prostate. Baseline R₂* (BOLD-contrast) was significantly higher in tumor than normal prostate. Upon the oxygen breathing challenge, R₂* decreased significantly in the tumor tissue, suggesting improved vascular oxygenation, however changes in R₁ were minimal. R₂* of contralateral normal prostate decreased in most cases upon oxygen challenge, although the differences were not significant. Moderate correlation was found between ADC and Gleason score. ADC and R₂* were correlated and trends were found between Gleason score and R₂*, as well as maximum-intensity-projection and area-under-the-curve calculated from DCE. Tumor ADC and R₂* have been associated with tumor hypoxia, and thus the correlations are of particular interest. A multi-parametric approach including oxygen-enhanced MRI is feasible and promises further insights into the pathophysiological information of tumor microenvironment.

  9. Statistical comparison of dynamic contrast-enhanced MRI pharmacokinetic models in human breast cancer.

    Science.gov (United States)

    Li, Xia; Welch, E Brian; Chakravarthy, A Bapsi; Xu, Lei; Arlinghaus, Lori R; Farley, Jaime; Mayer, Ingrid A; Kelley, Mark C; Meszoely, Ingrid M; Means-Powell, Julie; Abramson, Vandana G; Grau, Ana M; Gore, John C; Yankeelov, Thomas E

    2012-07-01

    By fitting dynamic contrast-enhanced MRI data to an appropriate pharmacokinetic model, quantitative physiological parameters can be estimated. In this study, we compare four different models by applying four statistical measures to assess their ability to describe dynamic contrast-enhanced MRI data obtained in 28 human breast cancer patient sets: the chi-square test (χ(2)), Durbin-Watson statistic, Akaike information criterion, and Bayesian information criterion. The pharmacokinetic models include the fast exchange limit model with (FXL_v(p)) and without (FXL) a plasma component, and the fast and slow exchange regime models (FXR and SXR, respectively). The results show that the FXL_v(p) and FXR models yielded the smallest χ(2) in 45.64 and 47.53% of the voxels, respectively; they also had the smallest number of voxels showing serial correlation with 0.71 and 2.33%, respectively. The Akaike information criterion indicated that the FXL_v(p) and FXR models were preferred in 42.84 and 46.59% of the voxels, respectively. The Bayesian information criterion also indicated the FXL_v(p) and FXR models were preferred in 39.39 and 45.25% of the voxels, respectively. Thus, these four metrics indicate that the FXL_v(p) and the FXR models provide the most complete statistical description of dynamic contrast-enhanced MRI time courses for the patients selected in this study. Copyright © 2011 Wiley Periodicals, Inc.

  10. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells.

    Science.gov (United States)

    Lin, Gaoyang; Liu, Boning; Meng, Zhaowei; Liu, Yunde; Li, Xuebing; Wu, Xiang; Zhou, Qinghua; Xu, Ke

    2017-03-15

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Differential diagnosis of solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomograph

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    Chu, Zhi-gang; Sheng, Bo; Liu, Meng-qi; Lv, Fa-jin; Li, Qi; Ouyang, Yu, E-mail: cyscitg@163.com [Hospital of Chongqing Medical University, Department of Radiology, Chongqing (China)

    2016-10-15

    Objectives: To clarify differences between solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomography. Methods: In total, 64 and 132 patients with solitary pulmonary inflammatory masses/nodules and peripheral lung cancers, respectively, were enrolled in this study. Their computed tomographic findings were summarized and compared retrospectively. Results: Compared with the peripheral lung cancers, the inflammatory lesions were located closer to the pleura (p<0.0001). The majority of the inflammatory lesions were patchy and oval-shaped (82.8%), whereas most of the tumors were lobulated (82.6%). Almost all the inflammatory cases were unclear (93.8%), whereas most of the tumors had speculated margins (72.7%). Computed tomography values were significantly higher for the inflammatory lesions than for the cancers (p<0.0001). More than half of the inflammatory lesions had defined necrosis (59.3%). Furthermore, 49.2% of the cancers enhanced inhomogeneously, but only 24.6% had ill-defined necrosis or cavities. The peripheral zones of 98.4% of the inflammatory lesions and 72.7% of the tumors were unclear, with peripheral scattered patches (92.2%) and beam-shaped opacity (66.7%) being the most common findings, respectively. Adjacent pleural thickening was more frequent for the inflammatory lesions than the cancers (95.3% vs. 21.1%, p<0.0001), whereas pleural indentation was found in 67.4% of the subjects with cancer. In addition, hilar (p=0.034) and mediastinal (p=0.003) lymphadenopathy were more commonly detected in the cancers than in the inflammatory cases. Conclusions: Contrast-enhanced computed tomography findings for pulmonary inflammatory lesions and peripheral lung cancers were significantly different in many aspects. Developing a comprehensive understanding of these differences is helpful for directing their management. (author)

  12. A cytokinin receptor homologue is induced during root nodule organogenesis and senescence in Lupinus albus L.

    Science.gov (United States)

    Coba de la Peña, Teodoro; Cárcamo, Claudia B; Almonacid, Luis; Zaballos, Angel; Lucas, M Mercedes; Balomenos, Dimitrios; Pueyo, José J

    2008-02-01

    Here we report the isolation of a new cytokinin receptor homologue, LaHK1, from lupin (Lupinus albus) root nodules. LaHK1 transcript accumulation was detected in different plant organs, and expression was analyzed throughout nodule development. We observed notably higher expression in nodule primordia and young nodules compared to the root or to mature nodules. We also detected elevated transcript accumulation in naturally senescent nodules and in senescent nodules subjected to foliar dark stress. The results could be an indication of a putative role of this cytokinin receptor homologue in nodule development, from morphogenesis through senescence.

  13. Autophagy inhibition enhances RAD001-induced cytotoxicity in human bladder cancer cells

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    Lin JF

    2016-04-01

    Full Text Available Ji-Fan Lin,1 Yi-Chia Lin,2,3 Shan-Che Yang,1 Te-Fu Tsai,2,3 Hung-En Chen,2 Kuang-Yu Chou,2,3 Thomas I-Sheng Hwang2–4 1Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 3Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 4Department of Urology, Taipei Medical University, Taipei, Taiwan Background: Mammalian target of rapamycin (mTOR, involved in PI3K/AKT/mTOR pathway, is known to play a central role in regulating the growth of cancer cells. The PI3K/AKT/mTOR pathway enhances tumor survival and proliferation through suppressing autophagy, which sustains energy homeostasis by collecting and recycling cellular components under stress conditions. Conversely, inhibitors of the mTOR pathway such as RAD001 induce autophagy, leading to promotion of tumor survival and limited antitumor efficacy. We thus hypothesized that the use of autophagy inhibitor in combination with mTOR inhibition improves the cytotoxicity of mTOR inhibitors in bladder cancer.Materials and methods: The cytotoxicity of RT4, 5637, HT1376, and T24 human bladder cancer cells treated with RAD001 alone or combined with autophagy inhibitors (3-methyladenine (3-MA, bafilomycin A1 (Baf A1, chloroquine, or hydroxychloroquine was assessed using the WST-8 cell viability kit. The autophagy status in cells was analyzed by the detection of microtubule-associated light chain 3 form II (LC3-II, using immunofluorescent staining and Western blot. Acidic vesicular organelle (AVO formation in treated cells was determined by acridine orange vital staining. Inhibition of mTOR pathway by RAD001 was monitored by using a homemade quantitative polymerase chain reaction gene array, while phospho-mTOR was detected using Western blot. Induced apoptosis was determined by measurement of caspase 3/7 activity and DNA fragmentation in cells after

  14. Contrast Enhanced Ultrasound of a Gallbladder Lesion in a Patient with a History of Renal Cell and Rectal Cancer

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    Markus Reiser

    2013-01-01

    Full Text Available The gallbladder is an uncommon site of metastatic cancer. Although ultrasound can be regarded as a first line investigation for the detection of gallbladder lesions, differentiation between benign and malignant tumors usually requires resection. Real-time contrast enhanced ultrasound (CEUS is a well-established technique for the classification of liver, pancreatic, and renal diseases (Weskott, 2008. The application of CEUS in the diagnosis of gallbladder tumors has rarely been described. We report the application of contrast enhanced ultrasound for the characterization of a gallbladder lesion in a 63-year-old patient with a history of renal cell and rectal cancer.

  15. Self-Efficacy for Coping with Cancer Enhances the Effect of Reiki Treatments During the Pre-Surgery Phase of Breast Cancer Patients.

    Science.gov (United States)

    Chirico, Andrea; D'Aiuto, Giuseppe; Penon, Antonella; Mallia, Luca; DE Laurentiis, Michelino; Lucidi, Fabio; Botti, Gerardo; Giordano, Antonio

    2017-07-01

    Self-efficacy for coping with cancer plays a critical role in influencing psychological cancer-related outcomes, some studies suggested its role in enhancing or reducing the effects of psychological interventions in cancer patients. Reiki has recently been included among the efficacious complementary therapeutic intervention for cancer patients. The present study evaluated the role of self-efficacy for coping with cancer as buffer of the Reiki treatment effects on cancer-related symptoms in a randomized controlled trial (intervention versus control group) of breast cancer patients (N=110) during the pre-surgery phase. Results showed that self-efficacy for coping with cancer can influence the effect of a Reiki treatment. Higher efficacious patients showed a more powerful effect of the Reiki intervention on both anxiety and mood than the low efficacious patients. From a practical perspective, the study provides insightful results for healthcare professionals. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Differentiation of breast cancer from fibroadenoma with dual-echo dynamic contrast-enhanced MRI.

    Science.gov (United States)

    Wang, Shiwei; Delproposto, Zachary; Wang, Haoyu; Ding, Xuewei; Ji, Conghua; Wang, Bei; Xu, Maosheng

    2013-01-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) of the breast is a routinely used imaging method which is highly sensitive for detecting breast malignancy. Specificity, though, remains suboptimal. Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI), an alternative dynamic contrast imaging technique, evaluates perfusion-related parameters unique from DCE MRI. Previous work has shown that the combination of DSC MRI with DCE MRI can improve diagnostic specificity, though an additional administration of intravenous contrast is required. Dual-echo MRI can measure both T1W DCE MRI and T2*W DSC MRI parameters with a single contrast bolus, but has not been previously implemented in breast imaging. We have developed a dual-echo gradient-echo sequence to perform such simultaneous measurements in the breast, and use it to calculate the semi-quantitative T1W and T2*W related parameters such as peak enhancement ratio, time of maximal enhancement, regional blood flow, and regional blood volume in 20 malignant lesions and 10 benign fibroadenomas in 38 patients. Imaging parameters were compared to surgical or biopsy obtained tissue samples. Receiver operating characteristic (ROC) curves and area under the ROC curves were calculated for each parameter and combination of parameters. The time of maximal enhancement derived from DCE MRI had a 90% sensitivity and 69% specificity for predicting malignancy. When combined with DSC MRI derived regional blood flow and volume parameters, sensitivity remained unchanged at 90% but specificity increased to 80%. In conclusion, we show that dual-echo MRI with a single administration of contrast agent can simultaneously measure both T1W and T2*W related perfusion and kinetic parameters in the breast and the combination of DCE MRI and DSC MRI parameters improves the diagnostic performance of breast MRI to differentiate breast cancer from benign fibroadenomas.

  17. Use of contrast-enhanced spectral mammography for intramammary cancer staging: preliminary results.

    Science.gov (United States)

    Blum, Katrin S; Rubbert, Christian; Mathys, Britta; Antoch, Gerald; Mohrmann, Svjetlana; Obenauer, Silvia

    2014-11-01

    To prospectively evaluate and compare the accuracy of contrast-enhanced spectral mammography (CESM) and ultrasound (US) in size measurement of breast cancer with histologic tumor sizes as gold standard. Twenty women aged between 40-73 years (mean age, 57 ± 10 years) with histologically proven invasive ductal/lobular carcinomas were included in the study. Agreement between imaging tumor size (CESM and US) and histopathologic tumor size was evaluated with Bland-Altman analysis. Stereotactically guided vacuum biopsy was performed in four patients after CESM. Two independent reviewers described artifacts of CESM. Motion artifacts did not occur in the study. CESM-specific artifacts caused by scattered radiation mostly occurred in oblique view of CESM. Background enhancement of breast tissue was seen in four patients. Mean difference of tumor sizes was 0.3 mm (6.34%) between CESM and histology and -2.2 mm (-7.59%) between US and histology. Limits of agreement ranged from -18.9 to 19.48 mm for CESM and from -17.1 to 12.7 mm with US. Especially smaller tumors with a size <23 mm were measured more precisely with CESM. Enhancement of breast tissue around microcalcifications correlated with abnormalities. CESM is accurate in size measurements of small breast tumors. On average CESM leads to a slight overestimation of tumor size, whereas US tends to underestimate tumor size. Assessment of the breast tissue can be limited by the scattered radiation artifact and background enhancement of breast tissue. CESM seems to be helpful in the characterization of breast tissue around microcalcifications. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  18. Redox-Responsive Manganese Dioxide Nanoparticles for Enhanced MR Imaging and Radiotherapy of Lung Cancer

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    Mi Hyeon Cho

    2017-12-01

    Full Text Available In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid and analyzed their effect on non-small cell lung cancer (NSCLC cells with or without gefitinib resistance in vitro. MnO2 NPs showed glutathione (GSH-responsive dissolution and subsequent enhancement in magnetic resonance (MR imaging. Of note, treatment with MnO2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.

  19. Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line

    DEFF Research Database (Denmark)

    Vasquez, Juan Luis; Gehl, Julie; Hermann, Gregers G

    2012-01-01

    Intravesical mitomycin instillation combined with electric pulses is being used experimentally for the treatment of T1 bladder tumors, in patients unfit for surgery. Electroporation may enhance the uptake of chemotherapeutics by permeabilization of cell membranes. We investigated if electroporation...... improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability...... was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000μM in both pulsed and unpulsed cells. On T24 cells, electroporation and mitomycin caused (relative reduction) RR of survival of: 25%, 31% and 29%, by concentrations 0μM, 500μM and 1000μM respectively. For DC3...

  20. RGD-Functionalization of Poly(2-oxazoline-Based Networks for Enhanced Adhesion to Cancer Cells

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    Verena Schenk

    2014-01-01

    Full Text Available Poly(2-oxazoline networks with varying swelling degrees and varying hydrophilicity can be synthesized from 2-ethyl-2-oxazoline, 2-nonyl-2-oxazoline, 2-9’-decenyl-2-oxazoline and 2,2’-tetramethylene-bis-2-oxazoline in one-pot/one-step strategies. These gels can be loaded with organic molecules, such as fluorescein isothiocyanate, either during the polymerization (covalent attachment of the dye or according to post-synthetic swelling/deswelling strategies (physical inclusion of the dye. Surface functionalization of ground gels by thiol-ene reactions with cysteine-bearing peptides exhibiting the arginine-glycine-aspartic acid (RGD motif yields microparticles with enhanced recognition of human cancer cells compared to healthy endothelial cells.

  1. HIV-1 Tat Protein Enhances Expression and Function of Breast Cancer Resistance Protein.

    Science.gov (United States)

    Zhou, Yancong; Zhang, Kun; Yin, Xiaojie; Nie, Qichang; Ma, Yonggang

    2016-01-01

    ATP binding cassette (ABC) transporters can transfer a variety of antiviral agents from the cytoplasm to body fluid, which results in a reduced intracellular concentration of the drugs. Proteins of HIV-1, e.g., Tat and gp120, altered some types of ABC transporter expression in brain microvascular endothelial cells and astrocytes. However, the effect of Tat on ABC transporters in T lymphocytes is unclear. In this study the status of breast cancer resistance protein (BCRP) in Tat expressing cell lines was examined with real-time PCR and flow cytometry. It was found that HIV-1 Tat protein upregulated BCRP expression and enhanced efflux mediated by BCRP significantly, which could inhibit antiviral drugs from entering infected cells and interfere with the therapeutic effect of HAART.

  2. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gaoyang; Liu, Boning [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Meng, Zhaowei [Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052 (China); Liu, Yunde [School of Laboratory Medicine, Tianjin Medical University, Tianjin 300052 (China); Li, Xuebing [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Wu, Xiang [Core Facility Center, Tianjin Medical University General Hospital, Tianjin 300052 (China); Zhou, Qinghua [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Xu, Ke, E-mail: ke_xu@hotmail.com [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China)

    2017-03-15

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. - Highlights: • miR-26a enhances migration and invasion of lung cancer cells. • GSK3β is identified as a direct target of miR-26a. • miR-26a activates β-catenin pathway by targeting GSK3β. • miR-26a promotes lung cancer cell growth in vivo.

  3. Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation.

    Science.gov (United States)

    Wang, Caihua; Li, Peiwei; Xuan, Junmei; Zhu, Chunpeng; Liu, Jingjing; Shan, Lizhen; Du, Qin; Ren, Yuezhong; Ye, Jun

    2017-01-01

    Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC), while the effect of cholesterol on CRC metastasis has not been widely studied. CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL) and CRC metastases, and LDL receptor (LDLR) level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD) on tumor growth and intestinal tumorigenicity were investigated in vivo. ROS assays, gene expression array analysis and western blot were used to explore the mechanisms of LDL in CRC progression. The level of LDL was positively correlated with liver metastases, and a higher level of LDL receptor (LDLR) expression was associated with advanced N and M stages of CRC. In vitro, LDL promoted the migration and sphere formation of CRC cells and induced upregulated expression of "stemness" genes including Sox2, Oct4, Nanog and Bmi 1. High-fat diet (HFD) significantly enhanced tumor growth in vivo, and was associated with a shorter intestinal length in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice. Furthermore, LDL significantly elevated reactive oxygen species (ROS) levels and Whole Human Genome Microarray found 87 differentially expressed genes between LDL-treated CRC cells and controls, which were largely clustered in the MAP kinase (MAPK) signaling pathway. LDL enhances intestinal inflammation and CRC progression via activation of ROS and signaling pathways including the MAPK pathway. Inflammation is strongly associated with cancer initiation, and the role of LDL in intestinal tumorigenicity should be further explored. © 2017 The Author(s). Published by S. Karger AG, Basel.

  4. Communication and intimacy-enhancing interventions for men diagnosed with prostate cancer and their partners.

    Science.gov (United States)

    Nelson, Christian J; Kenowitz, Joslyn

    2013-02-01

    The sexual dysfunction following prostate cancer treatments often leads to a reduction in intimate contact for couples. A number of psychosocial interventions have been developed to enhance intimacy in these couples. This paper reviews three of these interventions and is a summary of a presentation given as part of a symposium at the 2011 Cancer Survivorship and Sexual Health Meeting. The goal of this presentation was to: (i) review three types of psychosocial interventions; and (ii) describe the methodological issues highlighted by these interventions. Validated measures of relationship intimacy and communication. To be selected, the interventions had to be: a randomized control trial, focus on a couples approach to therapy, and report at least one relationship outcome. The results were not consistent within or across studies, and suggest that some specific aspects of the interventions may be helpful for the patient, while other aspects of the studies may be helpful for the partner. The Northouse et al. study suggests that partners may benefit from a focus on couple work, as compared to the patient. The Canada et al. study indicates that when focusing on sexual functioning, working with a couple did not show significant benefit compared to working with a man alone. The study did show, however, that a sexual-based intervention can improve the use of erectile dysfunction treatments and suggests patients may benefit from specific focus on side effects of treatment. The Manne et al. study highlights the importance of targeting these interventions to couples who report distress, and for distressed couples, an intervention can show positive results. Intimacy enhancing interventions can be effective for couples, while the partners may benefit more from couples work; the patients may benefit more from focus on specific side effects. © 2013 International Society for Sexual Medicine.

  5. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

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    Carolina Nör

    2014-02-01

    Full Text Available Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs. These unique cells, named here cancer stem cells (CSCs, proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B cells and observed that cisplatin treatment increased (P = .0013 the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1 and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3 phosphorylation (indicative of stemness was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK phosphorylation (indicative of differentiation processes was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

  6. Combination of Active Components Enhances the Efficacy of Prunella in Prevention and Treatment of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Feng Shi

    2010-11-01

    Full Text Available The efficacy of Prunella extracts in the prevention and treatment of lung cancer has been attributed to different components. In this study, an "active components combination model" hypothesis was proposed to explain the anti-tumor activity of Prunella. The efficacy of Prunella extracts from different regions was compared in vitro and in vivo, and the TNF-α activity in serum of tumor-bearing mice was also evaluated. High performance liquid chromatography (HPLC was used to analyze the extracts and identify 26 common peaks. Prunella samples from different regions were classified by the cluster analysis method; both P. vulgaris L. from Bozhou and P. asiatica Nakai from Nanjing, which had the highest activities, were further divided into different classes. Six peaks from the HPLC analysis were very similar, and were identified as caffeic acid, rosmarinic acid, rutin, quercetin, oleanolic acid and ursolic acid. The total ratio of these compounds in Prunella from Bozhou and Nanjing were 1.0:14.7:3.9:1.0:4.4:1.4 and 1.0:14.8:4.0:0.8:5.6:1.8, respectively. Total triterpenes and total phenols in Prunella were separated by macroporous resin purification for activity studies. The results showed that total triterpenes and total phenols had anti-lung cancer activity and their combination significantly enhanced the activity. In addition, the combination also significantly increased the TNF-α content compared to total triterpenes or total phenols. The results indicated that the efficacy of Prunella against lung cancer was attributable to multiple components acting at an optimal ratio.

  7. Enhanced Ovarian Cancer Tumorigenesis and Metastasis by the Macrophage Colony-Stimulating Factor

    Directory of Open Access Journals (Sweden)

    Eugene P. Toy

    2009-02-01

    Full Text Available Coexpression of the macrophage colony-stimulating factor (CSF-1 and its receptor (CSF-1R in metastatic ovarian cancer specimens is a predictor of poor outcome in epithelial ovarian cancer. This suggests that an autocrine loop is produced by which ovarian tumors can secrete CSF-1 stimulating the CSF-1R resulting in a more aggressive phenotype. Our current work sought to validate this autocrine stimulation model using stable transfection of a 4-kb CSF-1 construct into otherwise nonvirulent Bix3 ovarian cancer cells. A representative clone, Bix3T8.2, produced a 72-fold increase in CSF-1 gene transcription rate (by nuclear run-off assays and a 57-fold increase in secreted CSF-1 protein (by sandwich ELISA, compared to parent cells. Comparison of Bix3T8.2 invasion, adhesion, and motility in vitro and metastasis in vivo were made to parental and transfectant controls. Up to 12-fold higher invasiveness was seen with Bix3T8.2 and 2- and 6-fold higher adhesion and motility, respectively, over controls in vitro. In nude mice, i.p. injection of Bix3T8.2 produced a wide array of visceral, nodal, and distant metastasis with a degree of enhanced tumor burden not seen in any of the 10 mice inoculated with transfectant control cells. Complete absence of tumor take distinguished 40% of mice implanted with transfectant control cells. Disruption of this autocrine loop using antisense oligomer therapy against CSF-1R and 3′ untranslated region knockdown of CSF-1 protein resulted in reversal of in vitro and in vivo tumor phenotypes. This CSF-1 feedback loop offers a model by which novel biologic therapies can potentially target multiple levels of this pathway.

  8. Enhanced solubility and functionality of valrubicin (AD-32) against cancer cells upon encapsulation into biocompatible nanoparticles.

    Science.gov (United States)

    Sabnis, Nirupama; Nair, Maya; Israel, Mervyn; McConathy, Walter J; Lacko, Andras G

    2012-01-01

    Among numerous drug-delivery approaches, reconstituted high-density lipoprotein (rHDL) nanocarriers have proven particularly applicable for delivering highly hydrophobic drugs. In this study, we have investigated the enhancement of the therapeutic impact of valrubicin (AD-32), an antineoplastic agent that has been limited to intravesicular application against bladder cancer, despite the encouraging original preclinical data. Earlier studies validated the superior therapeutic efficacy of AD-32 over doxorubicin. In the present study, rHDL/AD-32 nanoparticles were formulated and characterized with regard to encapsulation efficiency, physicochemical properties, selective toxicity, and receptor-mediated uptake. The half maximal inhibitory concentration values (IC(50)) for rHDL/AD-32 nanoparticles were 1.8 and 2.6 times lower than the free AD-32 for prostate (PC-3) and ovarian (SKOV-3) cancer cell lines, respectively, whereas nonmalignant cell lines demonstrated 5 and 1.48 times higher IC(50) doses with rHDL/AD-32 formulations. The data obtained demonstrated effective receptor- mediated uptake of AD-32 from the rHDL nanocarriers by PC-3 and SKOV-3 cancer cells via a targeted drug-delivery process. The rHDL/AD-32 formulation was stable for 6 months when stored at 4°C or at -20°C, as 92% of the AD-32 was retained in the nanoparticles. The findings from this study show that the rHDL/AD-32 formulation can overcome the solubility barriers of AD-32 and thus serve as an effective systemically administered chemotherapeutic agent.

  9. A patient recall program to enhance decisions about prostate cancer screening: A feasibility study

    Directory of Open Access Journals (Sweden)

    Denberg Thomas

    2009-01-01

    Full Text Available Abstract Background Lack of time and competing demands limit the ability of patients and providers to engage in informed decision-making discussions about prostate cancer screening during primary care visits. We evaluated a patient recall invervention to mitigate these challenges. Methods Using mail and telephone outreach we invited men age 50-74 years without a PSA test in the prior 12 months to make appointments with their primary care providers in order to discuss the pros and cons of PSA-based prostate cancer screening. We assessed patient responsiveness to the program, provider documentation of screening discussions, orders for PSA laboratories, and provider attitudes. Results Out of 80 eligible patients, 37 (46% scheduled and 28 (35% completed a recall appointment. A large majority (91% of patients eligible for PSA screening received an order for this test. Providers documented PSA discussions more often for these patients than for a recent sample of their other patients who received traditional care (47.8% vs. 12.5%, p = 0.009. Twelve of 14 participating providers felt the program improved their ability to impart information about the risks and benefits of screening, but were uncertain whether it influenced their patients' preexisting preferences for screening. Some expressed doubts about the advisability of PSA-specific appointments. Conclusion To a limited extent, this pilot recall intervention enhanced opportunities for discussions of prostate cancer screening between patients and their primary care providers. As currently configured, however, this program was not found to be feasible for this purpose. A future version should promote screening discussions in the context of a broader range of health maintenance concerns and include more detailed, low-literacy information to educate patients in advance of clinic visits.

  10. Breast MRI background parenchymal enhancement (BPE) correlates with the risk of breast cancer.

    Science.gov (United States)

    Telegrafo, Michele; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe; Moschetta, Marco

    2016-02-01

    To investigate whether background parenchymal enhancement (BPE) and breast cancer would correlate searching for any significant difference of BPE pattern distribution in case of benign or malignant lesions. 386 patients, including 180 pre-menopausal (group 1) and 206 post-menopausal (group 2), underwent MR examination. Two radiologists evaluated MR images classifying normal BPE as minimal, mild, moderate or marked. The two groups of patients were subdivided into 3 categories based on MRI findings (negative, benign and malignant lesions). The distribution of BPE patterns within the two groups and within the three MR categories was calculated. The χ2 test was used to evaluate BPE type distribution in the three patient categories and any statistically significant correlation of BPE with lesion type was calculated. The Student t test was applied to search for any statistically significant difference between BPE type rates in group 1 and 2. The χ2 test demonstrated a statistically significant difference in the distribution of BPE types in negative patients and benign lesions as compared with malignant ones (p0.05). Normal BPE could correlate with the risk of breast cancer being such BPE patterns as moderate and marked associated with patients with malignant lesions in both pre and post-menopausal women. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Enhanced identification and functional protective role of carbon nanoparticles on parathyroid in thyroid cancer surgery

    Science.gov (United States)

    Shi, Chenlei; Tian, Bo; Li, Shengze; Shi, Tiefeng; Qin, Huadong; Liu, Shaoyan

    2016-01-01

    Abstract The aim of this study was to determine the effects of nanocarbon particles in combination with meticulous capsular dissection on enhancing the identification and protecting the function of parathyroid glands in thyroid cancer surgery. The data of 97 patients with papillary thyroid tumors diagnosed and treated at the Second Affiliated Hospital, Harbin Medical University between January 2014 and February 2015 were reviewed. Data regarding the sex, age, calcium and parathyroid hormone (PTH) levels, tumor size, multifocality, T stage, and extrathyroid invasion were collected. The incidence of surgeries in which the parathyroid glands were cut mistakenly, the concentration of serum calcium and parathyroid hormone before surgery (baseline) and after surgery on days 1, 3, and 7, and 1 and 6 months in the patients of the two groups (the nanocarbon and control groups) were analyzed. Fifty-two patients underwent meticulous capsular dissection combined with nanocarbon treatment (nanocarbon group), and 45 underwent meticulous capsular dissection alone (control group). The nanocarbon group showed a significantly higher total and average number of revealed parathyroid glands (average number is the mean for different individuals have different number) and a lower incidence of the parathyroid glands being mistakenly cut, in addition to a lower level of hypoparathyroidism than control group following surgery (P parathyroid in thyroid cancer surgery, reduce the risk of mistakenly cutting the parathyroid, and reduce the incidence of postoperative hypoparathyroidism. PMID:27861338

  12. Modified protocol for enhanced recovery after surgery is beneficial for Chinese cancer patients undergoing pancreaticoduodenectomy.

    Science.gov (United States)

    Deng, Xiaxing; Cheng, Xi; Huo, Zhen; Shi, Yuan; Jin, Zhijian; Feng, Haoran; Wang, Yue; Wen, Chenlei; Qian, Hao; Zhao, Ren; Qiu, Weihua; Shen, Baiyong; Peng, Chenghong

    2017-07-18

    Radical surgical resection remains the only effective treatment for advanced pancreatic cancer. Effective protocols for recovery from post-operative complications that result in high rates of morbidity and mortality are therefore essential. The enhanced recovery after surgery (ERAS) protocol is an interdisciplinary multimodal concept based on modern anesthesia and analgesia combined with other fast rehabilitation parameters. It was first applied in the field of elective colorectal surgery, and eventually extended to several surgical diseases. In this study, we investigated the feasibility and safety of implementing the ERAS protocol in patients undergoing pancreaticoduodenectomy (PD). We randomly divided 159 patients who underwent PD into two groups who were managed using either ERAS or the conventional protocol. We observed that in those treated with the ERAS protocol several post-operative recovery factors were greatly improved, and there were no complications requiring readmission. We therefore propose that ERAS can improve post-operative recovery of PD patients and shorten the waiting time to chemotherapy, which may improve the overall survival of surgically treated pancreatic cancer patients.

  13. Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate) nanoparticles.

    Science.gov (United States)

    Melguizo, Consolación; Cabeza, Laura; Prados, Jose; Ortiz, Raúl; Caba, Octavio; Rama, Ana R; Delgado, Ángel V; Arias, José L

    2015-01-01

    Doxorubicin (Dox) is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate) (PBCA). The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP) matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic) drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations). Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug's antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma.

  14. Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jie Xiao

    2016-09-01

    Full Text Available The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC, we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4− or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

  15. Contrast-enhanced spectral mammography in patients referred from the breast cancer screening programme

    Energy Technology Data Exchange (ETDEWEB)

    Lobbes, Marc B.I.; Wildberger, Joachim E. [Maastricht University Medical Center, Department of Radiology, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht (Netherlands); Lalji, Ulrich; Houwers, Janneke; Nijssen, Estelle C. [Maastricht University Medical Center, Department of Radiology, Maastricht (Netherlands); Nelemans, Patty J. [Maastricht University, Department of Epidemiology, Maastricht (Netherlands); Roozendaal, Lori van; Heuts, Esther [Maastricht University Medical Center, Department of Surgical Oncology, Maastricht (Netherlands); Smidt, Marjolein L. [Maastricht University Medical Center, Department of Surgical Oncology, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht (Netherlands)

    2014-07-15

    Feasibility studies have shown that contrast-enhanced spectral mammography (CESM) increases diagnostic accuracy of mammography. We studied diagnostic accuracy of CESM in patients referred from the breast cancer screening programme, who have a lower disease prevalence than previously published papers on CESM. During 6 months, all women referred to our hospital were eligible for CESM. Two radiologists blinded to the final diagnosis provided BI-RADS classifications for conventional mammography and CESM. Statistical significance of differences between mammography and CESM was calculated using McNemar's test. Receiver operating characteristic (ROC) curves were constructed for both imaging modalities. Of the 116 eligible women, 113 underwent CESM. CESM increased sensitivity to 100.0 % (+3.1 %), specificity to 87.7 % (+45.7 %), PPV to 76.2 % (+36.5 %) and NPV to 100.0 % (+2.9 %) as compared to mammography. Differences between conventional mammography and CESM were statistically significant (p < 0.0001). A similar trend was observed in the ROC curve. For conventional mammography, AUC was 0.779. With CESM, AUC increased to 0.976 (p < 0.0001). In addition, good agreement between tumour diameters measured using CESM, breast MRI and histopathology was observed. CESM increases diagnostic performance of conventional mammography, even in lower prevalence patient populations such as referrals from breast cancer screening. (orig.)

  16. Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer.

    Science.gov (United States)

    Upreti, Meenakshi; Jyoti, Amar; Johnson, Sara E; Swindell, Elden P; Napier, Dana; Sethi, Pallavi; Chan, Ryan; Feddock, Jonathan M; Weiss, Heidi L; O'Halloran, Thomas V; Evers, B Mark

    2016-07-05

    Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The 'rigorous' combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment.

  17. ZNF217 is associated with poor prognosis and enhances proliferation and metastasis in ovarian cancer.

    Science.gov (United States)

    Li, Jing; Song, Lanlin; Qiu, Yuwen; Yin, Ailan; Zhong, Mei

    2014-01-01

    ZNF217 is an alternatively spliced Kruppel-like transcription factor that has recently been implicated to play a role in human carcinogenesis. Here, we used immunohistochemistry (IHC) to show that ZNF217 protein is overexpressed in nearly 60% of ovarian tumor samples. The disease-free survival time was shorter in patients with positive ZNF217 expression than in ZNF217-negative patients (P=0.042). Fluorescence in situ hybridization (FISH) analysis showed ZNF217 genomic amplification in the poorly differentiated tumors, suggesting that ZNF217 is associated with the progression of ovarian cancer. Invasion was enhanced in HO-8910 cells stably transfected with constructs carrying full-length ZNF217 relative to cells transfected with the empty vector. To confirm our findings in vivo, we performed a tumorigenicity assay in nude mice inoculated with the HO-8910 overexpressing ZNF217 cells. As expected, tumors grown in the ZNF217 group were more invasive and prone to metastasis than those formed control groups. Based on these clinical and laboratory observations, we conclude that ZNF217 may contribute to ovarian cancer invasion and metastasis, and associated with worse clinical outcomes.

  18. Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Xiao, Jie; Xu, Xiaobo; Li, Xiao; Li, Yanli; Liu, Guobing; Tan, Hui; Shen, Hua; Shi, Hongcheng; Cheng, Dengfeng

    2016-09-30

    The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO₄- or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

  19. Transfer learning from RF to B-mode temporal enhanced ultrasound features for prostate cancer detection.

    Science.gov (United States)

    Azizi, Shekoofeh; Mousavi, Parvin; Yan, Pingkun; Tahmasebi, Amir; Kwak, Jin Tae; Xu, Sheng; Turkbey, Baris; Choyke, Peter; Pinto, Peter; Wood, Bradford; Abolmaesumi, Purang

    2017-07-01

    We present a method for prostate cancer (PCa) detection using temporal enhanced ultrasound (TeUS) data obtained either from radiofrequency (RF) ultrasound signals or B-mode images. For the first time, we demonstrate that by applying domain adaptation and transfer learning methods, a tissue classification model trained on TeUS RF data (source domain) can be deployed for classification using TeUS B-mode data alone (target domain), where both data are obtained on the same ultrasound scanner. This is a critical step for clinical translation of tissue classification techniques that primarily rely on accessing RF data, since this imaging modality is not readily available on all commercial scanners in clinics. Proof of concept is provided for in vivo characterization of PCa using TeUS B-mode data, where different nonlinear processing filters in the pipeline of the RF to B-mode conversion result in a distribution shift between the two domains. Our in vivo study includes data obtained in MRI-guided targeted procedure for prostate biopsy. We achieve comparable area under the curve using TeUS RF and B-mode data for medium to large cancer tumor sizes in biopsy cores (>4 mm). Our result suggests that the proposed adaptation technique is successful in reducing the divergence between TeUS RF and B-mode data.

  20. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA, which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS, down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

  1. Contrast-enhanced ultrasound vs multidetector-computed tomography for detecting liver metastases in colorectal cancer: a prospective, blinded, patient-by-patient analysis

    DEFF Research Database (Denmark)

    Rafaelsen, S R; Jakobsen, A

    2011-01-01

    This study compared the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and multidetector-computed tomography (MDCT) in the detection of liver metastases in patients with colorectal cancer.......This study compared the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and multidetector-computed tomography (MDCT) in the detection of liver metastases in patients with colorectal cancer....

  2. Migration and invasion enhancer 1 (MIEN1) is overexpressed in breast cancer and is a potential new therapeutic molecular target.

    Science.gov (United States)

    Zhao, H-B; Zhang, X-F; Wang, H-B; Zhang, M-Z

    2017-02-08

    Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein that is highly expressed in various types of cancer, and is correlated with the PI3K/AKT pathway. The aim of this study was to investigate the expression of MIEN1 and its clinical pathological significance in breast cancer. We used immunohistochemical staining to examine the expression of MIEN1 in 40 samples of human breast cancer tissue and 10 samples taken from regions adjacent to normal breast tissue. The rate of detection of MIEN1 protein was 67.5%, which was significantly higher than that in adjacent non-cancerous breast tissue (0%, P cancer. Kaplan-Meier survival analysis showed that patients with positive MIEN1 protein expression had a lower overall survival rate than patients who did not express MIEN1. Downregulation of MIEN1 suppressed the expression of matrix metallopeptidase 9 by downregulating the expression of protein kinase B (also known as AKT) in breast cancer cells. Our results indicate that MIEN1 overexpression may facilitate migration and invasion in breast cancer, and MIEN1 is a potential molecular target for cancer chemotherapy.

  3. A CD44v+ subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity.

    Science.gov (United States)

    Hu, Jing; Li, Gang; Zhang, Peiyuan; Zhuang, Xueqian; Hu, Guohong

    2017-03-16

    Cancer stem-like cells (CSCs) are a subpopulation of cancer cells responsible for tumor growth, and recent evidence suggests that CSCs also contribute to cancer metastasis. However, the heterogeneity of CSCs in metastasis capacities is still unclear in breast cancer. Here we show that among the CD24-/CD44+ breast CSCs, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform CD44s. Increasing or reducing the CD44v/CD44s ratio of breast cancer cells by regulating the expression of epithelial splicing regulatory protein 1 (ESRP1) leads to promotion or suppression of lung metastasis without influencing cancer cell stemness. Directly suppressing CD44v expression significantly alleviates the metastasis burden in lungs. Mechanically, CD44v, but not CD44s, responds to osteopontin (OPN) in the lung environment to enhance cancer cell invasiveness and promote lung metastasis. In clinical samples expression of ESRP1 and CD44v, rather than CD44s or total CD44, positively correlates with distant metastasis. Overall, our data identify a subset of metastatic breast CSCs characterized by CD44v expression, and suggest that CD44v and ESRP1 might be better prognosis markers and therapeutic targets for breast cancer metastasis.

  4. Lysophosphatidic acid enhances vascular endothelial growth factor-C expression in human prostate cancer PC-3 cells.

    Directory of Open Access Journals (Sweden)

    Chuan-En Lin

    Full Text Available Clinical evidence suggests that lymphangiogenesis and lymphatic metastasis are important processes during the progression of prostate cancer. Vascular endothelial growth factor (VEGF-C was shown to be a key regulator in these processes. Our previous studies demonstrated that lysophosphatidic acid (LPA, a low-molecular-weight lipid growth factor, enhances VEGF-C expression in human endothelial cells. We previously demonstrated that the LPA receptor plays an important role in lymphatic development in zebrafish embryos. However, the effects of LPA on VEGF-C expression in prostate cancer are not known. Herein, we demonstrate that LPA up-regulated VEGF-C expression in three different human prostate cancer cell lines. In PC-3 human prostate cancer cells, the enhancing effects of LPA were mediated through both LPA1 and LPA3. In addition, reactive oxygen species (ROS production and lens epithelium-derived growth factor (LEDGF expression were involved in LPA(1/3-dependent VEGF-C expression. Furthermore, autotaxin (ATX, an enzyme responsible for LPA synthesis, also participates in regulating VEGF-C expression. By interrupting LPA(1/3 of PC-3, conditioned medium (CM -induced human umbilical vein endothelial cell (HUVEC lymphatic markers expression was also blocked. In summary, we found that LPA enhances VEGF-C expression through activating LPA(1/3-, ROS-, and LEDGF-dependent pathways. These novel findings could potentially shed light on developing new strategies for preventing lymphatic metastasis of prostate cancer.

  5. Carbohydrate specificities of the murine DC-SIGN homologue mSIGNR1

    NARCIS (Netherlands)

    Koppel, Estella A.; Ludwig, Irene S.; Appelmelk, Ben J.; van Kooyk, Yvette; Geijtenbeek, Teunis B. H.

    2005-01-01

    C-type lectins are important receptors expressed by antigen presenting cells that are involved in cellular communications as well as in pathogen uptake. An important C-type lectin family is represented by DC-SIGN and its homologues in human and mouse. Here we have investigated the carbohydrate

  6. A Hexose Transporter Homologue Controls Glucose Repression in the Methylotrophic Yeast Hansenula polymorpha

    NARCIS (Netherlands)

    Stasyk, Oleh V.; Stasyk, Olena G.; Komduur, Janet; Veenhuis, Marten; Cregg, James M.; Sibirny, Andrei A.

    2004-01-01

    Peroxisome biogenesis and synthesis of peroxisomal enzymes in the methylotrophic yeast Hansenula polymorpha are under the strict control of glucose repression. We identified an H. polymorpha glucose catabolite repression gene (HpGCR1) that encodes a hexose transporter homologue. Deficiency in GCR1

  7. The actin homologue MreB organizes the bacterial cell membrane

    NARCIS (Netherlands)

    Strahl, H.; Burmann, F.; Hamoen, L.W.

    2014-01-01

    The eukaryotic cortical actin cytoskeleton creates specific lipid domains, including lipid rafts, which determine the distribution of many membrane proteins. Here we show that the bacterial actin homologue MreB displays a comparable activity. MreB forms membrane-associated filaments that coordinate

  8. Drosomycin-like defensin, a human homologue of Drosophila melanogaster drosomycin with antifungal activity.

    NARCIS (Netherlands)

    Simon, A.; Kullberg, B.J.; Tripet, B.; Boerman, O.C.; Zeeuwen, P.L.J.M.; Ven-Jongekrijg, J. van der; Verweij, P.; Schalkwijk, J.; Hodges, R.; Meer, J.W.M. van der; Netea, M.G.

    2008-01-01

    Innate antifungal defense in Drosophila melanogaster relies on the activation of the Toll molecule and the release of drosomycin, a defensin-like molecule with antifungal properties. Ten human homologues of Toll have been described, with central roles in activation of the innate host defense. In the

  9. Cloning and characterization of maize ZmSPK1, a homologue to ...

    African Journals Online (AJOL)

    hope&shola

    2006-03-15

    Mar 15, 2006 ... 1College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China. 2Beijing ... homologue was isolated from maize by RT-PCR and named as ZmSPK1 (for stress-induced protein kinase). ... RT-PCR analysis showed that the ZmSPK1 expression was induced by mannitol, salt and abscisic ...

  10. Identification and analysis of putative homologues of mechanosensitive channels in pathogenic protozoa.

    Directory of Open Access Journals (Sweden)

    David L Prole

    Full Text Available Mechanosensitive channels play important roles in the physiology of many organisms, and their dysfunction can affect cell survival. This suggests that they might be therapeutic targets in pathogenic organisms. Pathogenic protozoa lead to diseases such as malaria, dysentery, leishmaniasis and trypanosomiasis that are responsible for millions of deaths each year worldwide. We analyzed the genomes of pathogenic protozoa and show the existence within them of genes encoding putative homologues of mechanosensitive channels. Entamoeba histolytica, Leishmania spp., Trypanosoma cruzi and Trichomonas vaginalis have genes encoding homologues of Piezo channels, while most pathogenic protozoa have genes encoding homologues of mechanosensitive small-conductance (MscS and K(+-dependent (MscK channels. In contrast, all parasites examined lack genes encoding mechanosensitive large-conductance (MscL, mini-conductance (MscM and degenerin/epithelial Na(+ (DEG/ENaC channels. Multiple sequence alignments of evolutionarily distant protozoan, amoeban, plant, insect and vertebrate Piezo channel subunits define an absolutely conserved motif that may be involved in channel conductance or gating. MscS channels are not present in humans, and the sequences of protozoan and human homologues of Piezo channels differ substantially. This suggests the possibility for specific targeting of mechanosensitive channels of pathogens by therapeutic drugs.

  11. Partial functional complementation between human and mouse cytomegalovirus chemokine receptor homologues

    DEFF Research Database (Denmark)

    Farrell, Helen E; Abraham, Alexander M; Cardin, Rhonda D

    2011-01-01

    The human cytomegalovirus (CMV) proteins US28 and UL33 are homologous to chemokine receptors (CKRs). Knockout of the mouse CMV M33 protein (UL33 homologue) results in substantial attenuation of salivary gland infection/replication and reduced efficiency of reactivation from tissue explants. M33...

  12. Simian Homologues of Human Gamma-2 and Betaherpesviruses in Mandrill and Drill Monkeys

    Science.gov (United States)

    Lacoste, Vincent; Mauclere, Philippe; Dubreuil, Guy; Lewis, John; Georges-Courbot, Marie-Claude; Rigoulet, Jacques; Petit, Thierry; Gessain, Antoine

    2000-01-01

    Recent serological and molecular surveys of different primate species allowed the characterization of several Kaposi's sarcoma-associated herpesvirus (KSHV) homologues in macaques, African green monkeys, chimpanzees, and gorillas. Identification of these new primate rhadinoviruses revealed the existence of two distinct genogroups, called RV1 and RV2. Using a degenerate consensus primer PCR method for the herpesvirus DNA polymerase gene, the presence of KSHV homologues has been investigated in two semi-free-ranging colonies of eight drill (Mandrillus leucophaeus), five mandrill (Mandrillus sphinx), and two hybrid (Mandrillus leucophaeus-Mandrillus sphinx) monkeys, living in Cameroon and Gabon, Central Africa. This search revealed the existence of not only two distinct KSHV homologues, each one belonging to one of the two rhadinovirus genogroups, but also of two new betaherpesvirus sequences, one being close to cytomegaloviruses and the other being related to human herpesviruses 6 and 7 (HHV-6 and -7). The latter viruses are the first simian HHV-6 and -7 homologues identified to date. These data show that mandrill and drill monkeys are the hosts of at least four novel distinct herpesviruses. Moreover, mandrills, like macaques and African green monkeys, harbor also two distinct gamma-2 herpesviruses, thus strongly suggesting that a second gamma-2 herpesvirus, belonging to the RV2 genogroup, may exist in humans. PMID:11090203

  13. Identification of Plant Homologues of Dual Specificity Yak1-Related Kinases

    Directory of Open Access Journals (Sweden)

    Pavel Karpov

    2014-01-01

    Full Text Available Currently, Dual Specificity YAK1-Related Kinases (MNB/DYRK were found in slime molds, protista, fungi, and animals, but the existence of plant homologues is still unclear. In the present study, we have identified 14 potential plant homologues with the previously unknown functions, based on the strong sequence similarity. The results of bioinformatics analysis revealed their correspondence to DYRK1A, DYRK1B, DYRK3, and DYRK4. For two plant homologues of animal DYRK1A from Physcomitrella patens and Arabidopsis thaliana spatial structures of catalytic domains were predicted, as well as their complexes with ADP and selective inhibitor d15. Comparative analysis of 3D-structures of the human DYRK1A and plant homologues, their complexes with the specific inhibitors, and results of molecular dynamics confirm their structural and functional similarity with high probability. Preliminary data indicate the presence of potential MNB/DYRK specific phosphorylation sites in such proteins associated with plant cytoskeleton as plant microtubule-associated proteins WVD2 and WDL1, and FH5 and SCAR2 involved in the organization and polarity of the actin cytoskeleton and some kinesin-like microtubule motor proteins.

  14. Structure of HLA-A*1101 in complex with a hepatitis B peptide homologue

    DEFF Research Database (Denmark)

    Blicher, Thomas; Kastrup, Jette Sandholm; Pedersen, Lars Østergaard

    2006-01-01

    A high-resolution structure of the human MHC-I molecule HLA-A*1101 is presented in which it forms a complex with a sequence homologue of a peptide that occurs naturally in hepatitis B virus DNA polymerase. The sequence of the bound peptide is AIMPARFYPK, while that of the corresponding natural...

  15. A lesion mimic phenotype in tomato obtained by isolating and silencing an Lls1 homologue

    NARCIS (Netherlands)

    Spassieva, S; Hille, J

    Lesion mimic phenotypes serve as a tool to study the regulation of cell death in plants. In order to obtain a tomato lesion mimic phenotype, we used the conservation of the lethal leaf spot 1 (Lls1) genes between plant species. The tomato Lls1 homologue was cloned, sequenced and analyzed. It showed

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

    Directory of Open Access Journals (Sweden)

    Held Kathryn D

    2008-06-01

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

  17. PSES-a Novel Prostate Specific Chimeric Enhancer for Prostate Cancer Gene Therapy

    Science.gov (United States)

    2007-02-01

    most new cancer diagnoses, aside from skin cancer, at 234,460 men in the United States and will be the second most common cause of cancer deaths at...that prostate cancer will account for the most new cancer diagnoses, aside from skin cancer, at 234,460 men in the United States and will be the second...prostatectomy, cryoablation therapy, external beam radiation and brachytherapy ; however, 25% of these men will experience biochemical disease recurrence

  18. Interobserver and Intraobserver Reproducibility with Volume Dynamic Contrast Enhanced Computed Tomography (DCE-CT) in Gastroesophageal Junction Cancer

    DEFF Research Database (Denmark)

    Lundsgaard Hansen, Martin; Fallentin, Eva; Axelsen, Thomas

    2016-01-01

    The purpose of this study was to assess inter- and intra-observer reproducibility of three different analytic methods to evaluate quantitative dynamic contrast-enhanced computed tomography (DCE-CT) measures from gastroesophageal junctional cancer. Twenty-five DCE-CT studies with gastroesophageal...

  19. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

    NARCIS (Netherlands)

    Best, Myron G.; Sol, Nik; In ‘t Veld, Sjors G.J.G.; Vancura, Adrienne; Muller, Mirte; Niemeijer, Anna Larissa N.; Fejes, Aniko V.; Tjon Kon Fat, Lee Ann; Huis in 't Veld, Anna E; Leurs, Cyra; Le Large, Tessa Y.; Meijer, Laura L.; Kooi, Irsan E.; Rustenburg, François; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Wedekind, Laurine E.; Bracht, Jillian; Esenkbrink, Michelle; Wils, Leon; Favaro, Francesca; Schoonhoven, Jilian D.; Tannous, Jihane; Meijers-Heijboer, Hanne; Kazemier, Geert; Giovannetti, Elisa; Reijneveld, Jaap C.; Idema, Sander; Killestein, Joep; Heger, Michal; de Jager, Saskia C.; Urbanus, Rolf T.; Hoefer, Imo E.; Pasterkamp, Gerard; Mannhalter, Christine; Gomez-Arroyo, Jose; Bogaard, Harm-Jan; Noske, David P.; Vandertop, W. Peter; van den Broek, Daan; Ylstra, Bauke; Nilsson, R. Jonas A; Wesseling, Pieter; Karachaliou, Niki; Rosell, Rafael; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent B.; Tannous, Bakhos A.; de Langen, Adrianus J.; Smit, Egbert F.; van den Heuvel, Michel M; Wurdinger, Thomas

    2017-01-01

    Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from

  20. Comparison between CT Net enhancement and PET/CT SUV for N staging of gastric cancer: A case series

    Directory of Open Access Journals (Sweden)

    Amato Antonio Stabile Ianora

    2017-09-01

    Conclusion: CT Net enhancement represents an accurate tool for N staging of gastric cancer and could be considered as the CT corresponding quantitative parameter of F-FDG PET/CT SUV. It could be applied in the clinical practice for differentiating reactive lymph nodes from metastatic ones improving accuracy and specificity of CT.

  1. Adaptive enhancement and visualization techniques for 3D THz images of breast cancer tumors

    Science.gov (United States)

    Wu, Yuhao; Bowman, Tyler; Gauch, John; El-Shenawee, Magda

    2016-03-01

    This paper evaluates image enhancement and visualization techniques for pulsed terahertz (THz) images of tissue samples. Specifically, our research objective is to effectively differentiate between heterogeneous regions of breast tissues that contain tumors diagnosed as triple negative infiltrating ductal carcinoma (IDC). Tissue slices and blocks of varying thicknesses were prepared and scanned using our lab's THz pulsed imaging system. One of the challenges we have encountered in visualizing the obtained images and differentiating between healthy and cancerous regions of the tissues is that most THz images have a low level of details and narrow contrast, making it difficult to accurately identify and visualize the margins around the IDC. To overcome this problem, we have applied and evaluated a number of image processing techniques to the scanned 3D THz images. In particular, we employed various spatial filtering and intensity transformation techniques to emphasize the small details in the images and adjust the image contrast. For each of these methods, we investigated how varying filter sizes and parameters affect the amount of enhancement applied to the images. Our experimentation shows that several image processing techniques are effective in producing THz images of breast tissue samples that contain distinguishable details, making further segmentation of the different image regions promising.

  2. DNA Tetrahedron Delivery Enhances Doxorubicin-Induced Apoptosis of HT-29 Colon Cancer Cells

    Science.gov (United States)

    Zhang, Guiyu; Zhang, Zhiyong; Yang, Junen

    2017-08-01

    As a nano-sized drug carrier with the advantage of modifiability and proper biocompatibility, DNA tetrahedron (DNA tetra) delivery is hopeful to enhance the inhibitory efficiency of nontargeted anticancer drugs. In this investigation, doxorubicin (Dox) was assembled to a folic acid-modified DNA tetra via click chemistry to prepare a targeted antitumor agent. Cellular uptake efficiency was measured via fluorescent imaging. Cytotoxicity, inhibition efficiency, and corresponding mechanism on colon cancer cell line HT-29 were evaluated by MTT assay, cell proliferation curve, western blot, and flow cytometry. No cytotoxicity was induced by DNA tetra, but the cellular uptake ratio increased obviously resulting from the DNA tetra-facilitated penetration through cellular membrane. Accordingly, folic acid-DNA tetra-Dox markedly increased the antitumor efficiency with increased apoptosis levels. In details, 100 μM was the effective concentration and a 6-h incubation period was needed for apoptosis induction. In conclusion, nano-sized DNA tetrahedron was a safe and effective delivery system for Dox and correspondingly enhanced the anticancer efficiency.

  3. Targeting Aerobic Glycolysis and HIF-1α Expression Enhance Imiquimod-induced Apoptosis in Cancer Cells

    Science.gov (United States)

    Huang, Shi-Wei; Kao, Jun-Kai; Wu, Chun-Ying; Wang, Sin-Ting; Lee, Hsin-Chen; Liang, Shu-Mei; Chen, Yi-Ju; Shieh, Jeng-Jer

    2014-01-01

    Tumor cells rely on aerobic glycolysis to maintain unconstrained cell growth and proliferation. Imiquimod (IMQ), a synthetic Toll-like receptor (TLR) 7/8 ligand, exerts anti-tumor effects directly by inducing cell death in cancer cells and/or indirectly by activating cellular immune responses against tumor cells. However, whether IMQ modulates glucose metabolism pathways remains unclear. In this study, we demonstrated that IMQ can enhance aerobic glycolysis by up-regulating HIF-1α expression at the transcriptional and translational levels via ROS mediated STAT3- and Akt-dependent pathways, independent of TLR7/8 signaling. The genetic silencing of HIF-1α not only repressed IMQ-induced aerobic glycolysis but also sensitized cells to IMQ-induced apoptosis due to faster ATP and Mcl-1 depletion. Moreover, the glucose analog 2-DG and the Hsp90 inhibitor 17-AAG, which destabilizes the HIF-1α protein, synergized with IMQ to induce tumor cell apoptosis in vitro and significantly inhibited tumor growth in vivo. Thus, we hypothesize that the IMQ-induced up-regulation of HIF-1α and aerobic glycolysis is a protective response to the metabolic stress generated by IMQ treatment, and thus, co-treatment with inhibitors of HIF-1α and/or glycolysis may be a useful therapeutic strategy to enhance the anti-tumor effects of IMQ in clinical settings. PMID:24658058

  4. Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells.

    Science.gov (United States)

    Zhang, Shumin; Wang, Yanru; Chen, Zhengjia; Kim, Sungjin; Iqbal, Shareen; Chi, Andrew; Ritenour, Chad; Wang, Yongqiang A; Kucuk, Omer; Wu, Daqing

    2013-11-01

    Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models. The in vitro and in vivo effect of genistein in enhancing the response of mCRPC cells to cabazitaxel chemotherapy was evaluated in experimental models. Genistein increases the expression of pro-apoptotic protein Bax, activates apoptotic signals, and enhances the response to cabazitaxel treatment in mCRPC cells. In a PC3-luciferase xenograft model, the combined treatment with genistein and cabazitaxel significantly retarded the growth of mCRPC when compared to vehicle control, cabazitaxel, or genistein. Tissue staining confirmed the in vivo effect of genistein on the induction of Bax and activation of apoptosis. This study provided the first preclinical evidence supporting that genistein could be beneficial in improving cabazitaxel chemotherapy in mCRPC. © 2013 Wiley Periodicals, Inc.

  5. Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase

    Energy Technology Data Exchange (ETDEWEB)

    Jayakumar, Sundarraj; Patwardhan, R.S.; Pal, Debojyoti [Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Sharma, Deepak [Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094 (India); Sandur, Santosh K., E-mail: sskumar@barc.gov.in [Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094 (India)

    2016-09-09

    Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratio and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. - Highlights: • DIMC enhances radiosensitivity of cancer cells by inducing cell death. • DIMC with radiation disrupted the cellular redox and targeted cancer stem cells. • DNA repair is hampered when cells are treated with DIMC. • DIMC inhibited thioredoxin reductase in cancer cells.

  6. Contrast-enhanced ultrasonography for the detection and characterization of prostate cancer: correlation with microvessel density and Gleason score.

    Science.gov (United States)

    Jiang, J; Chen, Y; Zhu, Y; Yao, X; Qi, J

    2011-08-01

    To determine whether there is a correlation between the peak intensity of the lesion at contrast-enhanced ultrasonography and the microvessel density (MVD) and Gleason score in biopsy specimens of prostate cancer. Contrast-enhanced ultrasonography using cadence-contrast pulse sequence (CPS) technology was performed in 147 patients with suspected prostate cancer before biopsy. An auto-tracking contrast quantification (ACQ) software was used to analyse the peak intensity (PI) of the lesion. The Gleason score and MVD immunoreactivity were determined in the prostate biopsy specimens. Ultrasound findings were correlated with biopsy findings. Prostate cancer was detected in 73 of 147 patients. The PI values of prostate cancer patients were significantly higher than those of non-malignant patients [9.81 (4.23) versus 5.69 (3.19) dB; pPI value increased significantly with a higher Gleason score (pPI and MVD in prostate cancer, with a correlation coefficient of 0.617. No correlation was found between PI value and age, prostate specific antigen (PSA) or prostate specific antigen density (PSAD) level (p>0.05). The PI obtained by CPS harmonic ultrasonography appears to be of value as an indicator of MVD and increases with a higher Gleason score. CPS harmonic ultrasonography could be promising as a useful imaging technique in the detection and characterization of prostate cancer. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  7. Rad51 siRNA delivered by HVJ envelope vector enhances the anti-cancer effect of cisplatin.

    Science.gov (United States)

    Ito, Makoto; Yamamoto, Seiji; Nimura, Keisuke; Hiraoka, Kazuya; Tamai, Katsuto; Kaneda, Yasufumi

    2005-08-01

    Every cancer therapy appears to be transiently effective for cancer regression, but cancers gradually transform to be resistant to the therapy. Cancers also develop machineries to resist chemotherapy. Short interfering RNA (siRNA) has been evaluated as an attractive and effective tool for suppressing a target protein by specifically digesting its mRNA. Suppression of the machineries using siRNA may enhance the sensitivity to chemotherapy in cancers when combined with an effective delivery system. To enhance the anti-cancer effect of chemotherapy, we transferred siRNA against Rad51 into various human cancer cells using the HVJ (hemagglutinating virus of Japan, Sendai virus) envelope vector in the presence or absence of cis-diamminedichloroplatinum(II) (CDDP, cisplatin). The inhibition of cell growth was assessed by a modified MTT assay, counting cell number, or fluorescence-activated cell sorting (FACS) analysis after Annexin V labeling. The synthetic Rad51 siRNA was also introduced into subcutaneous tumor masses of HeLa cells in SCID mice with or without intraperitoneal injection of CDDP, and tumor growth was monitored. When synthetic Rad51 siRNA was delivered into HeLa cells using the HVJ envelope vector, no Rad51 transcripts were detected on day 2, and Rad51 protein completely disappeared for 4 days after siRNA transfer. When HeLa cells were incubated with 0.02 microg/ml CDDP for 3 h after siRNA transfer, the number of colonies decreased to approximately 10% of that with scrambled siRNA. The sensitivity to CDDP was enhanced in various human cancer cells, but not in normal human fibroblasts. When Rad51 siRNA was delivered into tumors using the HVJ envelope vector, the Rad51 transcript level was reduced to approximately 25%. Rad51 siRNA combined with CDDP significantly inhibited tumor growth when compared to siRNA or CDDP alone. Rad51 siRNA could enhance the sensitivity to CDDP in cancer cells both in vitro and in vivo. Our results suggest that the combination of

  8. Nano and Microparticle-Enhanced Immunosensor Approaches for the Detection of Cancer Biomarker Proteins

    Science.gov (United States)

    Mani, Vigneshwaran

    Accurate, sensitive, point-of-care multiplexed protein measurements are critical for early disease detection and monitoring, impacting biomarker and drug discovery, and personalized medicine. Significant application involves monitoring panels of proteins in the blood that are biomarkers for diagnosing cancer. However, measurements of biomarker panels in blood or other bodily fluids have been slow to integrate into current practice of cancer diagnostics partly due to the lack of technically simple, low-cost, sensitive, point-of-care multiplexed measurement devices, as well as the lack of rigorously validated protein panels. The present thesis in part addresses these limitations by the development of electrochemical and surface plasmon resonance (SPR) immunosensors utilizing 1mum superparamagnetic labels for accurate detection of prostate cancer biomarker proteins in patient serum samples. Electrochemical discrete immunosensors featuring nanostructured surface with densely packed 5 nm glutathione-coated gold nanoparticles coupled with multi-enzyme magnetic particle (MP) labels enabled measurement of prostate specific antigen (PSA) with a detection limit (DL) of 0.5 pg mL-1 in undiluted serum. Such low DLs are attributed to high surface area, conductivity of nanostructured surface, and multi-enzyme signal amplification. DLs are further improved by utilizing MP bioconjugated with more than 100,000 antibody labels to offline capture proteins from the serum sample matrix, minimizing nonspecific binding of interfering proteins on sensor surface before detection. This approach provided an unprecedented 10 fg DL mL-1 for PSA in undiluted serum using a flow SPR biosensor. Finally electrochemical microfluidic immunoarrays featuring nanostructured surface and offline protein capture by multi-label MPs enabled multiplexed detection of prostate cancer biomarkers PSA and interleukin-6 (IL-6). These approaches provided up to 1000-fold lower DLs compared to commercial bead based

  9. Impact of Adding a Pictorial Display to Enhance Recall of Cancer Patient Histories: A Randomized Trial.

    Science.gov (United States)

    Wolch, Gary; Ghosh, Sunita; Boyington, Curtiss; Watanabe, Sharon M; Fainsinger, Robin; Burton-Macleod, Sarah; Thai, Vincent; Thai, JoAnn; Fassbender, Konrad

    2017-01-01

    Current health care delivery models have increased the need for safe and concise patient handover. Handover interventions in the literature have focused on the use of structured tools but have not evaluated their ability to facilitate retention of patient information. In this study, mock pictorial displays were generated in an attempt to create a snapshot of each patient's medical and social circumstances. These pictorial displays contained the patient's photograph and other disease- and treatment-related images. The objective of this randomized trial was to assess the ability of these snapshots to enhance delayed information recall by care providers. Participating physicians were given four advanced cancer patient histories to review, two at a time over two weeks. Pictorial image displays, referred to as the Electronic Whiteboard (EWB) were added, in a randomized manner to half of the textual histories. The impact of the EWB on information recall was tested in immediate and delayed time frames. Overall, patient information recall declined significantly over time, with or without the EWB. Still, this trial demonstrates significantly higher test scores after 24 hours with the addition of pictures to textual patient information, compared with textual information alone (P = 0.0002). A more modest improvement was seen with the addition of the EWB for questionnaires administered immediately after history review (P = 0.008). Most participants agreed that the EWB was a useful enhancement and that seeing a patient's photograph improved their ability to retain information. Most studies examining the institution of handover protocols in the health care setting have failed to harness the power of pictures and other representative images. This study demonstrates the ability of pictorial displays to improve both immediate and delayed recall of patient histories without increasing review time. These types of displays may be amenable to generation by software programs and

  10. Does the degree of background enhancement in breast MRI affect the detection and staging of breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Uematsu, Takayoshi [Shizuoka Cancer Center Hospital, Breast Imaging and Breast Intervention Section, Shizuoka (Japan); Kasami, Masako [Shizuoka Cancer Center Hospital, Department of Pathology, Naga-izumi, Shizuoka (Japan); Watanabe, Junichiro [Shizuoka Cancer Center Hospital, Division of Medical Oncology, Naga-izumi, Shizuoka (Japan)

    2011-11-15

    The purpose of this study was to assess the influence of background enhancement on the detection and staging of breast cancer using MRI as an adjunct to mammography or ultrasound. One hundred forty-six bilateral breast MRI examinations were evaluated to assess the extent of a known primary tumour and to problem solve after mammography or ultrasound without adjusting for the phase in the patients' menstrual cycle. The background enhancement was classified into four categories by visual evaluation: minimal, mild, moderate and marked. In total, 131 histologically confirmed abnormal cases (104 malignant and 27 benign) and 15 normal cases were included in the analysis. There was no tumour size-related bias between the groups (p = 0.522). For the primary index tumour, the sensitivities of MRI with minimal/mild and moderate/marked background enhancement were 100% and 76% (p = 0.001), respectively. Thus, the degree of background enhancement did not affect the specificity. For evaluating tumour extent (n = 104), the accuracy of MRI with moderate/marked background enhancement (52%) was significantly lower than that with minimal/mild background enhancement (84%; p = 0.002). The degree of background enhancement affected the detection and staging of breast cancer using MRI. (orig.)

  11. Radiogenomic analysis of breast cancer: dynamic contrast enhanced - magnetic resonance imaging based features are associated with molecular subtypes

    Science.gov (United States)

    Wang, Shijian; Fan, Ming; Zhang, Juan; Zheng, Bin; Wang, Xiaojia; Li, Lihua

    2016-03-01

    Breast cancer is one of the most common malignant tumor with upgrading incidence in females. The key to decrease the mortality is early diagnosis and reasonable treatment. Molecular classification could provide better insights into patient-directed therapy and prognosis prediction of breast cancer. It is known that different molecular subtypes have different characteristics in magnetic resonance imaging (MRI) examination. Therefore, we assumed that imaging features can reflect molecular information in breast cancer. In this study, we investigated associations between dynamic contrasts enhanced MRI (DCE-MRI) features and molecular subtypes in breast cancer. Sixty patients with breast cancer were enrolled and the MR images were pre-processed for noise reduction, registration and segmentation. Sixty-five dimensional imaging features including statistical characteristics, morphology, texture and dynamic enhancement in breast lesion and background regions were semiautomatically extracted. The associations between imaging features and molecular subtypes were assessed by using statistical analyses, including univariate logistic regression and multivariate logistic regression. The results of multivariate regression showed that imaging features are significantly associated with molecular subtypes of Luminal A (p=0.00473), HER2-enriched (p=0.00277) and Basal like (p=0.0117), respectively. The results indicated that three molecular subtypes are correlated with DCE-MRI features in breast cancer. Specifically, patients with a higher level of compactness or lower level of skewness in breast lesion are more likely to be Luminal A subtype. Besides, the higher value of the dynamic enhancement at T1 time in normal side reflect higher possibility of HER2-enriched subtype in breast cancer.

  12. The enhancement of radiosensitivity by celecoxib, selective cyclooxygenase-2 inhibitor, on human cancer cells expressing differential levels of cyclooxygenase-2

    Energy Technology Data Exchange (ETDEWEB)

    Pyo, Hong Ryull; Shin, You Keun; Kim, Hyun Seok [National Cancer Center, Seoul (Korea, Republic of); Seong, Jin Sil; Suh, Chang Ok; Kim, Gwi Eon [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2003-09-01

    To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and 10% fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the 10% FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with 30 {mu} M and 50 {mu} M celecoxib. This enhanced radiosensitivity disappeared in the medium containing the 1% FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.

  13. Contrast-Enhancing Meningeal Lesions Are Associated with Longer Survival in Breast Cancer-Related Leptomeningeal Metastasis.

    Science.gov (United States)

    Regierer, Anne Constanze; Stroux, Andrea; Kühnhardt, Dagmar; Dieing, Annette; Lehenbauer-Dehm, Silvia; Flath, Bernd; Possinger, Kurt; Eucker, Jan

    2008-01-01

    BACKGROUND: Leptomeningeal metastasis (LM) is a devastating complication of advanced cancer. Despite aggressive therapy survival is very poor. METHODS: Data of all breast cancer patients with LM were retrospectively analyzed (n = 27). RESULTS: Median survival was 9 weeks. Patients with contrast-enhancing meningeal lesions (n = 11) detected by MRI had a median survival of 33 weeks versus 8 weeks for patients without contrast-enhancing lesions (n = 9; p = 0.0407). Patients who received systemic chemotherapy (n = 18) had a median survival of 15 weeks versus 7 weeks (n = 9; p = 0.0106). Patients undergoing radiotherapy (n = 8) had a median survival of 17 weeks as compared to 5 weeks for patients without radiotherapy (n = 18; p = 0.0188). In a multiple Cox regression analysis, lack of systemic therapy (hazard ratio, HR 89.5; p = 0.002) and negative hormone receptor status (HR 4.2; p = 0.027) emerged as significant main risk factors, together with contrast-enhancing lesion as effect modifier for systemic therapy (p = 0.03). CONCLUSION: Contrast-enhancing meningeal lesions, systemic therapy, and radiotherapy were significantly associated with longer survival. Patients with contrast-enhancing lesions who were treated systemically had the longest survival. Evidence is increasing that systemic therapy plays an important role and should be applied in breast cancer patients with LM.

  14. New insight of squaraine-based biocompatible surface-enhanced Raman scattering nanotag for cancer-cell imaging.

    Science.gov (United States)

    Ramya, An; Samanta, Animesh; Nisha, N; Chang, Young-Tae; Maiti, Kaustabh Kumar

    2015-03-01

    Development of highly sensitive diagnostic nanoprobe for cancer imaging based on surface-enhanced Raman scattering (SERS) platform. Synthesis of novel squaraine dyes as a Raman signature molecule denoted as lipoic-squaraine-lipoic (LSL), propyl-squaraine-lipoic (PSL) and propyl-squaraine-propyl (PSP). The SERS-nanotag constructed with a Raman signature molecule which is attached on gold nanoparticle and further encapsulated with heterofunctionalized PEG. Antibody conjugation with best SERS-nanotag for target specific recognition. SERS nanotag Au-LSL-PEG showed significant signal intensity and remarkable stability. Anti-EGF receptor and Her2-conjugated Au-LSL-PEG-nanotag were successfully applied for selective recognition of cancer cells like A549, OSCC and MCF7. The newly developed SERS-nanotag Au-LSL-PEG serves as a valuable tool for diagnostic detection of cancer cells, and may find potential applications for cancer screening in real patient samples.

  15. Enhanced breast cancer cell adherence to the lung endothelium via PAF acetylhydrolase inhibition: a potential mechanism for enhanced metastasis in smokers.

    Science.gov (United States)

    Kispert, Shannon E; Marentette, John O; McHowat, Jane

    2014-11-15

    Cancer deaths are primarily caused by distant metastases, rather than by primary tumor growth; however, the role of smoking in metastasis remains unclear. We demonstrated previously that endothelial cell platelet-activating factor (PAF) production results in enhanced inflammatory cell recruitment to the lung. We propose that endothelial cell PAF accumulation plays a role in cancer cell migration to distal locations. We used cigarette smoke extract (CSE) to inhibit the activity of endothelial cell PAF acetylhydrolase (PAF-AH), which hydrolyzes and inactivates PAF, and determined whether this results in increased endothelial cell PAF accumulation and breast cancer adherence. Incubation of human lung microvascular endothelial cells (HMVEC-L) with CSE resulted in a significant inhibition of PAF-AH activity that was accompanied by increased PAF production and adherence of highly invasive MDA-MB-231 breast cancer cells. Pretreatment of HMVEC-L with (S)-bromoenol lactone to inhibit calcium-independent phospholipase A2β (iPLA2β, which initiates endothelial cell PAF production) prior to CSE exposure resulted in complete inhibition of MDA-MB-231 cell adherence. Similarly, pretreatment of MDA-MB-231 cells with the PAF receptor antagonist Ginkgo biloba resulted in inhibition of adherence to the endothelium. Immunoblot analysis indicated an increase in MDA-MB-231 cell PAF receptor expression with CSE exposure. Taken together, our data indicate that CSE exposure increases endothelial cell PAF production, resulting in enhanced adherence of tumor cells to the endothelium. Our in vitro data indicate that increased tumor cell adherence would lead to enhanced metastasis formation in smokers. Potential therapeutic targets include endothelial cell iPLA2β or the tumor cell PAF receptor. Copyright © 2014 the American Physiological Society.

  16. Inactivated Sendai virus particle upregulates cancer cell expression of intercellular adhesion molecule-1 and enhances natural killer cell sensitivity on cancer cells.

    Science.gov (United States)

    Li, Simin; Nishikawa, Tomoyuki; Kaneda, Yasufumi

    2017-09-25

    We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has multiple anticancer effects, including induction of cancer-selective cell death and activation of anticancer immunity. The HVJ-E stimulates dendritic cells to produce cytokines and chemokines such as β-interferon, interleukin-6, chemokine (C-C motif) ligand 5, and chemokine (C-X-C motif) ligand 10, which activate both CD8(+) T cells and natural killer (NK) cells and recruit them to the tumor microenvironment. However, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated. In this study, we found that HVJ-E induced the production of intercellular adhesion molecule-1 (ICAM-1, CD54), a ligand of lymphocyte function-associated antigen 1, in several cancer cell lines through the activation of nuclear factor-κB downstream of retinoic acid-inducible gene I and the mitochondrial antiviral signaling pathway. The upregulation of ICAM-1 on the surface of cancer cells increased the sensitivity of cancer cells to NK cells. Knocking out expression of ICAM-1 in MDA-MB-231 cells using the CRISPR/Cas9 method significantly reduced the killing effect of NK cells on ICAM-1-depleted MDA-MB-231 cells. In addition, HVJ-E suppressed tumor growth in MDA-MB-231 tumor-bearing SCID mice, and the HVJ-E antitumor effect was impaired when NK cells were depleted by treatment with the anti-asialo GM1 antibody. Our findings suggest that HVJ-E enhances NK cell sensitivity against cancer cells by increasing ICAM-1 expression on the cancer cell surface. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Uropathogenic E. coli (UPEC) Infection Induces Proliferation through Enhancer of Zeste Homologue 2 (EZH2).

    Science.gov (United States)

    Ting, Kenneth; Aitken, Karen J; Penna, Frank; Samiei, Alaleh Najdi; Sidler, Martin; Jiang, Jia-Xin; Ibrahim, Fadi; Tolg, Cornelia; Delgado-Olguin, Paul; Rosenblum, Norman; Bägli, Darius J

    2016-01-01

    Host-pathogen interactions can induce epigenetic changes in the host directly, as well as indirectly through secreted factors. Previously, uropathogenic Escherichia coli (UPEC) was shown to increase DNA methyltransferase activity and expression, which was associated with methylation-dependent alterations in the urothelial expression of CDKN2A. Here, we showed that paracrine factors from infected cells alter expression of another epigenetic writer, EZH2, coordinate with proliferation. Urothelial cells were inoculated with UPEC, UPEC derivatives, or vehicle (mock infection) at low moi, washed, then maintained in media with Gentamycin. Urothelial conditioned media (CM) and extracellular vesicles (EV) were isolated after the inoculations and used to treat naïve urothelial cells. EZH2 increased with UPEC infection, inoculation-induced CM, and inoculation-induced EV vs. parallel stimulation derived from mock-inoculated urothelial cells. We found that infection also increased proliferation at one day post-infection, which was blocked by the EZH2 inhibitor UNC1999. Inhibition of demethylation at H3K27me3 had the opposite effect and augmented proliferation. Uropathogen-induced paracrine factors act epigenetically by altering expression of EZH2, which plays a key role in early host cell proliferative responses to infection.

  18. CD38 enhances the proliferation and inhibits the apoptosis of cervical cancer cells by affecting the mitochondria functions.

    Science.gov (United States)

    Liao, Shan; Xiao, Songshu; Chen, Hongxiang; Zhang, Manying; Chen, Zhifang; Long, Yuehua; Gao, Lu; Zhu, Guangchao; He, Junyu; Peng, Shuping; Xiong, Wei; Zeng, Zhaoyang; Li, Zheng; Zhou, Ming; Li, Xiaoling; Ma, Jian; Wu, Minghua; Xiang, Juanjuan; Li, Guiyuan; Zhou, Yanhong

    2017-10-01

    Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP-ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over-expressed. CCK8 assay and colony formation assay indicated that CD38 promoted cervical cancer cell proliferation. Nude mouse tumorigenicity assay showed that CD38 significantly promotes tumor growth in vivo. CD38 also induced S phase accumulation in cell cycle analysis and suppressed cell apoptosis in cervical cancer cells. Meanwhile, flow cytometry analysis of mitochondria functions suggested that CD38 decreased intracellular Ca2+ levels in cervical cancer cells and CD38 was involved in down-regulation of ROS levels and prevented mitochondrial apoptosis in cervical cancer cells. The percentage of cells with loss of mitochondrial membrane potential (Δψm) in CD38-overexpressed cervical cancer cells was less than control groups. Furthermore, we found an up-regulation of MDM2, cyclinA1, CDK4, cyclinD1, NF-kB P65, c-rel, and a downregulation of P53, P21, and P38 by Western blot analysis. These results indicated that CD38 enhanced the proliferation and inhibited the apoptosis of cervical cancer cells by affecting the mitochondria functions. © 2017 Wiley Periodicals, Inc.

  19. Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip.

    Science.gov (United States)

    Sheng, Weian; Ogunwobi, Olorunseun O; Chen, Tao; Zhang, Jinling; George, Thomas J; Liu, Chen; Fan, Z Hugh

    2014-01-07

    Circulating tumor cells (CTCs) from peripheral blood hold important information for cancer diagnosis and disease monitoring. Analysis of this "liquid biopsy" holds the promise to usher in a new era of personalized therapeutic treatments and real-time monitoring for cancer patients. But the extreme rarity of CTCs in blood makes their isolation and characterization technologically challenging. This paper reports the development of a geometrically enhanced mixing (GEM) chip for high-efficiency and high-purity tumor cell capture. We also successfully demonstrated the release and culture of the captured tumor cells, as well as the isolation of CTCs from cancer patients. The high-performance microchip is based on geometrically optimized micromixer structures, which enhance the transverse flow and flow folding, maximizing the interaction between CTCs and antibody-coated surfaces. With the optimized channel geometry and flow rate, the capture efficiency reached >90% with a purity of >84% when capturing spiked tumor cells in buffer. The system was further validated by isolating a wide range of spiked tumor cells (50-50,000) in 1 mL of lysed blood and whole blood. With the combination of trypsinization and high flow rate washing, captured tumor cells were efficiently released. The released cells were viable and able to proliferate, and showed no difference compared with intact cells that were not subjected to the capture and release process. Furthermore, we applied the device for detecting CTCs from metastatic pancreatic cancer patients' blood; and CTCs were found from 17 out of 18 samples (>94%). We also tested the potential utility of the device in monitoring the response to anti-cancer drug treatment in pancreatic cancer patients, and the CTC numbers correlated with the clinical computed tomograms (CT scans) of tumors. The presented technology shows great promise for accurate CTC enumeration, biological studies of CTCs and cancer metastasis, as well as for cancer

  20. Cancer

    Science.gov (United States)

    ... Prostate cancer Lung cancer Colorectal cancer In US women, other than skin cancer the three most common cancers are: Breast cancer Lung cancer Colorectal cancer Some cancers are more common in certain parts of the world. For example, in Japan, there are many cases of stomach cancer . But ...

  1. Enhanced recovery after surgery in patients with colorectal cancer in Slovenia 2012

    Directory of Open Access Journals (Sweden)

    Miran Rems

    2014-03-01

    Full Text Available Background: Enhanced recovery after surgery (ERAS protocol is a model of perioperative patient management where process optimisation helps to shorten patients’ recovery time. Application of ERAS protocol in colorectal cancer surgery is a demanding process, challenging our professional and organisational measures.Methods: A questionnaire regarding ERAS was sent to all thirteen heads of departments performing surgical treatment of colorectal cancer patients in Slovenia. The questionnaire was analyzed using Microsoft Excel Program.Results: There is a strong agreement among all the respondents that ERAS is a relevant clinical concept. Only seven clinical departments have developed a clinical pathway consistent with ERAS protocol, but principles of ERAS are followed at least partly or completely in twelve clinical departments. The most obvious is lack of activity before surgery, and particularly the educational interview with a dietitian and a physiotherapist. Less than half of the patients drink the glucose drink before surgery, and the same applies to the prophylaxis of nausea and vomiting. More than two thirds of patients are still subjected to mechanical bowel preparation before surgery. More than half of them have a central line and are admitted to intensive care unit (ICU after surgery. More than 75 % of the patients do not sit up in bed or stand up on day 1 after surgery. More than half of them still have the nasogastric tube. Laparoscopy is used more frequently for colon and less for rectal surgery.Conclusions: Comparing this analysis with the one done in 2004, we can conclude that there is an important shortening of average planned hospital stay. Nevertheless, still the majority of patients are not managed according to the ERAS protocol. The implementation of ERAS concept in Slovenia is rather poor, contrary to what we would expect considering evidence-based positive effects, but nevertheless comparable to other’s experience.

  2. Establishment of Orthotopic Lung Cancer Model Expressing Enhanced Green Fluorescent Protein

    Directory of Open Access Journals (Sweden)

    Shuzhen WEI

    2010-07-01

    Full Text Available Background and objective In vivo molecular imaging with mouse model could continuously and in real-time monitor the changes of the tumor. The aim of this study is to establish stable enhanced green fluorescent protein (EGFP expressing NCI-H460 cell lines and relevant mouse model via orthotopic transplantation, and to study the characteristic of this model and the quantitative detection method of the primary tumor and metastatic lesions. Methods Human lung cancer NCI-H460 cells were transfected with retroviral vector containing the EGFP. Stable high-level expression of EGFP was maintained in the subcutaneously-growing tumors. Fragments of the subcutaneously growing tumor, which were comprised of EGFP-expressing cells, were implanted by surgical orthotopic implantation (SOI in the lung of nude mice. The dynamic growth of orthotopic tumor was observed using in vivo fluorescence imaging. The correlation of fluorescence area and tumor volume was tested. Results After the model established, green fluorescent can be observed through the flap in day 7. Tumor formation rate was 100%. Mean survival time of tumor-bearing nude mice was 34.2 days. The metastasis sites were the contralateral lung, mediastinal and hilar lymph nodes, pleura and diaphragm; metastasis rates were 87.5%, 75%, 25% and 12.5%, respectively. Tumor volume and fluorescence area was correlated (r=0.873, P=0.001. Conclusion The nude mouse model bearing orthotopic human lung cancer expressing EGFP has been successfully established. The model might be used for further molecular studies on tumor metastasis, angiogenesis and also be applied to anti-tumor drug screening in preclinical stage.

  3. Resveratrol enhances palmitate-induced ER stress and apoptosis in cancer cells.

    Directory of Open Access Journals (Sweden)

    Cristina Rojas

    Full Text Available Palmitate, a saturated fatty acid (FA, is known to induce toxicity and cell death in various types of cells. Resveratrol (RSV is able to prevent pathogenesis and/or decelerate the progression of a variety of diseases. Several in vitro and in vivo studies have also shown a protective effect of RSV on fat accumulation induced by FAs. Additionally, endoplasmic reticulum (ER stress has recently been linked to cellular adipogenic responses. To address the hypothesis that the RSV effect on excessive fat accumulation promoted by elevated saturated FAs could be partially mediated by a reduction of ER stress, we studied the RSV action on experimentally induced ER stress using palmitate in several cancer cell lines.We show that, unexpectedly, RSV promotes an amplification of palmitate toxicity and cell death and that this mechanism is likely due to a perturbation of palmitate accumulation in the triglyceride form and to a less important membrane fluidity variation. Additionally, RSV decreases radical oxygen species (ROS generation in palmitate-treated cells but leads to enhanced X-box binding protein-1 (XBP1 splicing and C/EBP homologous protein (CHOP expression. These molecular effects are induced simultaneously to caspase-3 cleavage, suggesting that RSV promotes palmitate lipoapoptosis primarily through an ER stress-dependent mechanism. Moreover, the lipotoxicity reversion induced by eicosapentaenoic acid (EPA or by a liver X receptor (LXR agonist reinforces the hypothesis that RSV-mediated inhibition of palmitate channeling into triglyceride pools could be a key factor in the aggravation of palmitate-induced cytotoxicity.Our results suggest that RSV exerts its cytotoxic role in cancer cells exposed to a saturated FA context primarily by triglyceride accumulation inhibition, probably leading to an intracellular palmitate accumulation that triggers a lipid-mediated cell death. Additionally, this cell death is promoted by ER stress through a CHOP

  4. Mitochondrial division inhibitor 1 (mdivi-1) enhances death receptor-mediated apoptosis in human ovarian cancer cells

    Science.gov (United States)

    Wang, Jingnan; Hansen, Karyn; Edwards, Robert; Van Houten, Bennett; Qian, Wei

    2014-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) based strategy is a promising targeted therapeutic approach for the treatment of a variety of cancers including ovarian cancer. However, the inherent or acquired resistance of tumor cells to TRAIL limits the potential application of TRAIL-mediated therapy. In this study, we identified that mitochondrial division inhibitor-1 (mdivi-1) is able to enhance the sensitivity of human ovarian cancer cells to death receptor ligands including TRAIL, FAS ligands, and TNF-α. Importantly, the combination of TRAIL and mdivi-1 has no apparent cytotoxic effect on non-transformed human cells, indicating a significant therapeutic window. We identified that caspase-8 and not the modulation of TRAIL receptors is required for the combination effect of TRAIL and mdivi-1. We further demonstrated that the enhanced efficacy of combination of mdivi-1 and death ligands is not dependent on the originally reported target of mdivi-1, Drp1, and is also not dependent on the two important pro-apoptotic Bcl-2 family proteins Bax and Bak. Thus, our study presents a novel strategy in enhancing the apoptotic effect of death receptor ligands and provides a new effective TRAIL-based combination approach for treating human ovarian cancer. PMID:25446129

  5. Berberine promotes antiproliferative effects of epirubicin in T24 bladder cancer cells by enhancing apoptosis and cell cycle arrest
.

    Science.gov (United States)

    Zhuo, Yumin; Chen, Qibiao; Chen, Bo; Zhan, Xiongyu; Qin, Xiaoping; Huang, Jun; Lv, Xiuxiu

    2017-01-01

    The present study was aimed to observe the effect of berberine (Ber) on epirubicin (EPI)-induced growth inhibition, apoptosis, and cell cycle arrest in T24 bladder cancer cells. The cancer cells were exposed to EPI, with or without different concentrations of Ber. The viability of the cancer cells was measured by cell counting Kit-8, the apoptosis was determined by Hoechst 33258 staining and the expression of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, and P53 proteins were detected by Western blot assay. In addition, cell cycle arrest and the production of reactive oxygen species (ROS) were also measured. We found that Ber enhanced the inhibitory effect of EPI on the viability of T24 cells and promoted EPI-induced cell cycle arrest at G0/G1 and apoptosis in T24 cells. EPI increased the expression of cleaved caspase-3, cleaved caspase-9, Bax, P53, and P21 proteins, all of which were enhanced by treatment with Ber. In contrast, Ber exposure further decreased the expression of Bcl-2 in EPI-treated T24 cells. Furthermore, we also demonstrated that Ber significantly increased ROS production in EPI-treated T24 cells. These data indicate that Ber enhances the antiproliferative effects of EPI in bladder cancer cells by promoting apoptosis and cell cycle arrest.
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  6. An increase in reactive oxygen species by deregulation of ARNT enhances chemotherapeutic drug-induced cancer cell death.

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    Jiunn-Min Shieh

    Full Text Available BACKGROUND: Unique characteristics of tumor microenvironments can be used as targets of cancer therapy. The aryl hydrocarbon receptor nuclear translocator (ARNT is an important mediator of tumor progression. However, the functional role of ARNT in chemotherapeutic drug-treated cancer remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we found that knockdown of ARNT in cancer cells reduced the proliferation rate and the transformation ability of those cells. Moreover, cisplatin-induced cell apoptosis was enhanced in ARNT-deficient cells. Expression of ARNT also decreased in the presence of cisplatin through proteasomal degradation pathway. However, ARNT level was maintained in cisplatin-treated drug-resistant cells, which prevented cell from apoptosis. Interestingly, reactive oxygen species (ROS dramatically increased when ARNT was knocked down in cancer cells, enhancing cisplatin-induced apoptosis. ROS promoted cell death was inhibited in cells treated with the ROS scavenger, N-acetyl-cysteine (NAC. CONCLUSIONS/SIGNIFICANCE: These results suggested that the anticancer activity of cisplatin is attributable to its induction of the production of ROS by ARNT degradation. Targeting ARNT could be a potential strategy to eliminate drug resistance in cancer cells.

  7. Enhancing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through pulse zoledronate stimulation.

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    Nada, Mohanad H; Wang, Hong; Workalemahu, Grefachew; Tanaka, Yoshimasa; Morita, Craig T

    2017-01-01

    Human γδ T cells expressing Vγ2Vδ2 T cell receptors monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Adoptive immunotherapy with Vγ2Vδ2 T cells has been used to treat cancer patients with partial and complete remissions. Most clinical trials and preclinical studies have used continuous zoledronate exposure to expand Vγ2Vδ2 cells where zoledronate is slowly diluted over the course of the culture. Zoledronate inhibits farnesyl diphosphate synthase (FDPS) in monocytes causing isopentenyl pyrophosphate to accumulate that then stimulates Vγ2Vδ2 cells. Because zoledronate inhibition of FDPS is also toxic for T cells, we hypothesized that a short period of exposure would reduce T cell toxicity but still be sufficient for monocytes uptake. Additionally, IL-15 increases the anti-tumor activity of murine αβ T cells in mice but its effect on the in vivo anti-tumor activity of human Vγ2Vδ2 cells has not been assessed. Human Vγ2Vδ2 T cells were expanded by pulse or continuous zoledronate stimulation with IL-2 or IL-15. Expanded Vγ2Vδ2 cells were tested for their expression of effector molecules and killing of tumor cells as well as their in vivo control of human prostate cancer tumors in immunodeficient NSG mice. Pulse zoledronate stimulation with either IL-2 or IL-15 resulted in more uniform expansion of Vγ2Vδ2 cells with higher purity and cell numbers as compared with continuous exposure. The Vγ2Vδ2 cells had higher levels of CD107a and perforin and increased tumor cytotoxicity. Adoptive immunotherapy with Vγ2Vδ2 cells derived by pulse stimulation controlled human PC-3 prostate cancer tumors in NSG mice significantly better than those derived by continuous stimulation, halting tumor growth. Although pulse zoledronate stimulation with IL-15 preserved early memory subsets, adoptive immunotherapy with IL-15-derived Vγ2Vδ2 cells equally inhibited PC-3 tumor growth as those

  8. Shikonin enhances efficacy of a gene-based cancer vaccine via induction of RANTES

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    Chen Hui-Ming

    2012-04-01

    effectively enhance anti-tumor potency of a gene-based cancer vaccine via the induction of RANTES expression at the skin immunization site.

  9. Smac/DIABLO enhances the therapeutic potential of chemotherapeutic drugs and irradiation, and sensitizes TRAIL-resistant breast cancer cells

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    Srivastava Rakesh K

    2008-06-01

    Full Text Available Abstract Background Drug resistance is a major concern in cancer therapy. Here, we investigate the clinical potential of the second mitochondria-derived activator of caspase (Smac/DIABLO in enhancing the apoptosis-inducing potential of commonly used anticancer drugs (paclitaxel, doxorubicin, etoposide, tamoxifen, irradiation and TRAIL in breast carcinoma. Methods Breast cancer cells were overexpressed with Smac/DIABLO gene (full-length or Δ55 Smac/DIABLO or treated with Smac/DIABLO peptide to enhance the apoptosis-inducing potential of chemotherapeutic drugs and irradiation, and sensitize TRAIL-resistant cells. Cell viability and apoptosis were measured by XTT assay and DAPI staining, respectively. Protein-protein interaction was determined by immunoprecipitation followed by the Western blot analysis. Results Overexpression of Smac/DIABLO gene (full-length or Δ55 Smac/DIABLO or treatment with Smac/DIABLO peptide enhances apoptosis induced by paclitaxel, doxorubicin, etoposide, tamoxifen, and irradiation in breast cancer cells. Overexpression of Smac/DIABLO resulted in an increased interaction of Smac/DIABLO with IAPs, which correlated with an increase in caspase-3 activity and apoptosis. Furthermore, Smac/DIABLO sensitized TRAIL-resistant breast cancer cell lines to undergo apoptosis through caspase-3 activation. These data suggest that apoptotic events down-stream of mitochondria were intact in TRAIL-resistant cells since ectopic expression of Smac/DIABLO or pretreatment of cells with Smac/DIABLO peptide completely restored TRAIL sensitivity. Conclusion The ability of Smac/DIABLO agonists to enhance the apoptosis-inducing potential of chemotherapeutic drugs and irradiation, and sensitize TRAIL-resistant tumor cells suggests that Smac/DIABLO may induce fundamental alterations in cell signaling pathways. Thus, Smac/DIABLO agonists can be used as promising new candidates for cancer treatment by potentiating cytotoxic therapies.

  10. Dynamic contrast-enhanced magnetic resonance imaging for prediction of response to neoadjuvant chemotherapy in breast cancer

    Science.gov (United States)

    Fu, Juzhong; Fan, Ming; Zheng, Bin; Shao, Guoliang; Zhang, Juan; Li, Lihua

    2016-03-01

    Breast cancer is the second leading cause of women death in the United States. Currently, Neoadjuvant Chemotherapy (NAC) has become standard treatment paradigms for breast cancer patients. Therefore, it is important to find a reliable non-invasive assessment and prediction method which can evaluate and predict the response of NAC on breast cancer. The Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) approach can reflect dynamic distribution of contrast agent in tumor vessels, providing important basis for clinical diagnosis. In this study, the efficacy of DCE-MRI on evaluation and prediction of response to NAC in breast cancer was investigated. To this end, fifty-seven cases of malignant breast cancers with MRI examination both before and after two cycle of NAC were analyzed. After pre-processing approach for segmenting breast lesions and background regions, 126-dimensional imaging features were extracted from DCE-MRI. Statistical analyses were then performed to evaluate the associations between the extracted DCE-MRI features and the response to NAC. Specifically, pairwise t test was used to calculate differences of imaging features between MRI examinations before-and-after NAC. Moreover, the associations of these image features with response to NAC were assessed using logistic regression. Significant association are found between response to NAC and the features of lesion morphology and background parenchymal enhancement, especially the feature of background enhancement in normal side of breast (P=0.011). Our study indicate that DCE-MRI features can provide candidate imaging markers to predict response of NAC in breast cancer.

  11. Enhancement of the cytocidal effects of hypotonic solution using a chloride channel blocker in pancreatic cancer cells.

    Science.gov (United States)

    Nako, Yoshito; Shiozaki, Atsushi; Ichikawa, Daisuke; Komatsu, Shuhei; Konishi, Hirotaka; Iitaka, Daisuke; Ishii, Hiromichi; Ikoma, Hisashi; Kubota, Takeshi; Fujiwara, Hitoshi; Okamoto, Kazuma; Ochiai, Toshiya; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

    2012-01-01

    Tumor cells exfoliated during surgery for pancreatic cancer can cause peritoneal recurrence. Peritoneal lavage with distilled water has been performed during surgery, but there have been no systematic studies for its efficacy and no experimental data demonstrating the cytocidal effects of distilled water on pancreatic cancer cells. This study investigated the cytocidal effects of hypotonic shock and enhancement using chloride channel blocker in pancreatic cancer cells. Three human pancreatic cancer cell lines, KP4-1, PK-1, and PK45-H, were exposed to distilled water, and the resultant morphological changes were observed under a differential interference contrast microscope connected to a high-speed video camera. Analysis of cell volume changes was performed using a high-resolution flow cytometer. To investigate the cytocidal effects of water, re-incubation of cells was performed after exposure to hypotonic solution. Additionally, the effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), a Cl(-) channel blocker, on cells during exposure to hypotonic solution were analyzed. Video recordings demonstrated that hypotonic shock induced cell swelling followed by cell rupture. Measurement of cell volume changes indicated that severe hypotonicity increased broken fragments of cancer cells within 5 min. Re-incubation experiments demonstrated the cytocidal effects of hypotonic shock. In all cell lines, treatment with NPPB increased cell volume by inhibiting regulatory volume decreases, which are observed during hypotonic shock, and enhanced the cytocidal effects of hypotonic solution. These findings support the efficacy of peritoneal lavage with distilled water for pancreatic cancer and suggest that regulation of Cl(-) transport enhances the cytocidal effects of hypotonic shock. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  12. [Establish predictive model of colorectal cancer by using surface enhanced laser desorption/ionization-time of flight-mass spectrometry].

    Science.gov (United States)

    Lai, Yan-Han; Xu, Jian-Min; Yu, Xin-Zhe; Zhong, Yun-Shi; Wei, Ye; Ren, Li; Zhu, De-Xiang; Liu, Yin-Kun; Niu, Wei-Xin; Qin, Xin-Yu

    2008-07-01

    To establish serum proteome fingerprinting predictive models and search for proteins associated with colorectal cancer. Thirty-six randomly selected colorectal cancer patients and 36 cases with hernia or gall bladder diseases scheduled for elective operation were enrolled as cancer group and control group respectively. Peripheral venous blood samples were collected before the operations. Special serum protein or peptide fingerprint was investigated by using surface enhanced laser desorption/ ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after blood sample had been treated with weak cation exchange protein chip (CM10) for each case. The obtained data were analyzed by Biomarker Wizard software to screen serum proteome tumor markers and set up diagnosis predictive model for colorectal cancer. Blind validation of the model with 44 healthy controls and 88 colorectal cancer patients were carried out by using Biomarker Patterns Software. In comparing colorectal cancer group with control group, 5 specific protein peaks (P < 0.05) were found. The predictive model had a sensitivity of 100% and a specificity of 97.2%. A sensitivity of 71.6% and a specificity of 72.7% was got with the blind validation. The specific protein peaks with a mass-to-charge ratio (m/z) of 8908 and 13,707 showed in all the results and it showed their strong relationship with colorectal cancer. The predictive models built by the differences of serum proteome fingerprint could be a very useful diagnostic tool in colorectal cancer. Proteins with m/z of 8908 and 13,707 would possibly be the tumor markers of colorectal cancer.

  13. The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand.

    Science.gov (United States)

    Yang, Shan-Zhong; Xu, Fei; Zhou, Tong; Zhao, Xinyang; McDonald, Jay M; Chen, Yabing

    2017-06-23

    Pancreatic cancer is a malignant neoplasm with a high mortality rate. Therapeutic agents that activate TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis have shown promising efficacy, but many pancreatic cancers are resistant to TRAIL therapy. Epigenetic regulation plays important roles in tumor pathogenesis and resistance, and a recent study indicated that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is overexpressed in pancreatic cancer. However, the role of HOTAIR in pancreatic cancer resistance to anticancer agents is unknown. The present study determined the role of HOTAIR in pancreatic cancer TRAIL resistance and investigated the underlying molecular mechanisms. We observed that TRAIL-resistant pancreatic cancer cells had higher levels of HOTAIR expression, whereas TRAIL-sensitive pancreatic cancer cells had lower HOTAIR levels. Overexpressing HOTAIR in TRAIL-sensitive cells attenuated TRAIL-induced apoptosis, and shRNA-mediated HOTAIR knockdown in TRAIL-resistant PANC-1 cells sensitized them to TRAIL-induced apoptosis. These results support a causative effect of HOTAIR on TRAIL sensitivity. Mechanistically, we found that increased HOTAIR expression inhibited the expression of the TRAIL receptor death receptor 5 (DR5), whereas HOTAIR knockdown increased DR5 expression. We further demonstrated that HOTAIR regulates DR5 expression via the epigenetic regulator enhancer of zeste homolog 2 (EZH2) and that EZH2 controls histone H3 lysine 27 trimethylation on the DR5 gene. Taken together, these results demonstrate that high HOTAIR levels increase the resistance of pancreatic cancer cells to TRAIL-induced apoptosis via epigenetic regulation of DR5 expression. Our study therefore supports the notion that targeting HOTAIR function may represent a strategy to overcome TRAIL resistance in pancreatic cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. T-peptide Enhances the Killing Effects of Cisplatinum on Lung Cancer

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    Hongyi ZHANG

    2017-02-01

    Full Text Available Background and objective T peptide is extensively used in anti-tumor treatment. The aims of this study were to investigate whether T peptide enhances cisplatinum efficiency while reducing its side effects and to identify its effective mechanisms. Methods (1 Human macrophage U937 cells were treated with T peptide and/or cisplatinum. The levels of tumor necrosis factor-α (TNF-α and interferon-γ (IFN-γ of each group were detected by enzyme-linked immunosorbent assay (ELISA; (2 Xenograft mouse models of human lung cancer were treated with T peptide and/or cisplatinum once every five days for three times. Tumor volumes were measured during treatment; (3 The percentages of macrophages in the peripheral blood of the xenograft mouse models were measured by FACS. Results (1 Compared with other groups, the level of TNF-α was significantly higher in the human macrophage U937 cells that were treated with T peptide combined with cisplatinum. The levels of IFN-γ were significantly higher in human macrophage U937 cells that were treated with T peptide alone or T peptide combined with cisplatinum; (2 In the xenograft mouse models, T peptide combined with cisplatinum treatment significantly inhibited tumor growth without weight loss compared with the other groups; (3 The percentages of macrophages in the peripheral blood were significantly higher in the xenograft mouse models that were treated with T peptide combined with cisplatinum compared with in the other groups. Conclusion T peptide promotes macrophage proliferation and increases tumor cell killing factors (TNF-α, IFN-γ in vitro. Moreover, T peptide enhances the efficacy of cisplatin and reduces its toxicity in vivo.

  15. Celecoxib Enhances the Radiosensitizing Effect of 7-Hydroxystaurosporine (UCN-01) in Human Lung Cancer Cell Lines

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    Kim, Young-Mee; Jeong, In-Hye [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Pyo, Hongryull, E-mail: Quasar93@yahoo.co.kr [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-07-01

    Purpose: 7-Hydroxystaurosporine (UCN-01), a Chk1-specific inhibitor, showed promising in vitro and in vivo chemo- or radiosensitizing activity. However, there have been concerns about its limited therapeutic efficacy and risk of side effects. A method of enhancing the treatment efficacy of UCN-01 while not increasing its side effects on normal tissue may therefore be required to apply this drug in clinical settings. Celecoxib is a cyclooxygenase-2 (COX-2)-specific inhibitor that downregulates ataxia telangiectasia and rad3-related (ATR) protein, an upstream kinase of Chk1. In this study, we investigated whether the addition of celecoxib can potentiate the radiosensitizing effect of UCN-01. Methods and Materials: The cooperative radiosensitizing effects and the underlying molecular mechanisms of UCN-01 plus celecoxib were determined by clonogenic assay, tumor growth delay assay, flow cytometry, and Western blotting. Synergism of the three agents combined (UCN-01 plus celecoxib plus radiation) were evaluated using median drug effect analysis and drug-independent action model analysis. Results: The combination of UCN-01 and celecoxib could induce synergistic cytotoxicity and radiosensitizing effects in in vitro and in vivo systems. The combination of both drugs also cooperatively inhibited IR-induced G{sub 2}/M arrest, and increased the G{sub 2} to mitotic transition. Conclusions: Combined treatment with UCN-01 and celecoxib can exert synergistically enhanced radiosensitizing effects via cooperative inhibition of the ionizing radiation-activated G{sub 2} checkpoint. We propose that this combination strategy may be useful in clinical applications of UCN-01 for radiotherapy of cancer patients.

  16. [Evodiamine enhances the radiosensitivity of esophageal squamous cell cancer Eca-109 cells].

    Science.gov (United States)

    Feng, Hui; Guo, Baorui; Kong, Xiangmei; Wu, Biao

    2016-07-01

    Objective To investigate the effect of evodiamine on the radiosensitivity of esophageal squamous cell cancer Eca-109 cells. Methods Eca-109 cells were treated with various concentrations of evodiamine [(10, 20, 40, 60, 80, 100, 120) μg/mL], and then cell proliferation was examined by MTT assay. After the optimal evodiamine concentration was determined, the cells were divided into radiation group (0, 2, 4, 6, 8 Gy X-ray radiation) and radiation combined with evodiamine group (80 μg/mL evodiamine and 0, 2, 4, 6, 8 Gy X-ray radiation) .The radiosensitivity of Eca-109 cells was detected using colony formation assay. Flow cytometry was used to determine cell cycle of Eca-109 cells. The protein expressions of Ku70, Ku80, DNA-PKcs and Rad51 were examined by Western blotting. Results MTT assay showed that evodiamine decreased the proliferation of Eca-109 cells in a concentration-dependent manner. The inhibition reached the maximal level at 80 μg/mL. Compared with radiotherapy alone, the combination of 80 μg/mL evodiamine and radiotherapy improved survival curve and decreased the values of D0 and Dq. Sensitizer enhancement ratio was 1.86±0.06. Furthermore, cell cycle analysis revealed that evodiamine suppressed radiotherapy-induced the G2/M arrest. Additionally, evodiamine treatment also significantly inhibited radiotherapy-induced increase in Ku70, Ku80, DNA-PKcs and Rad51 expressions. Conclusion Evodiamine enhances radiosensitivity of Eca-109 cells during radiotherapy. The effect may be associated with the inhibition of G2/M arrest and the attenuation of Ku70, Ku80, DNA-PKcs and Rad51 expressions.

  17. Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis.

    Science.gov (United States)

    Wu, Zhiyong; Yang, Xiaowei; Chen, Li; Wang, Zhikuan; Shi, Yan; Mao, Hui; Dai, Guanghai; Yu, Xiaoling

    2017-05-01

    The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.

  18. Molecular cloning, sequence characterization and expression analysis of a CD63 homologue from the coleopteran beetle, Tenebrio molitor.

    Science.gov (United States)

    Patnaik, Bharat Bhusan; Kang, Seong Min; Seo, Gi Won; Lee, Hyo Jeong; Patnaik, Hongray Howrelia; Jo, Yong Hun; Tindwa, Hamisi; Lee, Yong Seok; Lee, Bok Luel; Kim, Nam Jung; Bang, In Seok; Han, Yeon Soo

    2013-10-15

    CD63, a member of the tetraspanin membrane protein family, plays a pivotal role in cell growth, motility, signal transduction, host-pathogen interactions and cancer. In this work, the cDNA encoding CD63 homologue (TmCD63) was cloned from larvae of a coleopteran beetle, Tenebrio molitor. The cDNA is comprised of an open reading frame of 705 bp, encoding putative protein of 235 amino acid residues. In silico analysis shows that the protein has four putative transmembrane domains and one large extracellular loop. The characteristic "Cys-Cys-Gly" motif and "Cys188" residues are highly conserved in the large extracellular loop. Phylogenetic analysis of TmCD63 revealed that they belong to the insect cluster with 50%-56% identity. Analysis of spatial expression patterns demonstrated that TmCD63 mRNA is mainly expressed in gut and Malphigian tubules of larvae and the testis of the adult. Developmental expression patterns of CD63 mRNA showed that TmCD63 transcripts are detected in late larval, pupal and adult stages. Interestingly, TmCD63 transcripts are upregulated to the maximum level of 4.5 fold, in response to DAP-type peptidoglycan during the first 6 h, although other immune elicitors also caused significant increase to the transcript level at later time-points. These results suggest that CD63 might contribute to T. molitor immune response against various microbial pathogens.

  19. Molecular Cloning, Sequence Characterization and Expression Analysis of a CD63 Homologue from the Coleopteran Beetle, Tenebrio molitor

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    Yeon Soo Han

    2013-10-01

    Full Text Available CD63, a member of the tetraspanin membrane protein family, plays a pivotal role in cell growth, motility, signal transduction, host-pathogen interactions and cancer. In this work, the cDNA encoding CD63 homologue (TmCD63 was cloned from larvae of a coleopteran beetle, Tenebrio molitor. The cDNA is comprised of an open reading frame of 705 bp, encoding putative protein of 235 amino acid residues. In silico analysis shows that the protein has four putative transmembrane domains and one large extracellular loop. The characteristic “Cys-Cys-Gly” motif and “Cys188” residues are highly conserved in the large extracellular loop. Phylogenetic analysis of TmCD63 revealed that they belong to the insect cluster with 50%–56% identity. Analysis of spatial expression patterns demonstrated that TmCD63 mRNA is mainly expressed in gut and Malphigian tubules of larvae and the testis of the adult. Developmental expression patterns of CD63 mRNA showed that TmCD63 transcripts are detected in late larval, pupal and adult stages. Interestingly, TmCD63 transcripts are upregulated to the maximum level of 4.5 fold, in response to DAP-type peptidoglycan during the first 6 h, although other immune elicitors also caused significant increase to the transcript level at later time-points. These results suggest that CD63 might contribute to T. molitor immune response against various microbial pathogens.

  20. Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231 and MCF-7 Breast Cancer Cells

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    Zhongyuan Zhang

    2013-01-01

    Full Text Available Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.

  1. A New Green Titania with Enhanced NIR Absorption for Mitochondria-Targeted Cancer Therapy

    Science.gov (United States)

    Mou, Juan; Lin, Tianquan; Huang, Fuqiang; Shi, Jianlin; Chen, Hangrong

    2017-01-01

    A new kind of green titania (G-TiO2-x) with obvious green color was facilely synthesized from black titania (B-TiO2-x) through subsequently strong ultrasonication. Comparatively, this stable G-TiO2-x shows much enhanced near infrared (NIR) absorption, especially around 920 nm, which can be ascribed to the obvious change of TiO2-x lattice order owing to the effect of ultrasonication. This feature enables G-TiO2-x to be stimulated with 980 nm laser in the combined photodynamic therapy (PDT) and photothermal therapy (PTT), which is greatly beneficial for improving tissue penetration depth. Furthermore, since mitochondria are preferred subcellular organelles for PDT/PTT, G-TiO2-x was further designed to conjugate with triphenylphosphonium (TPP) ligand for mitochondria-targeted PDT/PTT to obtain precise cancer treatment. Attributing to the high mitochondria-targeting efficiency and simultaneously synergistic PDT/PTT, high phototherapeutic efficacy and safety with a much lower laser power density (980 nm, 0.72 W cm-2) and low materials dosage were achieved both in vitro and in vivo. In addition, negligible toxicity was found, indicating high biocompatibility. This novel G-TiO2-x could provide new strategies for future precise minimal/non-invasive tumor treatment. PMID:28529636

  2. Cytolethal Distending Toxin Enhances Radiosensitivity in Prostate Cancer Cells by Regulating Autophagy

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    Hwai-Jeng Lin

    2017-06-01

    Full Text Available Cytolethal distending toxin (CDT produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa. However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR. In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1 expression and the inhibition of acidic vesicular organelle (AVO formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.

  3. Head and Neck Cancer Tumor Segmentation Using Support Vector Machine in Dynamic Contrast-Enhanced MRI

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    Wei Deng

    2017-01-01

    Full Text Available Objective. We aimed to propose an automatic method based on Support Vector Machine (SVM and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI to segment the tumor lesions of head and neck cancer (HNC. Materials and Methods. 120 DCE-MRI samples were collected. Five curve features and two principal components of the normalized time-intensity curve (TIC in 80 samples were calculated as the dataset in training three SVM classifiers. The other 40 samples were used as the testing dataset. The area overlap measure (AOM and the corresponding ratio (CR and percent match (PM were calculated to evaluate the segmentation performance. The training and testing procedure was repeated for 10 times, and the average performance was calculated and compared with similar studies. Results. Our method has achieved higher accuracy compared to the previous results in literature in HNC segmentation. The average AOM with the testing dataset was 0.76 ± 0.08, and the mean CR and PM were 79 ± 9% and 86 ± 8%, respectively. Conclusion. With improved segmentation performance, our proposed method is of potential in clinical practice for HNC.

  4. Simultaneous loss of the DLC1 and PTEN tumor suppressors enhances breast cancer cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Heering, Johanna; Erlmann, Patrik [University of Stuttgart, Institute of Cell Biology and Immunology, Allmandring 31, 70569 Stuttgart (Germany); Olayioye, Monilola A., E-mail: monilola.olayioye@izi.uni-stuttgart.de [University of Stuttgart, Institute of Cell Biology and Immunology, Allmandring 31, 70569 Stuttgart (Germany)

    2009-09-10

    The phosphatase and tensin homolog (PTEN) gene is a tumor suppressor frequently deleted or mutated in sporadic tumors of the breast, prostate, endometrium and brain. The protein acts as a dual specificity phosphatase for lipids and proteins. PTEN loss confers a growth advantage to cells, protects from apoptosis and favors cell migration. The deleted in liver cancer 1 (DLC1) gene has emerged as a novel tumor suppressor downregulated in a variety of tumor types including those of the breast. DLC1 contains a Rho GTPase activating domain that is involved in the inhibition of cell proliferation, migration and invasion. To investigate how simultaneous loss of PTEN and DLC1 contributes to cell transformation, we downregulated both proteins by RNA interference in the non-invasive MCF7 breast carcinoma cell line. Joint depletion of PTEN and DLC1 resulted in enhanced cell migration in wounding and chemotactic transwell assays. Interestingly, both proteins were found to colocalize at the plasma membrane and interacted physically in biochemical pulldowns and coimmunoprecipitations. We therefore postulate that the concerted local inactivation of signaling pathways downstream of PTEN and DLC1, respectively, is required for the tight control of cell migration.

  5. [Era of enhanced recovery after surgery and robotic gastric cancer surgery].

    Science.gov (United States)

    Zhou, Yanbing

    2017-05-25

    Enhanced recovery after surgery (ERAS) has been rapidly developing by combining several techniques with evidence-based adjustments, including preoperative education, preoperative carbohydrate loading, epidural or regional anesthesia, early initiation of enteral nutrition, ambulation and multi-modal pain management. The core part of ERAS is to reduce and reverse surgical stress and therefore greatly improve clinical outcome. Under the guidance of ERAS, perioperative management of robotic gastric cancer operation should follow the basic principles of ERAS and clinical pathway to maximize the advantages of the robotic surgery. ERAS protocol is safe and feasible for patients undergoing robotic radical gastrectomy and it can reduce surgical stress, shorten hospital stay, improve quality of life and does not increase complications, whose mechanism may be associated with the reduction of inflammation and insulin resistance, the decrease of resting energy exposure, and the protection of mitochondria function. It is worth emphasizing that it is very important to fully understand the changes of pathophysiology during perioperative period, to strictly implement the ERAS pathway based on optimized evidence-based medicine, to cooperate closely with the multidisciplinary team, to observe and manage the postoperative complications dynamically by systemic classification. The improvement of ERAS program on the outcome of patients should be summarized regularly and the new interventional strategies should be evaluated further according to the international standard.

  6. Sulforaphane Potentiates the Efficacy of 17-Allylamino 17-Demethoxygeldanamycin Against Pancreatic Cancer Through Enhanced Abrogation of Hsp90 Chaperone Function

    Science.gov (United States)

    Li, Yanyan; Zhang, Tao; Schwartz, Steven J.; Sun, Duxin

    2013-01-01

    Heat shock protein 90 (Hsp90), an essential molecular chaperone that regulates the stability of a wide range of oncogenic proteins, is a promising target for cancer therapeutics. We investigated the combination efficacy and potential mechanisms of sulforaphane, a dietary component from broccoli and broccoli sprouts, and 17-allylamino 17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, in pancreatic cancer. MTS assay demonstrated that sulforaphane sensitized pancreatic cancer cells to 17-AAG in vitro. Caspase-3 was activated to 6.4-fold in response to simultaneous treatment with sulforaphane and 17-AAG, whereas 17-AAG alone induced caspase-3 activity to 2-fold compared to control. ATP binding assay and coimmunoprecipitation revealed that sulforaphane disrupted Hsp90-p50Cdc37 interaction, whereas 17-AAG inhibited ATP binding to Hsp90. Concomitant use of sulforaphane and 17-AAG synergistically downregulated Hsp90 client proteins in Mia Paca-2 cells. Co-administration of sulforaphane and 17-AAG in pancreatic cancer xenograft model led to more than 70% inhibition of the tumor growth, whereas 17-AAG alone only suppressed the tumor growth by 50%. Our data suggest that sulforaphane potentiates the efficacy of 17-AAG against pancreatic cancer through enhanced abrogation of Hsp90 function. These findings provide a rationale for further evaluation of broccoli/broccoli sprout preparations combined with 17-AAG for better efficacy and lower dose-limiting toxicity in pancreatic cancer. PMID:21875325

  7. Co-treatment with BEZ235 Enhances Sensitivity of BRCA1-negative Breast Cancer Cells to Olaparib.

    Science.gov (United States)

    Yi, Yong Weon; Park, Jeong-Soo; Kwak, Sahng-June; Seong, Yeon-Sun

    2015-07-01

    The poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib has been reported as having preferential anti-proliferative effects on breast cancer 1 (BRCA1)-deficient breast and ovarian cancer cells and was recently approved by the US Food and Drug Administration (FDA) for advanced, BRCA1-mutated ovarian cancer. Herein, we show that BEZ235, a protein kinase inhibitor, enhanced the tumor cell-killing effect of olaparib in BRCA1-mutated breast cancer cells in vitro. BEZ235 reduced olaparib-induced phosphorylation of p53 binding protein 1 (53BP1) and 53BP1 foci formation, as well as phosphorylation of AKT (S473). Long-term colony-formation assay revealed more strong synergistic effects of this combination in SUM149PT and MDA-MB-468 breast cancer cell lines. BEZ235 treatment combined with olaparib may be a candidate for effective therapeutic treatment of BRCA1-mutated breast cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. 2-O-Methylmagnolol upregulates the long non-coding RNA, GAS5, and enhances apoptosis in skin cancer cells.

    Science.gov (United States)

    Wang, Tong-Hong; Chan, Chieh-Wen; Fang, Jia-You; Shih, Ya-Min; Liu, Yi-Wen; Wang, Tzu-Chien V; Chen, Chi-Yuan

    2017-03-02

    Magnolol, a hydroxylated biphenol compound isolated from the bark of Magnolia officinalis, has been shown to exhibit anti-proliferative effect in various cancer cells, including skin cancer cells. Methoxylation of magnolol appears to improve its anti-inflammatory activity, yet the effect of this modification on the agent's antitumor activity remains unknown. In this work, we report that 2-O-methylmagnolol (MM1) displays improved antitumor activity against skin cancer cells compared to magnolol both in vitro and in vivo. The increased antitumor activity of MM1 appears to correlate with its increased ability to induce apoptosis. DNA microarray and network pathway analyses suggest that MM1 affects certain key factors involved in regulating apoptosis and programmed cell death. Interestingly, the level of the long non-coding (lnc) RNA of growth arrest-specific 5 (GAS5) was increased in MM1-treated cells, and inhibition of lncRNA GAS5 inhibited MM1-induced apoptosis. Conversely, overexpression of lncRNA GAS5 inhibited cell proliferation and promoted cell apoptosis in skin cancer cells. The expression of lncRNA GAS5 in the skin cancer tissues was found to be lower than that in the adjacent normal tissues in a majority of patients. Taken together, our findings suggest that MM1 has improved antitumor activity in skin cancer cells, and that this is due, at least in part, to the upregulation of lncRNA GAS5 and the enhancement of apoptosis.

  9. Monascuspiloin enhances the radiation sensitivity of human prostate cancer cells by stimulating endoplasmic reticulum stress and inducing autophagy.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is a very common cancer among males. Traditional treatments for prostate cancer have limited efficacy; therefore, new therapeutic strategies and/or new adjuvant drugs must be explored. Red yeast rice (RYR is a traditional food spice made in Asia by fermenting white rice with Monascus purpureus Went yeast. Accumulating evidence indicates that RYR has antitumor activity. In this study, PC-3 cells (human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with monascuspiloin (MP, a yellow pigment isolated from Monascus pilosus M93-fermented rice and to determine the underlying mechanisms of these effects in vitro and in vivo. We found that IR combined with MP showed increased therapeutic efficacy when compared with either treatment alone in PC-3 cells. In addition, the combined treatment enhanced DNA damage and endoplasmic reticulum (ER stress. The combined treatment induced primarily autophagy in PC-3 cells, and the cell death that was induced by the combined treatment was chiefly the result of inhibition of the Akt/mTOR signaling pathways. In an in vivo study, the combination treatment showed greater anti-tumor growth effects. These novel findings suggest that the combined treatment could be a potential therapeutic strategy for prostate cancer.

  10. Expression of CCAAT/Enhancer Binding Protein Beta in Muscle Satellite Cells Inhibits Myogenesis in Cancer Cachexia.

    Directory of Open Access Journals (Sweden)

    François Marchildon

    Full Text Available Cancer cachexia is a paraneoplastic syndrome that causes profound weight loss and muscle mass atrophy and is estimated to be the cause of up to 30% of cancer deaths. Though the exact cause is unknown, patients with cancer cachexia have increased muscle protein catabolism. In healthy muscle, injury activates skeletal muscle stem cells, called satellite cells, to differentiate and promote regeneration. Here, we provide evidence that this mechanism is inhibited in cancer cachexia due to persistent expression of CCAAT/Enhancer Binding Protein beta (C/EBPβ in muscle myoblasts. C/EBPβ is a bzip transcription factor that is expressed in muscle satellite cells and is normally downregulated upon differentiation. However, in myoblasts exposed to a cachectic milieu, C/EBPβ expression remains elevated, despite activation to differentiate, resulting in the inhibition of myogenin expression and myogenesis. In vivo, cancer cachexia results in increased number of Pax7+ cells that also express C/EBPβ and the inhibition of normal repair mechanisms. Loss of C/EBPβ expression in primary myoblasts rescues differentiation under cachectic conditions without restoring myotube size, indicating that C/EBPβ is an important inhibitor of myogenesis in cancer cachexia.

  11. n-Butyl benzyl phthalate promotes breast cancer progression by inducing expression of lymphoid enhancer factor 1.

    Directory of Open Access Journals (Sweden)

    Tsung-Hua Hsieh

    Full Text Available Environmental hormones play important roles in regulating the expression of genes involved in cell proliferation, drug resistance, and breast cancer risk; however, their precise role in human breast cancer cells during cancer progression remains unclear. To elucidate the effect of the most widely used industrial phthalate, n-butyl benzyl phthalate (BBP, on cancer progression, we evaluated the results of BBP treatment using a whole human genome cDNA microarray and MetaCore software and selected candidate genes whose expression was changed by more than ten-fold by BBP compared with controls to analyze the signaling pathways in human breast cancer initiating cells (R2d. A total of 473 genes were upregulated, and 468 were downregulated. Most of these genes are involved in proliferation, epithelial-mesenchymal transition, and angiogenesis signaling. BBP induced the viability, invasion and migration, and tube formation in vitro, and Matrigel plug angiogenesis in vivo of R2d and MCF-7. Furthermore, the viability and invasion and migration of these cell lines following BBP treatment was reduced by transfection with a small interfering RNA targeting the mRNA for lymphoid enhancer-binding factor 1; notably, the altered expression of this gene consistently differentiated tumors expressing genes involved in proliferation, epithelial-mesenchymal transition, and angiogenesis. These findings contribute to our understanding of the molecular impact of the environmental hormone BBP and suggest possible strategies for preventing and treating human breast cancer.

  12. Tenascin-C enhances pancreatic cancer cell growth and motility and affects cell adhesion through activation of the integrin pathway.

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    Igor Paron

    Full Text Available BACKGROUND: Pancreatic cancer (PDAC is characterized by an abundant fibrous tissue rich in Tenascin-C (TNC, a large ECM glycoprotein mainly synthesized by pancreatic stellate cells (PSCs. In human pancreatic tissues, TNC expression increases in the progression from low-grade precursor lesions to invasive cancer. Aim of this study was the functional characterization of the effects of TNC on biologic relevant properties of pancreatic cancer cells. METHODS: Proliferation, migration and adhesion assays were performed on pancreatic cancer cell lines treated with TNC or grown on a TNC-rich matrix. Stable transfectants expressing the large TNC splice variant were generated to test the effects of endogenous TNC. TNC-dependent integrin signaling was investigated by immunoblotting, immunofluorescence and pharmacological inhibition. RESULTS: Endogenous TNC promoted pancreatic cancer cell growth and migration. A TNC-rich matrix also enhanced migration as well as the adhesion to the uncoated growth surface of poorly differentiated cell lines. In contrast, adhesion to fibronectin was significantly decreased in the presence of TNC. The effects of TNC on cell adhesion were paralleled by changes in the activation state of paxillin and Akt. CONCLUSION: TNC affects proliferation, migration and adhesion of poorly differentiated pancreatic cancer cell lines and might therefore play a role in PDAC spreading and metastasis in vivo.

  13. Activation of RARα induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity.

    Science.gov (United States)

    Brigger, D; Schläfli, A M; Garattini, E; Tschan, M P

    2015-08-27

    All-trans retinoic acid (ATRA), a pan-retinoic acid receptor (RAR) agonist, is, along with other retinoids, a promising therapeutic agent for the treatment of a variety of solid tumors. On the one hand, preclinical studies have shown promising anticancer effects of ATRA in breast cancer; on the other hand, resistances occurred. Autophagy is a cellular recycling process that allows the degradation of bulk cellular contents. Tumor cells may take advantage of autophagy to cope with stress caused by anticancer drugs. We therefore wondered if autophagy is activated by ATRA in mammary tumor cells and if modulation of autophagy might be a potential novel treatment strategy. Indeed, ATRA induces autophagic flux in ATRA-sensitive but not in ATRA-resistant human breast cancer cells. Moreover, using different RAR agonists as well as RARα-knockdown breast cancer cells, we demonstrate that autophagy is dependent on RARα activation. Interestingly, inhibition of autophagy in breast cancer cells by either genetic or pharmacological approaches resulted in significantly increased apoptosis under ATRA treatment and attenuated epithelial differentiation. In summary, our findings demonstrate that ATRA-induced autophagy is mediated by RARα in breast cancer cells. Furthermore, inhibition of autophagy results in enhanced apoptosis. This points to a potential novel treatment strategy for a selected group of breast cancer patients where ATRA and autophagy inhibitors are applied simultaneously.

  14. Automated segmentation of reference tissue for prostate cancer localization in dynamic contrast enhanced MRI

    Science.gov (United States)

    Vos, Pieter C.; Hambrock, Thomas; Barentsz, Jelle O.; Huisman, Henkjan J.

    2010-03-01

    For pharmacokinetic (PK) analysis of Dynamic Contrast Enhanced (DCE) MRI the arterial input function needs to be estimated. Previously, we demonstrated that PK parameters have a significant better discriminative performance when per patient reference tissue was used, but required manual annotation of reference tissue. In this study we propose a fully automated reference tissue segmentation method that tackles this limitation. The method was tested with our Computer Aided Diagnosis (CADx) system to study the effect on the discriminating performance for differentiating prostate cancer from benign areas in the peripheral zone (PZ). The proposed method automatically segments normal PZ tissue from DCE derived data. First, the bladder is segmented in the start-to-enhance map using the Otsu histogram threshold selection method. Second, the prostate is detected by applying a multi-scale Hessian filter to the relative enhancement map. Third, normal PZ tissue was segmented by threshold and morphological operators. The resulting segmentation was used as reference tissue to estimate the PK parameters. In 39 consecutive patients carcinoma, benign and normal tissue were annotated on MR images by a radiologist and a researcher using whole mount step-section histopathology as reference. PK parameters were computed for each ROI. Features were extracted from the set of ROIs using percentiles to train a support vector machine that was used as classifier. Prospective performance was estimated by means of leave-one-patient-out cross validation. A bootstrap resampling approach with 10,000 iterations was used for estimating the bootstrap mean AUCs and 95% confidence intervals. In total 42 malignant, 29 benign and 37 normal regions were annotated. For all patients, normal PZ was successfully segmented. The diagnostic accuracy obtained for differentiating malignant from benign lesions using a conventional general patient plasma profile showed an accuracy of 0.64 (0.53-0.74). Using the

  15. Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

    Science.gov (United States)

    Putney, S; Herlihy, W; Royal, N; Pang, H; Aposhian, H V; Pickering, L; Belagaje, R; Biemann, K; Page, D; Kuby, S

    1984-12-10

    A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

  16. The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with glycolysis blockade for cancer cell killing

    NARCIS (Netherlands)

    Tesori, V.; Piscaglia, A.C.; Samengo, D.; Barba, M.; Bernardini, C.; Scatena, R.; Pontoglio, A.; Castellini, L.; Spelbrink, H.; Maulucci, G.; Puglisi, M.A.; Pani, G.; Gasbarrini, A.

    2015-01-01

    Although the only effective drug against primary hepatocarcinoma, the multikinase inhibitor Sorafenib (SFB) usually fails to eradicate liver cancer. Since SFB targets mitochondria, cell metabolic reprogramming may underlie intrinsic tumor resistance. To characterize cancer cell metabolic response to

  17. Enhancing a Cancer Prevention and Control Curriculum through Interactive Group Discussions

    OpenAIRE

    Forsythe, L.P.; Gadalla, S.M.; Hamilton, J G; Heckman-Stoddard, B.M.; Kent, E.E.; Lai, G Y; Lin, S. W.; Luhn, P.; Faupel-Badger, J.M.

    2012-01-01

    The Principles and Practice of Cancer Prevention and Control course (Principles course) is offered annually by the National Cancer Institute Cancer Prevention Fellowship Program. This four-week post-graduate course covers the spectrum of cancer prevention and control research (e.g. epidemiology, laboratory, clinical, social, and behavioral sciences) and is open to attendees from medical, academic, government, and related institutions across the world. In this report, we describe a new additio...

  18. Enhanced

    Directory of Open Access Journals (Sweden)

    Martin I. Bayala

    2014-06-01

    Full Text Available Land Surface Temperature (LST is a key parameter in the energy balance model. However, the spatial resolution of the retrieved LST from sensors with high temporal resolution is not accurate enough to be used in local-scale studies. To explore the LST–Normalised Difference Vegetation Index relationship potential and obtain thermal images with high spatial resolution, six enhanced image sharpening techniques were assessed: the disaggregation procedure for radiometric surface temperatures (TsHARP, the Dry Edge Quadratic Function, the Difference of Edges (Ts∗DL and three models supported by the relationship of surface temperature and water stress of vegetation (Normalised Difference Water Index, Normalised Difference Infrared Index and Soil wetness index. Energy Balance Station data and in situ measurements were used to validate the enhanced LST images over a mixed agricultural landscape in the sub-humid Pampean Region of Argentina (PRA, during 2006–2010. Landsat Thematic Mapper (TM and Moderate Resolution Imaging Spectroradiometer (EOS-MODIS thermal datasets were assessed for different spatial resolutions (e.g., 960, 720 and 240 m and the performances were compared with global and local TsHARP procedures. Results suggest that the Ts∗DL technique is the most adequate for simulating LST to high spatial resolution over the heterogeneous landscape of a sub-humid region, showing an average root mean square error of less than 1 K.

  19. Mechanisms by which low glucose enhances the cytotoxicity of metformin to cancer cells both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yongxian Zhuang

    Full Text Available Different cancer cells exhibit altered sensitivity to metformin treatment. Recent studies suggest these findings may be due in part to the common cell culture practice of utilizing high glucose, and when glucose is lowered, metformin becomes increasingly cytotoxic to cancer cells. In low glucose conditions ranging from 0 to 5 mM, metformin was cytotoxic to breast cancer cell lines MCF7, MDAMB231 and SKBR3, and ovarian cancer cell lines OVCAR3, and PA-1. MDAMB231 and SKBR3 were previously shown to be resistant to metformin in normal high glucose medium. When glucose was increased to 10 mM or above, all of these cell lines become less responsive to metformin treatment. Metformin treatment significantly reduced ATP levels in cells incubated in media with low glucose (2.5 mM, high fructose (25 mM or galactose (25 mM. Reductions in ATP levels were not observed with high glucose (25 mM. This was compensated by enhanced glycolysis through activation of AMPK when oxidative phosphorylation was inhibited by metformin. However, enhanced glycolysis was either diminished or abolished by replacing 25 mM glucose with 2.5 mM glucose, 25 mM fructose or 25 mM galactose. These findings suggest that lowering glucose potentiates metformin induced cell death by reducing metformin stimulated glycolysis. Additionally, under low glucose conditions metformin significantly decreased phosphorylation of AKT and various targets of mTOR, while phospho-AMPK was not significantly altered. Thus inhibition of mTOR signaling appears to be independent of AMPK activation. Further in vivo studies using the 4T1 breast cancer mouse model confirmed that metformin inhibition of tumor growth was enhanced when serum glucose levels were reduced via low carbohydrate ketogenic diets. The data support a model in which metformin treatment of cancer cells in low glucose medium leads to cell death by decreasing ATP production and inhibition of survival signaling pathways. The enhanced

  20. Mechanisms by which low glucose enhances the cytotoxicity of metformin to cancer cells both in vitro and in vivo.

    Science.gov (United States)

    Zhuang, Yongxian; Chan, Daniel K; Haugrud, Allison B; Miskimins, W Keith

    2014-01-01

    Different cancer cells exhibit altered sensitivity to metformin treatment. Recent studies suggest these findings may be due in part to the common cell culture practice of utilizing high glucose, and when glucose is lowered, metformin becomes increasingly cytotoxic to cancer cells. In low glucose conditions ranging from 0 to 5 mM, metformin was cytotoxic to breast cancer cell lines MCF7, MDAMB231 and SKBR3, and ovarian cancer cell lines OVCAR3, and PA-1. MDAMB231 and SKBR3 were previously shown to be resistant to metformin in normal high glucose medium. When glucose was increased to 10 mM or above, all of these cell lines become less responsive to metformin treatment. Metformin treatment significantly reduced ATP levels in cells incubated in media with low glucose (2.5 mM), high fructose (25 mM) or galactose (25 mM). Reductions in ATP levels were not observed with high glucose (25 mM). This was compensated by enhanced glycolysis through activation of AMPK when oxidative phosphorylation was inhibited by metformin. However, enhanced glycolysis was either diminished or abolished by replacing 25 mM glucose with 2.5 mM glucose, 25 mM fructose or 25 mM galactose. These findings suggest that lowering glucose potentiates metformin induced cell death by reducing metformin stimulated glycolysis. Additionally, under low glucose conditions metformin significantly decreased phosphorylation of AKT and various targets of mTOR, while phospho-AMPK was not significantly altered. Thus inhibition of mTOR signaling appears to be independent of AMPK activation. Further in vivo studies using the 4T1 breast cancer mouse model confirmed that metformin inhibition of tumor growth was enhanced when serum glucose levels were reduced via low carbohydrate ketogenic diets. The data support a model in which metformin treatment of cancer cells in low glucose medium leads to cell death by decreasing ATP production and inhibition of survival signaling pathways. The enhanced cytotoxicity of metformin

  1. Synthetic peptides derived from the C-terminal region of Lys49 phospholipase A2 homologues from viperidae snake venoms: biomimetic activities and potential applications.

    Science.gov (United States)

    Lomonte, Bruno; Angulo, Yamileth; Moreno, Edgardo

    2010-01-01

    Lys49-phospholipase A(2) homologues constitute a large family of toxins present in the venoms of viperid snake species, which despite lacking catalytic activity, cause significant skeletal muscle necrosis. The main structural determinants of this toxic effect have been experimentally mapped to a region near their C-terminus (115-129), which combines cationic and hydrophobic/aromatic amino acid residues. Short (13-mer) synthetic peptides representing this C-terminal region can mimick several of the effects of Lys49 PLA(2) homologues. In addition to their ability to damage muscle cells, these peptides display antibacterial, antiendotoxic, antifungal, antiparasite, and antitumor activities, as well as VEGF-receptor 2 (KDR)-binding and heparin-binding properties. Modifications of their sequences have shown possibilities to enhance their effects upon prokaryotic cells, while decreasing toxicity for eukaryotic cells. This review presents an updated summary on the biomimetic actions exerted by such peptides, and highlights their potential value as molecular tools or as drug leads in diverse biomedical areas.

  2. Breast vascular mapping obtained with contrast-enhanced MR imaging: implications for cancer diagnosis, treatment, and risk stratification.

    Science.gov (United States)

    Sardanelli, Francesco; Fausto, Alfonso; Menicagli, Laura; Esseridou, Anastassia

    2007-12-01

    The value of breast vascular maps obtained using contrast-enhanced MR imaging has recently been explored. Additional information is obtained only by evaluating maximum intensity projections of the first dynamic subtraction to achieve a form of MR angiography of the breast. No increase in acquisition time and no dedicated contrast injections are needed. Four studies have been performed to evaluate the one-sided (asymmetric) increase in vascularity associated with ipsilateral cancer in a total of 404 patients with a cancer prevalence ranging from 38% to 80%. Sensitivity ranged from 72% to 88%, specificity from 57% to 100%, positive predictive value from 85% to 100%, negative predictive value from 38% to 88%, and overall accuracy from 73% to 87%. An asymmetric increase in breast vascularity ipsilateral to a cancer may be due to reduced flow resistance in the tumour, to a high metabolic rate (more likely in large tumours) or to angiogenic stimulation of the whole breast harbouring the lesion (more likely in small tumours). Tumour size could play a specific role in determining the ipsilaterally increased vascularity, and invasive cancers might be more frequently associated with ipsilaterally increased vascularity than in situ cancers. Moreover, while a reduction in breast vasculature has anecdotically been observed in breasts with locally advanced cancers treated with neoadjuvant chemotherapy, especially when taxanes are used, the higher incidence of breast cancer in patients with size asymmetry between the breasts as determined on screening mammography suggests that a role for breast MR vascular mapping in breast cancer risk stratification should be explored. Finally, arteries and veins might be differentiated with dedicated techniques. High-relaxivity agents may be used with advantage in these future investigations.

  3. High-resolution modeling of transmembrane helical protein structures from distant homologues.

    Directory of Open Access Journals (Sweden)

    Kuang-Yui M Chen

    2014-05-01

    Full Text Available Eukaryotic transmembrane helical (TMH proteins perform a wide diversity of critical cellular functions, but remain structurally largely uncharacterized and their high-resolution structure prediction is currently hindered by the lack of close structural homologues. To address this problem, we present a novel and generic method for accurately modeling large TMH protein structures from distant homologues exhibiting distinct loop and TMH conformations. Models of the adenosine A2AR and chemokine CXCR4 receptors were first ranked in GPCR-DOCK blind prediction contests in the receptor structure accuracy category. In a benchmark of 50 TMH protein homolog pairs of diverse topology (from 5 to 12 TMHs, size (from 183 to 420 residues and sequence identity (from 15% to 70%, the method improves most starting templates, and achieves near-atomic accuracy prediction of membrane-embedded regions. Unlike starting templates, the models are of suitable quality for computer-based protein engineering: redesigned models and redesigned X-ray structures exhibit very similar native interactions. The method should prove useful for the atom-level modeling and design of a large fraction of structurally uncharacterized TMH proteins from a wide range of structural homologues.

  4. Structure-activity studies of homologues of short chain neurotoxins from Elapid snake venoms.

    Science.gov (United States)

    Harvey, A L; Hider, R C; Hodges, S J; Joubert, F J

    1984-07-01

    Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata) were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer cervicis nerve-muscle preparations. All three homologues had acetylcholine receptor blocking activity, as they abolished responses to indirect stimulation, acetylcholine and carbachol but had no effect on responses to direct muscle stimulation. CM10 was only about 5 times less potent than the short neurotoxin CM14; S5C10 and CM12 were respectively 30 and 300 times less active. The block induced by the three homologues, but not by the neurotoxins, was readily reversed by washing. CM10 and CM12 had virtually identical c.d. spectra which were closely similar to those of the neurotoxins. The spectrum of S5C10 indicated changes in the environment of tyrosine-25 and in the position of tryptophan-29. These alterations could distort the 3-dimensional arrangement of the residues postulated to form the receptor binding site. The results with CM10 and CM12 highlight a role for the first loop (residues 6-16) in the binding of neurotoxins to acetylcholine receptors, in addition to the previously postulated reactive site.

  5. [Homologue pairing: initiation sites and effects on crossing over and chromosome disjunction in Drosophila melanogaster].

    Science.gov (United States)

    Chubykin, V L

    1996-01-01

    The role of homologue pairing and chromocentral association of chromosomes in recombination and segregation during cell division is discussed. Peculiarities of mitotic and meiotic chromosome pairing in Drosophila males and females are considered. On the basis of our own and published data, the presence and localization of sites of homologue pairing initiation in euchromatin are substantiated. The effects of transfer of initiation sites along a chromosome (exemplified by inversions) on chromosome pairing (asynapsis), crossing over (intrachromosomal, interchromosomal, and centromeric effects), and segregation are discussed. To record the effects of pairing sites on crossing over, a method of comparing crossing-over frequencies in an inverted region with those in a region of the same size and position with regard to the centromere on cytological maps was proposed. Chromosomes orient toward opposite division poles during paracentromeric heterochromatin pairing. This occurs after successful euchromatin pairing, during which the chromocentral circular structure is reorganized. If heterochromatin pairing is disrupted because of structural or locus mutations, nonexchange bivalents segregate randomly. In this case, chromosome coordination may occur due to proximal chiasmata or chromocentral associations between homologues.

  6. Functional and Biochemical Characterization of Alvinella pompejana Cys-Loop Receptor Homologues.

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    Eveline Wijckmans

    Full Text Available Cys-loop receptors are membrane spanning ligand-gated ion channels involved in fast excitatory and inhibitory neurotransmission. Three-dimensional structures of these ion channels, determined by X-ray crystallography or electron microscopy, have revealed valuable information regarding the molecular mechanisms underlying ligand recognition, channel gating and ion conductance. To extend and validate the current insights, we here present promising candidates for further structural studies. We report the biochemical and functional characterization of Cys-loop receptor homologues identified in the proteome of Alvinella pompejana, an extremophilic, polychaete annelid found in hydrothermal vents at the bottom of the Pacific Ocean. Seven homologues were selected, named Alpo1-7. Five of them, Alpo2-6, were unidentified prior to this study. Two-electrode voltage clamp experiments revealed that wild type Alpo5 and Alpo6, both sharing remarkably high sequence identity with human glycine receptor α subunits, are anion-selective channels that can be activated by glycine, GABA and taurine. Furthermore, upon expression in insect cells fluorescence size-exclusion chromatography experiments indicated that four homologues, Alpo1, Alpo4, Alpo6 and Alpo7, can be extracted out of the membrane by a wide variety of detergents while maintaining their oligomeric state. Finally, large-scale purification efforts of Alpo1, Alpo4 and Alpo6 resulted in milligram amounts of biochemically stable and monodisperse protein. Overall, our results establish the evolutionary conservation of glycine receptors in annelids and pave the way for future structural studies.

  7. Structure-activity studies of homologues of short chain neurotoxins from Elapid snake venoms.

    Science.gov (United States)

    Harvey, A. L.; Hider, R. C.; Hodges, S. J.; Joubert, F. J.

    1984-01-01

    Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata) were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer cervicis nerve-muscle preparations. All three homologues had acetylcholine receptor blocking activity, as they abolished responses to indirect stimulation, acetylcholine and carbachol but had no effect on responses to direct muscle stimulation. CM10 was only about 5 times less potent than the short neurotoxin CM14; S5C10 and CM12 were respectively 30 and 300 times less active. The block induced by the three homologues, but not by the neurotoxins, was readily reversed by washing. CM10 and CM12 had virtually identical c.d. spectra which were closely similar to those of the neurotoxins. The spectrum of S5C10 indicated changes in the environment of tyrosine-25 and in the position of tryptophan-29. These alterations could distort the 3-dimensional arrangement of the residues postulated to form the receptor binding site. The results with CM10 and CM12 highlight a role for the first loop (residues 6-16) in the binding of neurotoxins to acetylcholine receptors, in addition to the previously postulated reactive site. PMID:6743920

  8. Three TFL1 homologues regulate floral initiation in the biofuel plant Jatropha curcas

    Science.gov (United States)

    Li, Chaoqiong; Fu, Qiantang; Niu, Longjian; Luo, Li; Chen, Jianghua; Xu, Zeng-Fu

    2017-01-01

    Recent research revealed that TERMINAL FLOWER 1 (TFL1) homologues are involved in the critical developmental process of floral initiation in several plant species. In this study, the functions of three putative TFL1 homologues (JcTFL1a, JcTFL1b and JcTFL1c) in the biofuel plant Jatropha curcas were analysed using the transgenic approach. JcTFL1b and JcTFL1c, but not JcTFL1a, could complement the TFL1 function and rescue early flowering and determinate inflorescence phenotype in tfl1-14 Arabidopsis mutant, thus suggesting that JcTFL1b and JcTFL1c may be homologues of TFL1. Transgenic Jatropha overexpressing JcTFL1a, JcTFL1b or JcTFL1c showed late flowering, whereas only JcTFL1b and JcTFL1c overexpression delayed flowering in transgenic Arabidopsis. JcTFL1b-RNAi transgenic Jatropha consistently exhibited moderately early flowering phenotype. JcFT and JcAP1 were significantly downregulated in transgenic Jatropha overexpressing JcTFL1a, JcTFL1b or JcTFL1c, which suggested that the late flowering phenotype of these transgenic Jatropha may result from the repressed expression of JcFT and JcAP1. Our results indicate that these three JcTFL1 genes play redundant roles in repressing flowering in Jatropha. PMID:28225036

  9. Chemosensitizing effects of carbon-based nanomaterials in cancer cells: enhanced apoptosis and inhibition of proliferation as underlying mechanisms.

    Science.gov (United States)

    Erdmann, Kati; Ringel, Jessica; Hampel, Silke; Rieger, Christiane; Huebner, Doreen; Wirth, Manfred P; Fuessel, Susanne

    2014-10-10

    Recent studies have shown that carbon nanomaterials such as carbon nanofibres (CNFs) and multi-walled carbon nanotubes (CNTs) can exert antitumor activities themselves and sensitize cancer cells to conventional chemotherapeutics such as carboplatin and cisplatin. In the present study, the chemosensitizing effect of CNFs and CNTs on cancer cells of urological origin was investigated regarding the underlying mechanisms. Prostate cancer (DU-145, PC-3) and bladder cancer (EJ28) cells were treated with carbon nanomaterials (CNFs, CNTs) and chemotherapeutics (carboplatin, cisplatin) alone as well as in combination for 24 h. Forty-eight(EJ28) or 72 h (DU-145, PC-3) after the end of treatment the effects on cellular proliferation,clonogenic survival, cell death rate and cell cycle distribution were evaluated. Depending on the cell line, simultaneous administration of chemotherapeutics and carbon nanomaterials produced an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98%, respectively, compared to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced antiproliferative effects were accompanied by an elevated cell death rate, which was predominantly mediated via apoptosis and not by necrosis. The antitumor effects of combinations with CNTs were less pronounced than those with CNFs. The enhanced effects of the combinatory treatments on cellular function were mostly of additive to partly synergistic nature. Furthermore, cell cycle analysis demonstrated an arrest at the G2/M phase mediated by a monotreatment with chemotherapeutics. Following combinatory treatments, mostly less than or nearly additive increases of cell fractions in the G2/M phase could be observed. In conclusion,the pronounced chemosensitizing effects of CNFs and CNTs were mediated by an enhanced apoptosis and inhibition of proliferation. The combination of carbon-based nanomaterials and conventional chemotherapeutics represents a novel approach

  10. Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size.

    Science.gov (United States)

    Fallenberg, E M; Dromain, C; Diekmann, F; Engelken, F; Krohn, M; Singh, J M; Ingold-Heppner, B; Winzer, K J; Bick, U; Renz, D M

    2014-01-01

    To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography (CESM) is slowly being introduced into clinical practice. • Access to breast MRI is limited by availability and lack of reimbursement. • Initial results show a better sensitivity of CESM and MRI than conventional mammography. • CESM showed a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography offers promise, seemingly providing information comparable to MRI.

  11. 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

    Science.gov (United States)

    Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

  12. Dynamic contrast-enhanced MR imaging of endometrial cancer. Optimizing the imaging delay for tumour-myometrium contrast

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Bin [Chung-Ang University Hospital, Chung-Ang University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Moon, Min Hoan; Sung, Chang Kyu [Seoul National University College of Medicine, 41, Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Oh, Sohee [Seoul National University College of Medicine, 41, Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Lee, Young Ho [Kwandong University College of Medicine, Department of Radiology, Cheil General Hospital and Women' s Healthcare Center, Seoul (Korea, Republic of)

    2014-11-15

    To investigate the optimal imaging delay time of dynamic contrast-enhanced magnetic resonance (MR) imaging in women with endometrial cancer. This prospective single-institution study was approved by the institutional review board, and informed consent was obtained from the participants. Thirty-five women (mean age, 54 years; age range, 29-66 years) underwent dynamic contrast-enhanced MR imaging with a temporal resolution of 25-40 seconds. The signal intensity difference ratios between the myometrium and endometrial cancer were analyzed to investigate the optimal imaging delay time using single change-point analysis. The optimal imaging delay time for appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of -0.01 to 0.06, on the pre-contrast MR imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging. An imaging delay of approximately 90 seconds after initiating contrast material injection may be optimal for obtaining appropriate tumour-myometrium contrast in women with endometrial cancer. (orig.)

  13. Downregulation of Choline Kinase-Alpha Enhances Autophagy in Tamoxifen-Resistant Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Hoe Suk Kim

    Full Text Available Choline kinase-α (Chk-α and autophagy have gained much attention, as they relate to the drug-resistance of breast cancer. Here, we explored the potential connection between Chk-α and autophagy in the mechanisms driving to tamoxifen (TAM resistance, in estrogen receptor positive (ER+ breast cancer cells (BCCs. Human BCC lines (MCF-7 and TAM-resistant MCF-7 (MCF-7/TAM cells were used. Chk-α expression and activity was suppressed by the transduction of shRNA (shChk-α with lentivirus and treatment with CK37, a Chk-α inhibitor. MCF-7/TAM cells had higher Chk-α expression and phosphocholine levels than MCF-7 cells. A specific downregulation of Chk-α by the transduction of shChk-α exhibited a significant decrease in phosphocholine levels in MCF-7 and MCF-7/TAM cells. The autophagy-related protein, cleaved microtubule-associated protein light chain 3 (LC3 and autophagosome-like structures were significantly increased in shChk-α-transduced or CK37-treated MCF-7 and MCF-7/TAM cells. The downregulation of Chk-α attenuated the phosphorylation of AKT, ERK1/2, and mTOR in both MCF-7 and MCF-7/TAM cells. In MCF-7 cells, the downregulation of Chk-α resulted in an induction of autophagy, a decreased proliferation ability and an activation of caspase-3. In MCF-7/TAM cells, despite a significant decrease in proliferation ability and an increase in the percentage of cells in the G0/G1 phase of the cell cycle, the downregulation of Chk-α did not induced caspase-dependent cell death and further enhanced autophagy and G0/G1 phase arrest. An autophagy inhibitor, methyladenine (3-MA induced death and attenuated the level of elevated LC3 in MCF-7/TAM cells. Elucidating the interplay between choline metabolism and autophagy will provide unique opportunities to identify new therapeutic targets and develop novel treatment strategies that preferentially target TAM-resistance.

  14. Enhancing photodynamic therapy of a metastatic mouse breast cancer by immune stimulation

    Science.gov (United States)

    Castano, Ana P.; Hamblin, Michael R.

    2006-02-01

    One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 410.4 variant 4T1 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that produces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines

  15. Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Yan Nan; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun-Ran; Kim, Su-Hyeon; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Park, Sang Jun; Kim, Chun-Ho [Laboratory of Tissue Engineering, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2014-01-17

    Highlights: •HAS2 may be a promising target for the radiosensitization of human cancer. •HAS2 is elevated (up to ∼10-fold) in irradiated radioresistant and -sensitive cancer cells. •HAS2 knockdown sensitizes cancer cells to radiation. •HAS2 knockdown potentiates irradiation-induced DNA damage and apoptotic death. •Thus, the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. -- Abstract: Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24 h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells.

  16. c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hongliang; Li, Xiaoying; Sun, Shaoqian [Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing (China); Gao, Xianshu, E-mail: xsgao777@hotmail.com [Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing (China); Zhou, Demin, E-mail: deminzhou@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer c-Met inhibition could significantly enhance the radiosensitivity of DU145 cells. Black-Right-Pointing-Pointer The mechanisms of the radiosensitization effect of c-Met inhibition on DU145 cells were also presented in this paper. Black-Right-Pointing-Pointer This is the first study demonstrating the effectiveness of c-Met inhibition on treating HRPC cells with radiotherapy. -- Abstract: Hormone-refractory prostate cancer shows substantial resistance to most conventional therapies including radiotherapy, constitutes a key impediment to curing patients with the disease. c-Met overexpression plays a key role in prostate cancer tumorigenesis and disease progression. Here, we demonstrate that c-Met inhibition by SU11274 could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. The underlying mechanisms of the effects of SU11274 on DU145 cells may include the inhibition of c-Met signaling, depolarization of the mitochondrial membrane potential, impairment of DNA repair function, abrogation of cell cycle arrest, and enhancement of cell death. Our study is the first to show the effectiveness of combining c-Met inhibition with ionizing radiation to cure hormone-refractory prostate cancer.

  17. Dynamic Nucleosome-Depleted Regions at Androgen Receptor Enhancers in the Absence of Ligand in Prostate Cancer Cells ▿

    Science.gov (United States)

    Andreu-Vieyra, Claudia; Lai, John; Berman, Benjamin P.; Frenkel, Baruch; Jia, Li; Jones, Peter A.; Coetzee, Gerhard A.

    2011-01-01

    Nucleosome positioning at transcription start sites is known to regulate gene expression by altering DNA accessibility to transcription factors; however, its role at enhancers is poorly understood. We investigated nucleosome positioning at the androgen receptor (AR) enhancers of TMPRSS2, KLK2, and KLK3/PSA in prostate cancer cells. Surprisingly, a population of enhancer modules in androgen-deprived cultures showed nucleosome-depleted regions (NDRs) in all three loci. Under androgen-deprived conditions, NDRs at the TMPRSS2 enhancer were maintained by the pioneer AR transcriptional collaborator GATA-2. Androgen treatment resulted in AR occupancy, an increased number of enhancer modules with NDRs without changes in footprint width, increased levels of histone H3 acetylation (AcH3), and dimethylation (H3K4me2) at nucleosomes flanking the NDRs. Our data suggest that, in the absence of ligand, AR enhancers exist in an equilibrium in which a percentage of modules are occupied by nucleosomes while others display NDRs. We propose that androgen treatment leads to the disruption of the equilibrium toward a nucleosome-depleted state, rather than to enhancer de novo “remodeling.” This allows the recruitment of histone modifiers, chromatin remodelers, and ultimately gene activation. The “receptive” state described here could help explain AR signaling activation under very low ligand concentrations. PMID:21969603

  18. Aedes aegypti ferritin heavy chain homologue: feeding of iron or blood influences message levels, lengths and subunit abundance

    Directory of Open Access Journals (Sweden)

    Boris C. Dunkov

    2002-04-01

    Full Text Available Secreted ferritin in the mosquito, Aedes aegypti, has several subunits that are the products of at least two genes, one encoding a homologue of the vertebrate heavy chain (HCH and the other the light chain homologue (LCH. Here we report the developmental and organ specific pattern of expression of the ferritin HCH messages and of both subunit types in control sugar-fed mosquitoes, in those exposed to high levels of dietary iron, and after blood feeding.

  19. Acidified bile acids enhance tumor progression and telomerase activity of gastric cancer in mice dependent on c-Myc expression.

    Science.gov (United States)

    Wang, Xiaolong; Sun, Lei; Wang, Xijing; Kang, Huafeng; Ma, Xiaobin; Wang, Meng; Lin, Shuai; Liu, Meng; Dai, Cong; Dai, Zhijun

    2017-04-01

    c-Myc overexpression has been implicated in several malignancies including gastric cancer. Here, we report that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer via c-Myc activation both in vivo and in vitro. c-Myc mRNA and protein levels were assessed in ten primary and five local recurrent gastric cancer samples by quantitative real-time polymerase chain reaction and western blotting analysis. The gastric cancer cell line MGC803 was exposed to bile salts (100 μmol/L glycochenodeoxycholic acid and deoxycholic acid) in an acid medium (pH 5.5) for 10 min daily for 60 weeks to develop an MGC803-resistant cell line. Control MGC803 cells were grown without acids or bile salts for 60 weeks as a control. Cell morphology, proliferation, colony formation and apoptosis of MGC803-resistant cells were analyzed after 60 weeks. To determine the involvement of c-Myc in tumor progression and telomere aging in MGC803-resistant cells, we generated xenografts in nude mice and measured xenograft volume and in vivo telomerase activity. The c-Myc and hTERT protein and mRNA levels were significantly higher in local recurrent gastric cancer samples than in primary gastric cancer samples. MGC803-resistant cells showed a marked phenotypic change under normal growth conditions with more clusters and acini, and exhibited increased cell viability and colony formation and decreased apoptosis in vitro. These phenotypic changes were found to be dependent on c-Myc activation using the c-Myc inhibitor 10058-F4. MGC803-resistant cells also showed a c-Myc-dependent increase in xenograft growth and telomerase activity in vivo. In conclusion, these observations support the hypothesis that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer and that these effects are dependent on c-Myc activity. These findings suggest that acidified bile acids play an important role in the malignant progression of local recurrent

  20. Reducing Breast Cancer Recurrence with Weight Loss, a Vanguard Trial: The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial

    OpenAIRE

    Rock, Cheryl L.; Byers, Tim E.; Colditz, Graham A; Demark-Wahnefried, Wendy; Ganz, Patricia A; WOLIN, KATHLEEN Y.; Elias, Anthony; Krontiras, Helen; Liu, Jingxia; Naughton, Michael; Pakiz, Bilgé; Parker, Barbara A.; Sedjo, Rebecca L; Wyatt, Holly

    2012-01-01

    Breast cancer is the most common invasive cancer among women in developed countries. Obesity is a major risk factor for breast cancer recurrence and mortality in both pre-and postmenopausal women. Co-morbid medical conditions are common among breast cancer survivors. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is a 4-year randomized clinical trial of 693 overweight/obese women aged ≥21 years diagnosed with any early stage breast cancer (stages I[≥1 cm...

  1. Enhancement of Cisplatin-Mediated Apoptosis in Ovarian Cancer Cells through Potentiating G2/M Arrest and p21 Upregulation by Combinatorial Epigallocatechin Gallate and Sulforaphane

    Directory of Open Access Journals (Sweden)

    Huaping Chen

    2013-01-01

    Full Text Available Advanced-stage ovarian cancer is characterized by high mortality due to development of resistance to conventional chemotherapy. Novel compounds that can enhance the efficacy of conventional chemotherapy in ovarian cancer may overcome this drug resistance. Consumption of green tea (epigallocatechin gallate, EGCG and cruciferous vegetables (sulforaphane, SFN is inversely associated with occurrence of ovarian cancer and has anticancer effects through targeting multiple molecules in cancer cells. However, the effects of EGCG and SFN combinational treatment on ovarian cancer cells and on efficacy of cisplatin to these cells are unknown. In this study, EGCG or SFN was used to treat both cisplatin-sensitive (A2780 and cisplatin-resistant (A2780/CP20 ovarian cancer cells alone or in combination with cisplatin. We found that EGCG and SFN combinational treatment can reduce cell viability of both ovarian cancer cell lines time- and dose-dependently. Furthermore, EGCG and SFN combinational treatment can enhance cisplatin-induced apoptosis and G2/M phase arrest, thereby enhancing the efficacy of cisplatin on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. EGCG and SFN combinational treatment upregulated p21 expression induced by cisplatin in cisplatin-sensitive ovarian cancer cells, while p27 expression was not regulated by these treatments. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer.

  2. Functional Characterization of Aspergillus nidulans ypkA, a Homologue of the Mammalian Kinase SGK

    Science.gov (United States)

    Colabardini, Ana Cristina; Brown, Neil Andrew; Savoldi, Marcela; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2013-01-01

    The serum- and glucocorticoid-regulated protein kinase (SGK) is an AGC kinase involved in signal cascades regulated by glucocorticoid hormones and serum in mammals. The Saccharomyces cerevisiae ypk1 and ypk2 genes were identified as SGK homologues and Ypk1 was shown to regulate the balance of sphingolipids between the inner and outer plasma membrane. This investigation characterized the Aspergillus nidulans YPK1 homologue, YpkA, representing the first filamentous fungal YPK1 homologue. Two conditional mutant strains were constructed by replacing the endogenous ypk1 promoter with two different regulatable promoters, alcA (from the alcohol dehydrogenase gene) and niiA (from the nitrate reductase gene). Both constructs confirmed that ypkA was an essential gene in A. nidulans. Repression of ypkA caused decreased radial growth, a delay in conidial germination, deficient polar axis establishment, intense branching during late stages of growth, a lack of asexual spores, and a terminal phenotype. Membrane lipid polarization, endocytosis, eisosomes and vacuolar distribution were also affected by ypkA repression, suggesting that YpkA plays a role in hyphal morphogenesis via coordinating the delivery of cell membrane and wall constituents to the hyphal apex. The A. nidulans Pkh1 homologue pkhA was also shown to be an essential gene, and preliminary genetic analysis suggested that the ypkA gene is not directly downstream of pkhA or epistatic to pkhA, rather, ypkA and pkhA are genetically independent or in parallel. BarA is a homologue of the yeast Lag1 acyl-CoA-dependent ceramide synthase, which catalyzes the condensation of phytosphingosine with a fatty acyl-CoA to form phytoceramide. When barA was absent, ypkA repression was lethal to the cell. Therefore, there appears to be a genetic interaction between ypkA, barA, and the sphingolipid synthesis. Transcriptional profiling of ypkA overexpression and down-regulation revealed several putative YpkA targets associated with the

  3. Functional characterization of Aspergillus nidulans ypkA, a homologue of the mammalian kinase SGK.

    Directory of Open Access Journals (Sweden)

    Ana Cristina Colabardini

    Full Text Available The serum- and glucocorticoid-regulated protein kinase (SGK is an AGC kinase involved in signal cascades regulated by glucocorticoid hormones and serum in mammals. The Saccharomyces cerevisiae ypk1 and ypk2 genes were identified as SGK homologues and Ypk1 was shown to regulate the balance of sphingolipids between the inner and outer plasma membrane. This investigation characterized the Aspergillus nidulans YPK1 homologue, YpkA, representing the first filamentous fungal YPK1 homologue. Two conditional mutant strains were constructed by replacing the endogenous ypk1 promoter with two different regulatable promoters, alcA (from the alcohol dehydrogenase gene and niiA (from the nitrate reductase gene. Both constructs confirmed that ypkA was an essential gene in A. nidulans. Repression of ypkA caused decreased radial growth, a delay in conidial germination, deficient polar axis establishment, intense branching during late stages of growth, a lack of asexual spores, and a terminal phenotype. Membrane lipid polarization, endocytosis, eisosomes and vacuolar distribution were also affected by ypkA repression, suggesting that YpkA plays a role in hyphal morphogenesis via coordinating the delivery of cell membrane and wall constituents to the hyphal apex. The A. nidulans Pkh1 homologue pkhA was also shown to be an essential gene, and preliminary genetic analysis suggested that the ypkA gene is not directly downstream of pkhA or epistatic to pkhA, rather, ypkA and pkhA are genetically independent or in parallel. BarA is a homologue of the yeast Lag1 acyl-CoA-dependent ceramide synthase, which catalyzes the condensation of phytosphingosine with a fatty acyl-CoA to form phytoceramide. When barA was absent, ypkA repression was lethal to the cell. Therefore, there appears to be a genetic interaction between ypkA, barA, and the sphingolipid synthesis. Transcriptional profiling of ypkA overexpression and down-regulation revealed several putative YpkA targets

  4. Using a positive self-talk intervention to enhance coping skills in breast cancer survivors: lessons from a community-based group delivery model

    National Research Council Canada - National Science Library

    Hamilton, R; Miedema, B; Macintyre, L; Easley, J

    2011-01-01

    .... The purpose of the present study was to evaluate the effectiveness of a positive self-talk (pst) intervention in enhancing the coping skills and improving the psychological well-being of breast cancer survivors...

  5. Enhanced heme function and mitochondrial respiration promote the progression of lung cancer cells.

    Science.gov (United States)

    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 of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer

  6. Enhanced Mortality to Metastatic Bladder Cancer Cell Line MB49 in Vasoactive Intestinal Peptide Gene Knockout Mice

    Directory of Open Access Journals (Sweden)

    Niely Mirsaidi

    2017-08-01

    Full Text Available To identify if the absence of the vasoactive intestinal peptide (VIP gene enhances susceptibility to death from metastatic bladder cancer, two strains of mice were injected with MB49 murine bladder cancer cells. The growth and spread of the cancer was measured over a period of 4 weeks in C57BL/6 mice and 5 weeks in VIP knockout (KO mice. A Kaplan–Meier plot was constructed to compare control C57BL/6 mice and C57BL/6 mice with MB49 vs. VIP KO controls and VIP KO mice with MB49. The wild-type (WT strain (C57BL/6 contained the VIP gene, while the other strain, VIP knockout backcrossed to C57BL/6 (VIP KO did not and was thus unable to endogenously produce VIP. VIP KO mice had increased mortality compared to C57BL/6 mice at 4 weeks. The number of ulcers between both groups was not statistically significant. In vitro studies indicated that the presence VIP in high doses reduced MB49 cell growth, as well as macrophage inhibitory factor (MIF, a growth factor in bladder cancer cells. These findings support the concept that VIP may attenuate susceptibility to death from bladder cancer, and that it exerts its effect via downregulation of MIF.

  7. Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size

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    Fallenberg, E.M.; Renz, D.M. [Charite - Universitaetsmedizin Berlin, Clinic of Radiology, Berlin (Germany); Dromain, C. [Institut Gustave Roussy, Department of Radiology, Villejuif cedex (France); Diekmann, F. [St. Joseph-Stift Bremen, Department of Medical Imaging, Bremen (Germany); Engelken, F.; Krohn, M.; Singh, J.M.; Bick, U. [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Ingold-Heppner, B. [Charite - Universitaetsmedizin Berlin, Institute of Pathology, Berlin (Germany); Winzer, K.J. [Charite - Universitaetsmedizin Berlin, Breast Center, Department of Gynecology, Berlin (Germany)

    2014-01-15

    To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. (orig.)

  8. Low-dose methotrexate enhances cycling of highly anaplastic cancer cells.

    Science.gov (United States)

    Cipolleschi, Maria Grazia; Marzi, Ilaria; Rovida, Elisabetta; Olivotto, Massimo; Dello Sbarba, Persio

    2017-02-01

    We previously showed that cellular RedOx state governs the G1-S transition of AH130 hepatoma, a tumor spontaneously reprogrammed to the embryonic stem cell stage. This transition is impaired when the mithocondrial electron transport system is blocked by specific inhibitors (antimycin A) or the respiratory chain is saturated by adding to the cells high concentrations of pyruvate. The antimycin A or pyruvate block is removed by the addition of adequate concentrations of folate (F). This suggests that the G1-S transition of AH130 cells depends on a respiration-linked step of DNA synthesis related to folate metabolism. In the study reported here, we characterized the effects of methotrexate (MTX), an inhibitor of dihydofolate-reductase, on the G1-S transition of hepatoma cells, in the absence or the presence of exogenously added F, dihydrofolate (FH2) or tetrahydrofolate (FH4). MTX, at 1 μM or higher concentrations, inhibited G1-S transition. This inhibition was completely removed by exogenous folates. Surprisingly, 10 nM MTX stimulated G1-S transition. The addition of F, but not FH2 or FH4, significantly increased this effect. Furthermore, 10 nM MTX removed the block of the G1-S transition operated by antimycin A or pyruvate, an effect which was enhanced in the presence of F. Finally, the stimulatory effect of 10 nM MTX was inhibited in the presence of serine. Our findings indicated that, under certain conditions, MTX may stimulate, rather than inhibiting, the cycling of cancer cells exhibiting a stem cell-like phenotype, such as AH130 cells. This may impact the therapeutic use of MTX and of folates as supportive care.

  9. Vitamin D as a potential enhancer of aminolevulinate-based photodynamic therapy for nonmelanoma skin cancer

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay; Atanaskova, Natasha; Wilson, Clara

    2010-02-01

    Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

  10. Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

    Science.gov (United States)

    Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

    2013-05-01

    Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

  11. Characterisation of Nicotine and Cancer-Enhancing Anions in the Common Smokeless Tobacco Afzal in Oman

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    Nawal M. Al-Mukhaini

    2015-11-01

    Full Text Available Objectives: Afzal is a common smokeless tobacco product (STP available illegally in Oman. This study aimed to assess pH and moisture levels and determine cancer-enhancing factors in a randomly selected sample of Afzal. Methods: This study was carried out at the Sultan Qaboos University in Muscat, Oman, between April and December 2013. A package of Afzal was purchased from a single provider and divided into samples. The pH and moisture content of the samples were measured according to the protocols of the Centers for Disease Control and Prevention. Gas chromatography-mass spectrometry was used to analyse nicotine levels and ionexchange chromatography (IC was used to determine concentrations of nitrate, nitrite, chloride, fluoride, bromide, sulphate and phosphate anions. Results: The samples had an alkaline pH of 10.46 with high levels of total (48,770.00 μg per g of STP [μg/g] and unionised (48,590.00 μg/g nicotine. The concentration of nitrate (8,792.20 μg/g was alarmingly high. The chloride concentration (33,170.80 μg/g showed a surge on IC chromatography. The moisture content percentage was 52.00%. Conclusion: The moisture content percentage and chloride concentration of Afzal was consistent with those of other STPs. In contrast, nitrite, sulphate and phosphate concentrations were below reported levels of other STPs. All anion concentrations were below the maximum daily limit set by international health organisations. However, the high concentrations of nitrite, nitrate and nicotine and the elevated alkaline pH observed in the analysed Afzal samples suggest that STP users will face health risks as a result of their use.

  12. Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection.

    Science.gov (United States)

    van Niekerk, Gustav; Hattingh, Suzèl M; Engelbrecht, Anna-Mart

    2016-01-01

    Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to upregulate autophagy, an evolutionarily conserved catabolic process that is upregulated in response to various cell stressors. Here, we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. First, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts.

  13. Triple-negative invasive breast cancer on dynamic contrast-enhanced and diffusion-weighted MR imaging: comparison with other breast cancer subtypes

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    Youk, Ji Hyun; Son, Eun Ju; Chung, Jin; Kim, Jeong-Ah; Kim, Eun-kyung [Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-08-15

    To determine the MRI features of triple-negative invasive breast cancer (TNBC) on dynamic contrast-enhanced MR imaging (DCE-MRI) and diffusion-weighted MR imaging (DWI) in comparison with ER-positive/HER2-negative (ER+) and HER2-positive cancer (HER2+). A total of 271 invasive cancers in 269 patients undergoing preoperative MRI and surgery were included. Two radiologists retrospectively assessed morphological and kinetic characteristics on DCE-MRI and tumour detectability on DWI. Apparent diffusion coefficient (ADC) values of lesions were measured. Clinical and MRI features of the three subtypes were compared. Compared with ER+ (n = 119) and HER2+ (n = 94), larger size, round/oval mass shape, smooth mass margin, and rim enhancement on DCE-MRI were significantly associated with TNBC (n = 58; P < 0.0001). On DWI, mean ADC value (x 10{sup -3} mm{sup 2}/s) of TNBC (1.03) was higher than the mean ADC values for ER+ and HER2+ (0.89 and 0.84; P < 0.0001). There was no difference in tumour detectability (P = 0.099). Tumour size (P = 0.009), mass margin (smooth, P < 0.0001; irregular, P = 0.020), and ADC values (P = 0.002) on DCE-MRI and DWI were independent features of TNBC. In addition to the morphological features, higher ADC values on DWI were independently associated with TNBC and could be useful in differentiating TNBC from ER+ and HER2+. (orig.)

  14. Tandem-multimeric F3-gelonin fusion toxins for enhanced anti-cancer activity for prostate cancer treatment.

    Science.gov (United States)

    Shin, Meong Cheol; Min, Kyoung Ah; Cheong, Heesun; Moon, Cheol; Huang, Yongzhuo; He, Huining; Yang, Victor C

    2017-05-30

    Despite significant progress in prostate cancer treatment, yet, it remains the leading diagnosed cancer and is responsible for high incidence of cancer related deaths in the U.S. Because of the insufficient efficacy of small molecule anti-cancer drugs, significant interest has been drawn to more potent macromolecular agents such as gelonin, a plant-derived ribosome inactivating protein (RIP) that efficiently inhibits protein translation. However, in spite of the great potency to kill tumor cells, gelonin lacks ability to internalize tumor cells and furthermore, cannot distinguish between tumor and normal cells. To address this challenge, we genetically engineered gelonin fusion proteins with varied numbers of F3 peptide possessing homing ability to various cancer cells and angiogenic blood vessels. The E. coli produced F3-gelonin fusion proteins possessed equipotent activity to inhibit protein translation in cell-free protein translation systems to unmodified gelonin; however, they displayed higher cell uptake that led to significantly augmented cytotoxicity. Compared with gelonin fusion with one F3 peptide (F3-Gel), tandem-multimeric F3-gelonins showed even greater cell internalization and tumor cell killing ability. Moreover, when tested against LNCaP s.c. xenograft tumor bearing mice, more significant tumor growth inhibition was observed from the mice treated with tandem-multimeric F3-gelonins. Overall, this research demonstrated the potential of utilizing tandem multimeric F3-modified gelonin as highly effective anticancer agents to overcome the limitations of current chemotherapeutic drugs. Copyright © 2017. Published by Elsevier B.V.

  15. Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects

    Directory of Open Access Journals (Sweden)

    Kamil Brzóska

    2014-09-01

    Full Text Available [b]Introduction and objective[/b]. Chronic obstructive pulmonary disease (COPD is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer. [b]Materials and methods[/b]. We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases ([i]MMP1, MMP2, MMP3, MMP9, MMP12[/i] as well as tissue inhibitor of metalloproteinases ([i]TIMP1[/i] in two groups of subjects: COPD patients (54 subjects and COPD patients diagnosed for lung cancer occurrence (53 subjects.The levels of the respective proteins in blood serum were also analyzed. [b]Results[/b]. The frequencies of 2 genotypes, [i]MMP3[/i] rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in[i] MMPs[/i] blood levels between the studied groups. In addition, no genotype-associated differences in [i]TIMP1[/i] or[i] MMPs[/i] blood levels were observed. [b]Conclusions[/b]. Homozygocity for [i]MMP3[/i] rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects.

  16. Gd2O3-doped silica @ Au nanoparticles for in vitro imaging cancer biomarkers using surface-enhanced Raman scattering

    Science.gov (United States)

    Xiao, Lifu; Tian, Xiumei; Harihar, Sitaram; Li, Qifei; Li, Li; Welch, Danny R.; Zhou, Anhong

    2017-06-01

    There has been an interest in developing multimodal approaches to combine the advantages of individual imaging modalities, as well as to compensate for respective weaknesses. We previously reported a composite nano-system composed of gadolinium-doped mesoporous silica nanoparticle and gold nanoparticle (Gd-Au NPs) as an efficient MRI contrast agent for in vivo cancer imaging. However, MRI lacks sensitivity and is unsuitable for in vitro cancer detection. Thus, here we performed a study to use the Gd-Au NPs for detection and imaging of a widely recognized human cancer biomarker, epidermal growth factor receptor (EGFR), in individual human cancer cells with surface-enhanced Raman scattering (SERS). The Gd-Au NPs were sequentially conjugated with a monoclonal antibody recognizing EGFR and a Raman reporter molecule, 4-meraptobenzoic acid (MBA), to generate a characteristic SERS signal at 1075 cm- 1. By spatially mapping the SERS intensity at 1075 cm- 1, cellular distribution of EGFR and its relocalization on the plasma membrane were measured in situ. In addition, the EGFR expression levels in three human cancer cell lines (S18, A431 and A549) were measured using this SERS probe, which were consistent with the comparable measurements using immunoblotting and immunofluorescence. Our SERS results show that functionalized Gd-Au NPs successfully targeted EGFR molecules in three human cancer cell lines and monitored changes in single cell EGFR distribution in situ, demonstrating its potential to study cell activity under physiological conditions. This SERS study, combined with our previous MRI study, suggests the Gd-Au nanocomposite is a promising candidate contrast agent for multimodal cancer imaging.

  17. 3, 3′-diindolylmethane Enhances the Effectiveness of Herceptin against HER-2/Neu-Expressing Breast Cancer Cells

    Science.gov (United States)

    Ahmad, Aamir; Ali, Shadan; Ahmed, Alia; Ali, Azfur S.; Raz, Avraham; Sakr, Wael A.; Rahman, KM Wahidur

    2013-01-01

    Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance develops and to design new combined treatments that benefit patients with aggressive breast cancer and have minimal toxicity. We hypothesized that 3, 3′-diindolylmethane (DIM), a non-toxic agent can be combined with Herceptin to treat breast cancers with high levels of HER-2/neu. Here, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER-2/neu-expressing) and MDA-MB-468 (HER-2/neu negative) breast cancer cells. We found that DIM could enhance the effectiveness of Herceptin by significantly reducing cell viability, which was associated with apoptosis-induction and significant inhibition of colony formation, compared with single agent treatment. These results were consistent with the down-regulation of Akt and NF-kB p65. Mechanistic investigations revealed a significant upregulation of miR-200 and reduction of FoxM1 expression in DIM and Herceptin-treated breast cancer cells. We, therefore, transfected cells with pre-miR-200 or silenced FoxM1 in these cells for understanding the molecular mechanism involved. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients with breast cancer, particularly for the patients whose tumors express high levels of HER-2/neu. PMID:23372748

  18. 3, 3'-Diindolylmethane enhances the effectiveness of herceptin against HER-2/neu-expressing breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Aamir Ahmad

    Full Text Available Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance develops and to design new combined treatments that benefit patients with aggressive breast cancer and have minimal toxicity. We hypothesized that 3, 3'-diindolylmethane (DIM, a non-toxic agent can be combined with Herceptin to treat breast cancers with high levels of HER-2/neu. Here, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER-2/neu-expressing and MDA-MB-468 (HER-2/neu negative breast cancer cells. We found that DIM could enhance the effectiveness of Herceptin by significantly reducing cell viability, which was associated with apoptosis-induction and significant inhibition of colony formation, compared with single agent treatment. These results were consistent with the down-regulation of Akt and NF-kB p65. Mechanistic investigations revealed a significant upregulation of miR-200 and reduction of FoxM1 expression in DIM and Herceptin-treated breast cancer cells. We, therefore, transfected cells with pre-miR-200 or silenced FoxM1 in these cells for understanding the molecular mechanism involved. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients with breast cancer, particularly for the patients whose tumors express high levels of HER-2/neu.

  19. DNA damage enhanced by the attenuation of SLD5 delays cell cycle restoration in normal cells but not in cancer cells.

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    Zhi-Yuan Gong

    Full Text Available SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor.

  20. Differentiation of benign periablational enhancement from residual tumor following radio-frequency ablation using contrast-enhanced ultrasonography in a rat subcutaneous colon cancer model.

    Science.gov (United States)

    Wu, Hanping; Patel, Ravi B; Zheng, Yuanyi; Solorio, Luis; Krupka, Tianyi M; Ziats, Nicholas P; Haaga, John R; Exner, Agata A

    2012-03-01

    Benign periablational enhancement (BPE) response to thermal injury is a barrier to early detection of residual tumor in contrast enhanced imaging after radio-frequency (RF) ablation. The objective of this study was to evaluate the role of quantitative of contrast-enhanced ultrasound (CEUS) in early differentiation of BPE from residual tumor in a BD-IX rat subcutaneous colon cancer model. A phantom study was first performed to test the validity of the perfusion parameters in predicting blood flow of two US contrast imaging modes-contrast harmonic imaging (CHI) and microflow imaging (MFI). To create a simple model of BPE, a peripheral portion of the tumor was ablated along with surrounding normal tissue, leaving part of the tumor untreated. First-pass dynamic enhancement (FPDE) and MFI scans of CEUS were performed before ablation and immediately, 1, 4 and 7 days after ablation. Time-intensity-curves in regions of BPE and residual tumor were fitted to the function y = A(1-exp[-β{t-t0}])+C, in which A, β, t0 and C represent blood volume, flow speed, time to start and baseline intensity, respectively. In the phantom study, positive linear correlations were noted between A, β, Aβ and contrast concentration, speed and flow rate, respectively, in both CHI and MFI. On CEUS images of the in vivo study, the unenhanced ablated zone was surrounded by BPE and irregular peripheral enhancement consistent with residual tumor. On days 0, 4 and 7, blood volume (A) in BPE was significantly higher than that in residual tumor in both FPDE imaging and MFI. Significantly greater blood flow (Aβ) was seen in BPE compared with residual tumor tissue in FPDE on day 7 and in MFI on day 4. The results of this study demonstrate that qualitative CEUS can be potentially used for early detection of viable tumor in post-ablation assessment. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  1. Mechanism-Based Enhanced Delivery of Drug-Loaded Targeted Nanoparticles for Breast Cancer Therapy

    Science.gov (United States)

    2014-02-01

    by confocal immunofluorescence microscopy. B, a zoom image of boxed regions from two independent fields demonstrating co- localization (yellow) of...nanogel in ErbB2+ breast cancer mouse model: The cytotoxic effects of the DOX and 17-AAG combination have been reported in literature . We have...overexpressing breast cancer cells. Cancer Biol Ther 2008;7(10):1630-40. 8. Waterhouse, D.N., Tardi , P. G., Mayer, L. D., Bally, M. B., A comparison

  2. A potential role for immunotherapy in thyroid cancer by enhancing NY-ESO-1 cancer antigen expression.

    Science.gov (United States)

    Gunda, Viswanath; Frederick, Dennie T; Bernasconi, Maria J; Wargo, Jennifer A; Parangi, Sareh

    2014-08-01

    NY-ESO-1 is one of the most immunogenic members of the cancer/testis antigen family and its levels can be increased after exposure to demethylating and deacetylating agents. This cytoplasmic antigen can serve as a potent target for cancer immunotherapy and yet has not been well studied in differentiated thyroid cancer cells. We studied the baseline expression of NY-ESO-1 messenger RNA and protein before and after exposure to 5-aza-2'-deoxycytidine (DAC) (72 hours) in a panel of thyroid cancer cell lines using quantitative polymerase chain reaction and Western blot. HLA-A2+, NY-ESO-1+ thyroid cell lines were then co-cultured with peripheral blood lymphocytes transduced with NY-ESO-1 specific T-cell receptor (TCR) and assayed for interferon-gamma and Granzyme-B release in the medium. SCID mice injected orthotopically with BCPAP cells were treated with DAC to evaluate for NY-ESO-1 gene expression in vivo. None of the thyroid cancer cell lines showed baseline expression of NY-ESO-1. Three cell lines, BCPAP, TPC-1, and 8505c, showed an increase in NY-ESO-1 gene expression with DAC treatment and were found to be HLA-A2 positive. DAC-treated target BCPAP and TPC-1 tumor cells with up-regulated NY-ESO-1 levels were able to mount an appropriate interferon-gamma and Granzyme-B response upon co-culture with the NY-ESO-1-TCR-transduced peripheral blood lymphocytes. In vivo DAC treatment was able to increase NY-ESO-1 expression in an orthotopic mouse model with BCPAP cells. Our data suggest that many differentiated thyroid cancer cells can be pressed to express immune antigens, which can then be utilized in TCR-based immunotherapeutic interventions.

  3. Enhancing return-to-work in cancer patients, development of an intervention and design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Taskila Taina

    2010-07-01

    Full Text Available Abstract Background Compared to healthy controls, cancer patients have a higher risk of unemployment, which has negative social and economic impacts on the patients and on society at large. Therefore, return-to-work of cancer patients needs to be improved by way of an intervention. The objective is to describe the development and content of a work-directed intervention to enhance return-to-work in cancer patients and to explain the study design used for evaluating the effectiveness of the intervention. Development and content of the intervention The work-directed intervention has been developed based on a systematic literature review of work-directed interventions for cancer patients, factors reported by cancer survivors as helping or hindering their return-to-work, focus group and interview data for cancer patients, health care professionals, and supervisors, and vocational rehabilitation literature. The work-directed intervention consists of: 1 4 meetings with a nurse at the treating hospital department to start early vocational rehabilitation, 2 1 meeting with the participant, occupational physician, and supervisor to make a return-to-work plan, and 3 letters from the treating physician to the occupational physician to enhance communication. Study design to evaluate the intervention The treating physician or nurse recruits patients before the start of initial treatment. Patients are eligible when they have a primary diagnosis of cancer, will be treated with curative intent, are employed at the time of diagnosis, are on sick leave, and are between 18 and 60 years old. After the patients have given informed consent and have filled out a baseline questionnaire, they are randomised to either the control group or to the intervention group and receive either care as usual or the work-directed intervention, respectively. Primary outcomes are return-to-work and quality of life. The feasibility of the intervention and direct and indirect costs will be

  4. Long-term exposure to estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells.

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    Yu-Wei Chang

    Full Text Available Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2 on the efficacy of chemotherapeutic drugs in breast cancer cells. Estrogen responsive MCF-7 and T47D breast cancer cells were long-term exposed to 100 pg/ml estr