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Sample records for line brain cancer

  1. Brain cancer spreads

    DEFF Research Database (Denmark)

    Perryman, Lara; Erler, Janine Terra

    2014-01-01

    The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue).......The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue)....

  2. Biofabrication of morphology improved cadmium sulfide nanoparticles using Shewanella oneidensis bacterial cells and ionic liquid: For toxicity against brain cancer cell lines.

    Science.gov (United States)

    Wang, Li; Chen, Siyuan; Ding, Yiming; Zhu, Qiang; Zhang, Nijia; Yu, Shuqing

    2018-01-01

    The present work determines the anticancer activity of bio-mediated synthesized cadmium sulfide nanoparticles using the ionic liquid and bacterial cells (Shewanella oneidensis). Bacterial cells have been exposed to be important resources that hold huge potential as ecofriendly, cost-effective, evading toxic of dangerous chemicals and the alternative of conventional physiochemical synthesis. The Shewanella oneidensis is an important kind of metal reducing bacterium, known as its special anaerobic respiratory and sulfate reducing capacity. The crystalline nature, phase purity and surface morphology of biosynthesized cadmium sulfide nanoparticles were analyzed by Fourier transform infrared spectroscopy, X-ray diffraction, Field emission scanning electron microscopy, Energy dispersive spectroscopy and Transmission electron microscopy. The use of imidazolium based ionic liquids as soft templating agent for controlling self-assembly and crystal growth direction of metal sulfide nanoparticles has also advanced as an important method. The microscopic techniques showed that the nanoparticles are designed on the nano form and have an excellent spherical morphology, due to the self-assembled mechanism of ionic liquid assistance. The antitumor efficiency of the cadmium sulfide nanoparticles was investigated against brain cancer cell lines using rat glioma cell lines. The effectively improved nano-crystalline and morphological structure of CdS nanoparticles in the presence of IL exhibit excellent cytotoxicity and dispersion ability on the cell shape is completely spread out showing a nice toxic environment against cancer cells. The cytotoxicity effect of cadmium sulfide nanoparticles was discussed with a diagrammatic representation. Copyright © 2017. Published by Elsevier B.V.

  3. Brain cancer treatment

    International Nuclear Information System (INIS)

    Gruszow, S.

    1998-01-01

    As soon as 1936 an American physicist proposed to treat certain forms of cancer by using the nuclear reaction: n + 10 B → 7 Li + 4 He where the alpha particles produced could destroy the DNA of surrounding cells. From 1951 to 1961 62 patients underwent this treatment for brain cancer. The results were unsatisfactory: the neutrons were not energetic enough to enter brain tissues deeply and were accompanied by strongly damaging gamma radiation. In Netherlands an installation using the high flux reactor of Petten has been set up. A highly focused neutron beam of about 10 keV with reduced gamma radiation is produced. The first step is to determine the limit exposure and the maximal permissible concentration of boron. (A.C.)

  4. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  5. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  6. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  7. Breast cancer cell lines: friend or foe?

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  8. Computer screens and brain cancer

    International Nuclear Information System (INIS)

    Wood, A.W.

    1995-01-01

    Australia, both in the media and at the federal government level, over possible links between screen-based computer use and cancer, brain tumour in particular. The screen emissions assumed to be the sources of the putative hazard are the magnetic fields responsible for horizontal and vertical scanning of the display. Time-varying fluctuations in these magnetic fields induce electrical current flows in exposed tissues. This paper estimates that the induced current densities in the brain of the computer user are up to 1 mA/m 2 (due to the vertical flyback). Corresponding values for other electrical appliances or installations are in general much less than this. The epidemiological literature shows no obvious signs of a sudden increase in brain tumour incidence, but the widespread use of computers is a relatively recent phenomenon. The occupational use of other equipment based on cathode ray tubes (such as TV repair) has a much longer history and has been statistically linked to brain tumour in some studies. A number of factors make this an unreliable indicator of the risk from computer screens, however. 42 refs., 3 tabs., 2 figs

  9. Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and ... The morphology of the HepG2 cell nucleus was investigated by Hoechst 33342, ..... Gong F, Liang Y, Xie P, Chau F. Information theory.

  10. (Asteraceae) Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

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

  11. Difference in membrane repair capacity between cancer cell lines and a normal cell line

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; McNeil, Anna K.; Novak, Ivana

    2016-01-01

    repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique...... cancer cell lines (p immortalized cell line (p

  12. Nanotherapeutic approaches for brain cancer management.

    Science.gov (United States)

    Saenz del Burgo, Laura; Hernández, Rosa María; Orive, Gorka; Pedraz, Jose Luis

    2014-07-01

    Around the world, cancer remains one of the most important causes of morbidity and mortality. Worldwide, approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed every year. Nanotherapeutic approaches hold tremendous potential for diagnosis and treatment of brain cancer, including the ability to target complex molecular cargoes to the tumor sites and the capacity of crossing the blood-brain barrier and accessing to the brain after systemic administration. A new generation of "smart" nanoparticles has been designed as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic and thermotherapy. This review highlights the latest research, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers. This comprehensive review highlights the latest research results, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers, with a special focus on "smart" nanoparticles as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic therapy and localized thermotherapy. © 2014.

  13. Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

    Directory of Open Access Journals (Sweden)

    Thirugnanam Sivasakthivel

    2013-02-01

    Full Text Available Abstract Background The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs, which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and

  14. Treatment strategies for lung cancer brain metastases

    International Nuclear Information System (INIS)

    Nakade, Masaharu; Kohno, Keijirou; Watanabe, Hiroyoshi

    1997-01-01

    Forty-one patients suffered initial relapses with brain metastasis after surgery for non-small lung cancer at our hospital between 1978 and 1995. These patients were a total of 8.4% of all cases of surgical removal, and had an average relapse period of 8.6 months ± 8.0 months after surgery on the primary lesions. Of these, surgical removal of metastasized lesions was performed on 18 patients (43%), in which the 5-year post-operative survival rate was 35.7%, and the median survival time was good at 28 months. It was found that the survival period was significantly extended in the group whose relapse period was less than one year after surgery on the primary lesions, and in the group who received cranial irradiation post-operatively on the metastasized brain lesion. Following surgery on the metastasized lesion, second relapses occurred in nine patients, and six patients suffered from second relapses in the brain, of which four did not receive cranial irradiation post-operatively. Cases of radiotherapy in patients of 70 years of age or more frequently manifested post-radiotherapy subacute neuropathy. From the above, it is thought that the following procedures should be adopted: Periodic examination for brain metastasis during the 24 months following surgery for non-small cell lung carcinoma for purposes of early detection; in cases where brain metastasis is detected, if no metastasis is identified in other organs, a policy of surgical removal should be adopted where possible; and, in cases of 70 years of age or less following surgery on the metastasized lesion, cranial irradiation should be considered. (author)

  15. Overexpression of LINE-1 Retrotransposons in Autism Brain.

    Science.gov (United States)

    Shpyleva, Svitlana; Melnyk, Stepan; Pavliv, Oleksandra; Pogribny, Igor; Jill James, S

    2018-02-01

    Long interspersed nuclear elements-1 (LINE-1 or L1) are mobile DNA sequences that are capable of duplication and insertion (retrotransposition) within the genome. Recently, retrotransposition of L1 was shown to occur within human brain leading to somatic mosaicism in hippocampus and cerebellum. Because unregulated L1 activity can promote genomic instability and mutagenesis, multiple mechanisms including epigenetic chromatin condensation have evolved to effectively repress L1 expression. Nonetheless, L1 expression has been shown to be increased in patients with Rett syndrome and schizophrenia. Based on this evidence and our reports of oxidative stress and epigenetic dysregulation in autism cerebellum, we sought to determine whether L1 expression was increased in autism brain. The results indicated that L1 expression was significantly elevated in the autism cerebellum but not in BA9, BA22, or BA24. The binding of repressive MeCP2 and histone H3K9me3 to L1 sequences was significantly lower in autism cerebellum suggesting that relaxation of epigenetic repression may have contributed to increased expression. Further, the increase in L1 expression was inversely correlated with glutathione redox status consistent with reports indicating that L1 expression is increased under pro-oxidant conditions. Finally, the expression of transcription factor FOXO3, sensor of oxidative stress, was significantly increased and positively associated with L1 expression and negatively associated with glutathione redox status. While these novel results are an important first step, future understanding of the contribution of elevated L1 expression to neuronal CNVs and genomic instability in autism will depend on emerging cell-specific genomic technologies, a challenge that warrants future investigation.

  16. Apoptosis induction of epifriedelinol on human cervical cancer cell line

    African Journals Online (AJOL)

    Background: Present investigation evaluates the antitumor activity of epifriedelinol for the management of cervical cancer by inducing process of apoptosis. Methods: Human Cervical Cancer Cell Line, C33A and HeLa were selected for study and treated with epifriedelinol at a concentration of (50-1000 μg/ml). Cytotoxicity of ...

  17. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    International Nuclear Information System (INIS)

    Yang, Heekyoung; Yoon, Su Jin; Jin, Juyoun; Choi, Seung Ho; Seol, Ho Jun; Lee, Jung-Il

    2011-01-01

    Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  18. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    International Nuclear Information System (INIS)

    Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

    2009-01-01

    The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BK Ca ) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BK Ca channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BK Ca channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BK Ca channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BK Ca channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BK Ca channel expression in breast cancer metastatic to brain and the mechanism of its

  19. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  20. Antiproliferative effect of isopentenylated coumarins on several cancer cell lines.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y; Ito, C; Furukawa, H

    2001-01-01

    33 coumarins, mainly the simple isopentenylated coumarins and derived pyrano- and furanocoumarins, were examined for their antiproliferative activity towards several cancer and normal human cell lines. The pyrano- and furanocoumarins showed strong activity against the cancer cell lines, whereas they had weak antiproliferative activity against the normal human cell lines. The decreasing rank order of potency was osthenone (10), clausarin (25), clausenidin (26), dentatin (24), nordentatin (23), imperatorin (29), seselin (27), xanthyletin (21), suberosin (17), phebalosin (8) and osthol (12). The structure-activity relationship established from the results revealed that the 1,1-dimethylallyl and isopentenyl groups have an important role for antiproliferative activity.

  1. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tarek H. Mouhieddine

    2015-11-01

    Full Text Available Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma and SHSY-5Y (neuroblastoma cell lines.Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence.

  2. Radiation sensitivity of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

    1989-01-01

    X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

  3. Investigation of the selenium metabolism in cancer cell lines

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines

    DEFF Research Database (Denmark)

    Viticchiè, Giuditta; Lena, Anna Maria; Latina, Alessia

    2011-01-01

    Prostate cancers show a slow progression from a local lesion (primary tumor) to a metastatic and hormone-resistant phenotype. After an initial step of hyperplasia, in a high percentage of cases a neoplastic transformation event occurs that, less frequently, is followed by epithelial to mesenchymal...... cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2...

  5. Conformity index for brain cancer patients

    International Nuclear Information System (INIS)

    Petkovska, Sonja; Tolevska, Cveta; Kraleva, Slavica; Petreska, Elena

    2010-01-01

    The purpose of this study is to present the level of conformity achieved by using 3D conformal radiotherapy for brain cancer patients. Conformity index is a helpful quantitative tool for assessing (evaluating) the quality of a treatment plan. Treatment plans made for ninety patients with brain tumor are worked on this paper. The patients are in supine position and immobilized with thermoplastic masks for the head. Computed tomography data sets with 5 mm scan thickness are used to create a 3D image. All structures of interest are contoured. In order to obtain an optimal dose distribution, treatment fields are fit around target volume with set-up margins of 7mm in each direction. The conformity index values are between 1.21 and 2.04. Value of 1.8 is exceeded in eighteen cases; nine of them are bigger than 1.9 and only three of them are above 2. The target volume for each of these extreme CI values is ideal covered (between 95% and 105% of the prescribed dose). The most acceptable conformity index value in this paper belongs to the plan with the lowest minimal dose (84.7%). It can be concluded that conformity index is necessary but not sufficient factor for assessing radiation treatment plan conformity. To be able to estimate the acceptability of some treatment plan in daily practice, additional information as minimal, maximal and mean dose into target volume, as well as health tissues coverage must be taken into account.(Author)

  6. In vitro study of combined cilengitide and radiation treatment in breast cancer cell lines

    International Nuclear Information System (INIS)

    Lautenschlaeger, Tim; Perry, James; Peereboom, David; Li, Bin; Ibrahim, Ahmed; Huebner, Alexander; Meng, Wei; White, Julia; Chakravarti, Arnab

    2013-01-01

    Brain metastasis from breast cancer poses a major clinical challenge. Integrins play a role in regulating adhesion, growth, motility, and survival, and have been shown to be critical for metastatic growth in the brain in preclinical models. Cilengitide, an αvβ3/αvβ5 integrin inhibitor, has previously been studied as an anti-cancer drug in various tumor types. Previous studies have shown additive effects of cilengitide and radiation in lung cancer and glioblastoma cell lines. The ability of cilengitide to enhance the effects of radiation was examined preclinically in the setting of breast cancer to assess its possible efficacy in the setting of brain metastasis from breast cancer. Our panel of breast cells was composed of four cell lines: T-47D (ER/PR+, Her2-, luminal A), MCF-7 (ER/PR+, Her2-, luminal A), MDA-MB-231 (TNBC, basal B), MDA-MB-468 (TNBC, basal A). The presence of cilengitide targets, β3 and β5 integrin, was first determined. Cell detachment was determined by cell counting, cell proliferation was determined by MTS proliferation assay, and apoptosis was measured by Annexin V staining and flow cytometry. The efficacy of cilengitide treatment alone was analyzed, followed by assessment of combined cilengitide and radiation treatment. Integrin β3 knockdown was performed, followed by cilengitide and radiation treatment to test for incomplete target inhibition by cilengitide, in high β3 expressing cells. We observed that all cell lines examined expressed both β3 and β5 integrin and that cilengitide was able to induce cell detachment and reduced proliferation in our panel. Annexin V assays revealed that a portion of these effects was due to cilengitide-induced apoptosis. Combined treatment with cilengitide and radiation served to further reduce proliferation compared to either treatment alone. Following β3 integrin knockdown, radiosensitization in combination with cilengitide was observed in a previously non-responsive cell line (MDA-MB-231

  7. Survey of Differentially Methylated Promoters in Prostate Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Yipeng Wang

    2005-08-01

    Full Text Available DNA methylation, copy number in the genomes of three immortalized prostate epithelial, five cancer cell lines (LNCaP, PC3, PC3M, PC3M-Pro4, PC3MLN4 were compared using a microarray-based technique. Genomic DNA is cut with a methylation-sensitive enzyme Hpall, followed by linker ligation, polymerase chain reaction (PCR amplification, labeling, hybridization to an array of promoter sequences. Only those parts of the genomic DNA that have unmethylated restriction sites within a few hundred base pairs generate PCR products detectable on an array. Of 2732 promoter sequences on a test array, 504 (18.5% showed differential hybridization between immortalized prostate epithelial, cancer cell lines. Among candidate hypermethylated genes in cancer-derived lines, there were eight (CD44, CDKN1A, ESR1, PLAU, RARB, SFN, TNFRSF6, TSPY previously observed in prostate cancer, 13 previously known methylation targets in other cancers (ARHI, bcl-2, BRCA1, CDKN2C, GADD45A, MTAP, PGR, SLC26A4, SPARC, SYK, TJP2, UCHL1, WIT-1. The majority of genes that appear to be both differentially methylated, differentially regulated between prostate epithelial, cancer cell lines are novel methylation targets, including PAK6, RAD50, TLX3, PIR51, MAP2K5, INSR, FBN1, GG2-1, representing a rich new source of candidate genes used to study the role of DNA methylation in prostate tumors.

  8. Brain abscess mimicking lung cancer metastases; a case report.

    Science.gov (United States)

    Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

    2013-01-01

    A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

    Directory of Open Access Journals (Sweden)

    He YY

    2016-04-01

    Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

  10. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn

    2008-01-01

    BACKGROUND: The past years' therapy for colorectal cancer has evolved rapidly with the introduction of novel cytotoxic agents such as irinotecan, capecitabine and oxaliplatin. Further advances have been achieved with the integration of targeted agents such as bevacizumab, cetuximab and recently......, panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...

  11. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

  12. Crossing the LINE toward genomic instability: LINE-1 retrotransposition in cancer

    Science.gov (United States)

    Kemp, Jacqueline; Longworth, Michelle

    2015-12-01

    Retrotransposons are repetitive DNA sequences that are positioned throughout the human genome. Retrotransposons are capable of copying themselves and mobilizing new copies to novel genomic locations in a process called retrotransposition. While most retrotransposon sequences in the human genome are incomplete and incapable of mobilization, the LINE-1 retrotransposon, which comprises approximately 17% of the human genome, remains active. The disruption of cellular mechanisms that suppress retrotransposon activity is linked to the generation of aneuploidy, a potential driver of tumor development. When retrotransposons insert into a novel genomic region, they have the potential to disrupt the coding sequence of endogenous genes and alter gene expression, which can lead to deleterious consequences for the organism. Additionally, increased LINE-1 copy numbers provide more chances for recombination events to occur between retrotransposons, which can lead to chromosomal breaks and rearrangements. LINE-1 activity is increased in various cancer cell lines and in patient tissues resected from primary tumors. LINE-1 activity also correlates with increased cancer metastasis. This review aims to give a brief overview of the connections between LINE-1 retrotransposition and the loss of genome stability. We will also discuss the mechanisms that repress retrotransposition in human cells and their links to cancer.

  13. The Biology of Breast Cancer in Brain Metastasis

    National Research Council Canada - National Science Library

    Price, Janet

    2001-01-01

    ...% of breast cancer patients and found at autopsy in 20 to 30%. Survival after detection of brain metastases can be short, and the therapy currently available only offers the hope of surviving one year to 20% of patients...

  14. Exposure to magnetic field and brain cancer among child

    International Nuclear Information System (INIS)

    Mir, L.

    2008-01-01

    The risk of childhood brain cancer as a function of magnetic field exposure has been studied less than the risk of leukemia. this updated meta-analysis of thirteen epidemiologic studies thus provides an important contribution to the literature. No increased risk of brain cancer was found, and there were no differences by method of exposure assessment. Doubt remains only for the highest exposure levels, for which very limited data are available. (author)

  15. Relapsing pattern of brain metastasis after brain irradiation in small cell lung cancer

    International Nuclear Information System (INIS)

    Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki; Kono, Koichi; Yoden, Eisaku; Mori, Takeki

    1997-01-01

    Many reports concerning radiation therapy for brain metastasis have been published, and which of the various methods urged by these reports provide optional control is still controversial. According to developing diagnosis of metastasis in CNS, therapeutic problems should be referred. We reviewed 67 patients with small cell lung cancer and brain metastasis who underwent brain irradiation (Ave. 47 Gy/5W), and all 15 patients with brain relapse after the irradiation. Relapsing patterns in this clinical setting were divided into local regrowth in the same lesions and re-metastasis (reseeding) in other regions, by reviewing follow up CT and MRI studies. Total survival among 15 patients with brain relapse and 52 without relapse was longer in the former cases than the later: 1-, and 2-year survival (47/19%, 13/8%) and MST (10.8/5.7 months), from the initial brain irradiation. The concerned significant factors limited in younger age, low value of LDH and improvement of NF. Of the 15 patients with brain relapse, 4 developed local regrowth and 11 did re-metastasis. The period of remission since brain irradiation were 172±94.4 and 393±281 days, respectively. Lower number of brain metastasis and lower value of LDH were shown in re-metastasis patients. At the time of brain relapse, 11 patients had recurrence of carcinomatous meningitis. 4 patients were treated with whole brain re-irradiation. All patients died of cancer, including 12 of relapsing CNS diseases and 3 of primary lesion and hepatic metastasis. Leukoencephalopathy developed in 2 patients. Survival since the brain relapse was 2 to 238 days without significant difference in cases of local regrowth and re-metastasis. According to our data on relapsing pattern of brain metastasis after conventional fractionated brain irradiation with an objective dose of 50 Gy, 75% of brain relapse were re-metastasis, we appreciate this irradiation for initial brain metastasis if limited to the brain. (author)

  16. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  17. Value of brain computed tomography in small cell lung cancers

    International Nuclear Information System (INIS)

    Fernet, M.; Breau, J.L.; Goldlust, D.; Israel, L.

    1988-01-01

    88 patients with small cell lung cancer were studied. Brain scans were performed first at initial staging and repeated at regular intervals during the survey. The results confirm the limited value of brain scans in the detection of metastases in neurologically asymptomatic patients [fr

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

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  19. First line chemotherapy plus trastuzumab in metastatic breast cancer ...

    African Journals Online (AJOL)

    First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study. ... The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab ...

  20. Cytotoxicity against MCF-7 breast cancer cell line and interaction ...

    African Journals Online (AJOL)

    N6-furfuryladenine (kinetin) is a cytokinin growth factor with several biological effects observed in human cells and fruit flies. Kinetin exists naturally in the DNA of almost all organisms tested so far, including human cells and various plants. The cytotoxicity effect of kinetin on MCF-7 breast cancer cell lines was measured by ...

  1. Antibacterial and anti-breast cancer cell line activities of ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activity of extracts of Sanghuangporus sp.1 fungus against pathogenic bacteria and a breast cancer cell line. Methods: The wild fruiting body and mycelium of Sanghuangporus sp.1 were extracted with water and ethanol by ultrasonication extraction. The activity of the extracts against pathogenic ...

  2. Sensitivity of breast cancer cell lines to recombinant thiaminase I.

    Science.gov (United States)

    Liu, Shuqian; Monks, Noel R; Hanes, Jeremiah W; Begley, Tadhg P; Yu, Hui; Moscow, Jeffrey A

    2010-05-01

    We have previously shown that the expression of the thiamine transporter THTR2 is decreased sevenfold in breast cancer, which may leave breast cancer cells vulnerable to acute thiamine starvation. This concept was supported by the observation that MDA231 breast cancer xenografts demonstrated growth inhibition in mice fed a thiamine-free diet. We purified recombinant Bacillus thiaminolyticus thiaminase I enzyme, which digests thiamine, to study acute thiamine starvation in breast cancer. Thiaminase I enzyme was cytotoxic in six breast cancer cell lines with IC(50)s ranging from 0.012 to 0.022 U/ml. The growth inhibitory effects of the combination of thiaminase I with either doxorubicin or paclitaxel were also examined. Over a wide range of drug concentrations, thiaminase 1 was consistently synergistic or additive with doxorubicin and paclitaxel in MCF-7, ZR75, HS578T and T47D cell lines, with most combinations having a calculated combination index (CI) of less than 0.8, indicating synergy. Although thiaminase I exposure did not stimulate the energy-sensing signaling kinases AKT, AMPK and GSK-3beta in MCF-7, ZR75, HS578T and T47D cell lines, thiaminase I exposure did stimulate expression of the ER stress response protein GRP78. In summary, thiaminase I is cytotoxic in breast cancer cell lines and triggers the unfolded protein response. These findings suggest that THTR2 down-regulation in breast tumors may present a nutritional vulnerability that could be exploited by thiaminase I enzyme therapy.

  3. Results of radiotherapy for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

    1987-01-01

    Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation. (author)

  4. Results of radiotherapy for brain metastases from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

    1987-02-01

    Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation.

  5. Vinorelbine as first-line or second-line therapy for advanced breast cancer

    DEFF Research Database (Denmark)

    Langkjer, Sven T; Ejlertsen, Bent; Mouridsen, Henning

    2008-01-01

    INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

  6. Brain abscess mimicking brain metastasis in breast cancer

    International Nuclear Information System (INIS)

    Khullar, P.; Datta, N.R.; Wahi, I.K.; Kataria, S.

    2016-01-01

    61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acety- laspartate) ratios of 1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient’s previous history

  7. Brain abscess mimicking brain metastasis in breast cancer.

    Science.gov (United States)

    Khullar, Pooja; Datta, Niloy R; Wahi, Inderjeet Kaur; Kataria, Sabeena

    2016-03-01

    61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acetylaspartate) ratios of ∼1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient's previous history. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  8. The antiproliferative effect of coumarins on several cancer cell lines.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Ogawa, K; Sugiura, M; Yano, M; Yoshizawa, Y

    2001-01-01

    Twenty-one coumarins were examined for their antiproliferative activity towards several cancer cell lines, namely lung carcinoma (A549), melanin pigment producing mouse melanoma (B16 melanoma 4A5), human T-cell leukemia (CCRF-HSB-2), and human gastric cancer, lymph node metastasized (TGBC11TKB). The structure-activity relationship established from the results revealed that the 6,7-dihydroxy moiety had an important role for their antiproliferative activity. Analysis of cell cycle distribution indicated that esculetin-treated cells accumulated in the G1 (at 400 microM) or in S phase (at 100 microM).

  9. Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

    OpenAIRE

    Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

    1992-01-01

    Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-...

  10. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  11. Brain metastasis of breast cancer: clinical and radiologic findings

    International Nuclear Information System (INIS)

    An, Jin Kyung; Oh, Ki Keun; Kim, Eun Kyung; Chung, Tae Sub

    2001-01-01

    To analyse the clinical and radiologic findings brain metastasis of breast cancer. Sixty-one of 1399 patients in whom breast cancer was diagnosed between 1983 and 1999 were affected by brain metastasis. Among these 1399, the stage of the breast cancer, in descending order of frequency, was IIA (n=508), I (n=366), IIB (n=247), IIIA (n=189), IIIB (n=45), 0 (n=33) and IV (n=11). The stage of the 61 brain metastases, similarly ordered, was IIB (12.5%), IIA (3.9%), IIIA (3.1%), IIIB (2.2%) and I (0.8%). In all confirmed breast cancers, the age distribution, in descending order of frequency, was 40-49years (n=610), 50-59 (n=301), 30-39 (n=291), 60-69 (n=124), 20-19 (n=41), 70-79 (n=28), and 80-89 (n=4). The age distribution of brain metastasis was 20-29 (14.6%), 30-39 (7.9%), 50-59 (4.6%). 40-49 (2.6%) and 60-69 (1.6%). Imaging findings were available for 35 of the 61 patients affected by brain metastasis, and symptoms from brain among the 35, analysis of the symptoms of this metastasis, the site of the first distant metastasis to an extracranial or cranial organ, the interval from the diagnosis of breast cancer to brain metastasis, the interval from brain metastasis to death, and the difference in survival time between patients with initial and succeeding brain metastasis was undertaken. Brain CT findings were analysed in 29 cases and MRI findings in eight. The most common symptoms were headache and vomiting. Among the 35 brain metastasis patients for whom imaging findings were available, other systemic metastasis occurred in 22. Initial brain metastasis occurred in the remaining 13, and in seven of these there was also coincident organ metastasis, while six showed only brain metastasis, The most frequent intervals from the diagnosis of breast cancer to brain metastasis were 1-2 years(8/35) and 2-3years(8/35). Twenty-six of 35 patients died within one year of brain metastasis. Patients in whom this occurred later survived for longer than those in whom it occurred

  12. Long term imaging of living brain cancer cells

    Science.gov (United States)

    Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

    2018-02-01

    QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

  13. Comparative proteomics analysis of oral cancer cell lines: identification of cancer associated proteins

    Science.gov (United States)

    2014-01-01

    Background A limiting factor in performing proteomics analysis on cancerous cells is the difficulty in obtaining sufficient amounts of starting material. Cell lines can be used as a simplified model system for studying changes that accompany tumorigenesis. This study used two-dimensional gel electrophoresis (2DE) to compare the whole cell proteome of oral cancer cell lines vs normal cells in an attempt to identify cancer associated proteins. Results Three primary cell cultures of normal cells with a limited lifespan without hTERT immortalization have been successfully established. 2DE was used to compare the whole cell proteome of these cells with that of three oral cancer cell lines. Twenty four protein spots were found to have changed in abundance. MALDI TOF/TOF was then used to determine the identity of these proteins. Identified proteins were classified into seven functional categories – structural proteins, enzymes, regulatory proteins, chaperones and others. IPA core analysis predicted that 18 proteins were related to cancer with involvements in hyperplasia, metastasis, invasion, growth and tumorigenesis. The mRNA expressions of two proteins – 14-3-3 protein sigma and Stress-induced-phosphoprotein 1 – were found to correlate with the corresponding proteins’ abundance. Conclusions The outcome of this analysis demonstrated that a comparative study of whole cell proteome of cancer versus normal cell lines can be used to identify cancer associated proteins. PMID:24422745

  14. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    .2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain cancer......Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...

  15. Computed tomography in brain metastases of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuratsu, Jun-ichi; Matsukado, Yasuhiko; Sueyoshi, Nobuyuki [Kumamoto Univ. (Japan). School of Medicine; Nonaka, Nobuhito; Sano, Yoshinori; Itoyama, Yoichi; Miura, Giichi

    1984-10-01

    Metastatic brain tumors from colorectal cancers are relatively rare. In previous reports, the incidence ranged from 3 to 5 percent of all metastatic brain tumors. We report 7 cases of metastatic brain tumors from colorectal cancers. The time interval from the diagnosis of the primary tumors to the brain metastasis was 3 years on the average. Metastasis to the lung and liver were also found in 6 cases at the time of the diagnosis of the brain metastasis. The CEA levels in the serum were highly elevated in all cases. Solitary metastasis was found in all cases; cancers tend to metastasize in the deep area of the cerebrum or cerebellum. On a plain CT scan, tumors were demonstrated as ring-type, with a high-density mass, and ring-like enhancement was seen in 6 cases. Prognosis was very poor in most cases. The median survival time from diagnosis of brain metastasis was 4.5 months in the 2 cases with surgery and 3.5 months in the 4 cases without surgery.

  16. Management of lung cancer brain metastasis: An overview

    Directory of Open Access Journals (Sweden)

    Himanshu Srivastava

    2017-01-01

    Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

  17. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2013-10-01

    antibodies to the endothelial marker, CD31 (Serotec, Raleigh, NC) followed by Cy3-conjugated secondary antibody ( Jackson Immunoresearch Laboratories...in the brain. Cancer Res 67, 4190-4198, doi:67/9/4190 [pii] 10.1158/0008-5472.CAN-06- 3316 (2007). 7 Percy , D. B. et al. In vivo characterization of

  18. UV light blocks EGFR signalling in human cancer cell lines

    DEFF Research Database (Denmark)

    Olsen, BB; Neves-Petersen, M T; Klitgaard, S

    2007-01-01

    UV light excites aromatic residues, causing these to disrupt nearby disulphide bridges. The EGF receptor is rich in aromatic residues near the disulphide bridges. Herein we show that laser-pulsed UV illumination of two different skin-derived cancer cell lines i.e. Cal-39 and A431, which both...... antibodies. There was a threshold level, below which the receptor could not be blocked. In addition, illumination caused the cells to upregulate the cyclin-dependent kinase inhibitor p21WAF1, irrespective of the p53 status. Since the EGF receptor is often overexpressed in cancers and other proliferative skin...... disorders, it might be possible to significantly reduce the proliferative potential of these cells making them good targets for laser-pulsed UV light treatment....

  19. Effects of hypoxia on human cancer cell line chemosensitivity

    Science.gov (United States)

    2013-01-01

    Background Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia. Methods A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA). Results Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs. Conclusions A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia. PMID:23829203

  20. Radial bisection of words and lines in right-brain-damaged patients with spatial neglect.

    Science.gov (United States)

    Veronelli, Laura; Arduino, Lisa S; Girelli, Luisa; Vallar, Giuseppe

    2017-09-01

    The bisection of lines positioned radially (with the two ends of the line close and far, with respect to the participant's body) has been less investigated than that of lines placed horizontally (with their two ends left and right, with respect to the body's midsagittal plane). In horizontal bisection, patients with left neglect typically show a rightward bias for both lines and words, greater with longer stimuli. As for radial bisection, available data indicate that neurologically unimpaired participants make a distal error, while results from right-brain-damaged patients with left spatial neglect are contradictory. We investigated the bisection of radially oriented words, with the prediction that, during bisection, linguistic material would be recoded to its canonical left-to-right format in reading, with the performance of neglect patients being similar to that for horizontal words. Thirteen right-brain-damaged patients (seven with left spatial neglect) and fourteen healthy controls were asked to manually bisect 40 radial and 40 horizontal words (5-10 letters), and 80 lines, 40 radial and 40 horizontal, of comparable length. Right-brain-damaged patients with spatial neglect exhibited a proximal bias in the bisection of short radial words, with the proximal part corresponding to the final right part of horizontally oriented words. This proximal error was not found in patients without neglect and healthy controls. For bisection, short radial words may be recoded to the canonical orthographic horizontal format, unveiling the impact of left neglect on radially oriented stimuli. © 2015 The British Psychological Society.

  1. Screening and Establishment of Human Lung Cancer Cell Lines 
with Organ-specific Metastasis Potential

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2014-03-01

    Full Text Available Background and objective Cancer metastasis is not only the malignant marker and characteristics, but also the main cause of failure to cure and lose their life in the patients with lung cancer. Lung cancer metastasis has organ-specific characteristics. The most common sites of lung cancer metastasis are mediastinal lymph node, brain, bone, liver and adrenal gland. The aim of this study is to screen and establish lung cancer cell model with organ-specific metastasis potential with human high-metastatic large cell lung cancer cell line L9981 established by our laboratory previously, and to provide cell models for studying the mechanisms and signal regulation of organ-specific metastasis of lung cancer. Materials and methods The parent lung cancer cell line, L9981-Luc, was inoculated in the armpit of nude mice. The live animal imaging system, IVIS-200, was used to detect the lung cancer organ-specific metastasis every week. When the organ-specific metastasis were established, the nude mices bearing the lung cancer were sacrificed when they became moribund. Under sterile conditions, the organs (mediastinal lymph nodes, lung, spinal column and brain with lung cancer organ-specific metastasis were removed and the metastasized nodules were dissected free of connective tissue and blood clots, and rinsed twice with medium. The metastasized nodules were finely minced using sterile scalpel blades in medium, and the cells were seeded in tissue culture dishes. Then, the cells with organ-specific metastasis potential were reinoculated into the armpit of nude mice, respectively. This processes were repeated to establish the organ-specific metastatic sublines of L9981-Luc cell line more than 10 times. Finally, the organ-specific metastasis sublines of L9981-Luc were screened and established, which the four cell lines have the characteristics only metastasized to brian, lung, bone and mediastinal lymph node. Results A group of organ-specific metastasis cell

  2. No increase in brain cancer rates during period of expanding cell phone use

    Science.gov (United States)

    In a new examination of United States cancer incidence data, investigators at the National Cancer Institute (NCI) reported that incidence trends have remained roughly constant for glioma, the main type of brain cancer hypothesized to be related to cell ph

  3. Cell lines radiosensitization of thyroid cancer by histone deacetylase inhibitors

    International Nuclear Information System (INIS)

    Perona, M; Dagrosa, M A; Rossich, L; Casal, M; Pisarev, M A; Thomasz, L; Juvenal G J

    2012-01-01

    Introduction: Thyroid cancer is the most common endocrine neoplasia. Surgical resection and radioactive iodine is an effective treatment for well-differentiated tumors. Histone deacetylase inhibitors (HDAC-I) are agents that cause hyperacetylation of histone proteins and as a consequence remodeling of chromatin structure. They can induce growth arrest, differentiation and apoptotic cell death in different tumor cells. The use of HDAC-I agents could be of utility to enhance the response to external radiation therapy of those thyroid cancers that are refractory to most conventional therapeutic treatments. Objective: To study the effect of HDAC-I as radiosensitizers for the treatment of thyroid cancer and their ability to induce differentiation of thyroid cancer cells. Materials and methods: The human thyroid follicular (WRO) and papillary (TPC-1) carcinoma cell lines were seeded and incubated with increasing doses (0, 0.3, 0.5, 1 and 1.5 mM) of the HDAC-I sodium butirate (NaB) and valproic acid (VA) to evaluate cell proliferation and iodide uptake. Cells were irradiated with a 60 Co γ-ray source (1 ± 5% Gy/min) and postirradiation survival was quantified with the colony formation assay. Survival fraction at 2 Gy (SF2) was calculated for each cell line. Cell cycle and cell death were evaluated at a dose of 3 Gy. Iodide uptake, PCR analysis and transient transfection studies were performed. Results: Cell proliferation was not significantly suppressed after 24 hours of incubation with both drugs at all assayed doses. Iodide uptake was not modified after incubation with HDAC-I of both cell lines. SF2 was reduced from 68 ± 1.6 % in the control WRO cells to 42 ± 3.8 % (P<0.001) in NaB-treated cells. In TPC-1 SF2 was reduced from 32 ± 1.1 % in the control cells to 24 ± 0.8 % (P<0.01). In VA-treated cells SF2 was reduced from 69 ± 0.02 % in control WRO cells to 56 ± 0.01 % (P<0.01) and from 31 ± 2 % in control TPC-1 cells to 11 ± 1 % (P<0.01). There was an arrest

  4. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  5. Gamma knife radiosurgery for metastatic brain tumors from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

    2003-01-01

    The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

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

    International Nuclear Information System (INIS)

    Krarup, Marianne; Poulsen, Hans Skovgaard; Spang-Thomsen, Mogens

    1997-01-01

    Purpose: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based on the construction of continuous exponential growth curves. Methods and Materials: Fifteen SCLC cell lines were studied, applying a slightly modified clonogenic assay and a growth extrapolation method. A dose-survival curve was obtained for each experiment and used for calculating several survival parameters. The multitarget single hit model was applied to calculate the cellular radiosensitivity (D 0 ), the capacity for sublethal damage repair (D q ), and the extrapolation number (n). Values for α and β were determined from best-fit curves according to the linear-quadratic model and these values were applied to calculate the surviving fraction after 2-Gy irradiation (SF 2 ). Results: In our investigation, the extrapolation method proved to be inappropriate for the study of in vitro cellular radiosensitivity due to lack of reproducibility. The results obtained by the clonogenic assay showed that the cell lines studied were radiobiologically heterogeneous with no discrete features of the examined parameters including the repair capacity. Conclusion: The results indicate that SCLC tumors per se are not generally candidates for hyperfractionated radiotherapy

  7. *NO and oxyradical metabolism in new cell lines of rat brain capillary endothelial cells forming the blood-brain barrier.

    Science.gov (United States)

    Blasig, I E; Giese, H; Schroeter, M L; Sporbert, A; Utepbergenov, D I; Buchwalow, I B; Neubert, K; Schönfelder, G; Freyer, D; Schimke, I; Siems, W E; Paul, M; Haseloff, R F; Blasig, R

    2001-09-01

    To investigate the relevance of *NO and oxyradicals in the blood-brain barrier (BBB), differentiated and well-proliferating brain capillary endothelial cells (BCEC) are required. Therefore, rat BCEC (rBCEC) were transfected with immortalizing genes. The resulting lines exhibited endothelial characteristics (factor VIII, angiotensin-converting enzyme, high prostacyclin/thromboxane release rates) and BBB markers (gamma-glutamyl transpeptidase, alkaline phosphatase). The control line rBCEC2 (mock transfected) revealed fibroblastoid morphology, less factor VIII, reduced gamma-glutamyl transpeptidase, weak radical defence, low prostanoid metabolism, and limited proliferation. Lines transfected with immortalizing genes (especially rBCEC4, polyoma virus large T antigen) conserved primary properties: epitheloid morphology, subcultivation with high proliferation rate under pure culture conditions, and powerful defence against reactive oxygen species (Mn-, Cu/Zn-superoxide dismutase, catalase, glutathione peroxidase, glutathione) effectively controlling radical metabolism. Only 100 microM H2O2 overcame this defence and stimulated the formation of eicosanoids similarly as in primary cells. Some BBB markers were expressed to a lower degree; however, cocultivation with astrocytes intensified these markers (e.g., alkaline phosphatase) and paraendothelial tightness, indicating induction of BBB properties. Inducible NO synthase was induced by a cytokine plus lipopolysaccharide mixture in all lines and primary cells, resulting in *NO release. Comparing the cell lines obtained, rBCEC4 are stable immortalized and reveal the best conservation of properties from primary cells, including enzymes producing or decomposing reactive species. These cells can be subcultivated in large amounts and, hence, they are suitable to study the role of radical metabolism in the BBB and in the cerebral microvasculature. Copyright 2001 Academic Press.

  8. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  9. Brain imaging before primary lung cancer resection: a controversial topic.

    Science.gov (United States)

    Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

    2017-01-01

    International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have

  10. Line and word bisection in right-brain-damaged patients with left spatial neglect.

    Science.gov (United States)

    Veronelli, Laura; Vallar, Giuseppe; Marinelli, Chiara V; Primativo, Silvia; Arduino, Lisa S

    2014-01-01

    Right-brain-damaged patients with left unilateral spatial neglect typically set the mid-point of horizontal lines to the right of the objective center. By contrast, healthy participants exhibit a reversed bias (pseudoneglect). The same effect has been described also when bisecting orthographic strings. In particular, for this latter kind of stimulus, some recent studies have shown that visuo-perceptual characteristics, like stimulus length, may contribute to both the magnitude and the direction bias of the bisection performance (Arduino et al. in Neuropsychologia 48:2140-2146, 2010). Furthermore, word stress was shown to modulate reading performances in both healthy participants, and patients with left spatial neglect and neglect dyslexia (Cubelli and Beschin in Brain Lang 95:319-326, 2005; Rusconi et al. in Neuropsychology 18:135-140, 2004). In Experiment I, 22 right-brain-damaged patients (11 with left visuo-spatial neglect) and 11 matched neurologically unimpaired control participants were asked to set the subjective mid-point of word letter strings, and of lines of comparable length. Most patients exhibited an overall disproportionate rightward bias, sensitive to stimulus length, and similar for words and lines. Importantly, in individual patients, biases differed according to stimulus type (words vs. lines), indicating that at least partly different mechanisms may be involved. In Experiment II, the putative effects on the bisection bias of ortho-phonological information (i.e., word stress endings), arising from the non-neglected right hand side of the stimulus were investigated. The orthographic cue induced a rightward shift of the perceived mid-point in both patients and controls, with short words stressed on the antepenultimate final sequence inducing a smaller rightward deviation with respect to short words stressed on the penultimate final sequence. In conclusion, partly different mechanisms, including both visuo-spatial and lexical factors, may support

  11. Magnetic fields and cancer in people residing near Swedish high voltage power lines

    Energy Technology Data Exchange (ETDEWEB)

    Feychting, M; Ahlbom, A

    1992-01-01

    The study was designed as a case-control study, based on the population comprised of everyone who have lived on a property located within 300 meters from any of the 220 and 400 kV power lines in Sweden during the period from 1960 through 1985. For adults it was required that the duration of residence was at least one year. The corridor was chosen to be wide enough to ensure that it included both exposed and unexposed homes. The cases were all instances of cancer diagnosed between 1960-85. For children, all types of cancer were included, while for adults the study was restricted to leukemia and brain tumors. The controls were matched to the cases on time of diagnosis, age, sex, parish, and power line. Exposure was assessed in several different ways. First, spot measurements were performed in the homes of the subjects. Second, the magnetic fields generated by the power lines were calculated by means of a computer program taking distance, line configuration, and load into account. For childhood leukemia and with cut off points at 0.1 and 0.2 [mu]T, the relative risk (RR) increased over the two exposure levels and was estimated at 2.7 (95% c.l.: 1.0-6,3) for 0.2 [mu]T and over. The test for trend gave a p-value of 0.02. When the upper cut off point was shifted to 0.3 [mu]T the RR was instead 3.8 (1.4-9.3) and the corresponding trend test gave a p-value of 0.005. In adults and for magnetic fields of 0.2 [mu]T and over, the RR for acute myeloid (AML) and chronic myeloid leukemia (CML) were estimated at 1.7 (0.8-3.5) and 1.7 (0.7-3.8), respectively. This result persisted in most analyses. For brain tumours no association was seen. The results provide support for the hypothesis that exposure to magnetic fields increase the risk of cancer. This is most evident in childhood leukemia. What aspect of the fields that might be involved remains unclear. (6 figs., 82 tabs., 16 refs.).

  12. Magnetic fields and cancer in people residing near Swedish high voltage power lines

    Energy Technology Data Exchange (ETDEWEB)

    Feychting, M; Ahlbom, A

    1993-12-31

    The study was designed as a case-control study, based on the population comprised of everyone who have lived on a property located within 300 meters from any of the 220 and 400 kV power lines in Sweden during the period from 1960 through 1985. For adults it was required that the duration of residence was at least one year. The corridor was chosen to be wide enough to ensure that it included both exposed and unexposed homes. The cases were all instances of cancer diagnosed between 1960-85. For children, all types of cancer were included, while for adults the study was restricted to leukemia and brain tumors. The controls were matched to the cases on time of diagnosis, age, sex, parish, and power line. Exposure was assessed in several different ways. First, spot measurements were performed in the homes of the subjects. Second, the magnetic fields generated by the power lines were calculated by means of a computer program taking distance, line configuration, and load into account. For childhood leukemia and with cut off points at 0.1 and 0.2 {mu}T, the relative risk (RR) increased over the two exposure levels and was estimated at 2.7 (95% c.l.: 1.0-6,3) for 0.2 {mu}T and over. The test for trend gave a p-value of 0.02. When the upper cut off point was shifted to 0.3 {mu}T the RR was instead 3.8 (1.4-9.3) and the corresponding trend test gave a p-value of 0.005. In adults and for magnetic fields of 0.2 {mu}T and over, the RR for acute myeloid (AML) and chronic myeloid leukemia (CML) were estimated at 1.7 (0.8-3.5) and 1.7 (0.7-3.8), respectively. This result persisted in most analyses. For brain tumours no association was seen. The results provide support for the hypothesis that exposure to magnetic fields increase the risk of cancer. This is most evident in childhood leukemia. What aspect of the fields that might be involved remains unclear. (6 figs., 82 tabs., 16 refs.).

  13. Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Rottenfusser Andrea

    2009-10-01

    Full Text Available Abstract Background In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression. Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy. Methods Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values Results Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26, and 8 months (95% CI 6.25-9.74 on first-line, respectively (n.s.. In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter. Conclusion Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.

  14. Prediction of epigenetically regulated genes in breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Loss, Leandro A; Sadanandam, Anguraj; Durinck, Steffen; Nautiyal, Shivani; Flaucher, Diane; Carlton, Victoria EH; Moorhead, Martin; Lu, Yontao; Gray, Joe W; Faham, Malek; Spellman, Paul; Parvin, Bahram

    2010-05-04

    Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations according to their epigenetic regulation. Dimensionality reduction is performed in two steps: (i) methylation sites are grouped across the genome to identify regions of interest, and (ii) methylation profles are clustered within each region. Associations between the clustered methylation and the gene expression data sets generate candidate matches within a fxed neighborhood around each gene. Finally, the methylation-expression associations are ranked through a logistic regression, and their significance is quantified through permutation analysis. Our two-step dimensionality reduction compressed 90% of the original data, reducing 137,688 methylation sites to 14,505 clusters. Methylation-expression associations produced 18,312 correspondences, which were used to further analyze epigenetic regulation. Logistic regression was used to identify 58 genes from these correspondences that showed a statistically signifcant negative correlation between methylation profles and gene expression in the

  15. Oxygen-related Differences in Cellular and Vesicular Phenotypes Observed for Ovarian Cell Cancer Lines

    Directory of Open Access Journals (Sweden)

    Evo K. Lindersson Søndergaard

    2016-01-01

    The phenotyping of EVs from cancer cell lines provides information about their molecular composition. This information may be translated to knowledge regarding the functionality of EVs and lead to a better understanding of their role in cancer.

  16. 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.

  17. Lung cancer brain metastases – the role of neurosurgery

    Directory of Open Access Journals (Sweden)

    V. A. Aleshin

    2016-01-01

    Full Text Available Lung cancer is mostly common occurring oncological disease in the developed countries. Currently lung cancers are subdivided into nonsmall-cell (adenocarcinoma, large-cell, squamous cell and small-cell. The difference in the clinical and morphological picture leads to the necessity of choosing therapeutic approaches to patients of various groups.Lung cancer should be referred to encephalotropic diseases since metastatic lesion of the central nervous system is sufficiently common complication. Successes of complex treatment of primary tumor result in increase of total longlivety currently ther is ageing of patients suffering lung cancer. These factors increase the risk of metastatic lesions of the brain.Interest to the problem of neurosurgical treatment of patients suffering lung cancer is determined by frequency of lesion, varicosity of morphological variants of the disease, requiring various algorithms of treatment and diagnosis.The main role of neurosurgical intervention in cerebral metastases of lung cancer consist in creation of the paled of carrying out combined therapy. Ideally, a neurosurgical operation should be carried out with clearcut observance of oncological principles of ablasty.Adequate comprehensive approach to treatment or patients with cerebral metastases of various forms of lung cancer with the developed of optimal tactics of and stages of treatment would make it possible to increase duration and quality of life of patients.

  18. Radiological Patterns of Brain Metastases in Breast Cancer Patients : A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry

    NARCIS (Netherlands)

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Wuerschmidt, Florian; Fehm, Tanja; Moebus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain

  19. Precursor States of Brain Tumor Initiating Cell Lines Are Predictive of Survival in Xenografts and Associated with Glioblastoma Subtypes

    Directory of Open Access Journals (Sweden)

    Carlo Cusulin

    2015-07-01

    Full Text Available In glioblastoma multiforme (GBM, brain-tumor-initiating cells (BTICs with cancer stem cell characteristics have been identified and proposed as primordial cells responsible for disease initiation, recurrence, and therapeutic resistance. However, the extent to which individual, patient-derived BTIC lines reflect the heterogeneity of GBM remains poorly understood. Here we applied a stem cell biology approach and compared self-renewal, marker expression, label retention, and asymmetric cell division in 20 BTIC lines. Through cluster analysis, we identified two subgroups of BTIC lines with distinct precursor states, stem- or progenitor-like, predictive of survival after xenograft. Moreover, stem and progenitor transcriptomic signatures were identified, which showed a strong association with the proneural and mesenchymal subtypes, respectively, in the TCGA cohort. This study proposes a different framework for the study and use of BTIC lines and provides precursor biology insights into GBM.

  20. The Fine LINE: Methylation Drawing the Cancer Landscape

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    Isabelle R. Miousse

    2015-01-01

    Full Text Available LINE-1 (L1 is the most abundant mammalian transposable element that comprises nearly 20% of the genome, and nearly half of the mammalian genome has stemmed from L1-mediated mobilization. Expression and retrotransposition of L1 are suppressed by complex mechanisms, where the key role belongs to DNA methylation. Alterations in L1 methylation may lead to aberrant expression of L1 and have been described in numerous diseases. Accumulating evidence clearly indicates that loss of global DNA methylation observed in cancer development and progression is tightly associated with hypomethylation of L1 elements. Significant progress achieved in the last several years suggests that such parameters as L1 methylation status can be potentially utilized as clinical biomarkers for determination of the disease stage and in predicting the disease-free survival in cancer patients. In this paper, we summarize the current knowledge on L1 methylation, with specific emphasis given to success and challenges on the way of introduction of L1 into clinical practice.

  1. Study of radiosensitization of chloroquine on esophageal cancer cell line

    International Nuclear Information System (INIS)

    Yuan Xiaoli; Li Tao; Huang Jianming; Zha Xiao; Deng Bifang; Lang Jinyi

    2014-01-01

    Objective: To investigate the possibility of chloroquine radiosensitization of esophageal cancer cell line TE-1 and its further mechanism. Methods: Effect of chloroquine on cell viability of TE-1 cells was determined by MTT method. Expression of LC3, Beclin-1 and formation of acidic vesicular organelles (AVOs) were determined by Western blot, and fluorescence staining with Lyso-Tracker Red DND-99, respectively. Clonogenic survival of TE-1 cells was examined by clonogenic forming assay. Results: Chloroquine showed dose-dependent inhibition of TE-1 cell growth, and its values of IC_5_0 and IC_1_0 were (72.33±5.28) and (15.42±3.33) μmol/L, respectively. The expression of Beclin-1 and LC3-II/I markedly increased in irradiated TE-1 cells. The addition of chloroquine with IC_1_0 concentration significantly reduced the fluorescence and intensity of AVOs accumulation in the cytoplasm of TE-1 cells. Clonogenic survival fraction decreased obviously in TE-1 cells with addition of chloroquine after radiation and the value of SERD0 was 1.439. Conclusions: Chloroquine could radiosensitize esophageal cancer cells by blocking autophagy-lysosomal pathway and be used as a potential radiosensitizing strategy. (authors)

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

    International Nuclear Information System (INIS)

    Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A. Ivana; Mondello, Chiara

    2011-01-01

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

  3. Aberrant over-expression of a forkhead family member, FOXO1A, in a brain tumor cell line

    International Nuclear Information System (INIS)

    Dallas, Peter B; Egli, Simone; Terry, Philippa A; Kees, Ursula R

    2007-01-01

    The mammalian FOXO (forkhead box, O subclass) proteins are a family of pleiotropic transcription factors involved in the regulation of a broad range of cellular processes critical for survival. Despite the essential and diverse roles of the FOXO family members in human cells and their involvement in tumor pathogenesis, the regulation of FOXO expression remains poorly understood. We have addressed the mechanisms underlying the high level of expression of the FOXO1A gene in a cell line, PER-453, derived from a primitive neuroectodermal tumor of the central nervous system (CNS-PNET). The status of the FOXO1A locus in the PER-453 CNS-PNET cell line was investigated by Southern blotting and DNA sequence analysis of the proximal promoter, 5'-UTR, open reading frame and 3'-UTR. FOXO1A expression was assessed by conventional and quantitative RT-PCR, Northern and Western blotting. Quantitative real-time RT-PCR (qRT-PCR) data indicated that after normalization to ACTB mRNA levels, canonical FOXO1A mRNA expression in the PER-453 cell line was 124-fold higher than the average level of five other CNS-PNET cell lines tested, 24-fold higher than the level in whole fetal brain, and 3.5-fold higher than the level in fetal brain germinal matrix cells. No mutations within the FOXO1A open reading frame or gross rearrangements of the FOXO1A locus were detected. However, a single nucleotide change within the proximal promoter and several nucleotide changes within the 3'-UTR were identified. In addition, two novel FOXO1A transcripts were isolated that differ from the canonical transcript by alternative splicing within the 3'-UTR. The CNS-PNET cell line, PER-453, expresses FOXO1A at very high levels relative to most normal and cancer cells from a broad range of tissues. The FOXO1A open reading frame is wild type in the PER-453 cell line and the abnormally high FOXO1A mRNA expression is not due to mutations affecting the 5'-UTR or proximal promoter. Over expression

  4. [Timing of Brain Radiation Therapy Impacts Outcomes in Patients with 
Non-small Cell Lung Cancer Who Develop Brain Metastases].

    Science.gov (United States)

    Wang, Yang; Fang, Jian; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Ma, Xiangjuan; Han, Jindi; Chen, Xiaoling; Tian, Guangming; Wu, Di; Han, Sen; Long, Jieran

    2016-08-20

    Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; Pbrain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; Pbrain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed.

  5. Cognitive and brain structural changes in a lung cancer population.

    Science.gov (United States)

    Simó, Marta; Root, James C; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Ahles, Tim; Navarro, Arturo; Cardenal, Felipe; Bruna, Jordi; Rodríguez-Fornells, Antoni

    2015-01-01

    No study has examined structural brain changes specifically associated with chemotherapy in a lung cancer population. The aim of this cross-sectional study was to assess differences in brain structure between small-cell lung cancer patients (C+) following chemotherapy, non-small-cell lung cancer patients (C-) before chemotherapy and healthy controls (HC). Twenty-eight small-cell lung cancer patients underwent a neuropsychological assessment and a structural magnetic resonance imaging, including T1-weighted and diffusion tensor imaging to examine gray matter density and white matter (WM) integrity, respectively, 1 month following completion of platinum-based chemotherapy. This group was compared with 20 age and education-matched non-small-cell lung cancer patients before receiving chemotherapy and 20 HC. Both C+ and C- groups exhibited cognitive impairment compared with the HC group. The C+ group performed significantly worse than HC in verbal fluency and visuospatial subtests; C- performed significantly worse than both C+ and HC in verbal memory. Voxel-based morphometry analysis revealed lower gray matter density in the insula and parahippocampal gyrus bilaterally, and left anterior cingulate cortex in C+ compared with HC. Diffusion tensor imaging indices showed focal decreased WM integrity in left cingulum and bilateral inferior longitudinal fasciculus in the C+ group and more widespread decreased integrity in the C- group compared with the HC group. This study demonstrates that lung cancer patients exhibit cognitive impairment before and after chemotherapy. Before the treatment, C- showed verbal memory deficits as well as a widespread WM damage. Following treatment, the C+ group performed exhibited lower visuospatial and verbal fluency abilities, together with structural gray matter and WM differences in bilateral regions integrating the paralimbic system.

  6. Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

    Science.gov (United States)

    Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

    1992-07-15

    Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance.

  7. Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

    Science.gov (United States)

    Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

    1992-01-01

    Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance. Images PMID:1631137

  8. Treatment of brain metastases from primary lung cancer

    International Nuclear Information System (INIS)

    Ryan, Gail F.; Ball, David L.; Smith, Jennifer G.

    1995-01-01

    Purpose: A retrospective study of patients treated at the Peter MacCallum Cancer Institute for brain metastases from primary carcinoma of the lung is presented. Methods and Materials: The medical records of 416 patients with the diagnosis of primary carcinoma of the lung who presented with, or subsequently developed, brain metastases during the period January 1984 to December 1987 were reviewed. Information on a number of factors of potential prognostic significance (sex, age, histology, performance status and interval between diagnosis of the primary and brain metastases) was collected. Details of surgery, radiation and steroid usage were recorded, and any steroid side effects documented. Survival was calculated from the date of diagnosis of brain metastases. Stepwise regression based on Cox's proportional hazards model was used to determine significant prognostic factors affecting survival. Patients with and without steroid side effects were compared using Yate's corrected chi-square test. Results: The overall estimated median survival was only 3.3 months (95% confidence interval 2.9-3.7 months). Only two factors were found to be associated with a significantly improved survival--surgical intervention and good performance status. After taking these two factors into account, the dose of radiation used (< 30 Gy or ≥ 30 Gy) did not influence survival. There was a 3% incidence of gastric bleeding or perforation in patients taking steroids, with a 40% fatality rate. Predisposing factors to gastric side effects were a prior history of peptic ulcer and/or aspirin or nonsteroidal anti-inflammatory drug consumption. Conclusion: Radiation of brain metastases from primary lung cancer results in modest survival benefit. Radiation dose (< 30 Gy or ≥ 30 Gy) is not a significant determinant of survival. Other treatment modifications, such as concurrent radiation and chemotherapy, should be explored. Steroids should be used with caution as fatal side effects can occur

  9. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    OpenAIRE

    Zhou Weihua; Mukherjee Purna; Kiebish Michael A; Markis William T; Mantis John G; Seyfried Thomas N

    2007-01-01

    Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and su...

  10. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

  11. Characterisation and Manipulation of Docetaxel Resistant Prostate Cancer Cell Lines

    LENUS (Irish Health Repository)

    O'Neill, Amanda J

    2011-10-07

    Abstract Background There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel. Results The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-κB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-κB activity and IκB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-κB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel. Conclusion This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target.

  12. Identifying anti-growth factors for human cancer cell lines through genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Asplund, Anna

    2015-01-01

    Human cancer cell lines are used as important model systems to study molecular mechanisms associated with tumor growth, hereunder how genomic and biological heterogeneity found in primary tumors affect cellular phenotypes. We reconstructed Genome scale metabolic models (GEMs) for eleven cell lines...... based on RNA-Seq data and validated the functionality of these models with data from metabolite profiling. We used cell line-specific GEMs to analyze the differences in the metabolism of cancer cell lines, and to explore the heterogeneous expression of the metabolic subsystems. Furthermore, we predicted...... for inhibition of cell growth may provide leads for the development of efficient cancer treatment strategies....

  13. Monocarboxylate transporters in the brain and in cancer.

    Science.gov (United States)

    Pérez-Escuredo, Jhudit; Van Hée, Vincent F; Sboarina, Martina; Falces, Jorge; Payen, Valéry L; Pellerin, Luc; Sonveaux, Pierre

    2016-10-01

    Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Cetuximab in first line treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Carlo Barone

    2012-07-01

    Full Text Available The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI, compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to

  15. Effect of New Water-Soluble Dendritic Phthalocyanines on Human Colorectal and Liver Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ebru YABAŞ

    2017-08-01

    Full Text Available Human hepatocellular carcinoma (HepG2 cells and colorectal adenocarcinoma (DLD-1 cells were treated with the synthesized water soluble phthalocyanine derivatives to understand the effect of the compounds both on colorectal and liver cancer cells. The compounds inhibited cell proliferation and displayed cytotoxic effect on these cancer cell lines however; the effect of the compounds on healthy control fibroblast cell line was comparatively lower. The compounds can be employed for cancer treatment as anticancer agents.

  16. No inherent left and right side in human 'mental number line': evidence from right brain damage.

    Science.gov (United States)

    Aiello, Marilena; Jacquin-Courtois, Sophie; Merola, Sheila; Ottaviani, Teresa; Tomaiuolo, Francesco; Bueti, Domenica; Rossetti, Yves; Doricchi, Fabrizio

    2012-08-01

    Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial

  17. Association of brain cancer with dental x-rays and occupation in Missouri

    International Nuclear Information System (INIS)

    Neuberger, J.S.; Brownson, R.C.; Morantz, R.A.; Chin, T.D.

    1991-01-01

    This investigation of a brain cancer cluster in Missouri used two approaches to investigate associations with potential risk factors. In a case-control study in a rural town, we interviewed surrogates of cases and controls about potential risk factors. We found a statistically significant positive association of brain cancer with reported exposure to dental x-rays. Occupation was not associated with the cluster in the rural town. In a standardized proportional mortality study for the state of Missouri, we calculated the observed and expected proportion of brain cancers by occupation and industry in Missouri decedents. We found that motor vehicle manufacturers, beauty shop workers, managers and administrators, elementary school teachers, and hairdressers and cosmetologists had significantly elevated proportions of brain cancer. Brain tumors are inconsistently associated with occupation in the literature. Further study of brain cancer etiology with respect to dental x-ray exposures seems warranted

  18. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

    OpenAIRE

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

  19. CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain

    Directory of Open Access Journals (Sweden)

    Sebastiano Cavallaro

    2013-01-01

    Full Text Available Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC and the pharmacological tools that may be used to interfere with this signaling axis.

  20. Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain

    Directory of Open Access Journals (Sweden)

    Anna Koumarianou

    2016-01-01

    Full Text Available Patients with HER2-positive breast cancer and brain metastases have limited treatment options, and, as a result of their poor performance status and worse prognosis, they are underrepresented in clinical trials. Not surprisingly, these patients may not be fit enough to receive any active treatment and are offered supportive therapy. BRCA2 mutations are reported to be rarely associated with HER2-overexpressing advanced breast cancer and even more rarely with brain metastases at diagnosis. We report on a BRCA2-positive breast cancer patient with metastatic disease in multiple sites, including the brain, and poor performance status who exhibited an extraordinary clinical and imaging response to the novel anti-HER2 therapy pertuzumab after multiple lines of therapy including anti-HER2 targeting. To our knowledge, the clinicopathologic and therapeutic characteristics of this patient point to a unique case and an urgent need for further investigation of pertuzumab in patients with brain metastases.

  1. Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, Dirk; Huttenlocher, Stefan; Hornung, Dagmar; Blanck, Oliver; Schild, Steven E; Fischer, Dorothea

    2014-01-01

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1–3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p = 0.59). Age ≤59 years showed a trend towards improved local control on univariate (p = 0.066) and multivariate analysis (p = 0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p = 0.040) and ECOG 0–1 (p = 0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p = 0.039) and performance status (p = 0.028) maintained significance on multivariate analysis. ECOG 0–1 was positively correlated with survival on univariate analysis (p < 0.001); age ≤59 years showed a strong trend (p = 0.054). On multivariate analysis, performance status (p < 0.001) and age (p = 0.041) were significant. In breast cancer patients with few brain metastases, radiosurgery plus whole-brain

  2. Clonogenic cell line survival of a human liver cancer cell line SMMC-7721 after carbon ion irradiation with different LET

    International Nuclear Information System (INIS)

    Lei Suwen; Su Xu; Wang Jifang; Li Wenjian

    2003-01-01

    Objective: To investigate the survival fraction of a human liver cancer cell line SMMC-7721 following irradiation with carbon ions with different LET. Methods: cells of the human liver cancer cell line SMMC-7721 were irradiated with carbon ions (LET=30 and 70 keV/μm). The survival fraction was determined with clonogenic assay after 9 days incubation in a 5% CO 2 incubator at 37 degree C. Results: When the survival fractions of 70 keV/μm were D s = 0.1 and D s=0.01 absorption dose were 2.94 and 5.88 Gy respectively, and those of 30 keV/μm were 4.00 and 8.00 Gy respectively. Conclusion: For the SMMC-7721 cell line, 70 keV/μm is more effective for cell killing than 30 keV/μm

  3. Establishment and conventional cytogenetic characterization of three gastric cancer cell lines.

    Science.gov (United States)

    Leal, Mariana Ferreira; Martins do Nascimento, José Luiz; da Silva, Carla Elvira Araújo; Vita Lamarão, Maria Fernanda; Calcagno, Danielle Queiroz; Khayat, André Salim; Assumpção, Paulo Pimentel; Cabral, Isabel Rosa; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2009-11-01

    Gastric cancer is the fourth most frequent type of cancer and the second most frequent cause of cancer mortality worldwide. Only a modest number of gastric carcinoma cell lines have been isolated thus far. Here we describe the establishment and cytogenetic characterization of three new gastric cancer cell lines obtained from primary gastric adenocarcinoma (ACP02 and ACP03) and cancerous ascitic fluid (AGP01) of individuals from northern Brazil. ACP02, ACP03, and AGP01 cell lines are presently in the 60th passage. The cell lines grew in a disorganized single layer with some agglomerations and heterogeneous divisions (bipolar and multipolar). All cell lines exhibited a composite karyotype with several clonal chromosome alterations. Trisomy 8 was the most frequent alteration. Chromosome 8 aneusomy was confirmed by fluorescence in situ hybridization. All cell lines also exhibited trisomy 7 and deletion of chromosome arm 17p. These results suggest that, although frequent chromosome alterations are commonly observed due to culture process, the ACP02, ACP03, and AGP01 cell lines and primary gastric cancer from individuals of northern Brazil share genetic alterations, supporting use of these cell lines as a model of gastric carcinogenesis in this population.

  4. Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nagla Abdel Karim

    2015-01-01

    Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

  5. Radiotherapy for asymptomatic brain metastasis in epidermal growth factor receptor mutant non-small cell lung cancer without prior tyrosine kinase inhibitors treatment: a retrospective clinical study

    International Nuclear Information System (INIS)

    Liu, SongRan; Qiu, Bo; Chen, LiKun; Wang, Fang; Liang, Ying; Cai, PeiQiang; Zhang, Li; Chen, ZhaoLin; Liu, ShiLiang; Liu, MengZhong; Liu, Hui

    2015-01-01

    Non-small cell lung cancer (NSCLC) with brain metastasis (BM) harboring an epidermal growth factor receptor (EGFR) mutation shows good response to tyrosine kinase inhibitors (TKIs). This study is to assess the appropriate timing of brain radiotherapy (RT) for asymptomatic BM in EGFR mutant NSCLC patients. There were 628 patients diagnosed with EGFR mutant NSCLC between October 2005 and December 2011. Treatment outcomes had been retrospectively evaluated in 96 patients with asymptomatic BM without prior TKI treatment. 39 patients received first-line brain RT, 23 patients received delayed brain RT, and 34 patients did not receive brain RT. With a median follow-up of 26 months, the 2-year OS was 40.6 %. Univariate analyses revealed that ECOG performance status (p = 0.006), other distant metastases (p = 0.002) and first line systemic treatment (p = 0.032) were significantly associated with overall survival (OS). Multivariate analyses revealed that other sites of distant metastases (p = 0.030) were prognostic factor. The timing of brain RT was not significantly related to OS (p = 0.246). The 2-year BM progression-free survival (PFS) was 26.9 %. Brain RT as first-line therapy failed to demonstrate a significant association with BM PFS (p = 0.643). First-line brain RT failed to improve long-term survival in TKI-naïve EGFR mutant NSCLC patients with asymptomatic BM. Prospective studies are needed to validate these clinical findings

  6. Low-risk susceptibility alleles in 40 human breast cancer cell lines

    International Nuclear Information System (INIS)

    Riaz, Muhammad; Elstrodt, Fons; Hollestelle, Antoinette; Dehghan, Abbas; Klijn, Jan GM; Schutte, Mieke

    2009-01-01

    Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes. Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays. The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1. The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines

  7. LINE-1 hypomethylation in cancer is highly variable and inversely correlated with microsatellite instability.

    Directory of Open Access Journals (Sweden)

    Marcos R H Estécio

    2007-05-01

    Full Text Available Alterations in DNA methylation in cancer include global hypomethylation and gene-specific hypermethylation. It is not clear whether these two epigenetic errors are mechanistically linked or occur independently. This study was performed to determine the relationship between DNA hypomethylation, hypermethylation and microsatellite instability in cancer.We examined 61 cancer cell lines and 60 colorectal carcinomas and their adjacent tissues using LINE-1 bisulfite-PCR as a surrogate for global demethylation. Colorectal carcinomas with sporadic microsatellite instability (MSI, most of which are due to a CpG island methylation phenotype (CIMP and associated MLH1 promoter methylation, showed in average no difference in LINE-1 methylation between normal adjacent and cancer tissues. Interestingly, some tumor samples in this group showed increase in LINE-1 methylation. In contrast, MSI-showed a significant decrease in LINE-1 methylation between normal adjacent and cancer tissues (P<0.001. Microarray analysis of repetitive element methylation confirmed this observation and showed a high degree of variability in hypomethylation between samples. Additionally, unsupervised hierarchical clustering identified a group of highly hypomethylated tumors, composed mostly of tumors without microsatellite instability. We extended LINE-1 analysis to cancer cell lines from different tissues and found that 50/61 were hypomethylated compared to peripheral blood lymphocytes and normal colon mucosa. Interestingly, these cancer cell lines also exhibited a large variation in demethylation, which was tissue-specific and thus unlikely to be resultant from a stochastic process.Global hypomethylation is partially reversed in cancers with microsatellite instability and also shows high variability in cancer, which may reflect alternative progression pathways in cancer.

  8. The biochemical, nanomechanical and chemometric signatures of brain cancer

    Science.gov (United States)

    Abramczyk, Halina; Imiela, Anna

    2018-01-01

    % for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

  9. The effect of family therapy on the changes in the severity of on-line game play and brain activity in adolescents with on-line game addiction

    Science.gov (United States)

    Han, Doug Hyun; Kim, Sun Mi; Lee, Young Sik; Renshaw, Perry F.

    2015-01-01

    We evaluated whether a brief 3-week family therapy intervention would change patterns of brain activation in response to affection and gaming cues in adolescents from dysfunctional families who met criteria for on-line game addiction. Fifteen adolescents with on-line game addiction and fifteen adolescents without problematic on-line game play and an intact family structure were recruited. Over 3 weeks, families were asked to carry out homework assignments focused on increasing family cohesion for more than 1 hour/day and 4 days/week. Before therapy, adolescents with on-line game addiction demonstrated decreased activity as measured by functional magnetic resonance imaging (fMRI) within the caudate, middle temporal gyrus, and occipital lobe in response to images depicting parental affection and increased activity of the middle frontal and inferior parietal in response scenes from on-line games, relative to healthy comparison subjects. Improvement in perceived family cohesion following 3 weeks of treatment was associated with an increase in the activity of the caudate nucleus in response to affection stimuli and was inversely correlated with changes in on-line game playing time. With evidence of brain activation changes in response to on-line game playing cues and images depicting parental love, the present findings suggest that family cohesion may be an important factor in the treatment of problematic on-line game playing. PMID:22698763

  10. Altered resting brain connectivity in persistent cancer related fatigue

    Directory of Open Access Journals (Sweden)

    Johnson P. Hampson

    2015-01-01

    Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

  11. Intra-operative probe for brain cancer: feasibility study

    Science.gov (United States)

    Vu Thi, M. H.; Charon, Y.; Duval, M. A.; Lefebvre, F.; Menard, L.; Pitre, S.; Pinot, L.; Siebert, R.

    2007-07-01

    The present work aims a new medical probe for surgeons devoted to brain cancers, in particular glioblastoma multiforme. Within the last years, our group has started the development of a new intra-operative beta imaging probe. More recently, we took an alternative approach for the same application: a fluorescence probe. In both cases the purpose is to differentiate normal from tumor brain tissue. In a first step, we developed set-ups capable to measure autofluorescence. They are based on a dedicated epi-fluorescence design and on specific fiber optic probes. Relative signal amplitude, spectral shape and fluorescence lifetime measurements are foreseen to distinguish normal and cancer tissue by analyzing fluorophores like NADH, lipopigments and porphyrines. The autofluorescence spectra are recorded in the 460-640 nm range with a low resolution spectrometer. For lifetime measurements a fast detector (APD) is used together with a TCSPC-carte. Intrinsic wavelength- and time-resolutions are a few nm and 200 ps, respectively. Different samples have been analyzed to validate our new detection system and to allow a first configuration of our medical fluorescence probe. First results from the tissue measurements are shown.

  12. Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors

    Directory of Open Access Journals (Sweden)

    Schernhammer Eva S

    2010-05-01

    Full Text Available Abstract Background Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features. Design Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing. Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP, microsatellite instability, expression of TP53 (p53, CDKN1A (p21, CTNNB1 (β-catenin, PTGS2 (cyclooxygenase-2, and FASN, and mutations in KRAS, BRAF, and PIK3CA. Results Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6, and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation Conclusions LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers.

  13. Second-line systemic therapy for metastatic colorectal cancer.

    Science.gov (United States)

    Mocellin, Simone; Baretta, Zora; Roqué I Figuls, Marta; Solà, Ivan; Martin-Richard, Marta; Hallum, Sara; Bonfill Cosp, Xavier

    2017-01-27

    The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions. Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy. Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI). Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC.1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2

  14. Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology.

    Science.gov (United States)

    Azim, Hamdy A; Abdel-Malek, Raafat; Kassem, Loay

    2018-04-01

    Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype. Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P < .001), high tumor grade (P = .012), and HER2 positivity (P < .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P < .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P < .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P < .001), and lung metastasis (P < .001). Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Authentication of M14 melanoma cell line proves misidentification of MDA‐MB‐435 breast cancer cell line

    Science.gov (United States)

    Korch, Christopher; Hall, Erin M.; Dirks, Wilhelm G.; Ewing, Margaret; Faries, Mark; Varella‐Garcia, Marileila; Robinson, Steven; Storts, Douglas; Turner, Jacqueline A.; Wang, Ying; Burnett, Edward C.; Healy, Lyn; Kniss, Douglas; Neve, Richard M.; Nims, Raymond W.; Reid, Yvonne A.; Robinson, William A.

    2017-01-01

    A variety of analytical approaches have indicated that melanoma cell line UCLA‐SO‐M14 (M14) and breast carcinoma cell line MDA‐MB‐435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross‐contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA‐MB‐435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA‐MB‐435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA‐MB‐435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA‐MB‐435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research. PMID:28940260

  16. Dihydrochalcone Compounds Isolated from Crabapple Leaves Showed Anticancer Effects on Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Qin

    2015-11-01

    Full Text Available Seven dihydrochalcone compounds were isolated from the leaves of Malus crabapples, cv. “Radiant”, and their chemical structures were elucidated by UV, IR, ESI-MS, 1H-NMR and 13C-NMR analyses. These compounds, which include trilobatin (A1, phloretin (A2, 3-hydroxyphloretin (A3, phloretin rutinoside (A4, phlorizin (A5, 6′′-O-coumaroyl-4′-O-glucopyranosylphloretin (A6, and 3′′′-methoxy-6′′-O-feruloy-4′-O-glucopyranosyl-phloretin (A7, all belong to the phloretin class and its derivatives. Compounds A6 and A7 are two new rare dihydrochalcone compounds. The results of a MTT cancer cell growth inhibition assay demonstrated that phloretin and these derivatives showed significant positive anticancer activities against several human cancer cell lines, including the A549 human lung cancer cell line, Bel 7402 liver cancer cell line, HepG2 human ileocecal cancer cell line, and HT-29 human colon cancer cell line. A7 had significant effects on all cancer cell lines, suggesting potential applications for phloretin and its derivatives. Adding a methoxyl group to phloretin dramatically increases phloretin’s anticancer activity.

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

    Science.gov (United States)

    Mierke, Claudia T.

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

  18. [Effects of ezrin silencing on pancreatic cancer cell line Panc-1].

    Science.gov (United States)

    Meng, Yun-xiao; Yu, Shuang-ni; Lu, Zhao-hui; Chen, Jie

    2012-12-01

    To explore the effects of ezrin silencing on pancreatic cancer cell line Panc-1. Pancreatic cancer cell line Panc-1 was transfected with ezrin silencing plasmid. The proliferation and the cell cycle status were determined by CCK-8 assay and flow cytometry analysis, respectively. Cellular membrane protrusions/microvilli formation were visualized by scanning election microscopy. Colony formation assay was used to determine the cell anchor-independent growth ability in vitro. Trans-filter migration and invasion assays were performed with 8 µm pore inserts in a 24-well BioCoat chamber with/without Matrigel. Ezrin silencing decreased cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion, but had no effects on cell proliferation in vitro and cell cycle, in pancreatic cancer cell line Panc-1. Ezrin expression affects the cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion in pancreatic cancer cell line Panc-1.

  19. Effect of sirolimus on urinary bladder cancer T24 cell line

    Directory of Open Access Journals (Sweden)

    Oliveira Paula A

    2009-01-01

    Full Text Available Abstract Background Sirolimus is recently reported to have antitumour effects on a large variety of cancers. The present study was performed to investigate sirolimus's ability to inhibit growth in T24 bladder cancer cells. Methods T24 bladder cancer cells were treated with various concentrations of sirolimus. MTT assay was used to evaluate the proliferation inhibitory effect on T24 cell line. The viability of T24 cell line was determined by Trypan blue exclusion analysis. Results Sirolimus inhibits the growth of bladder carcinoma cells and decreases their viability. Significant correlations were found between cell proliferation and sirolimus concentration (r = 0.830; p Conclusion Sirolimus has an anti-proliferation effect on the T24 bladder carcinoma cell line. The information from our results is useful for a better understanding sirolimus's anti-proliferative activity in the T24 bladder cancer cell line.

  20. In vitro cytotoxicity of Indonesian stingless bee products against human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Paula M. Kustiawan

    2014-07-01

    Conclusions: Propolis from T. incisa and Trigona fusco-balteata contain an in vitro cytotoxic activity against human cancer cell lines. Further study is required, including the isolation and characterization of the active antiproliferative agent(s.

  1. Cytotoxicity screening of essential oils in cancer cell lines

    Directory of Open Access Journals (Sweden)

    Pollyanna Francielli de Oliveira

    Full Text Available Abstract This study evaluated the cytotoxicity activity of the essential oils of Tagetes erecta L., Asteraceae (TE-OE, Tetradenia riparia (Hochst. Codd, Lamiaceae (TR-OE, Bidens sulphurea (Cav. Sch. Bip., Asteraceae (BS-OE, and Foeniculum vulgare Mill., Apiaceae (FV-OE, traditionally used in folk medicine, against the tumor cell lines murine melanoma (B16F10, human colon carcinoma (HT29, human breast adenocarcinoma (MCF-7, human cervical adenocarcinoma (HeLa, human hepatocellular liver carcinoma (HepG2, and human glioblastoma (MO59J, U343, and U251. Normal hamster lung fibroblasts (V79 cells were included as control. The cells were treated with essential oil concentrations ranging from 3.12 to 400 µg/ml for 24 h. The cytotoxic activity was evaluated using the XTT assay; results were expressed as IC50, and the selectivity index was calculated. The results were compared with those achieved for classic chemotherapeutic agents. TE-OE was the most promising among the evaluated oils: it afforded the lowest IC50 values for B16F10 cells (7.47 ± 1.08 µg/ml and HT29 cells (6.93 ± 0.77 µg/ml, as well as selectivity indices of 2.61 and 2.81, respectively. The major BS-EO, FV-EO and TE-EO chemical constituents were identified by gas chromatography mass spectrometry as being (E-caryophyllene (10.5%, germacrene D (35.0% and 2,6-di-tert-butyl-4-methylphenol (43.0% (BS-EO; limonene (21.3% and (E-anethole (70.2% (FV-EO; limonene (10.4%, dihydrotagetone (11.8%, α-terpinolene (18.1% and (E-ocimenone (13.0% (TE-EO; and fenchone (6.1%, dronabinol (11.0%, aromadendrene oxide (14.7% and (E,E–farnesol (15.0% (TR-EO. 2,6-di-tert-butyl-4-methylphenol (43.0%, (E-anethole (70.2% and α-terpinolene (18.1%, respectively. These results suggest that TE-OE may be used to treat cancer without affecting normal cells.

  2. Proteotranscriptomic Profiling of 231-BR Breast Cancer Cells: Identification of Potential Biomarkers and Therapeutic Targets for Brain Metastasis*

    Science.gov (United States)

    Dun, Matthew D.; Chalkley, Robert J.; Faulkner, Sam; Keene, Sheridan; Avery-Kiejda, Kelly A.; Scott, Rodney J.; Falkenby, Lasse G.; Cairns, Murray J.; Larsen, Martin R.; Bradshaw, Ralph A.; Hondermarck, Hubert

    2015-01-01

    Brain metastases are a devastating consequence of cancer and currently there are no specific biomarkers or therapeutic targets for risk prediction, diagnosis, and treatment. Here the proteome of the brain metastatic breast cancer cell line 231-BR has been compared with that of the parental cell line MDA-MB-231, which is also metastatic but has no organ selectivity. Using SILAC and nanoLC-MS/MS, 1957 proteins were identified in reciprocal labeling experiments and 1584 were quantified in the two cell lines. A total of 152 proteins were confidently determined to be up- or down-regulated by more than twofold in 231-BR. Of note, 112/152 proteins were decreased as compared with only 40/152 that were increased, suggesting that down-regulation of specific proteins is an important part of the mechanism underlying the ability of breast cancer cells to metastasize to the brain. When matched against transcriptomic data, 43% of individual protein changes were associated with corresponding changes in mRNA, indicating that the transcript level is a limited predictor of protein level. In addition, differential miRNA analyses showed that most miRNA changes in 231-BR were up- (36/45) as compared with down-regulations (9/45). Pathway analysis revealed that proteome changes were mostly related to cell signaling and cell cycle, metabolism and extracellular matrix remodeling. The major protein changes in 231-BR were confirmed by parallel reaction monitoring mass spectrometry and consisted in increases (by more than fivefold) in the matrix metalloproteinase-1, ephrin-B1, stomatin, myc target-1, and decreases (by more than 10-fold) in transglutaminase-2, the S100 calcium-binding protein A4, and l-plastin. The clinicopathological significance of these major proteomic changes to predict the occurrence of brain metastases, and their potential value as therapeutic targets, warrants further investigation. PMID:26041846

  3. Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature.

    Science.gov (United States)

    Piccirilli, Manolo; Sassun, Tanya Enny; Brogna, Christian; Giangaspero, Felice; Salvati, Maurizio

    2007-01-01

    Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor. Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30). Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years). Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.

  4. Probing the O-glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery

    DEFF Research Database (Denmark)

    Vieira Campos, Diana Alexandra; Freitas, Daniela; Gomes, Joana

    2015-01-01

    biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO "SimpleCell" (SC) strategy to characterize the O-glycoproteome of two gastric cancer SC lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses...... at least partially truncated O-glycans. Overall we identified 499 O-glycoproteins and 1,236 O-glycosites in gastric cancer SCs, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer...... with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to demonstrate that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set...

  5. Methylation Status of miR-182 Promoter in Lung Cancer Cell Lines

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    Yongwen LI

    2015-05-01

    Full Text Available Background and objective It has been proven that the abnormal expression of miR-182 was related to the occurrence and development of tumors. The aim of this study is to explore the relationship between the methylation of miR-182 promoter and its expression in lung cancer cell lines. Methods Real-time quantitative PCR and methylation-specific PCR were used to detect the expression level of miR-182 and its promoter methylation status in five lung cancer cell lines (A549, L9981, NL9980, 95C and 95D. DNA sequencing was used to confirm the methylation results. Results The level of miR-182 expression significantly differs among these lung cancer cell lines. The highly metastatic human lung cancer cell lines, namely, A549 and L9981, demonstrate a relatively lower expression level of miR-182 compared with the lowly metastatic human lung cancer cell line 95C. Methylation-specific PCR and DNA sequencing assay results indicate that these lung cancer cell lines present different levels of miR-182 promoter methylation, and the highest methylation level is observed in A549 cells. Furthermore, the expression of miR-182 in these cell lines significantly increases when treated with 10 μM 5’-Aza-dC. Conclusion DNA methylation occurs in the miR-182 promoter region in lung cancer cell lines. This methylation can regulate the expression level of miR-182. Further study must be conducted to explore the function of miR-182 promoter methylation in lung cancer occurrence and development.

  6. Molecular characterization of breast cancer cell lines through multiple omic approaches.

    Science.gov (United States)

    Smith, Shari E; Mellor, Paul; Ward, Alison K; Kendall, Stephanie; McDonald, Megan; Vizeacoumar, Frederick S; Vizeacoumar, Franco J; Napper, Scott; Anderson, Deborah H

    2017-06-05

    Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated. We determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer. The cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated

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

    African Journals Online (AJOL)

    Regarding the traditional utilization of Sambucus ebulus, Iranian native botany and its active ingredients (e.g. ebulitin and ebulin 1), cytotoxicity of ethyl acetate ... cytotoxic agent on liver and colon cancer cells and suggest that vitamins C and E may protect normal cells, when SEE were used in cancer therapy in future.

  8. Cytotoxic activity of kenaf (Hibiscus cannabinus L.) seed extract and oil against human cancer cell lines

    Science.gov (United States)

    Wong, Yu Hua; Tan, Wai Yan; Tan, Chin Ping; Long, Kamariah; Nyam, Kar Lin

    2014-01-01

    Objective To examine the cytotoxic properties of both the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cervical cancer, human breast cancer, human colon cancer and human lung cancer cell lines. Methods The in vitro cytotoxic activity of the kenaf (Hibiscus cannabinus L.) seed extract and kenaf seed oil on human cancer cell lines was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamine B assays. Cell morphological changes were observed by using an inverted light microscope. Results The kenaf seed extract (KSE) exhibited a lower IC50 than kenaf seed oil (KSO) in all of the cancer cell lines. Morphological alterations in the cell lines after KSE and KSO treatment were observed. KSE and KSO possessed effective cytotoxic activities against all the cell lines been selected. Conclusions KSE and KSO could be potential sources of natural anti-cancer agents. Further investigations on using kenaf seeds for anti-proliferative properties are warranted. PMID:25183141

  9. Advances in Diagnosis and Treatment of Brain Metastases from the Primary Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yi LIU

    2013-07-01

    Full Text Available Lung cancer with brain metastasis was 23% to 65%, and is the most common type in brain metastasis tumors with the poor prognosis. At present, diagnosis and treatment of brain metastases from lung carcinoma and its molecular mechanism have become one hot spot of amount researches. Here, we made a systematic review of the progress of the clinical features, diagnosis and treatment of brain metastases from lung and its molecular mechanism.

  10. Brain Tumor’s Radioresistance: The Neighborhood Helps | Center for Cancer Research

    Science.gov (United States)

    Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. The primary treatment for GBM is radiation therapy. Unfortunately, while some patients initially respond, the vast majority of GBM patients fail radiotherapy, and the tumor usually grows back within two years. To gain a better understanding of the biological basis for GBM resistance to radiation, researchers initially studied GBM cell lines in vitro. In recent years, the focus has been on so-called tumor stem-like cells (TSCs), which are thought to be responsible for driving and maintaining tumor growth. To the researchers’ surprise, TSCs grown in vitro did not have the same ability to resist radiation as TSCs in the GBM tumors.

  11. Investigating the role of caveolin-2 in prostate cancer cell line

    Directory of Open Access Journals (Sweden)

    Jin-Yih Low

    2017-02-01

    Full Text Available Prostate cancer is a worldwide problem. While the role of caveolin-1 has been extensively studied, little is known about the role of caveolin-2 (CAV2 in prostate cancer. Up-regulation of CAV2 in androgen independent PC3 cells compared to normal prostate cell line and androgen dependent prostate cancer cell lines has been observed. Recent studies suggest that up-regulation of CAV2 plays an important role in androgen independent prostate cancer. This study investigates whether CAV2 is important in mediating the aggressive phenotypes seen in androgen independent prostate cancer cells. The androgen independent prostate cancer cell line, PC3 was used that has been shown to express CAV2, and CAV2 knock down was performed using siRNA system. Changes to cell number, migration and invasion were assessed after knocking down CAV2. Our results showed that down-regulating CAV2 resulted in reduced cell numbers, migration and invasion in PC3 cells. This preliminary study suggests that CAV2 may act to promote malignant behavior in an androgen independent prostate cancer cell line. Further studies are required to fully elucidate the role of CAV2 in androgen independent prostate cancer.

  12. Application of machine learning on brain cancer multiclass classification

    Science.gov (United States)

    Panca, V.; Rustam, Z.

    2017-07-01

    Classification of brain cancer is a problem of multiclass classification. One approach to solve this problem is by first transforming it into several binary problems. The microarray gene expression dataset has the two main characteristics of medical data: extremely many features (genes) and only a few number of samples. The application of machine learning on microarray gene expression dataset mainly consists of two steps: feature selection and classification. In this paper, the features are selected using a method based on support vector machine recursive feature elimination (SVM-RFE) principle which is improved to solve multiclass classification, called multiple multiclass SVM-RFE. Instead of using only the selected features on a single classifier, this method combines the result of multiple classifiers. The features are divided into subsets and SVM-RFE is used on each subset. Then, the selected features on each subset are put on separate classifiers. This method enhances the feature selection ability of each single SVM-RFE. Twin support vector machine (TWSVM) is used as the method of the classifier to reduce computational complexity. While ordinary SVM finds single optimum hyperplane, the main objective Twin SVM is to find two non-parallel optimum hyperplanes. The experiment on the brain cancer microarray gene expression dataset shows this method could classify 71,4% of the overall test data correctly, using 100 and 1000 genes selected from multiple multiclass SVM-RFE feature selection method. Furthermore, the per class results show that this method could classify data of normal and MD class with 100% accuracy.

  13. Study of cancer cell lines with Fourier transform infrared (FTIR)/vibrational absorption (VA) spectroscopy

    DEFF Research Database (Denmark)

    Uceda Otero, E. P.; Eliel, G. S. N.; Fonseca, E. J. S.

    2013-01-01

    In this work we have used Fourier transform infrared (FTIR) / vibrational absorption (VA) spectroscopy to study two cancer cell lines: the Henrietta Lacks (HeLa) human cervix carcinoma and 5637 human bladder carcinoma cell lines. Our goal is to experimentally investigate biochemical changes...

  14. ERC/mesothelin is expressed in human gastric cancer tissues and cell lines.

    Science.gov (United States)

    Ito, Tomoaki; Kajino, Kazunori; Abe, Masaaki; Sato, Koichi; Maekawa, Hiroshi; Sakurada, Mutsumi; Orita, Hajime; Wada, Ryo; Kajiyama, Yoshiaki; Hino, Okio

    2014-01-01

    ERC/mesothelin is expressed in mesothelioma and other malignancies. The ERC/mesothelin gene (MSLN) encodes a 71-kDa precursor protein, which is cleaved to yield 31-kDa N-terminal (N-ERC/mesothelin) and 40-kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin is a soluble protein and has been reported to be a diagnostic serum marker of mesothelioma and ovarian cancer. Gastric cancer tissue also expresses C-ERC/mesothelin, but the significance of serum N-ERC levels for diagnosing gastric cancer has not yet been studied. We examined the latter issue in the present study as well as C-ERC/mesothelin expression in human gastric cancer tissues and cell lines. We immunohistochemically examined C-ERC/mesothelin expression in tissue samples from 50 cases of gastric cancer, and we also assessed the C-ERC/mesothelin expression in 6 gastric cancer cell lines (MKN-1, MKN-7, MKN-74, NUGC-3, NUGC-4 and TMK-1) using reverse transcription-polymerase chain reaction, flow cytometry, immunohistochemistry and immunoblotting. We also examined the N-ERC/mesothelin concentrations in the supernatants of cultured cells and in the sera of gastric cancer patients using an enzyme-linked immunosorbent assay (ELISA). N-ERC/mesothelin was detected in the supernatants of 3 gastric cancer cell lines (MKN-1, NUGC-4 and TMK-1) by ELISA, but its concentration in the sera of gastric cancer patients was almost same as that observed in the sera of the normal controls. In the gastric cancer tissues, C-ERC/mesothelin expression was associated with lymphatic invasion. N-ERC/mesothelin was secreted into the supernatants of gastric cancer cell lines, but does not appear to be a useful serum marker of gastric cancer.

  15. Antiproliferative activity of Eremanthus crotonoides extracts and centratherin demonstrated in brain tumor cell lines

    Directory of Open Access Journals (Sweden)

    Jonathas F. R. Lobo

    2012-12-01

    Full Text Available The genus Eremanthus is recognized by the predominance of sesquiterpene lactones from the furanoheliangolide type, a class of substances extensively tested against cancer cell lines. Thus, the species E. crotonoides (DC. Sch. Bip., Asteraceae, obtained on "restinga" vegetation was evaluated against U251 and U87-MG glioma cell lines using the MTT colorimetric assay. Dichloromethane fraction was cytotoxic to both glioblastoma multiforme cell lines. We then conducted UPLC-PDA-ESI-MS/MS analysis of the dichloromethane fraction, which allowed the identification of the sesquiterpene lactones centratherin and goyazensolide. The isolation of centratherin was performed using chromatographic techniques and the identification of this substance was confirmed according to NMR data. Cytotoxic activity of centratherin alone was also evaluated against both U251 and U87-MG cells, which showed IC50 values comparable with those obtained for the commercial anticancer drug doxorubicin. All the tested samples showed cytotoxic activity against glioblastoma multiforme cells which suggests that E. crotonoides extracts may be important sources of antiproliferative substances and that the centratherin may serve as prototype for developing new antiglioblastoma drugs.

  16. Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

    Science.gov (United States)

    Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

    2012-01-01

    The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

  17. Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

    Science.gov (United States)

    Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

    2017-06-01

    Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Characterization of newly established colorectal cancer cell lines ...

    Indian Academy of Sciences (India)

    Unknown

    2000-12-19

    Dec 19, 2000 ... ... Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA .... with biotinylated horse anti-mouse IgG (Vector Labora- ...... development of new therapies or prognosis of the disease,.

  19. Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

    International Nuclear Information System (INIS)

    Viani, Gustavo A; Castilho, Marcus S; Salvajoli, João V; Pellizzon, Antonio Cassio A; Novaes, Paulo E; Guimarães, Flavio S; Conte, Maria A; Fogaroli, Ricardo C

    2007-01-01

    Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001). Our

  20. Survival predictors for second-line chemotherapy in Caucasian patients with metastatic gastric cancer

    OpenAIRE

    Bohanes, Pierre; Courvoisier, Delphine; Perneger, Thomas; Morel, Philippe; Huber, Olivier; Roth, Arnaud

    2011-01-01

    There are very limited data suggesting a benefit for second-line chemotherapy in advanced gastric cancer. Therefore, the number of patients who receive further treatment after failure of first-line chemotherapy varies considerably, ranging from 14% to 75%. In the absence of a demonstrated survival benefit of second-line chemotherapy, appropriate selection of patients based on survival predictors is essential. However, no clinico-pathologic parameters are currently widely adopted in clinical p...

  1. Identification of alternatively spliced TIMP-1 mRNA in cancer cell lines and colon cancer tissue

    DEFF Research Database (Denmark)

    Usher, Pernille Autzen; Sieuwerts, A.M.; Bartels, Annette

    2007-01-01

    TIMP-1 is a promising new candidate as a prognostic marker in colorectal and breast cancer. We now describe the discovery of two alternatively spliced variants of TIMP-1 mRNA. The two variants lacking exon 2 (del-2) and 5 (del-5), respectively, were identified in human cancer cell lines by RT......-PCR. The del-2 variant was, furthermore, detected in extracts from 12 colorectal cancer tissue samples. By western blotting additional bands of lower molecular mass than full-length TIMP-1 were identified in tumor tissue, but not in plasma samples obtained from cancer patients. The two splice variants of TIMP...

  2. WE-EF-303-06: Feasibility of PET Image-Based On-Line Proton Beam-Range Verification with Simulated Uniform Phantom and Human Brain Studies

    International Nuclear Information System (INIS)

    Lou, K; Sun, X; Zhu, X; Grosshans, D; Clark, J; Shao, Y

    2015-01-01

    Purpose: To study the feasibility of clinical on-line proton beam range verification with PET imaging Methods: We simulated a 179.2-MeV proton beam with 5-mm diameter irradiating a PMMA phantom of human brain size, which was then imaged by a brain PET with 300*300*100-mm 3 FOV and different system sensitivities and spatial resolutions. We calculated the mean and standard deviation of positron activity range (AR) from reconstructed PET images, with respect to different data acquisition times (from 5 sec to 300 sec with 5-sec step). We also developed a technique, “Smoothed Maximum Value (SMV)”, to improve AR measurement under a given dose. Furthermore, we simulated a human brain irradiated by a 110-MeV proton beam of 50-mm diameter with 0.3-Gy dose at Bragg peak and imaged by the above PET system with 40% system sensitivity at the center of FOV and 1.7-mm spatial resolution. Results: MC Simulations on the PMMA phantom showed that, regardless of PET system sensitivities and spatial resolutions, the accuracy and precision of AR were proportional to the reciprocal of the square root of image count if image smoothing was not applied. With image smoothing or SMV method, the accuracy and precision could be substantially improved. For a cylindrical PMMA phantom (200 mm diameter and 290 mm long), the accuracy and precision of AR measurement could reach 1.0 and 1.7 mm, with 100-sec data acquired by the brain PET. The study with a human brain showed it was feasible to achieve sub-millimeter accuracy and precision of AR measurement with acquisition time within 60 sec. Conclusion: This study established the relationship between count statistics and the accuracy and precision of activity-range verification. It showed the feasibility of clinical on-line BR verification with high-performance PET systems and improved AR measurement techniques. Cancer Prevention and Research Institute of Texas grant RP120326, NIH grant R21CA187717, The Cancer Center Support (Core) Grant CA016672

  3. Mechanisms and Therapy for Cancer Metastasis to the Brain

    Directory of Open Access Journals (Sweden)

    Federica Franchino

    2018-05-01

    Full Text Available Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs. Intracranial metastases are symptomatic in 60–70% of patients. Magnetic resonance imaging (MRI with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry. Molecular alterations not always reflect those of the primary tumor. More sophisticated methods of tumor analysis detecting circulating biomarkers in fluids (liquid biopsy, including circulating DNA, circulating tumor cells, and extracellular vesicles, containing tumor DNA and macromolecules (microRNA, have shown promise regarding tumor treatment response and progression. The choice of therapeutic approaches is guided by prognostic scores (Recursive Partitioning Analysis and diagnostic-specific Graded Prognostic Assessment-DS-GPA. The survival benefit of surgical resection seems limited to the subgroup of patients with controlled systemic disease and good performance status. Leptomeningeal disease (LMD can be a complication, especially in posterior fossa metastases undergoing a “piecemeal” resection. Radiosurgery of the resection cavity may offer comparable survival and local control as postoperative whole-brain radiotherapy (WBRT. WBRT alone is now the treatment of choice only for patients with single or multiple BMs not amenable to surgery or radiosurgery, or with poor prognostic factors. To reduce the neurocognitive sequelae of WBRT intensity modulated radiotherapy with hippocampal sparing, and pharmacological approaches (memantine and donepezil have been investigated. In the last decade, a multitude of molecular abnormalities have been discovered. Approximately 33% of patients with non

  4. Biomimetic brain tumor niche regulates glioblastoma cells towards a cancer stem cell phenotype.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Chen, Pin-Yuan

    2018-05-01

    Glioblastoma (GBM) is the most malignant primary brain tumor and contains tumorigenic cancer stem cells (CSCs), which support the progression of tumor growth. The selection of CSCs and facilitation of the brain tumor niches may assist the development of novel therapeutics for GBM. Herein, hydrogel materials composed of agarose and hydroxypropyl methyl cellulose (HMC) in different concentrations were established and compared to emulate brain tumor niches and CSC microenvironments within a label-free system. Human GBM cell line, U-87 MG, was cultured on a series of HMC-agarose based culture system. Cell aggregation and spheroids formation were investigated after 4 days of culture, and 2.5% HMC-agarose based culture system demonstrated the largest spheroids number and size. Moreover, CD133 marker expression of GBM cells after 6 days of culture in 2.5% HMC-agarose based culture system was 60%, relatively higher than the control group at only 15%. Additionally, cells on 2.5% HMC-agarose based culture system show the highest chemoresistance, even at the high dose of 500 µM temozolomide for 72 h, the live cell ratio was still > 80%. Furthermore, the results also indicate that the expression of ABCG2 gene was up-regulated after culture in 2.5% HMC-agarose based culture system. Therefore, our results demonstrated that biomimetic brain tumor microenvironment may regulate GBM cells towards the CSC phenotype and expression of CSC characteristics. The microenvironment selection and spheroids formation in HMC-agarose based culture system may provide a label-free CSC selection strategy and drug testing model for future biomedical applications.

  5. Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors...

  6. Anti-Cancer Activity of Methanol Extracts of Cichorium Intybus on Human Breast Cancer SKBR3 Cell Line

    Directory of Open Access Journals (Sweden)

    Reza Mehrandish

    2016-11-01

    Full Text Available Background Breast cancer is the most prevalent cancer and the second cause of death among women around the world. In many cancers, including breast cancer, Fatty acid synthase (FASN gene expression is increased significantly. In breast cancer cell lines, expression of FASN is higher in HER2 positive cell line like SKBR3 than the others. FASN is the key enzyme for fatty acid synthesis de novo pathway and it is producing palmitate which is necessary for cell membrane formation. Cichorium intybus is a medicinal plant that effectively leads to inhibition of fatty acid synthase and thus reduces the percentage of survival of cancer cell lines. Objectives The aim of this study was to evaluate the effect of methanol extract of Chicorium intybus root on percentage of survival in SKBR3 cell line. Methods Human breast cancer SKBR3 cell line was cultured in DMEM medium. Methanol extract of Cichorium intybus root was extracted and different dilutions (200, 300, 400, 500 and 600µg/mL were added to cell culture. Cell viability was quantitated by MTT assay after 24, 48 and 72 hours. Results Cichorium intybus could decrease cell viability. The effects of extract on cell viability were observed after 24, 48 and 72 hours on SKBR3 cell line and IC50 was 800, 400 and 300 after 24, 48 and 72 hours of treatment, respectively. Conclusions Our study shows that methanol extract of Cichorium intybus has cytotoxic effects on tumor cells. This is a pilot work for further evaluation in the future.

  7. Pesticides and brain cancer linked in orchard farmers of Kashmir.

    Science.gov (United States)

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R; Raina, T H

    2010-10-01

    -related patients. The significantcase/control odds ratio (OR) of 0.28, hospital control SCE OR of 1.1 and family control SCE OR of 1.5, points the finger of suspicion toward the link between pesticides and brain cancer.

  8. Ethanolic Extract Cytotoxic Effect of Zingiber Afficinale in Breast Cancer (MCF7 Cell Line

    Directory of Open Access Journals (Sweden)

    J Tavakkol Afshari

    2010-07-01

    Full Text Available Introduction & Objective: Biological activities of Zingiber afficieale plants have been reported as possessing anticancer, antibacterial, anti ulcer, antifungal, and insecticidal properties. However, its antitumor effects haven't been studied in cancer cell lines. The aim of this study was to investigate the antitumor effect of zingiber afficieale on breast cancer cell lines. Materials & Methods: This experimental study was conducted in 2010 at Mashhad University of medical Sciences. Breast cancer cell line (MCF7 and normal connective tissue cell line (L929 were cultured in DMEM medium. Ethanolic extract of Zingiber afficinale was prepared and cell lines were treated with different concentration of extract (5000 to 78 µg. Cell viability was measured by MTT assay after 24, 48, and 72 hours. The collected data were statistically analyzed by SPSS software. Results: The effects of Zingiber afficinale on cell viability were observed after 48 hours on cell lines. Ginger doses in 2500 µg concentration inhibited 50% of cell growth (IC50 in cell lines after 48 hours. Conclusion: Our study revealed that fresh ginger extract has cytotoxic effects on tumor cells, but it doesn’t have any cytotoxic effect on normal cells. It seems that ginger could be considered as a promising chemotherapeutic agent in cancer treatment.

  9. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Maneckjee, R.; Minna, J.D.

    1990-01-01

    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for μ, δ, and κ opioid agonists and for nicotine and α-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas μ, δ, and κ opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides (β-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer

  10. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Maneckjee, R.; Minna, J.D. (National Cancer Institute-Navy Medical Oncology Branch, Bethesda, MD (USA) Uniformed Services Univ. of the Health Sciences, Bethesda, MD (USA))

    1990-05-01

    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.

  11. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

    OpenAIRE

    Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

    2011-01-01

    We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product b...

  12. Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines

    International Nuclear Information System (INIS)

    Schröpfer, Andrea; Kammerer, Ulrike; Kapp, Michaela; Dietl, Johannes; Feix, Sonja; Anacker, Jelena

    2010-01-01

    Matrix metalloproteinases (MMPs) are involved in the degradation of protein components of the extracellular matrix and thus play an important role in tumor invasion and metastasis. Their expression is related to the progression of gynecological cancers (e.g. endometrial, cervical or ovarian carcinoma). In this study we investigated the expression pattern of the 23 MMPs, currently known in humans, in different gynecological cancer cell lines. In total, cell lines from three endometrium carcinomas (Ishikawa, HEC-1-A, AN3 CA), three cervical carcinomas (HeLa, Caski, SiHa), three chorioncarcinomas (JEG, JAR, BeWo), two ovarian cancers (BG-1, OAW-42) and one teratocarcinoma (PA-1) were examined. The expression of MMPs was analyzed by RT-PCR, Western blot and gelatin zymography. We demonstrated that the cell lines examined can constitutively express a wide variety of MMPs on mRNA and protein level. While MMP-2, -11, -14 and -24 were widely expressed, no expression was seen for MMP-12, -16, -20, -25, -26, -27 in any of the cell lines. A broad range of 16 MMPs could be found in the PA1 cells and thus this cell line could be used as a positive control for general MMP experiments. While the three cervical cancer cell lines expressed 10-14 different MMPs, the median expression in endometrial and choriocarcinoma cells was 7 different enzymes. The two investigated ovarian cancer cell lines showed a distinctive difference in the number of expressed MMPs (2 vs. 10). Ishikawa, Caski, OAW-42 and BeWo cell lines could be the best choice for all future experiments on MMP regulation and their role in endometrial, cervical, ovarian or choriocarcinoma development, whereas the teratocarcinoma cell line PA1 could be used as a positive control for general MMP experiments

  13. Antiproliferative activity of flavonoids on several cancer cell lines.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

    1999-05-01

    Twenty-seven Citrus flavonoids were examined for their antiproliferative activities against several tumor and normal human cell lines. As a result, 7 flavonoids were judged to be active against the tumor cell lines, while they had weak antiproliferative activity against the normal human cell lines. The rank order of potency was luteolin, natsudaidain, quercetin, tangeretin, eriodictyol, nobiletin, and 3,3',4',5,6,7,8-heptamethoxyflavone. The structure-activity relationship established from comparison among these flavones and flavanones showed that the ortho-catechol moiety in ring B and a C2-C3 double bond were important for the antiproliferative activity. As to polymethoxylated flavones, C-3 hydroxyl and C-8 methoxyl groups were essential for high activity.

  14. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.

    Science.gov (United States)

    Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas; Venkatesan, Kavitha; Margolin, Adam A; Kim, Sungjoon; Wilson, Christopher J; Lehár, Joseph; Kryukov, Gregory V; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Murray, Lauren; Berger, Michael F; Monahan, John E; Morais, Paula; Meltzer, Jodi; Korejwa, Adam; Jané-Valbuena, Judit; Mapa, Felipa A; Thibault, Joseph; Bric-Furlong, Eva; Raman, Pichai; Shipway, Aaron; Engels, Ingo H; Cheng, Jill; Yu, Guoying K; Yu, Jianjun; Aspesi, Peter; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D; Wang, Li; Hatton, Charles; Palescandolo, Emanuele; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C; Liefeld, Ted; MacConaill, Laura; Winckler, Wendy; Reich, Michael; Li, Nanxin; Mesirov, Jill P; Gabriel, Stacey B; Getz, Gad; Ardlie, Kristin; Chan, Vivien; Myer, Vic E; Weber, Barbara L; Porter, Jeff; Warmuth, Markus; Finan, Peter; Harris, Jennifer L; Meyerson, Matthew; Golub, Todd R; Morrissey, Michael P; Sellers, William R; Schlegel, Robert; Garraway, Levi A

    2012-03-28

    The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.

  15. The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity

    Science.gov (United States)

    Barretina, Jordi; Caponigro, Giordano; Stransky, Nicolas; Venkatesan, Kavitha; Margolin, Adam A.; Kim, Sungjoon; Wilson, Christopher J.; Lehár, Joseph; Kryukov, Gregory V.; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Murray, Lauren; Berger, Michael F.; Monahan, John E.; Morais, Paula; Meltzer, Jodi; Korejwa, Adam; Jané-Valbuena, Judit; Mapa, Felipa A.; Thibault, Joseph; Bric-Furlong, Eva; Raman, Pichai; Shipway, Aaron; Engels, Ingo H.; Cheng, Jill; Yu, Guoying K.; Yu, Jianjun; Aspesi, Peter; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D.; Wang, Li; Hatton, Charles; Palescandolo, Emanuele; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C.; Liefeld, Ted; MacConaill, Laura; Winckler, Wendy; Reich, Michael; Li, Nanxin; Mesirov, Jill P.; Gabriel, Stacey B.; Getz, Gad; Ardlie, Kristin; Chan, Vivien; Myer, Vic E.; Weber, Barbara L.; Porter, Jeff; Warmuth, Markus; Finan, Peter; Harris, Jennifer L.; Meyerson, Matthew; Golub, Todd R.; Morrissey, Michael P.; Sellers, William R.; Schlegel, Robert; Garraway, Levi A.

    2012-01-01

    The systematic translation of cancer genomic data into knowledge of tumor biology and therapeutic avenues remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacologic annotation is available1. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number, and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacologic profiles for 24 anticancer drugs across 479 of the lines, this collection allowed identification of genetic, lineage, and gene expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Altogether, our results suggest that large, annotated cell line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of “personalized” therapeutic regimens2. PMID:22460905

  16. Systematic identification of combinatorial drivers and targets in cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Adel Tabchy

    Full Text Available There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

  17. Systematic identification of combinatorial drivers and targets in cancer cell lines.

    Science.gov (United States)

    Tabchy, Adel; Eltonsy, Nevine; Housman, David E; Mills, Gordon B

    2013-01-01

    There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

  18. Matrigel Basement Membrane Matrix influences expression of microRNAs in cancer cell lines

    International Nuclear Information System (INIS)

    Price, Karina J.; Tsykin, Anna; Giles, Keith M.; Sladic, Rosemary T.; Epis, Michael R.; Ganss, Ruth; Goodall, Gregory J.; Leedman, Peter J.

    2012-01-01

    Highlights: ► Matrigel alters cancer cell line miRNA expression relative to culture on plastic. ► Many identified Matrigel-regulated miRNAs are implicated in cancer. ► miR-1290, -210, -32 and -29b represent a Matrigel-induced miRNA signature. ► miR-32 down-regulates Integrin alpha 5 (ITGA5) mRNA. -- Abstract: Matrigel is a medium rich in extracellular matrix (ECM) components used for three-dimensional cell culture and is known to alter cellular phenotypes and gene expression. microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have roles in cancer. While miRNA profiles of numerous cell lines cultured on plastic have been reported, the influence of Matrigel-based culture on cancer cell miRNA expression is largely unknown. This study investigated the influence of Matrigel on the expression of miRNAs that might facilitate ECM-associated cancer cell growth. We performed miRNA profiling by microarray using two colon cancer cell lines (SW480 and SW620), identifying significant differential expression of miRNAs between cells cultured in Matrigel and on plastic. Many of these miRNAs have previously been implicated in cancer-related processes. A common Matrigel-induced miRNA signature comprised of up-regulated miR-1290 and miR-210 and down-regulated miR-29b and miR-32 was identified using RT-qPCR across five epithelial cancer cell lines (SW480, SW620, HT-29, A549 and MDA-MB-231). Experimental modulation of these miRNAs altered expression of their known target mRNAs involved in cell adhesion, proliferation and invasion, in colon cancer cell lines. Furthermore, ITGA5 was identified as a novel putative target of miR-32 that may facilitate cancer cell interactions with the ECM. We propose that culture of cancer cell lines in Matrigel more accurately recapitulates miRNA expression and function in cancer than culture on plastic and thus is a valuable approach to the in vitro study of miRNAs.

  19. Identifying risk factors for brain metastasis in breast cancer patients: Implication for a vigorous surveillance program

    Directory of Open Access Journals (Sweden)

    Lorraine Chow

    2015-10-01

    Conclusion: Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients.

  20. Anti-cancer effects of bioactive compounds from rose hip fruit in human breast cancer cell lines

    OpenAIRE

    Zhong, Lijie

    2017-01-01

    Rose hips have long been used in human diets as a food ingredient and supplement. Their multiple medical properties, which have been attributed to their abundant carotenoid composition, have attracted widespread scientific attention. This thesis examined the carotenoid composition in rose hips from five rose species. The anti-cancer effect of different carotenoid fractions from rose hips was investigated in human breast cancer cell lines, using the natural variation in carotenoid content in h...

  1. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P

    2011-01-01

    the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first-line...

  2. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

    Science.gov (United States)

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

  3. [Effects of icotinib hydrochloride on the proliferation and apoptosis of human lung cancer cell lines].

    Science.gov (United States)

    Ma, Li; Han, Xiao-hong; Wang, Shuai; Wang, Jian-fei; Shi, Yuan-kai

    2012-09-25

    To explore the effects of icotinib on the proliferation and apoptosis of various lung cancer cell lines. Human lung cancer cell lines HCC827, H1650, H1975, A549 and human epidermal cancer cell line A431 were treated in vitro with icotinib or gefitinib at a concentration gradient of 0 - 40 µmol/L. Their proliferation effects were analyzed by the thiazolyl blue (MTT) assay and the apoptotic effects detected by flow cytometer. The downstream signaling proteins were detected by Western blot. The median inhibitory concentrations (IC(50)) of icotinib for A431 and HCC827 cell lines were (0.04 ± 0.02) and (0.15 ± 0.06) µmol/L respectively. No significant differences existed between the inhibitions of gefitinib and icotinib on A431, HCC827, H1650, H1975 and A549 cell lines (all P > 0.05). Compared with H1650, H1975 and A549 cell lines, icotinib significantly inhibited A431 (P = 0.009, 0.005 and 0.000) and HCC827 (P = 0.001, 0.001 and 0.000) cell lines. And it lowered the expressions of p-AKT, p-ERK and survivin protein expression through the inhibited activity of p-EGFR protein. Icotinib can arrest the proliferation of lung adenocarcinoma cells with EGFR mutation or over-expression by inhibiting the signal pathways of AKT-ERK and survivin.

  4. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer.

    Science.gov (United States)

    Duchnowska, Renata; Loibl, Sibylle; Jassem, Jacek

    2018-06-01

    Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy. The small-molecule tyrosine kinase inhibitors of epidermal growth factor receptors family have established activity in HER2-positive breast cancer in both advanced disease and neoadjuvant setting. Favorable physico-chemical properties of these compounds allow them for a more efficient penetration through the blood-brain barrier, and hold the promise for more effective prevention and treatment of brain metastases. In this article we review the role of currently available or investigational HER2 tyrosine kinase inhibitors: lapatinib, neratinib, afatinib and tucatinib in the treatment of brain metastases in HER2-positive breast cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Cancers of the Brain and CNS: Global Patterns and Trends in Incidence.

    Science.gov (United States)

    Mortazavi, S M J; Mortazavi, S A R; Paknahad, M

    2018-03-01

    Miranda-Filho et al. in their recently published paper entitled "Cancers of the brain and CNS: global patterns and trends in incidence" provided a global status report of the geographic and temporal variations in the incidence of brain and CNS cancers in different countries across continents worldwide. While the authors confirm the role of genetic risk factors and ionizing radiation exposures, they claimed that no firm conclusion could be drawn about the role of exposure to non-ionizing radiation. The paper authored by Miranda-Filho et al. not only addresses a challenging issue, it can be considered as a good contribution in the field of brain and CNS cancers. However, our correspondence addresses a basic shortcoming of this paper about the role of electromagnetic fields and cancers and provides evidence showing that exposure to radiofrequency electromagnetic fields (RF-EMFs), at least at high levels and long durations, can increases the risk of cancer.

  6. Prognostic factors for survival and intracerebral control after irradiation for brain metastases from gynecological cancer

    NARCIS (Netherlands)

    Rades, Dirk; Fischer, Dorothea; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.

    2009-01-01

    The most appropriate treatment for the individual patient with brain metastases from gynecological cancer is unclear. Most of these patients receive whole-brain radiotherapy (WBRT) alone. Prognostic factors predicting the outcomes of these patients may guide the physician to select the appropriate

  7. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    Science.gov (United States)

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.; Fidler, Isaiah J.; Cantley, Lewis C.; Locasale, Jason W.; Weihua, Zhang

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the non-oxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBPs) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis, and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. PMID:25511375

  8. Synthesis of Chromonylthiazolidines and Their Cytotoxicity to Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Hoang Le Tuan Anh

    2015-01-01

    Full Text Available Nine new chromonylthiazolidine derivatives were successfully semi-synthesized from paeonol. All of the compounds, including starting materials, the intermediate compound and products, were evaluated for their cytotoxic effects toward eight human cancer cell lines. The synthesized chromonylthiazolidines displayed weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compounds 3a and 3b showed the most selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 ± 3.6 μg/mL and breast cancer (IC50 32.8 ± 1.4 μg/mL cell lines, respectively. The results suggest that chromoylthiazolidines are potential low-cost, and selective anticancer agents.

  9. Brain stem/brain stem occipital bone ratio and the four-line view in nuchal translucency images of fetuses with open spina bifida.

    Science.gov (United States)

    Iuculano, Ambra; Zoppi, Maria Angelica; Piras, Alessandra; Arras, Maurizio; Monni, Giovanni

    2014-09-10

    Abstract Objective: Brain stem depth/brain stem occipital bone distance (BS/BSOB ratio) and the four-line view, in images obtained for nuchal translucency (NT) screening in fetuses with open spina bifida (OSB). Methods: Single center, retrospective study based on the assessment of NT screening images of fetuses with OSB. A ratio between the BS depth and the BSOB distance was calculated (BS/BSOB ratio) and the four-line view observed, and the sensitivity for a BS/BSOB ratio superior/equal to 1, and for the lack of detection of the four-line view were calculated. Results: There were 17 cases of prenatal diagnosis OSB. In six cases, the suspicion on OSB was raised during NT screening, in six cases, the diagnosis was made before 20 weeks and in five cases during anomaly scan. The BS/BSOB ratio was superior/equal to 1 in all 17 cases, and three lines, were visualized in 15/17 images of the OSB cases, being the sensitivity 100% (95% CI, 81 to 100%) and 88% (95% CI, 65 to 96%). Conclusion: Assessment of BS/BSOB ratio and four-line view in NT images is feasible detecting affected by OSB with high sensitivity. The presence of associated anomalies or of an enlarged NT enhances the early detection.

  10. In vitro cytotoxicity of alpha conjugates for human pancreatic cancer cell lines

    International Nuclear Information System (INIS)

    Qu, C.; Li, Y.; Rizvi, M.A.; Allen, B.; Samra, J.; Smith, R.

    2003-01-01

    Targeted Alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The aim of this study is to demonstrate the cytotoxicity of different alpha conjugates in vitro to human metastatic pancreatic cancer cell lines (CAPAN-1, CFPAN-1 and PANC-1). We are labeling the C595 and J591 (non-specific controls) monoclonal antibodies (Mabs) with 213 Bi were performed according to the standard methods in our laboratory. 213 Bi-C595 is specifically cytotoxic to CAPAN-1, CFPAN-1 and PANC-1cell lines in a concentration-dependent fashion. While non-specific alpha conjugates only killed very small fractions of pancreatic cancer cells. These alpha conjugates might be useful agents for the treatment of micro-metastases in pancreatic cancer patients with over-expression of the targeted receptors

  11. Analysis of secretome of breast cancer cell line with an optimized semi-shotgun method

    International Nuclear Information System (INIS)

    Tang Xiaorong; Yao Ling; Chen Keying; Hu Xiaofang; Xu Lisa; Fan Chunhai

    2009-01-01

    Secretome, the totality of secreted proteins, is viewed as a promising pool of candidate cancer biomarkers. Simple and reliable methods for identifying secreted proteins are highly desired. We used an optimized semi-shotgun liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) method to analyze the secretome of breast cancer cell line MDA-MB-231. A total of 464 proteins were identified. About 63% of the proteins were classified as secreted proteins, including many promising breast cancer biomarkers, which were thought to be correlated with tumorigenesis, tumor development and metastasis. These results suggest that the optimized method may be a powerful strategy for cell line secretome profiling, and can be used to find potential cancer biomarkers with great clinical significance. (authors)

  12. Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu; Duraisamy, Prabhu Kumar; Ashok Kumar, Sekar, E-mail: sekarashok@gmail.com

    2015-08-28

    The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER{sup +} and ER{sup −} breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen.

  13. Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

    International Nuclear Information System (INIS)

    Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu; Duraisamy, Prabhu Kumar; Ashok Kumar, Sekar

    2015-01-01

    The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER + and ER − breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen

  14. Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model With Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport

    Directory of Open Access Journals (Sweden)

    Szilvia Veszelka

    2018-05-01

    Full Text Available Cell culture-based blood-brain barrier (BBB models are useful tools for screening of CNS drug candidates. Cell sources for BBB models include primary brain endothelial cells or immortalized brain endothelial cell lines. Despite their well-known differences, epithelial cell lines are also used as surrogate models for testing neuropharmaceuticals. The aim of the present study was to compare the expression of selected BBB related genes including tight junction proteins, solute carriers (SLC, ABC transporters, metabolic enzymes and to describe the paracellular properties of nine different culture models. To establish a primary BBB model rat brain capillary endothelial cells were co-cultured with rat pericytes and astrocytes (EPA. As other BBB and surrogate models four brain endothelial cells lines, rat GP8 and RBE4 cells, and human hCMEC/D3 cells with or without lithium treatment (D3 and D3L, and four epithelial cell lines, native human intestinal Caco-2 and high P-glycoprotein expressing vinblastine-selected VB-Caco-2 cells, native MDCK and MDR1 transfected MDCK canine kidney cells were used. To test transporter functionality, the permeability of 12 molecules, glucopyranose, valproate, baclofen, gabapentin, probenecid, salicylate, rosuvastatin, pravastatin, atorvastatin, tacrine, donepezil, was also measured in the EPA and epithelial models. Among the junctional protein genes, the expression level of occludin was high in all models except the GP8 and RBE4 cells, and each model expressed a unique claudin pattern. Major BBB efflux (P-glycoprotein or ABCB1 and influx transporters (GLUT-1, LAT-1 were present in all models at mRNA levels. The transcript of BCRP (ABCG2 was not expressed in MDCK, GP8 and RBE4 cells. The absence of gene expression of important BBB efflux and influx transporters BCRP, MRP6, -9, MCT6, -8, PHT2, OATPs in one or both types of epithelial models suggests that Caco-2 or MDCK models are not suitable to test drug candidates which

  15. Inhibition of Zoledronic Acid on Cell Proliferation and Invasion of Lung Cancer Cell Line 95D

    Directory of Open Access Journals (Sweden)

    Mingming LI

    2009-03-01

    Full Text Available Background and objective Abnormal proliferation and metastasis is the basic characteristic of malignant tumors. The aim of this work is to explore the effects of zoledronic acid on cell proliferation and invasion in lung cancer cell line 95D. Methods The effect of zoledrnic acid (ZOL on proliferation of lung cancer cell line 95D was detected by MTT. The expression of proliferation and invasion-relation genes and proteins were detected by Western blot, RT-PCR and immunofluorescence. Changes of invasion of lung cancer cell numbers were measured by polycarbonates coated with Matrigel. Results ZOL could inhibit the proliferation of lung cancer cell line 95D in vitro in a time-dependant and a dose-dependant manner. With time extending after ZOL treated, the mRNA expresion of VEGF, MMP9, MMP2 and protein expression of VEGF, MMP9, ERK1/ ERK2 were decreased. The results of Tanswell invasion showed the numbers of invasive cells were significantly reduced in 95D cells treated with ZOL 4 d and 6 d later. Conclusion ZOL could inhibit cell proliferation and invasion of lung cancer cell line 95D.

  16. Comparative analysis of gene expression in normal and cancer human prostate cell lines

    Directory of Open Access Journals (Sweden)

    E. E. Rosenberg

    2014-04-01

    Full Text Available Prostate cancer is one of the main causes of mortality in men with malignant tumors. The urgent problem was a search for biomarkers of prostate cancer, which would allow distinguishing between aggressive metastatic and latent tumors. The aim of this work was to search for differentially expressed genes in normal epithelial cells PNT2 and prostate cancer cell lines LNCaP, DU145 and PC3, produced from tumors with different aggressiveness and metas­tatic ability. Such genes might be used to create a panel of prognostic markers for aggressiveness and metastasis. Relative gene expression of 65 cancer-related genes was determined by the quantitative polymerase chain reaction (Q-PCR. Expression of 29 genes was changed in LNCaP cells, 20 genes in DU145 and 16 genes in PC3 cell lines, compared with normal line PNT2. The obtained data make it possible to conclude that the epithelial-mesenchymal cell transition took place, which involved the loss of epithelial markers, reduced cell adhesion and increased migration. We have also found few differentially expressed genes among 3 prostate cancer cell lines. We have found that genes, involved in cell adhesion (CDH1, invasiveness and metastasis (IL8, CXCL2 and cell cycle control (P16, CCNE1 underwent most changes. These genes might be used for diagnosis and prognosis of invasive metastatic prostate tumors.

  17. Integrated analysis of breast cancer cell lines reveals unique signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.; Laderoute, Keith R.; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L.; Laquerre, Sylvie; Jackson, Jeffrey R.; Wooster, Richard F.; Kuo, Wen-Lin; Gray, Joe W.; Spellman, Paul T.

    2009-03-31

    Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

  18. Integrated analysis of breast cancer cell lines reveals unique signaling pathways.

    Science.gov (United States)

    Heiser, Laura M; Wang, Nicholas J; Talcott, Carolyn L; Laderoute, Keith R; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L; Laquerre, Sylvie; Jackson, Jeffrey R; Wooster, Richard F; Kuo, Wen Lin; Gray, Joe W; Spellman, Paul T

    2009-01-01

    Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

  19. Radiolabeling and in vitro evaluation of 99mTc-methotrexate on breast cancer cell line

    International Nuclear Information System (INIS)

    Emre Ozgenc; Meliha Ekinci; Derya Ilem-Ozdemir; Evren Gundogdu; Makbule Asikoglu

    2016-01-01

    In the present study 99m Tc-MTX was prepared with high labeling yield by a new simple and easy formulation method. According to cell culture studies, 99m Tc- MTX incorporated with both MCF-7 and CRL8798 cells, with significant differences in the uptake percentages. Since 99m Tc-MTX highly uptake in cancer cell line, the results demonstrated that radiolabeled MTX may be promising for breast cancer diagnosis of oncological patients. (author)

  20. Brain metastases in lung cancer. Impact of prognostic factors on patient survival

    International Nuclear Information System (INIS)

    Smrdel, U.; Zwitter, M.; Kovac, V.

    2003-01-01

    Background. Brain metastases are common patterns of dissemination in lung cancer patients. In this paper we would like to assess the pattern of brain metastases in lung cancer patients and the impact of prognostic factors on the survival of lung cancer patients with brain metastases. Patients and methods. In the year 1998 there were 974 registered patients with lung cancer in Slovenia, six hundred and fifteen of them were treated at the Institute of Oncology Ljubljana and we analyzed them. Among 615 patients 137 (22.3 %) of them have had brain metastases during a natural course of disease. Results. For 12 patients presenting with solitary brain metastases (most of them were undertaken metastasectomy) median survival was 7.6 months, while in patients with multiple brain metastases the median survival was 2.8 months (p 0.0018). Of the 137 patients 45 (32.8 %) were small cell lung cancer patients, 43 (31.4 %) were adenocarcinoma patients and 19 (13.9 %) were squamous cell carcinoma patients. Patients with performance status (WHO scale) less than 2 had the median survival time 3.7 months while patients with performance status 2 or more had median survival time 2.7 moths (p=0.0448). Conclusions. Patients with solitary brain metastases had better survival comparing with those who had multiple metastases. It is surprisingly that the portion of brain metastases patients with adenocarcinoma is almost equal to those with small-call lung cancer therefore, the prophylactic cranial radiation becomes actual for both groups of patients. The performance status of patients with brain metastases remains very important prognostic factor. (author)

  1. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  2. Non-Viral Transfection Methods Optimized for Gene Delivery to a Lung Cancer Cell Line

    OpenAIRE

    Salimzadeh, Loghman; Jaberipour, Mansooreh; Hosseini, Ahmad; Ghaderi, Abbas

    2013-01-01

    Background Mehr-80 is a newly established adherent human large cell lung cancer cell line that has not been transfected until now. This study aims to define the optimal transfection conditions and effects of some critical elements for enhancing gene delivery to this cell line by utilizing different non-viral transfection Procedures. Methods In the current study, calcium phosphate (CaP), DEAE-dextran, superfect, electroporation and lipofection transfection methods were used to optimize deliver...

  3. Antiproliferative effects of small fruit juices on several cancer cell lines.

    Science.gov (United States)

    Yoshizawa, Y; Kawaii, S; Urashima, M; Fukase, T; Sato, T; Tanaka, R; Murofushi, N; Nishimura, H

    2000-01-01

    Juices prepared from small fruits, mainly growing in the northern part of Japan, were studied in an attempt to explore the feasibility of an assay that screens cytotoxic properties. Screening of 43 small fruit juices indicated that Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray and Sorbus sambucifolia Roem, strongly inhibited the proliferation of all cancer cell lines examined and yet these juices were substantially less cytotoxic toward normal human cell lines.

  4. EG-17SUV420-MEDIATED HETEROCHROMATIN CHANGES IN PEDIATRIC BRAIN CANCERS

    Science.gov (United States)

    Van Meter, Timothy E.; Terry, Jocelyn; Rockwell, Nathan; Goggin, Sarah; Nethala, Priya; Khan, Asadullah

    2014-01-01

    Silencing mechanisms play a role in genomic stability by maintaining condensed, non-active regions of the genome. SUV420 enzymes contain a SET domain conferring methyltransferase activity toward histones. The Histone H4 lysine 20 trimethylation (H4K20me3) mark maintained by SUV420H2 is associated with heterochromatin formation and gene silencing, whereas the dimethylated mark (H4K20me2) is associated with DNA repair. In studies of epigenetic factors in large patient cohorts with ependymoma, it was found that SUV420H2 expression was lost or diminished in patients with reciprocal increases in prognostic markers such as hTERT. To better understand the normal function of Suv4-20H1/H2 enzyme in neural progenitors, and pathological changes in cancers, a variety of differentiation paradigms were used. The NT2D1 neurally restricted cell line, and BGO1V and H9 human embryonic stem cells (ESCs), and differentiated progeny, were used alongside tumors to better understand enzyme targets and functional outcomes (e.g.,lineage, differentiation, regional chromatin modifications). Lineage stages were verified with stage-specific markers by immunofluorescence and qPCR. Suv4-20 H1 and H2 were present in ESCs and neural progenitors and decreased thereafter. RNAi knockdown of SUV420 enzymes led to decreased H4K20 methylation in cancer cells. DNA methylation microarrays and ChIP-PCR suggest 1) that SUV420 is not regulated by DNA methylation in ependymomas; 2) that active chromatin marks such as H3K4 dimethylation are enriched near the transcriptional start site in the SUV420H2 gene, and 3) that hTERT is hyper-methylated at specific CpG islands and histones in a tumor sub-group-specific manner. This data supports the hypothesis that Suv4-20H2 is highly active in progenitor cells and functionally lost in some brain cancers. These studies begin to elucidate coincident mechanisms of gene silencing active in neural progenitors that may be altered in a subset of pediatric brain cancers.

  5. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

  6. Integrin Alpha-v and HER2 in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    ZOOM live cell imaging machine (ESSEN Bioscience; Figure 2). c. Interactions of αv integrin and HER2 in breast cancer brain metastases. We found...HCC1954 breast cancer cells. C) Real time live cell imaging of MM2BH cells treated with cilengitide (0, .3, 1, 3, and 10 µg/mL) using IncuCyte ZOOM

  7. Occupational exposure to electromagnetic fields, leukemia and brain cancer: update of two meta-analysis

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    This new meta-analysis found a slight increase in the risk of brain cancer and of leukemia in populations occupationally exposed to electromagnetic fields. it does not, however, support the hypothesis that electromagnetic fields have an effect on these cancers. (author)

  8. Gene expression profile of colon cancer cell lines treated with SN-38

    DEFF Research Database (Denmark)

    Wallin, A; Francis, P; Nilbert, M

    2010-01-01

    the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor......Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though...

  9. Self-help on-line: an outcome evaluation of breast cancer bulletin boards.

    Science.gov (United States)

    Lieberman, Morton A; Goldstein, Benjamin A

    2005-11-01

    Many breast cancer patients find help from on-line self-help groups, consisting of self-directed, asynchronous, bulletin boards. These have yet to be empirically evaluated. Upon joining a group and 6 months later, new members (N=114) to breast cancer bulletin boards completed measures of depression (CES-D), growth (PTGI) and psychosocial wellbeing (FACT-B). Improvement was statistically significant on all three measures. This serves as a first validation of Internet bulletin boards as a source of support and help for breast cancer patients. These boards are of particular interest because they are free, accessible and support comes from peers and not from professional facilitators.

  10. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC Registry

    Directory of Open Access Journals (Sweden)

    Elena Laakmann

    2016-09-01

    Full Text Available Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT and magnetic resonance imaging (MRI scans of 300 breast cancer patients with brain metastases (BMs were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC in Germany. Patients with positive estrogen (ER, progesterone (PR, or human epidermal growth factor receptor 2 (HER2 statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001. Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021, whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038. The localization of Brain metastases (BMs was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025. A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012. Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment.

  11. Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

    International Nuclear Information System (INIS)

    Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli

    2012-01-01

    Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  12. Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ostrom, Quinn T. [Department of Anthropology, Case Western Reserve University, Cleveland, OH (United States); McCulloh, Christopher [Case Western Reserve University School of Medicine, Cleveland, OH (United States); Chen, Yanwen; Devine, Karen; Wolinsky, Yingli, E-mail: qto@case.edu [Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH (United States)

    2012-02-28

    Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  13. Family history of cancer in benign brain tumor subtypes versus gliomas

    Directory of Open Access Journals (Sweden)

    Quinn eOstrom

    2012-02-01

    Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  14. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

    Directory of Open Access Journals (Sweden)

    Ilaria eSciamanna

    2016-02-01

    Full Text Available In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1 retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT, which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can sequester RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

  15. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

    Science.gov (United States)

    Sciamanna, Ilaria; De Luca, Chiara; Spadafora, Corrado

    2016-02-01

    In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can “sequester” RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

  16. Expression of G-protein inwardly rectifying potassium channels (GIRKs in lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Schuller Hildegard M

    2005-08-01

    Full Text Available Abstract Background Previous data from our laboratory has indicated that there is a functional link between the β-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1 in human breast cancer cell lines. We wanted to determine if GIRK channels were expressed in lung cancers and if a similar link exists in lung cancer. Methods GIRK1-4 expression and levels were determined by reverse transcription polymerase chain reaction (RT-PCR and real-time PCR. GIRK protein levels were determined by western blots and cell proliferation was determined by a 5-bromo-2'-deoxyuridine (BrdU assay. Results GIRK1 mRNA was expressed in three of six small cell lung cancer (SCLC cell lines, and either GIRK2, 3 or 4 mRNA expression was detected in all six SCLC cell lines. Treatment of NCI-H69 with β2-adrenergic antagonist ICI 118,551 (100 μM daily for seven days led to slight decreases of GIRK1 mRNA expression levels. Treatment of NCI-H69 with the β-adrenergic agonist isoproterenol (10 μM decreased growth rates in these cells. The GIRK inhibitor U50488H (2 μM also inhibited proliferation, and this decrease was potentiated by isoproterenol. In the SCLC cell lines that demonstrated GIRK1 mRNA expression, we also saw GIRK1 protein expression. We feel these may be important regulatory pathways since no expression of mRNA of the GIRK channels (1 & 2 was found in hamster pulmonary neuroendocrine cells, a suggested cell of origin for SCLC, nor was GIRK1 or 2 expression found in human small airway epithelial cells. GIRK (1,2,3,4 mRNA expression was also seen in A549 adenocarcinoma and NCI-H727 carcinoid cell lines. GIRK1 mRNA expression was not found in tissue samples from adenocarcinoma or squamous cancer patients, nor was it found in NCI-H322 or NCI-H441 adenocarcinoma cell lines. GIRK (1,3,4 mRNA expression was seen in three squamous cell lines, GIRK2 was only expressed in one squamous cell line. However, GIRK1 protein

  17. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets

    Directory of Open Access Journals (Sweden)

    Nitesh Rohatgi

    2018-01-01

    Full Text Available Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10–16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

  18. The factors that have an impact on the development of brain metastasis in the patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Adem Dayan

    2012-01-01

    Conclusions: As the prognostic and predictive factors showing the development of brain metastasis in breast cancer patients may be identified, follow-up also including the brain is important in order to take preventive measures.

  19. Production of prostate-specific antigen by a breast cancer cell line, Sk-Br-3

    International Nuclear Information System (INIS)

    Kamali Sarvestani, E.; Ghaderi, A.

    2002-01-01

    Prostate-specific antigen is a 33-KDa serine protease that is produced predominantly by prostate epithelium. However, it has been shown that about 30-40% of female breast tumors produce prostate-specific antigen and its production is associated with the presence of estrogen and progesterone receptors. We have now developed a new tissue culture system to study prostate-specific antigen production in breast cancer and its association with prognostic factors such as progesterone receptor and c-erbB-2. For this purpose we investigated the ability of prostate-specific antigen production in five different cell lines, including two breast cancer cell lines, Sk-Br-3 and MDA-MB-453. The prostate-specific antigen in tissue culture supernatant and cytoplasm of the Sk-Br-3 cell line was detected by western blotting and immunoperoxidase, respectively. Furthermore, we found lower expression of c-erbB-2 in Sk-Br-3 than non-prostate-specific antigen producer breast cancer cell line, MDA-MB-453. Progesterone receptor was expressed by both prostate-specific antigen-positive and -negative cell lines and only the intensity of staining and the number of positive cells in Sk-Br-3 population was higher than MDA-MB-453. According to our findings prostate-specific antigen can be considered as a good prognostic factor in breast cancer and we suggest that these two cell lines are a good in vitro model to study the relationship of different breast cancer prognostic factors and their regulations

  20. LINES

    Directory of Open Access Journals (Sweden)

    Minas Bakalchev

    2015-10-01

    Full Text Available The perception of elements in a system often creates their interdependence, interconditionality, and suppression. The lines from a basic geometrical element have become the model of a reductive world based on isolation according to certain criteria such as function, structure, and social organization. Their traces are experienced in the contemporary world as fragments or ruins of a system of domination of an assumed hierarchical unity. How can one release oneself from such dependence or determinism? How can the lines become less “systematic” and forms more autonomous, and less reductive? How is a form released from modernistic determinism on the new controversial ground? How can these elements or forms of representation become forms of action in the present complex world? In this paper, the meaning of lines through the ideas of Le Corbusier, Leonidov, Picasso, and Hitchcock is presented. Spatial research was made through a series of examples arising from the projects of the architectural studio “Residential Transformations”, which was a backbone for mapping the possibilities ranging from playfulness to exactness, as tactics of transformation in the different contexts of the contemporary world.

  1. Cytotoxic activity of methanol extracts from Basidiomycete mushrooms on murine cancer cell lines.

    Science.gov (United States)

    Tomasi, S; Lohézic-Le Dévéhat, F; Sauleau, P; Bézivin, C; Boustie, J

    2004-04-01

    Crude methanol extracts of 58 mushroom species were screened for their cytotoxic activities against two murine cancer cell lines, L1210 and 3LL, using the tetrazolium assay. A majority of extracts (74%) exhibited IC50 > 100 microg/ml against both cell lines. A most marked activity against one of the cell lines was noted for nine species (14% of the tested species). While Amanitales and Russulales tested were not found active, Polyporales and Boletales gave better results. Four species exhibited a significant cytotoxic activity (IC50 Suillus granulatus, S. luteus). The last one had never been investigated for its cytotoxic compounds before.

  2. The antiproliferative effect of acridone alkaloids on several cancer cell lines.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M; Takemura, Y; Ju-ichi, M; Ito, C; Furukawa, H

    1999-04-01

    Fifteen acridone alkaloids were examined for their antiproliferative activity toward monolayers and suspension of several types of cancer and normal human cell lines. As a result, atalaphyllidine (9), 5-hydroxy-N-methylseverifoline (11), atalaphyllinine (12), and des-N-methylnoracronycine (13) showed potent antiproliferative activity against tumor cell lines, whereas they have weak cytotoxicity on normal human cell lines. The structure-activity relationship established from the results revealed that a secondary amine, hydroxyl groups at C-1 and C-5, and a prenyl group at C-2 played an important role for antiproliferative activities of the tetracyclic acridones.

  3. Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

    Science.gov (United States)

    Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

    2015-08-01

    Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Expression of a LINE-1 endonuclease variant in gastric cancer: its association with clinicopathological parameters

    International Nuclear Information System (INIS)

    Wang, Gangshi; Wu, Benyan; Wang, Mengwei; Gao, Jie; Huang, Haili; Tian, Yu; Xue, Liyan; Wang, Weihua; You, Weidi; Lian, Hongwei; Duan, Xiaojian

    2013-01-01

    Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human L1 sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain. Immunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases. Most primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Lauren’s classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (≥65 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation

  5. The Activity of Sirtuin 1 in MCF-7 Breast Cancer Cell Line: The Effects of Visfatin

    Directory of Open Access Journals (Sweden)

    kiarash behrouzfar

    2015-11-01

    Full Text Available Background & Objectives: Breast cancer is the most common cancer and the second leading cause of cancer deaths among women. Obesity, hormones, and growth factors are the risk factors for this kind of cancer. One of the changes observed in patients suffering from breast cancer is the elevated Visfatin or nicotinamide phosphoribosyl transferase (NAMPT in their tumor tissues and blood. The increased activity of Visfatin and SIRT1 (Sirtuin 1 in breast cancer and many other cancers has been determined, and its value is correlated with cancer prognosis. The aim of the present study is to investigate the effects of Visfatin on SIRT1 activity in MCF-7 breast cancer cell line. Materials & Methods: In this study, in order to investigate the effects of Visfatin on SIRT1 activity in MCF-7 cells, cells were treated after cell culture by Visfatin for 12, 24, and 48 hours. Subsequently, the cells were lysed by nuclear extraction kit, and their total protein concentrations were measured by Bradford assay. Finally, we estimated the general activity of SIRT1 by measuring the SIRT1 activity with the assay kit via spectrofluorometric device. Results: The findings of this research show that SIRT1 activity is not significantly changed following Visfatin treatments for 12 and 24 hours. However, after 48 hour, Visfatin increases SIRT1 activity about 2 times more than control group. Conclusion: The antiapoptotic effects of Visfatin are exerted by increasing SIRT1 activity in MCF-7 cells, and these effects happen after 24 hours. 

  6. Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

    Science.gov (United States)

    Du, Enming; Hu, Xunwu; Roy, Sona; Wang, Peng; Deasy, Kieran; Mochizuki, Toshiaki; Zhang, Ye

    2017-05-30

    The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

  7. A case of leukoencephalopathy caused by radiation and chemotherapy for brain metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Shigeru; Sonoo, Hiroshi; Nomura, Tsunehisa; Ohkubo, Sumiko; Yamamoto, Yutaka; Tanaka, Katsuhiro; Kurebayashi, Junichi; Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2002-08-01

    A case of treatment-related leukoencephalopathy is presented. A patient with breast cancer metastasis to the brain, liver, bone and distant lymph nodes was treated with whole brain radiation and docetaxcel. Eleven months after radiation, magnetic resonance imaging showed diffuse leukoencephalopathy. Twenty-two months after radiation, the patient had gait disturbance, parkinsonism, dementia and urinary incontinence. From this experience, stereotactic radiosurgery such as cyber knife and gamma knife therapy, representing a new modality for delivering intense focal radiation, should be come preferred techniques for treating patients with brain metastases, to avoid the potential cognitive side effects of fractionated whole-brain radiotherapy. (author)

  8. Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy

    Directory of Open Access Journals (Sweden)

    Wu S

    2016-12-01

    Full Text Available San-Gang Wu,1,* Jia-Yuan Sun,2,* Qin Tong,3 Feng-Yan Li,2 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 3Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China *These authors contributed equally to this work Objective: The objectives of this study were to describe the distribution of brain metastases (BM in breast cancer patients and investigate the risk factors for perihippocampal metastases (PHM. Patients and methods: Retrospective analysis of the clinicopathological characteristics and patterns of BM was performed. Associations between clinicopathological characteristics and PHM (the hippocampus plus 5 mm margin were evaluated using logistic regression analyses. Results: A total of 1,356 brain metastatic lesions were identified in 192 patients. Patients with 1–3 BM, 4–9 BM, and ≥10 BM accounted for 63.0%, 18.8%, and 18.2%, respectively. There were only 7 (3.6% patients with hippocampal metastases (HM and 14 (7.3% patients with PHM. On logistic regression, the number of BM was an independent risk factor for PHM. Patients with ≥10 BM had a significantly higher risk of PHM compared with those with <10 BM. Breast cancer subtype (BCS was not associated with PHM. The number of BM was significantly correlated with various BCSs. Patients with hormone receptor (HR+/human epidermal growth factor receptor 2 (HER2+, HR-/HER2+, and HR-/HER2- subtypes had a higher probability of ≥10 BM, relative to patients with an HR+/HER2- subtype. Conclusion: Our study suggests that a low incidence of PHM may be acceptable to perform hippocampal-sparing whole-brain radiation therapy for breast cancer patients

  9. Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

    Science.gov (United States)

    Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

    2017-01-01

    An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

  10. Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines.

    Science.gov (United States)

    Emadi Baygi, Modjtaba; Soheili, Zahra Soheila; Schmitz, Ingo; Sameie, Shahram; Schulz, Wolfgang A

    2010-12-01

    The epithelial-mesenchymal transition (EMT) is regarded as an important step in cancer metastasis. Snail, a master regulator of EMT, has been recently proposed to act additionally as a cell survival factor and inducer of motility. We have investigated the function of Snail (SNAI1) in prostate cancer cells by downregulating its expression via short (21-mer) interfering RNA (siRNA) and measuring the consequences on EMT markers, cell viability, death, cell cycle, senescence, attachment, and invasivity. Of eight carcinoma cell lines, the prostate carcinoma cell lines LNCaP and PC-3 showed the highest and moderate expression of SNAI1 mRNA, respectively, as measured by quantitative RT-PCR. Long-term knockdown of Snail induced a severe decline in cell numbers in LNCaP and PC-3 and caspase activity was accordingly enhanced in both cell lines. In addition, suppression of Snail expression induced senescence in LNCaP cells. SNAI1-siRNA-treated cells did not tolerate detachment from the extracellular matrix, probably due to downregulation of integrin α6. Expression of E-cadherin, vimentin, and fibronectin was also affected. Invasiveness of PC-3 cells was not significantly diminished by Snail knockdown. Our data suggest that Snail acts primarily as a survival factor and inhibitor of cellular senescence in prostate cancer cell lines. We therefore propose that Snail can act as early driver of prostate cancer progression.

  11. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

    NARCIS (Netherlands)

    Carbone, D.P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; Heuvel, M. van den; Ciuleanu, T.E.; Badin, F.; Ready, N.; Hiltermann, T.J.N.; Nair, S.; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J.M.; Rodriguez-Abreu, D.; Borghaei, H.; umenschein GR, J.r. Bl; Villaruz, L.C.; Havel, L.; Krejci, J.; rral Jaime, J. Co; Chang, H.; Geese, W.J.; Bhagavatheeswaran, P.; Chen, A.C.; Socinski, M.A.

    2017-01-01

    BACKGROUND: Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  12. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer

    NARCIS (Netherlands)

    Carbone, D. P.; Reck, M.; Paz-Ares, L.; Creelan, B.; Horn, L.; Steins, M.; Felip, E.; van den Heuvel, M. M.; Ciuleanu, T. -E.; Badin, F.; Ready, N.; Hiltermann, T. J. N.; Nair, S; Juergens, R.; Peters, S.; Minenza, E.; Wrangle, J. M.; Rodriguez-Abreu, D.; Borghaei, H.; Blumenschein, G. R.; Villaruz, L. C.; Havel, L.; Krejci, J.; Corral Jaime, J.; Chang, C. -H.; Geese, W. J.; Bhagavatheeswaran, P.; Chen, Alexander C.; Socinski, M. A.

    2017-01-01

    BACKGROUND Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1

  13. Analysis of P53 mutations and their expression in 56 colorectal cancer cell lines

    DEFF Research Database (Denmark)

    Liu, Ying; Bodmer, Walter F

    2006-01-01

    A comprehensive analysis of the TP53 gene and its protein status was carried out on a panel of 56 colorectal cancer cell lines. This analysis was based on a combination of denaturing HPLC mutation screening of all exons of the p53 gene, sequencing the cDNA, and assessing the function of the p53 p...

  14. Proteomics of cancer cell lines resistant to microtubule-stabilizing agents

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Angeletti, Ruth H; Horwitz, Susan Band

    2014-01-01

    Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellula...

  15. Establishment, characterization, virus susceptibility and transfection of cell lines from cobia, Rachycentron canadum (L.), brain and fin.

    Science.gov (United States)

    Cheng, T-C; Lai, Y-S; Lin, I-Y; Wu, C-P; Chang, S-L; Chen, T-I; Su, M-S

    2010-02-01

    Establishment and characterization of two cobia, Rachycentron canadum, cell lines derived from cobia brain (CB) and cobia fin (CF) are described. Caudal fin and brain from juvenile cobia were dissociated for 30 and 10 min, respectively, in phosphate-buffered saline containing 0.25% trypsin at 25 degrees C. The optimal culture condition for both dissociated cells (primary cell culture) was at 28 degrees C in Leibovitz-15 medium containing 10% foetal bovine serum. The cells have been sub-cultured at a ratio of 1:2 for more than 160 passages over a period of 3 years. Origin of the cultured cells was verified by comparison of their sequences of mitochondrial cytochrome oxidase subunit I genes (cox I) with the cox 1 sequence from cobia muscle tissue. The cell lines showed polyploidy. No mycoplasma contamination was detected. Susceptibility to grouper iridovirus was observed for the CB cell line but not the CF cell line. Both cell lines expressed green fluorescent protein after being transfected with green fluorescent reporter gene driven by the cytomegalovirus promoter.

  16. Trends in brain cancer mortality among U.S. Gulf War veterans: 21 year follow-up.

    Science.gov (United States)

    Barth, Shannon K; Dursa, Erin K; Bossarte, Robert M; Schneiderman, Aaron I

    2017-10-01

    Previous mortality studies of U.S. Gulf War veterans through 2000 and 2004 have shown an increased risk of brain cancer mortality among some deployed individuals. When veterans possibly exposed to environmental contaminants associated with demolition of the Khamisiyah Ammunition Storage Facility at Khamisiyah, Iraq, have been compared to contemporaneously deployed unexposed veterans, the results have suggested increased risk for mortality from brain cancer among the exposed. Brain cancer mortality risk in this cohort has not been updated since 2004. This study analyzes the risk for brain cancer mortality between 1991-2011 through two series of comparisons: U.S. Gulf War deployed and non-deployed veterans from the same era; and veterans possibly exposed to environmental contaminants at Khamisiyah compared to contemporaneously deployed but unexposed U.S. Gulf War veterans. Risk of brain cancer mortality was determined using logistic regression. Life test hazard models were created to plot comparisons of annual hazard rates. Joinpoint regression models were applied to assess trends in hazard rates for brain cancer mortality. U.S. Army veterans possibly exposed at Khamisiyah had similar rates of brain cancer mortality compared to those not possibly exposed; however, veterans possibly exposed had a higher risk of brain cancer in the time period immediately following the Gulf War. Results from these analyses suggest that veterans possibly exposed at Khamisiyah experienced different patterns of brain cancer mortality risk compared to the other groups. Published by Elsevier Ltd.

  17. Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ye-Hui Shi

    2016-04-01

    Full Text Available Recent studies have shown that sulforaphane (SFN selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH+ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX increased the ALDH+ subpopulation.

  18. FLAX OIL FROM TRANSGENIC LINUM USITATISSIMUM SELECTIVELY INHIBITS IN VITRO PROLIFERATION OF HUMAN CANCER CELL LINES.

    Science.gov (United States)

    Gebarowski, Tomasz; Gebczak, Katarzyna; Wiatrak, Benita; Kulma, Anna; Pelc, Katarzyna; Czuj, Tadeusz; Szopa, Jan; Gasiorowski, Kazimierz

    2017-03-01

    Emulsions made of oils from transgenic flaxseeds significantly decreased in vitro proliferation of six tested human cancer cell lines in 48-h cultures, as assessed with the standard sulforhodamine assay. However, the emulsions also increased proliferation rate of normal human dermal fibroblasts and, to a lower extend, of keratinocytes. Both inhibition of in vitro proliferation of human cancer cell lines and stimulation of proliferation of normal dermal fibroblasts and keratinocytes were especially strong with the emulsion type B and with emulsion type M. Oils from seeds of transgenic flax type B and M should be considered as valuable adjunct to standard cytostatic therapy of human cancers and also could be applied to improve the treatment of skin lesions in wound healing.

  19. In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

    DEFF Research Database (Denmark)

    Damstrup, L; Rude Voldborg, B; Spang-Thomsen, M

    1998-01-01

    receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot...... analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16......-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition...

  20. Antiproliferative Effects of Selected Chemotherapeutics in Human Ovarian Cancer Cell Line A2780

    Directory of Open Access Journals (Sweden)

    Kateřina Caltová

    2012-01-01

    Full Text Available The aim of our study was to determine the effect of selected cytostatics on a human ovarian cancer cell line A2780 as a model system for ovarian cancer treatment. This cell line is considered cisplatin-sensitive. Panel of tested cytostatics included cisplatin, paclitaxel, carboplatin, gemcitabine, topotecan and etoposide. These cytostatics have a different mechanism of action. To evaluate cytotoxic potential of the tested compounds, the methods measuring various toxicological endpoints were employed including morphological studies, MTT assay, dynamic monitoring of cell proliferation with xCELLigence, cell cycle analysis, caspase 3 activity and expression of proteins involved in cell cycle regulation and cell death. The A270 cell line showed different sensitivity towards the selected cytostatics, the highest cytotoxic effect was associated with paclitaxel and topotecan.

  1. Insights into brain metastasis in patients with ALK+ lung cancer: is the brain truly a sanctuary?

    Science.gov (United States)

    Toyokawa, Gouji; Seto, Takashi; Takenoyama, Mitsuhiro; Ichinose, Yukito

    2015-12-01

    Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy. Despite the excellent efficacy of ALK inhibitors, resistance to these drugs is inevitably encountered in most ALK-rearranged pts. Cases of resistance are subtyped into three groups, i.e., systemic, oligo, and central nervous system (CNS) types, with the CNS being used to be considered a sanctuary. With regard to the management of CNS lesions in pts with ALK+ NSCLC, a growing body of evidence has gradually demonstrated the intracranial (IC) efficacy of ALK inhibitor (ALKi) in ALK+ NSCLC pts with brain metastases (BMs). Although the efficacy of crizotinib for the CNS lesions remains controversial, a recent retrospective investigation of ALK+ pts with BM enrolled in PROFILE 1005 and PROFILE 1007 demonstrated that crizotinib is associated with a high disease control rate for BM. However, BM comprises the most common site of progressive disease in pts with or without baseline BMs, which is a serious problem for crizotinib. Furthermore, alectinib can be used to achieve strong and long-lasting inhibitory effects on BM. In addition to alectinib, the IC efficacy of other next-generation ALK inhibitors, such as ceritinib, AP26113 and PF-06463922, has been demonstrated. In this article, we review the latest evidence regarding the BM and IC efficacy of ALK inhibitors in pts with ALK+ NSCLC.

  2. Brain cancer and pesticide relationship in orchard farmers of Kashmir

    OpenAIRE

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A. R.

    2010-01-01

    Background: The increasing trend in the incidence of primary malignant brain tumors in orchard farmers and their families in Kashmir. Aim: To determine the relationship between the patients of primary malignant brain tumors and their occupation. Materials and Methods: Retrospectively, case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases), admitted for treatment simultaneously over a period of 4 years from Ja...

  3. Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Senchuan Song

    2013-12-01

    Full Text Available Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF and simulated intestinal fluid (SIF solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3, lung cancer (H460, breast cancer (MCF-7, colon cancer (HCT-5 and glioblastoma (SF-268. The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2-3, 2-16 and 3-2 was determined. The results showed: (1 among all compounds examined, 2-16 showed the highest antitumor activity and a broader spectrum of activity, with IC50 values ranging from 1–2 µM; (2 their solubility was obviously improved; (3 2-3, 2-16 and 3-2 had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.

  4. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  5. MRI of metastatic adenocarcinomas to the brain. Differential diagnosis of colorectal and pulmonary cancer

    International Nuclear Information System (INIS)

    Fukusumi, Akio; Nakagawa, Hiroyuki; Takayama, Katsutoshi

    1998-01-01

    To clarify the characteristic features of MR imagings of metastatic adenocarcinomas to the brain and search for differential points between the lesions from colorectal cancer and those of lung cancer, we evaluated retrospectively intraparenchymal metastatic lesions of 13 colorectal origins and 13 pulmonary origins on MR imagings, compared with resected specimens. Metastatic lesions from colorectal cancer showed marked hypointense solid components on T2WI, which correspond to the dense tumor cells and coagulated necrosis pathologically. Metastatic lesions from lung cancers showed mixed intensity and various components on T2WI, which correspond to various histological components, such as solid tumor cell's nests, hemorrhage, necrosis and cystic fluid collection. Pathological specimens suggested that the low signal intensity on T2WI of MRI derived from concentration of tumor cells and coagulated necrosis including macrophages and lymphocytes. This study may contribute to make the differential diagnosis of metastatic adenocarcinomas to the brain from colorectal and pulmonary cancers. (author)

  6. Antiproliferative effects of the readily extractable fractions prepared from various citrus juices on several cancer cell lines.

    Science.gov (United States)

    Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

    1999-07-01

    To eliminate the masking effect by flavonoid glycosides, which comprise approximately 70% of conventionally prepared sample, the readily extractable fraction from Citrus juice, which was prepared by adsorbing on HP-20 resin and eluting with ethanol and acetone from the resin, was subjected to antiproliferative tests against several cancer cell lines. Screening of 34 Citrus juices indicated that King (Citrus nobilis) strongly inhibited proliferation of all cancer cell lines examined. Sweet lime and Kabuchi inhibited three of the four cancer cell lines. In contrast, these samples were substantially less cytotoxic toward normal human cell lines.

  7. Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68

    International Nuclear Information System (INIS)

    Ascierto, Maria Libera; Bedognetti, Davide; Uccellini, Lorenzo; Rossano, Fabio; Ascierto, Paolo A; Stroncek, David F; Restifo, Nicholas P; Wang, Ena; Szalay, Aladar A; Marincola, Francesco M; Worschech, Andrea; Yu, Zhiya; Adams, Sharon; Reinboth, Jennifer; Chen, Nanhai G; Pos, Zoltan; Roychoudhuri, Rahul; Di Pasquale, Giovanni

    2011-01-01

    Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo. In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection. We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection. Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection

  8. Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy

    OpenAIRE

    LÜ, XINQUAN; DENG, QING; LI, HUIXIANG; SUO, ZHENHE

    2011-01-01

    Drug resistance of cancer stem/initiating cells has been considered to be one of the main reasons for tumor relapse. However, knowledge concerning the changes in stem/ initiating cells during chemotherapy is limited. In the present study, the breast cancer cell line MDA-MB-468 was cultured with 5-fluorouracil and serially passaged. Six cell generations were collected. Semi-quantitative RT-PCR and flow cytometric techniques were used to evaluate the protein and mRNA expression of stem/initiati...

  9. BRAIN METASTASES OF GERM CELL TUMORS. THE RUSSIAN CANCER RESEARCH CENTER'S EXPERIENCE

    Directory of Open Access Journals (Sweden)

    A. A. Tryakin

    2014-07-01

    Full Text Available This paper analyzes the experience in treating 20 patients with nonseminomatous germ cell tumors metastasizing to the brain. It presents brain metastasis-associated factors: multiple lung metastases; IGCCCG poor prognosis; and a baseline human chorionic gonadotropin level of > 50000 mIU/ml. The authors have identified a group to be screened for brain metastasis, which includes patients with intermediate/poor prognosis and multiple lung metastases. Long-term survival was achieved in 45 % of patients with baseline brain damage and in 22 % of those with metastases revealed after first-line chemotherapy. The positive prognostic factors associated with long-term survival were a single brain lesion, no neurological symptoms, and achievement of clinical complete personse in the brain.

  10. Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist

    International Nuclear Information System (INIS)

    Akech, Jacqueline; Roy, Somdutta Sinha; Das, Salil K.

    2005-01-01

    Changes in phospholipid and fatty acid profile are hallmarks of cancer progression. Increase in peripheral benzodiazepine receptor expression has been implicated in breast cancer. The benzodiazepine, Ro5-4864, increases cell proliferation in some breast cancer cell lines. Biosynthesis of phosphatidylcholine (PC) has been identified as a marker for cells proliferating at high rates. Cholinephosphotransferase (CPT) is the terminal enzyme for the de novo biosynthesis of PC. We have addressed here whether Ro5-4864 facilitates some cancer causing mechanisms in breast cancer. We report that cell proliferation increases exponentially in aggressive breast cancer cell lines 11-9-1-4 and BT-549 when treated with nanomolar concentrations of Ro5-4864. This increase is seen within 24 h of treatment, consistent with the cell doubling time in these cells. Ro5-4864 also upregulates c-fos expression in breast cancer cell lines 11-9-1-4 and BT-549, while expression in non-tumorigenic cell line MCF-12A was either basal or slightly downregulated. We further examined the expression of the CPT gene in breast cancer (11-9-1-4, BT-549) and non-tumorigenic cell lines (MCF-12A, MCF-12F). We found that the CPT gene is overexpressed in breast cancer cell lines compared to the non-tumorigenic cell lines. Furthermore, the activity of CPT in forming PC is increased in the breast cancer cell lines cultured for 24 h. Additionally, we examined the CPT activity in the presence of nanomolar concentrations of Ro5-4864. Biosynthesis of PC was increased in breast cancer cell lines upon treatment. We therefore propose that Ro5-4864 facilitates PC formation, a process important in membrane biogenesis for proliferating cells

  11. Oxygen-Related Differences in Cellular and Vesicular Phenotypes Observed for Ovarian Cell Cancer Lines

    DEFF Research Database (Denmark)

    Søndergaard, Evo K. Lindersson; Pugholm, Lotte Hatting; Bæk, Rikke

    2016-01-01

    Extracellular vesicles (EVs) are one of several tools that cells use to communicate with each other. This communication is facilitated by a number of surface-associated proteins and the cargo of the vesicles. For several cancer types, the amount of EVs is observed to be up-regulated in patients c...... produced more EVs.The phenotyping of EVs from cancer cell lines provides information about their molecular composition. This information may be translated to knowledge regarding the functionality of EVs and lead to a better understanding of their role in cancer.......Extracellular vesicles (EVs) are one of several tools that cells use to communicate with each other. This communication is facilitated by a number of surface-associated proteins and the cargo of the vesicles. For several cancer types, the amount of EVs is observed to be up-regulated in patients...

  12. Brain Tumor Trials Collaborative | Center for Cancer Research

    Science.gov (United States)

    Brain Tumor Trials Collaborative In Pursuit of a Cure The mission of the BTTC is to develop and perform state-of-the-art clinical trials in a collaborative and collegial environment, advancing treatments for patients with brain tumors, merging good scientific method with concern for patient well-being and outcome.

  13. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  14. Brain metastasis from male breast cancer treated 12 years ago ...

    African Journals Online (AJOL)

    A month ago, the patient had headache and vomiting complicated by the sudden onset of left hemiplegia. The brain MRI showed a huge right temporal process with a shift of the ... The development of brain metastases has been associated with young age, ... and immunohistochemistry different profiles regardless of gender.

  15. Pneumonia diagnosis in childhood and incidence of leukaemia, lymphoma and brain cancer

    DEFF Research Database (Denmark)

    Søgaard, Kirstine Kobberøe; Farkas, Dóra Körmendiné; Sørensen, Henrik Toft

    2017-01-01

    of pneumonia was a clinical marker of the three most common childhood cancers. DESIGN: Population-based cohort study. SETTING: Denmark, hospital diagnoses, 1994-2013. METHODS: Using national health registries, we compared the observed incidence of leukaemia, lymphoma and brain cancer among 83 935 children...... with a hospital-based pneumonia diagnosis with that expected among children in the general population. We calculated absolute cancer risks and standardised incidence ratios (SIRs) as a measure of relative risk. RESULTS: The cancer SIRs were substantially increased during the first 6 months of follow-up; lymphoid...

  16. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

    Science.gov (United States)

    Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

  17. Degradation of endothelial basement membrane by human breast cancer cell lines

    International Nuclear Information System (INIS)

    Yee, C.; Shiu, R.P.

    1986-01-01

    During metastasis, it is believed that tumor cells destroy the basement membrane (BM) of blood vessels in order to disseminate through the circulatory system. By radioactively labeling the extracellular matrix produced by primary endothelial cells in vitro, the ability of human breast cancer cells to degrade BM components was studied. We found that T-47D, a human breast cancer line, was able to degrade significant amounts of [35S]methionine-labeled and [3H]proline-labeled BM, but not 35SO4-labeled BM. Six other tumor cell lines of human breast origin were assayed in the same manner and were found to degrade BM to varying degrees. Several non-tumor cell lines tested showed relatively little degrading activity. The use of serum-free medium greatly enhanced degradation of the BM by tumor cells, suggesting a role for naturally occurring enzyme inhibitors in the serum. Direct cell contact with the BM was required for BM degradation, suggesting that the active enzymes are cell associated. The addition of hormones implicated in the etiology of breast cancer did not significantly alter the ability of T-47D cells to degrade the BM. The use of this assay affords future studies on the mechanism of invasion and metastasis of human breast cancer

  18. Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

    Science.gov (United States)

    Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

    2004-01-01

    In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

  19. Apoptotic Effect of the Urtica Dioica Plant Extracts on Breast Cancer Cell Line (MDA- MB- 468

    Directory of Open Access Journals (Sweden)

    A Mohammadi

    2015-09-01

    Full Text Available Background & objectives: Cancer is one of the most causes of mortality in worldwide. Components derived from natural plants that induce apoptosis are used for cancer treatment. Therefore investigation of different herbal components for new anti-cancer drug is one of the main research activities throughout the world. According to low cost, oral consumption and easy access to the public extracts of Urtica dioica, in this study we aimed to investigate the effectiveness of this herb on MDA-MB-468 breast cancer cells.   Methods: Cytotoxic effect of Urtica dioica extract was measured using MTT assays. To show induction of apoptosis by this plant TUNEL and DNA Fragmentation test were performed.   Results: In the present study dichloromethane extracts noticeably killed cancer cells. IC50 values related to human breast adenocarcinoma cell line MDA-MB-468 were 29.46±1.05 µg/ml in 24 hours and 15.54±1.04 µg/ml in 48 hours. TUNEL test and DNA Fragmentation assay showed apoptotic characteristic in the extract treated cells.   Conclusion: The results showed that MDA-MB-468 cells after treatment with dichloromethane extract of Urtica dioica, induces apoptosis in MDA-MB-468 cancer cells which may be useful in the treatment of cancer.

  20. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  1. An Inducible, Isogenic Cancer Cell Line System for Targeting the State of Mismatch Repair Deficiency

    Science.gov (United States)

    Bailis, Julie M.; Gordon, Marcia L.; Gurgel, Jesse L.; Komor, Alexis C.; Barton, Jacqueline K.; Kirsch, Ilan R.

    2013-01-01

    The DNA mismatch repair system (MMR) maintains genome stability through recognition and repair of single-base mismatches and small insertion-deletion loops. Inactivation of the MMR pathway causes microsatellite instability and the accumulation of genomic mutations that can cause or contribute to cancer. In fact, 10-20% of certain solid and hematologic cancers are MMR-deficient. MMR-deficient cancers do not respond to some standard of care chemotherapeutics because of presumed increased tolerance of DNA damage, highlighting the need for novel therapeutic drugs. Toward this goal, we generated isogenic cancer cell lines for direct comparison of MMR-proficient and MMR-deficient cells. We engineered NCI-H23 lung adenocarcinoma cells to contain a doxycycline-inducible shRNA designed to suppress the expression of the mismatch repair gene MLH1, and compared single cell subclones that were uninduced (MLH1-proficient) versus induced for the MLH1 shRNA (MLH1-deficient). Here we present the characterization of these MMR-inducible cell lines and validate a novel class of rhodium metalloinsertor compounds that differentially inhibit the proliferation of MMR-deficient cancer cells. PMID:24205301

  2. Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

    Science.gov (United States)

    Chen, Bihong T; Sethi, Sean K; Jin, Taihao; Patel, Sunita K; Ye, Ningrong; Sun, Can-Lan; Rockne, Russell C; Haacke, E Mark; Root, James C; Saykin, Andrew J; Ahles, Tim A; Holodny, Andrei I; Prakash, Neal; Mortimer, Joanne; Waisman, James; Yuan, Yuan; Somlo, George; Li, Daneng; Yang, Richard; Tan, Heidi; Katheria, Vani; Morrison, Rachel; Hurria, Arti

    2018-05-02

    Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = - 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = - 6.94) compared to the non-TC group (change = - 1.21, p for

  3. NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer

    International Nuclear Information System (INIS)

    Adkins, Chris E.; Nounou, Mohamed I.; Hye, Tanvirul; Mohammad, Afroz S.; Terrell-Hall, Tori; Mohan, Neel K.; Eldon, Michael A.; Hoch, Ute; Lockman, Paul R.

    2015-01-01

    Brain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity. Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively). NKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (>20 ng/g for 168 h) versus conventional irinotecan (>1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals. Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m 2 NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results. The online version of this article (doi:10.1186/s12885-015-1672-4) contains supplementary material, which is available to authorized users

  4. High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats.

    Science.gov (United States)

    Wu, Yingjen Jeffrey; Pagel, Michael A; Muldoon, Leslie L; Fu, Rongwei; Neuwelt, Edward A

    2017-08-01

    Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response.

    Science.gov (United States)

    Nickerson, M L; Witte, N; Im, K M; Turan, S; Owens, C; Misner, K; Tsang, S X; Cai, Z; Wu, S; Dean, M; Costello, J C; Theodorescu, D

    2017-01-05

    The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study

  6. Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

    International Nuclear Information System (INIS)

    Brodin, O.; Lennartsson, L.; Nilsson, S.

    1991-01-01

    Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

  7. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

    Science.gov (United States)

    Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna; Seyfried, Thomas N

    2010-07-23

    GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  8. Calorie Restriction as an Anti-Invasive Therapy for Malignant Brain Cancer in the VM Mouse

    Directory of Open Access Journals (Sweden)

    Laura M Shelton

    2010-07-01

    Full Text Available GBM (glioblastoma multiforme is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  9. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

    Directory of Open Access Journals (Sweden)

    Seyfried B

    2009-09-01

    Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  10. Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma

    Science.gov (United States)

    Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

    2013-01-01

    The electroencephalogram (EEG) reflects brain electrical activity. A flat (isoelectric) EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human) or by application of high doses of anesthesia (isoflurane in animals) leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes). Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region) we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma. PMID:24058669

  11. Rapid selection and proliferation of CD133+ cells from cancer cell lines: chemotherapeutic implications.

    Directory of Open Access Journals (Sweden)

    Sarah E Kelly

    2010-04-01

    Full Text Available Cancer stem cells (CSCs are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133+] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB (Celdyne, Houston, TX. For comparison, another bioreactor, the rotary cell culture system (RCCS manufactured by Synthecon (Houston, TX was used. Both the HFB and the RCCS bioreactors simulate aspects of hypogravity. In our study, the HFB increased CD133+ cell growth from various cell lines compared to the RCCS vessel and to normal gravity control. We observed a +15-fold proliferation of the CD133+ cellular fraction with cancer cells that were cultured for 7-days at optimized conditions. The RCCS vessel instead yielded a (-4.8-fold decrease in the CD133+cellular fraction respect to the HFB after 7-days of culture. Interestingly, we also found that the hypogravity environment of the HFB greatly sensitized the CD133+ cancer cells, which are normally resistant to chemo treatment, to become susceptible to various chemotherapeutic agents, paving the way to less toxic and more effective chemotherapeutic treatment in patients. To be able to test the efficacy of cytotoxic agents in vitro prior to their use in clinical setting on cancer cells as well as on cancer stem cells may pave the way to more effective chemotherapeutic strategies in patients. This could be an important advancement in the therapeutic options of oncologic patients, allowing for more targeted and personalized chemotherapy regimens as well as for higher response rates.

  12. Emerging role of brain metastases in the prognosis of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Hambrecht A

    2011-08-01

    Full Text Available Amanda Hambrecht1,2, Rahul Jandial2, Josh Neman21Department of Biology, University of Southern California; 2Department of Neurosurgery, Beckman Research Institute, City of Hope National Cancer Center, CA, USAAbstract: Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors. Keywords: metastasis, breast cancer, blood-brain barrier, epithelial-mesenchymal transition, mesenchymal-epithelial transition

  13. Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

    Directory of Open Access Journals (Sweden)

    Yamamoto D

    2012-09-01

    Full Text Available Daigo Yamamoto,1,3 Satoru Iwase,2 Yu Tsubota,1 Noriko Sueoka,1 Chizuko Yamamoto,3 Kaoru Kitamura,4 Hiroki Odagiri,5 Yoshinori Nagumo61Department of Surgery, Kansai Medical University, Hirakata, Osaka, 2Department of Palliative Medicine, University of Tokyo Hospital, Tokyo, 3Department of Internal Medicine, Seiko Hospital, Neyagawa, Osaka, 4Breast Unit, Nagumo Clinic, Fukuoka, 5Department of Surgery, Hirosaki National Hospital, Hirosaki, 6Breast Unit, Nagumo Clinic, Tokyo, JapanBackground: Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation.Methods: Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed.Results: The median time to disease progression was 86 days. Of five patients, two (40% achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades were hypertension (60%, neuropathy (40%, and proteinuria (20%. No grade 3 toxicity was seen. No intracranial hemorrhage was observed.Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.Keywords: brain, bevacizumab, metastatic breast cancer

  14. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

    Science.gov (United States)

    Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

    2008-11-01

    Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

  15. Changes in cytoskeletal dynamics and nonlinear rheology with metastatic ability in cancer cell lines

    International Nuclear Information System (INIS)

    Coughlin, Mark F; Fredberg, Jeffrey J

    2013-01-01

    Metastatic outcome is impacted by the biophysical state of the primary tumor cell. To determine if changes in cancer cell biophysical properties facilitate metastasis, we quantified cytoskeletal biophysics in well-characterized human skin, bladder, prostate and kidney cell line pairs that differ in metastatic ability. Using magnetic twisting cytometry with optical detection, cytoskeletal dynamics was observed through spontaneous motion of surface bound marker beads and nonlinear rheology was characterized through large amplitude forced oscillations of probe beads. Measurements of cytoskeletal dynamics and nonlinear rheology differed between strongly and weakly metastatic cells. However, no set of biophysical parameters changed systematically with metastatic ability across all cell lines. Compared to their weakly metastatic counterparts, the strongly metastatic kidney cancer cells exhibited both increased cytoskeletal dynamics and stiffness at large deformation which are thought to facilitate the process of vascular invasion. (paper)

  16. Data for identification of GPI-anchored peptides and ω-sites in cancer cell lines

    Directory of Open Access Journals (Sweden)

    Yusuke Masuishi

    2016-06-01

    Full Text Available We present data obtained using a focused proteomics approach to identify the glycosylphosphatidylinositol (GPI-anchored peptides in 19 human cancer cell lines. GPI-anchored proteins (GPI-APs, which localize to the outer leaflet of the membrane microdomains commonly referred to as lipid rafts play important roles in diverse biological processes. Due to the complex structure of the GPI-anchor moiety, it has been difficult to identify GPI-anchored peptide sequences on the proteomic scale by database searches using tools such as MASCOT. Here we provide data from 73 ω-sites derived from 49 GPI-APs in 19 human cancer cell lines. This article contains data related to the research article entitled “Identification of glycosylphosphatidylinositol-anchored proteins and ω-sites using TiO2-based affinity purification followed by hydrogen fluoride treatment” (Masuishi et al., 2016 [1].

  17. Role of infectious agents in the carcinogenesis of brain and head and neck cancers

    Directory of Open Access Journals (Sweden)

    Alibek Kenneth

    2013-02-01

    Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

  18. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    Science.gov (United States)

    Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

    2005-05-01

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

  19. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    International Nuclear Information System (INIS)

    Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

    2005-01-01

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment

  20. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kopelman, Raoul [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States)]. E-mail: kopelman@umich.edu; Lee Koo, Yong-Eun [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States); Philbert, Martin [Environmental Health Sciences, niversity of Michigan (United States); Moffat, Bradford A. [Department of Radiology, The University of Michigan (United States); Ramachandra Reddy, G. [Molecular Therapeutics, Inc., Ann Arbor, MI 48104 (United States); McConville, Patrick [Molecular Therapeutics, Inc., Ann Arbor, MI 48104 (United States); Hall, Daniel E. [Department of Radiology, University of Michigan (United States); Chenevert, Thomas L. [Department of Radiology, University of Michigan (United States); Bhojani, Mahaveer Swaroop [Department of Radiation Oncology, University of Michigan (United States); Buck, Sarah M. [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States); Rehemtulla, Alnawaz [Department of Radiation Oncology, University of Michigan (United States); Ross, Brian D. [Department of Radiology, University of Michigan (United States)

    2005-05-15

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

  1. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Francesca Carlini

    Full Text Available BACKGROUND: Transposable Elements (TEs comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1 and Human Endogenous Retroviruses (HERVs that code for their own endogenous reverse transcriptase (RT. Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC, a nucleoside reverse transcription inhibitor (NRTI, on PC3 and LNCaP prostate cancer cell lines. PRINCIPAL FINDINGS: ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. CONCLUSIONS: Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications.

  2. Metabolic characterization of invaded cells of the pancreatic cancer cell line, PANC?1

    OpenAIRE

    Fujita, Mayumi; Imadome, Kaori; Imai, Takashi

    2017-01-01

    We previously reported that about 0.4% of cells in the cultured human pancreatic cancer cell line, PANC?1, can invade matrigel during the transwell invasion assay, suggesting that these invaded PANC?1 cells may have specific characteristics to keep their invasive potential. To identify the metabolic characterization specific in the invaded PANC?1 cells, metabolome analysis of the invaded PANC?1 compared with the whole cultured PANC?1 was performed using CE?TOFMS, and concentrations of 110 met...

  3. Synergistic Effect of Carboplatin and Piroxicam on Two Bladder Cancer Cell Lines.

    Science.gov (United States)

    Silva, Jéssica; Arantes-Rodrigues, Regina; Pinto-Leite, Rosário; Faustino-Rocha, Ana I; Fidalgo-Gonçalves, Lio; Santos, Lúcio; Oliveira, Paula A

    2017-04-01

    This study aimed to evaluate the in vitro efficacy of carboplatin and piroxicam, both in isolation and combined, against T24 and 5637 human urinary bladder cancer cell lines. Cell viability, drug interaction, cell morphology, cell proliferation, apoptosis and autophagy were analyzed after 72 h of drug exposure. Statistical analysis was performed and values of ppiroxicam produced a more potent antiproliferative effect when compared to single drugs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. In vitro evaluation of a new nitrosourea, TCNU, against human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Roed, H; Vindeløv, L L; Spang-Thomsen, M

    1987-01-01

    The cytotoxic activity of a new nitrosourea, TCNU, was compared with that of BCNU in five human small cell lung cancer cell lines in vitro. TCNU was found to be equivalent or inferior to BCNU when compared on a microgram to microgram basis. If the potential of in vitro phase II trials for selection...... of new drugs can be validated, it can be concluded that TCNU is not superior to other nitrosoureas for the treatment of SCCL....

  5. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

    DEFF Research Database (Denmark)

    Jandu, Haatisha; Aluzaite, Kristina; Fogh, Louise

    2016-01-01

    Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this ......Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30 % response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim...... or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer...... of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan....

  6. Use and duration of chemotherapy in patients with metastatic breast cancer according to tumor subtype and line of therapy.

    Science.gov (United States)

    Seah, Davinia S E; Luis, Ines Vaz; Macrae, Erin; Sohl, Jessica; Litsas, Georgia; Winer, Eric P; Lin, Nancy U; Burstein, Harold J

    2014-01-01

    Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (Pchemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR(+) and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.

  7. Andrographolide radiosensitizes human esophageal cancer cell line ECA109 to radiation in vitro.

    Science.gov (United States)

    Wang, Z-M; Kang, Y-H; Yang, X; Wang, J-F; Zhang, Q; Yang, B-X; Zhao, K-L; Xu, L-P; Yang, L-P; Ma, J-X; Huang, G-H; Cai, J; Sun, X-C

    2016-01-01

    To explore the radiosensitivity of andrographolide on esophageal cancer cell line ECA109. The inhibition effects of andrographolide were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Clonogenic survival assay was used to evaluate the effects of andrographolide on the radiosensitivity of esophageal cancer cells. Immunofluorescence was employed to examine Bax expression. The changes in cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of NF-κb/Cleaved-Caspase3/Bax/Bcl-2 was measured using Western blot analysis. DNA damage was detected via γ-H2AX foci counting. With a clear dose and time effects, andrographolide was found to inhibit the proliferation of esophageal cell line ECA109. The results of the clonogenic survival assay show that andrographolide could markedly enhance radiosensitivity (P Andrographolide caused a dose-dependent increase in Cleaved-Caspase3/Bax protein expression and a decrease in Bcl-2/NF-κb expression. Apoptosis in andrographolide-treated ECA-109 increased significantly compared with the apoptosis in the simple drug and radiation combined with drug groups (P andrographolide combined with radiation group increased the number of DNA double chain breaks. Andrographolide can increase the radiosensitivity of esophageal cell line ECA109. This result may be associated with the decrease in the NF-κb level and the induced apoptosis of esophageal cancer cells. © 2014 International Society for Diseases of the Esophagus.

  8. Kelussia odoratissima potentiates cytotoxic effects of radiation in HeLa cancer cell line

    Directory of Open Access Journals (Sweden)

    Azar Hosseini

    2017-02-01

    Full Text Available Objective: Cervical cancer is the second most common cause of death from cancer in women throughout the world. The aim of this study was to evaluate the cytotoxic activity of Kelussia odoratissima (K. odoratissima extract associated with radiotherapy in cervical cancer cells (HeLa cell line.Materials and Methods: Different concentration of the extract (25-500µg/ml was tested in HeLa cell lines. Cell cytotoxicity of the extract and the effects of the extract on radiation (2Gy/min-induced damages were assessed by MTT assay. Apoptosis was assessed using flow cytometric analysis.Result: K. odoratissima decreased cell viability in HeLa cell line in a concentration and time-dependent manner. When compared to the control,K. odoratissima induced a sub-G1 peak in the flow cytometry histogram of treated cells, indicating that apoptotic cell death is involved in K. odoratissima-induced toxicity. It was also shown that K. odoratissima sensitizes cells to radiation-induced toxicity.Conclusion: Our result showed the extract increased the radiation effect. This observation may be related to the presence of active compounds such as phthalides and ferulic acid.

  9. Cancer antigens are expressed in a carcinogen-transformed Bloom syndrome B-lymphoblastoid cell line

    International Nuclear Information System (INIS)

    Shiraishi, Yukimasa; Soma, Hiroaki

    1988-01-01

    The authors have cloned malignant cells carrying specific antigens associated with ovarian cancer (OVC) and malignant lymphoma (ML) from BS-SHI-4M cells, a line derived from a 1-methyl-3-nitro-1-nitrosoguanidine-treated B-lymphoblastoid cell line isolated from a patient with Bloom syndrome. Since BS-SHI-4M cells react with sera from various individual cancer patients at relatively low frequencies (2-9%), as detected by an indirect immunofluorescence technique, cell clones that specifically react with sera from patients with OVC and ML were separated by the panning method in which polystyrene dishes were coated with sera from OVC and ML patients and cells with the corresponding antigens bound to the dishes. Subsequent cloning by limiting dilution provided cell clones highly enriched for OVC- and ML-associated antigens. Karyotype analyses revealed that cell clones with OVC and ML antigens had common marker chromosomes. Interestingly, in cell clones with a strong OVC antigen response, the distal part of the Y chromosome (Yq11) was missing in 100% of the cells. Therefore the cell line BS-SHI-4M appears to be a reservoir of cell clones each of which carries a specific tumor antigen and thus provides a potential tool for rapid serological diagnosis of cancer

  10. Exploring the Anticancer Activity of Grape Seed Extract on Skin Cancer Cell Lines A431

    Directory of Open Access Journals (Sweden)

    V. Mohansrinivasan

    2015-08-01

    Full Text Available In this study, grape seeds were extracted using ethyl acetate and petroleum ether by solvent-solvent extraction method. The phytochemical tests were performed to identify different phytochemical compounds present in the grape seed extract (GSE. Antibacterial activity of the GSE was determined using agar diffusion method against Gram- positive and Gram-negative bacteria. Gas chromatography-mass spectrometry (GC-MS and Fourier transform infrared spectroscopy (FTIR analysis was done to identify the presence of bioactive compounds and their functional groups. The GC-MS results revealed a total of four compounds, known to have potent activity against cancer cells, viz, squalene, the most potent compound found in ethyl acetate extract and diethyl phthalate, ethyl-9- cis -11- trans octadecadienoate and (R-(--14,-methyl-8-Hexadecyn-1-ol in petroleum ether extract. Cytotoxic activity of the GSE was observed against skin cancer cell lines A4321 using 3-(4, 5-dimethylthiazol-2-yl-2-5-diphenyl tetrazolium bromide MTT assay. The IC50 value of the GSE against A431 skin cancer cell line was 480 µg/mL. This is first such report against A4321 cell lines. The study gives the overall perception about importance of GSE in medicine and nutraceuticals purposes.

  11. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Marilyn Carrier

    Full Text Available Retinoic acid (RA, the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα, which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression.

  12. Cell line name recognition in support of the identification of synthetic lethality in cancer from text

    Science.gov (United States)

    Kaewphan, Suwisa; Van Landeghem, Sofie; Ohta, Tomoko; Van de Peer, Yves; Ginter, Filip; Pyysalo, Sampo

    2016-01-01

    Motivation: The recognition and normalization of cell line names in text is an important task in biomedical text mining research, facilitating for instance the identification of synthetically lethal genes from the literature. While several tools have previously been developed to address cell line recognition, it is unclear whether available systems can perform sufficiently well in realistic and broad-coverage applications such as extracting synthetically lethal genes from the cancer literature. In this study, we revisit the cell line name recognition task, evaluating both available systems and newly introduced methods on various resources to obtain a reliable tagger not tied to any specific subdomain. In support of this task, we introduce two text collections manually annotated for cell line names: the broad-coverage corpus Gellus and CLL, a focused target domain corpus. Results: We find that the best performance is achieved using NERsuite, a machine learning system based on Conditional Random Fields, trained on the Gellus corpus and supported with a dictionary of cell line names. The system achieves an F-score of 88.46% on the test set of Gellus and 85.98% on the independently annotated CLL corpus. It was further applied at large scale to 24 302 102 unannotated articles, resulting in the identification of 5 181 342 cell line mentions, normalized to 11 755 unique cell line database identifiers. Availability and implementation: The manually annotated datasets, the cell line dictionary, derived corpora, NERsuite models and the results of the large-scale run on unannotated texts are available under open licenses at http://turkunlp.github.io/Cell-line-recognition/. Contact: sukaew@utu.fi PMID:26428294

  13. An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-06-01

    Full Text Available Ying Zhang, Huaping Tang, Jun Li, Meng Li Department of Respiration Medicine, Municipal Hospital, Qingdao, People’s Republic of China Abstract: Lung cancer has the highest mortality rate of all cancers world­wide. A total of 70%–75% of all lung cancers are non-small cell lung cancer (NSCLC with two-thirds presenting with locally advanced or metastatic disease at diagnosis. Brain metastasis is one of the most common problems in the management of NSCLC, worsening the prognosis and quality of life of NSCLC patients. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs gefitinib and erlotinib have been tested in patients with NSCLC and brain metastasis. Icotinib is a new type of oral EGFR-TKI. In this report, we describe a patient with lung adenocarcinoma cancer with brain metastases who received icotinib treatment and kept satisfactory health-related quality of life for 1 year. Keywords: EGFR, non-small cell lung cancer, tyrosine kinase inhibitor

  14. CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

    Science.gov (United States)

    Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

    2015-04-01

    Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

  15. Evaluation of Stem Cell Markers, CD44/CD24 in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Masoud Hashemi Arabi

    2014-05-01

    Four breast cancer cell lines, MCF-7 ، T47D ، MDA-MB231 and MDA-MB468 were purchased from National cell Bank of Iran based in Iran Pasture Institute and were cultured in high glucose DMEM supplemented with 10% FCS. Cells were stained with antiCD44-PE and antiCD24-FITC antibodies and Status of CD44 and CD24 as markers of breast cancer stem cells were evaluated using flow cytometer and fluorescent microscopy.Evaluation of CD44 and CD24 as markers of breast cancer stem cells showed that MDA-MB231 with 97±1.2% CD44+/CD24-/low cells is significantly different from the others that they were mainly CD44 and CD24 positive cells(p

  16. FIRST-LINE TREATMENT IN PATIENTS WITH INOPERABLE METASTATIC COLON CANCER

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2014-01-01

    Full Text Available First-line therapy for metastatic colon cancer is most important for a patient. Its median time to progression constitutes the bulk of the patient’s survival. Clearly, it is necessary to choose the most effective combinations of targeted drugs and chemotherapy regimens. The choice of therapy for patients with colon cancer is governed by both the clinical characteristics of the disease and the molecular changes of a tumor. In recent literature, there has been a great deal of evidence for the use of targeted drugs in different clinical situations; the results of comparative trials of different treatment combinations have been published. This all determines the reconsideration of the choice of a treatment regimen in patients with metastatic colon cancer; it is the topic of the present review.

  17. Cytotoxic effect of Erythroxylum suberosum combined with radiotherapy in head and neck cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Macedo, Taysa B.C.; Torres, Hianne M.; Yamamoto-Silva, Fernanda Paula; Silva, Maria Alves G. [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Escola de Odontologia; Elias, Silvia T.; Silveira, Damaris; Magalhaes, Perola O.; Lofrano-Porto, Adriana; Guerra, Eliete N.S., E-mail: elieteneves@unb.br [Universidade de Brasilia (UnB), Brasilia, DF (Brazil). Faculdade de Ciencias da Saude

    2016-01-15

    The mouth and oropharynx cancer is the 6{sup th} most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as 'cabelo-de-negro'. The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. (author)

  18. Cytotoxic effect of Erythroxylum suberosum combined with radiotherapy in head and neck cancer cell lines

    International Nuclear Information System (INIS)

    Macedo, Taysa B.C.; Torres, Hianne M.; Yamamoto-Silva, Fernanda Paula; Silva, Maria Alves G.; Elias, Silvia T.; Silveira, Damaris; Magalhaes, Perola O.; Lofrano-Porto, Adriana; Guerra, Eliete N.S.

    2016-01-01

    The mouth and oropharynx cancer is the 6 th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as 'cabelo-de-negro'. The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. (author)

  19. Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines.

    Science.gov (United States)

    Emadi Baygi, Modjtaba; Soheili, Zahra-Soheila; Essmann, Frank; Deezagi, Abdolkhaleg; Engers, Rainer; Goering, Wolfgang; Schulz, Wolfgang A

    2010-08-01

    Many metastatic cancers recapitulate the epithelial-to-mesenchymal transition (EMT) resulting in enhanced cell motility and invasiveness. The EMT is regulated by several transcription factors, including the zinc finger protein SNAI2, also named Slug, which appears to exert additional functions during development and cancer progression. We have studied the function of SNAI2 in prostate cancer cells. Quantitative RT-PCR analysis showed strong SNAI2 expression particularly in the PC-3 and PC3-16 prostate carcinoma cell lines. Knockdown of SNAI2 by specific siRNA induced changes in EMT markers and inhibited invasion of both cell lines into a matrigel matrix. SNAI2 siRNA-treated cells did not tolerate detachment from the culture plates, likely at least in part due to downregulation of integrin alpha6beta4. SNAI2 knockdown disturbed the microtubular and actin cytoskeletons, especially severely in PC-3 cells, resulting in grossly enlarged, flattened, and sometimes multinuclear cells. Knockdown also decreased cell proliferation, with a prominent G0/G1 arrest in PC3-16. Together, our data imply that SNAI2 exerts strong effects on the cytoskeleton and adhesion of those prostate cancer cells that express it and is necessary for their proliferation and invasiveness.

  20. Effects of Monoclonal Antibody Cetuximab on Proliferation of Non-small Cell Lung Cancer Cell lines

    Directory of Open Access Journals (Sweden)

    Zhen CHEN

    2010-08-01

    Full Text Available Background and objective The epidermal growth factor receptor (EGFR monoclonal antibody cetuximab has been used widely in non-small cell lung cancer patients. The aim of this study is to explore the effect of lung cancer cells (A549, H460, H1299, SPC-A-1 which were treated by cetuximab in vitro. Methods We studied the effects of increasing concentrations of cetuximab (1 nmol/L-625 nmol/L in four human lung cancer cell lines (A549, SPC-A-1, H460, H1229. CCK8 measured the inhibition of cell proliferation in each group. A549, SPC-A-1 were marked by PI and the statuses of apoptosis were observed. Western blot were used to detect the proliferation-related signaling protein and apoptosis-related protein in A549. Results The treatment with cetuximab resulted in the effect on cell proliferation and apoptosis in a time- and dosedependent manner. The expression of activated key enzymes (p-AKT, p-EGFR, p-MAPK in EGFR signaling transduction pathway were down-regulated more obviously. Conclusion Cetuximab is an effective targeted drug in the treatment of lung cancer cell lines, tissues, most likely to contribute to the inhibition of key enzymes in EGFR signaling transduction pathway.

  1. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.

    Science.gov (United States)

    Malkin, D; Li, F P; Strong, L C; Fraumeni, J F; Nelson, C E; Kim, D H; Kassel, J; Gryka, M A; Bischoff, F Z; Tainsky, M A

    1990-11-30

    Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LFS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.

  2. Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Walker Mark S

    2012-06-01

    Full Text Available Abstract Background Bevacizumab (B and cetuximab (C are both approved for use in the treatment of metastatic colorectal cancer (mCRC in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O and who had completed ≥ 1 Patient Care Monitor (PCM surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. Primary endpoints were rash, dry skin, itching, nail changes, nausea, vomiting, fatigue, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores across B, C and O (B = reference. Results 182 patients were enrolled (B: n = 106, C: n = 38, O: n = 38. Patients were 51% female, 67% Caucasian, with mean age of 62.0 (SD = 12.6. Groups did not differ on demographic or clinical characteristics. The most common second-line regimens were FOLFIRI ± B or C (23.1% and FOLFOX ± B or C (22.5%. Results showed baseline scores to be strongly predictive of second-line symptoms across all PCM items (all p’s  Conclusions Patients receiving second-line treatment for mCRC with B report less symptom burden, especially dermatologic, compared to patients treated with C.

  3. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available Lung cancer (LC with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC, large cell carcinoma (LCC, squamous cell carcinoma (SCC and adenocarcinoma (AC. We identified a small population of cells strongly positive for CD44 (CD44(high and a main population which was either weakly positive or negative for CD44 (CD44(low/-. Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44(highCD90(+ sub-population. Moreover, these CD44(highCD90(+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44(highCD90(+ population a good candidate for the lung CSCs. Both CD44(highCD90(+ and CD44(highCD90(- cells in the PLCCL derived from SCC formed spheroids, whereas the CD44(low/- cells were lacking this potential. These results indicate that CD44(highCD90(+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44(high sub-population.

  4. Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

    Science.gov (United States)

    Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

    2013-01-01

    Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

  5. Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT

    International Nuclear Information System (INIS)

    Oh, Seungjong; Stewart, James; Moseley, Joanne; Kelly, Valerie; Lim, Karen; Xie, Jason; Fyles, Anthony; Brock, Kristy K.; Lundin, Anna; Rehbinder, Henrik; Milosevic, Michael; Jaffray, David

    2014-01-01

    Purpose: Substantial organ motion and tumor shrinkage occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes, therefore the adaptation of treatment plans may be warranted. Image guidance with off-line replanning, i.e. hybrid-adaptation, is recognized as one of the most practical adaptation strategies. In this study, we investigated the effects of soft tissue image guidance using on-line MR while varying the frequency of off-line replanning on the adaptation of cervix IMRT. Materials and method: 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of 33 were identified in a previous retrospective adaptive planning study, in which the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not acceptable given single off-line IMRT replan using a 3 mm PTV margin with bone matching. These 5 patients and a randomly selected 10 patients from the remaining 28 patients, a total of 15 patients of 33, were considered in this study. Two matching methods for image guidance (bone to bone and soft tissue to dose matrix) and three frequencies of off-line replanning (none, single, and weekly) were simulated and compared with respect to target coverage (cervix, GTV, lower uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV) and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time) and benefit (target coverage) were analyzed for comparison. Results: Hybrid adaptation (image guidance with off-line replanning) significantly enhanced target coverage for both 5 difficult and 10 standard cases. Concerning image guidance, bone matching was short of delivering enough doses for 5 difficult cases even with a weekly off-line replan. Soft tissue image guidance proved successful for all cases except one when single or more frequent replans were utilized in the difficult cases

  6. Selenium-regulated hierarchy of human selenoproteome in cancerous and immortalized cells lines.

    Science.gov (United States)

    Touat-Hamici, Zahia; Bulteau, Anne-Laure; Bianga, Juliusz; Jean-Jacques, Hélène; Szpunar, Joanna; Lobinski, Ryszard; Chavatte, Laurent

    2018-04-13

    Selenoproteins (25 genes in human) co-translationally incorporate selenocysteine using a UGA codon, normally used as a stop signal. The human selenoproteome is primarily regulated by selenium bioavailability with a tissue-specific hierarchy. We investigated the hierarchy of selenoprotein expression in response to selenium concentration variation in four cell lines originating from kidney (HEK293, immortalized), prostate (LNCaP, cancer), skin (HaCaT, immortalized) and liver (HepG2, cancer), using complementary analytical methods. We performed (i) enzymatic activity, (ii) RT-qPCR, (iii) immuno-detection, (iv) selenium-specific mass spectrometric detection after non-radioactive 76 Se labeling of selenoproteins, and (v) luciferase-based reporter constructs in various cell extracts. We characterized cell-line specific alterations of the selenoproteome in response to selenium variation that, in most of the cases, resulted from a translational control of gene expression. We established that UGA-selenocysteine recoding efficiency, which depends on the nature of the SECIS element, dictates the response to selenium variation. We characterized that selenoprotein hierarchy is cell-line specific with conserved features. This analysis should be done prior to any experiments in a novel cell line. We reported a strategy based on complementary methods to evaluate selenoproteome regulation in human cells in culture. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)

    International Nuclear Information System (INIS)

    Judge, S.M.; Chatterton, R.T. Jr.

    1983-01-01

    The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from [14C]acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed in larger numbers without concomitant accumulation of casein granules in cells incubated with progesterone, but secretion of lipid into the medium did not occur. An effect of progesterone on TG accumulation was detectable after 12 hr and was maximal at 72 hr. Increasing doses of progesterone (10(-9) to 10(-5) M) caused a progressive increase in TG accumulation. The presence of cortisol and/or prolactin did not alter TG formation nor the dose response of the cells to progesterone. The growth rate of T-47D cells was not altered by the presence of progesterone in the medium. Neither of the human mammary cancer cell lines, MCF-7 and HBL-100, nor the human fibroblast cell lines, 28 and 857, responded to progesterone. The data indicate that, while the normally lactogenic hormones do not stimulate milk product biosynthesis in the cell lines tested, progesterone specifically stimulated synthesis and accumulation of TG in the T-47D cells

  8. Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Theilade, M D; Gram, G J; Jensen, P B

    1999-01-01

    Multidrug resistance (MDR) remains a major problem in the successful treatment of small cell lung cancer (SCLC). New treatment strategies are needed, such as gene therapy specifically targeting the MDR cells in the tumor. Retroviral LacZ gene-containing vectors that were either pseudotyped...... for the gibbon ape leukemia virus (GALV-1) receptor or had specificity for the amphotropic murine leukemia virus (MLV-A) receptor were used for transduction of five SCLC cell lines differing by a range of MDR mechanisms. Transduction efficiencies in these cell lines were compared by calculating the percentage...... of blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC...

  9. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    Picano, Eugenio; Vano, Eliseo; Domenici, Luciano; Bottai, Matteo; Thierry-Chef, Isabelle

    2012-01-01

    According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed

  10. Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced Gastric Cancer.

    Science.gov (United States)

    Lam, Simon W; Wai, Maya; Lau, Jessica E; McNamara, Michael; Earl, Marc; Udeh, Belinda

    2017-01-01

    Gastric cancer is the fifth most common malignancy and second leading cause of cancer-related mortality. Chemotherapy options for patients who fail first-line treatment are limited. Thus the objective of this study was to assess the cost-effectiveness of second-line treatment options for patients with advanced or metastatic gastric cancer. Cost-effectiveness analysis using a Markov model to compare the cost-effectiveness of six possible second-line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care. The model was performed from a third-party payer's perspective to compare lifetime costs and health benefits associated with studied second-line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1-way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified

  11. Brain cancer incidence trends in relation to cellular telephone use in the United States.

    Science.gov (United States)

    Inskip, Peter D; Hoover, Robert N; Devesa, Susan S

    2010-11-01

    The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. Log-linear models were used to estimate the annual percent change in rates among whites. With the exception of the 20-29-year age group, the trends for 1992-2006 were downward or flat. Among those aged 20-29 years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males. The recent trend in 20-29-year-old women was driven by a rising incidence of frontal lobe cancers. No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones. Frontal lobe cancer rates also rose among 20-29-year-old males, but the increase began earlier than among females and before cell phone use was highly prevalent. Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer.

  12. Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Sundaresan, P.; Yeghiaian, R.; Gebski, V.

    2010-01-01

    Full text: Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks ('early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of'early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with 'early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of'early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for 'early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.

  13. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

  14. Systematic review of wireless phone use and brain cancer and other head tumors.

    Science.gov (United States)

    Repacholi, Michael H; Lerchl, Alexander; Röösli, Martin; Sienkiewicz, Zenon; Auvinen, Anssi; Breckenkamp, Jürgen; d'Inzeo, Guglielmo; Elliott, Paul; Frei, Patrizia; Heinrich, Sabine; Lagroye, Isabelle; Lahkola, Anna; McCormick, David L; Thomas, Silke; Vecchia, Paolo

    2012-04-01

    We conducted a systematic review of scientific studies to evaluate whether the use of wireless phones is linked to an increased incidence of the brain cancer glioma or other tumors of the head (meningioma, acoustic neuroma, and parotid gland), originating in the areas of the head that most absorb radiofrequency (RF) energy from wireless phones. Epidemiology and in vivo studies were evaluated according to an agreed protocol; quality criteria were used to evaluate the studies for narrative synthesis but not for meta-analyses or pooling of results. The epidemiology study results were heterogeneous, with sparse data on long-term use (≥ 10 years). Meta-analyses of the epidemiology studies showed no statistically significant increase in risk (defined as P brain cancer or other head tumors from wireless phone use. Analyses of the in vivo oncogenicity, tumor promotion, and genotoxicity studies also showed no statistically significant relationship between exposure to RF fields and genotoxic damage to brain cells, or the incidence of brain cancers or other tumors of the head. Assessment of the review results using the Hill criteria did not support a causal relationship between wireless phone use and the incidence of adult cancers in the areas of the head that most absorb RF energy from the use of wireless phones. There are insufficient data to make any determinations about longer-term use (≥ 10 years). © 2011 Wiley Periodicals, Inc.

  15. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  16. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR Staging

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  17. Radiotherapy of brain metastases of a breast cancer: present strategies, technological innovations and biological perspectives

    International Nuclear Information System (INIS)

    Chargari, C.; Vedrine, L.; Bauduceau, O.; Jacob, J.; Fayolle, M.; Chargari, C.; Campana, F.; Pierga, J.Y.; Idrissi, H.R.; Fourquet, A.; Kirova, Y.

    2010-01-01

    The authors propose an overview of strategies which are presently used for the treatment of brain metastases related to a breast cancer. They outline the perspectives and recent developments of encephalic irradiation with new technologies allowing an increased conformation to be obtained, and also in terms of radiosensitization and radioprotection experiences. Short communication

  18. Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.

    Science.gov (United States)

    Xia, Chun-Fang; Zhang, Yufeng; Zhang, Yun; Boado, Ruben J; Pardridge, William M

    2007-12-01

    The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood-brain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin-biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin. Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 microg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin-streptavidin linker. The intravenous administration of the siRNA caused a 69-81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin-biotin technology.

  19. The economic burden of brain metastasis among lung cancer patients in the United States.

    Science.gov (United States)

    Guérin, A; Sasane, M; Dea, K; Zhang, J; Culver, K; Nitulescu, R; Wu, E Q; Macalalad, A R

    2016-01-01

    Brain metastases among lung cancer patients can impair cognitive and functional ability, complicate care, and reduce survival. This study focuses on the economic burden of brain metastasis in lung cancer-direct healthcare costs to payers and indirect costs to patients, payers, and employers-in the US. Retrospective study using claims data from over 60 self-insured Fortune 500 companies across all US census regions (January 1999-March 2013). Adult, non-elderly lung cancer patients with brain metastasis were evaluated over two study periods: (1) pre-diagnosis (≤30 days prior to first observed lung cancer diagnosis to ≤30 days prior to first-observed brain metastasis diagnosis) and (2) post-diagnosis (≤30 days prior to first observed brain metastasis diagnosis to end of continuous eligibility or observation). Healthcare costs to payers and resource utilization, salary loss to patients, disability payouts for payers, and productivity loss to employers. A total of 132 patients were followed for a median of 8.4 and 6.6 months in the pre- and post-diagnosis periods, respectively. At diagnosis of brain metastasis, 21.2% of patients were on leave of absence and 6.1% on long-term disability leave. Substantial differences were observed in the pre- vs post-diagnosis periods. Specifically, patients incurred much greater healthcare utilization in the post-diagnosis period, resulting in $25,579 higher medical costs per-patient-per-6-months (PPP6M). During this period, patients missed significantly more work days, generating an incremental burden of $2853 PPP6M in salary loss for patients, $2557 PPP6M in disability payments for payers, and $4570 PPP6M in productivity loss for employers. Type of primary lung cancer and extent of brain metastasis could not be assessed in the data. The analysis was also limited to patients with comprehensive disability coverage. Development of brain metastasis among lung cancer patients is associated with a substantial economic burden to payers

  20. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    International Nuclear Information System (INIS)

    Lazarus, Kyren A.; Zhao, Zhe; Knower, Kevin C.; To, Sarah Q.; Chand, Ashwini L.; Clyne, Colin D.

    2013-01-01

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E 2 ), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E 2 , showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E 2 treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer

  1. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Lazarus, Kyren A. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Environmental and Biotechnology Centre, Swinburne University, Hawthorn, Victoria 3122 (Australia); Zhao, Zhe; Knower, Kevin C. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); To, Sarah Q. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia); Chand, Ashwini L. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Clyne, Colin D., E-mail: Colin.clyne@princehenrys.org [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia)

    2013-08-30

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E{sub 2}), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E{sub 2}, showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E{sub 2} treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer.

  2. Patients' experiences and care needs during the diagnostic phase of an Integrated Brain Cancer Pathway

    DEFF Research Database (Denmark)

    Vedelø, Tina Wang; Sørensen, Jens Christian Hedemann; Delmar, Charlotte

    2018-01-01

    of brain cancer, not knowing what to expect and participants' perceptions of the relationship with the health care providers. The analysis revealed that participants were in risk of having unmet information needs and that contextual factors seemed to cause fragmented care that led to feelings...... that the shock of the diagnosis, combined with the multiple symptoms, affect patients' ability to understand information and express needs of care and support. Unmet needs have been reported within this group of patients, however, the experiences and care needs of patients going through the diagnostic phase...... of a standardised Integrated Brain Cancer Pathway have not previously been explored. DESIGN: A Case Study design was used to provide detailed information of the complex needs of patients being diagnosed with a malignant brain tumour. METHODS: Research interviews and direct participant observation of four patients...

  3. Transfection of wild type ADVP53 gene into human brain tumor cell lines has a radiosensitizing effect independent of apoptosis

    International Nuclear Information System (INIS)

    Geng, L.; Walter, S; Vaughan, A.T.M.

    1997-01-01

    mechanism of radiosensitization cells were examined for the presence of apoptosis after transfection. In both T98G and U87MG cell lines containing either βgal, Advp53, or after irradiation of control or Advβgal containing cells, a slight increase in apoptosis over base line was seen which in no case exceeded 5%. Irradiation in the presence of the Advp53 vector produced significantly greater apoptosis, 40.8 ± 1.5% after 1 day in the T98 line which returned to control levels by 4 days. In the U87MG line 10.9 ± 1.3% apoptosis was seen in the irradiated and Advp53 transfected line, not significantly different from an additive response of radiation and p53 vector effects alone. One day after irradiation all cells exhibited significant arrest in G 2 M phase. However the ability of Advp53 vector containing cells to undergo mitosis, as scored microscopically, was tenfold less than cells which were irradiated alone. Conclusion: Three conclusions can be drawn from these studies: 1) AdvP53 adenovirus vectors are cytotxic to human brain tumor cell lines through a mechanism that does not involve apoptosis 2) Irradiation of Advp53 transfected cell lines produces marked radiosensitization in both lines studied but a synergystic induction of apoptosis in the T98G line only, suggesting that apoptosis is also not the mechanism of radiosensitization in these lines. 3) The marked reduction in mitotic figures seen after irradiation of Advp53 transfected lines suggests the mechanism of radiosensitization involves an inability to successfully exit from mitosis

  4. First-line targeted therapies in the treatment of metastatic colorectal cancer – role of cetuximab

    Directory of Open Access Journals (Sweden)

    Giuseppe Tonini

    2009-04-01

    Full Text Available Giuseppe Tonini, Alice Calvieri, Bruno Vincenzi, Daniele SantiniMedical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Worldwide, colorectal cancer (CRC is the fourth most commonly diagnosed malignant disease and the second leading cause of cancer-related death in Western nations. In 2008 there were an estimated 148,810 new cases and 49,960 deaths in the US. For several years different chemotherapeutic regimens, based on floropyrimidines, irinotecan and oxaliplatin, have been used in advanced CRC, but survival is still unsatisfactory. New targeted therapies, including drugs and monoclonal antibodies (MoABs , show great promise in the fight against CRC and have shown activity in different disease settings. Cetuximab, a chimeric IgG1 monoclonal antibody that binds to the extracellular domain of epidermal growth factor receptor (EGFR, is active in metastatic colorectal cancer (mCRC. As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The combination of this drug with classical chemotherapies has shown better clinical profiles reflected in an improvement in overall and progression-free survival. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. Whereas cetuximab has a clear indication in the salvage setting, its role in first-line therapy remains investigational. It is particularly encouraging that cetuximab may enhance curative opportunities in patients with early metastatic disease, suggesting that adding cetuximab in first-line therapy may downstage disease in some patients, and, as a result, allow potentially curative resection of previously unresectable metastases. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit, and the role of cetuximab in first-line treatment of metastatic CRC

  5. Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Chee, R. J.; Bydder, S.; Cameron, F.

    2007-01-01

    Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations

  6. Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

    Science.gov (United States)

    Li, Wei-Ling; Fu, Chang; Xuan, Ang; Shi, Da-Peng; Gao, Yong-Ju; Zhang, Jie; Xu, Jun-Ling

    2015-02-05

    Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  7. Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

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    Wei-Ling Li

    2015-01-01

    Full Text Available Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People′s Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases, squamous cell carcinoma (43 cases, and small-cell carcinoma (25 cases. The whole body 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/computed tomography (CT of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255 was larger than those in the adenocarcinoma group (total voxel value 1217 and squamous cell carcinoma group (total voxel value 1292. Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  8. Anticancer potential of Hericium erinaceus extracts against particular human cancer cell lines

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    Younis AM

    2017-06-01

    Full Text Available Cancer is a leading cause of death worldwide. Cancer resulted in 8.2 million human deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2013 to 22 million within the next two decades. Mushrooms are extensively used as nutritional supplements in many countries. Moreover, mushrooms have many medicinal properties, including anticancer activity. In this study, the anticancer activity of different polar and non-polar extracts of Hericium erinaceus were evaluated against different human cancer cell lines including human liver carcinoma (Hep G2, the human colonic epithelial carcinoma (HCT 116, the human cervical cancer cells (HeLa and the human breast adenocarcinoma (MCF-7 using 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Furthermore, as a control, the cytotoxicity effect of the different extracts were tested against isolated mouse hepatocytes. It was observed that the extracts by water and methanol from fresh and lyophilized fruiting bodies of H. erinaceus had the strongest anticancer effect. In contrast, the extracts by ether and ethyl acetate from mycelia and broth of H. erinaceus showed lower anticancer activity against the tested carcinoma cell lines. The highest anticancer activity was recorded for aqueous extract of lyophilized fruiting bodies with half maximal inhibitory concentration (IC50 values of 6.1±0.2, 5.1±0.1, 5.7±0.2 and 5.8±0.3 µg/ml against Hep G2, HCT 116, HeLa and MCF-7 cells, respectively with non-significant effect on the normal mouse hepatocytes. To summarise, polar extracts of H. erinaceus can be good sources for isolating natural anticancer compounds. I recommend further chemical studies to isolate the active principles of the extract of H. erinaceus evaluated in the present.

  9. Cytotoxic Activity of Selected Iranian Traditional Medicinal Plants on Colon, Colorectal and Breast Cancer Cell Lines

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    Leila Mohammad Taghizadeh Kashani

    2014-11-01

    Full Text Available Background: Many natural products from plants have been recognized to exert anticancer activity. In this study, ethanolic extracts of selected medicinal herbs from Iranian flora including Alyssum homolocarpum Fisch. (from seeds, Urtica dioica L. (from aerial parts, Cichorium intybus L. (from roots and Solanum nigrum L. (from fruits, were evaluated for their cytotoxic effect on different cell lines.Methods: Cytotoxic effect of these extracts was studied on three different cancer cell lines; colon carcinoma (HT-29, colorectal adenocarcinoma (Caco-2 and breast ductal carcinoma (T47D. In addition, Swiss mouse embryo fibroblasts (NIH 3T3 were used as normal nonmalignant cells. MTT assay (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide was utilized for calculating the cytotoxicity of extracts on cell lines.Results: Results showed the potent cytotoxic activity of U. dioica ethanolic extract against T47D cell line with IC50 value of 46.14±4.55 µg/ml. Other extracts showed poor activity with IC50>100 µg/ml.Conclusions: Cytotoxic activity recorded in the present study revealed high potential antiproliferative activity of U. dioica ethanolic extract against T47D cell line. The real IC50 values of this extract may be considerably lower than the IC50 measured in our study if its pharmacological active compounds become pure. The results emphasize the importance of studies on U. dioica ethanolic extract to characterize potential components as cytotoxic natural medicines.

  10. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

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    Dharmawardhane Suranganie F

    2005-04-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. Results Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive properties to basal lamina, but SUM 149 showed a marked increase in adhesion to collagen I. In vitro haptotaxis assays demonstrate that SUM 149 was less invasive, while wound healing assays show a less in vitro migratory phenotype for SUM 149 cells relative to SUM 102 cells. We also demonstrate a role for Rho and E-cadherin in the unique invasive phenotype of IBC. Immunoblotting reveals higher E-cadherin and RhoA expression in the IBC cell line but similar RhoC expression. Rhodamine phalloidin staining demonstrates increased formation of actin stress fibers and larger focal adhesions in SUM 149 relative to the SUM 102 cell line. Conclusion The observed unique actin and cellular architecture as well as the invasive and adhesive responses to the extracellular matrix of SUM 149 IBC cells suggest that the preference of IBC cells for connective tissue, possibly a mediator important for the vasculogenic mimicry via tubulogenesis seen in IBC pathological specimens. Overexpression of E-cadherin and RhoA may contribute to passive dissemination of IBC by promoting cell-cell adhesion and actin cytoskeletal structures that maintain tissue integrity. Therefore, we believe that these findings indicate a passive metastatic mechanism by which IBC cells invade the circulatory system as tumor emboli rather than by active migratory mechanisms.

  11. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  12. Pancreatic cancer cell lines as patient-derived avatars: genetic characterisation and functional utility.

    Science.gov (United States)

    Knudsen, Erik S; Balaji, Uthra; Mannakee, Brian; Vail, Paris; Eslinger, Cody; Moxom, Christopher; Mansour, John; Witkiewicz, Agnieszka K

    2018-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines. Exome sequencing was performed on the originating tumour and developed models. RNA sequencing, histological and functional analyses were employed to determine the relationship of the patient-derived models to clinical presentation of PDAC. The cohort employed captured the genetic diversity of PDAC. From most cases, both cell lines and xenograft models were developed. Exome sequencing confirmed preservation of the primary tumour mutations in developed cell lines, which remained stable with extended passaging. The level of genetic conservation in the cell lines was comparable to that observed with patient-derived xenograft (PDX) models. Unlike historically established PDAC cancer cell lines, patient-derived models recapitulated the histological architecture of the primary tumour and exhibited metastatic spread similar to that observed clinically. Detailed genetic analyses of tumours and derived models revealed features of ex vivo evolution and the clonal architecture of PDAC. Functional analysis was used to elucidate therapeutic vulnerabilities of relevance to treatment of PDAC. These data illustrate that with the appropriate methods it is possible to develop cell lines that maintain genetic features of PDAC. Such models serve as important substrates for analysing the significance of genetic variants and create a unique biorepository of annotated cell lines and xenografts that were established simultaneously from same primary tumour. These models can be used to infer genetic and empirically determined

  13. The combination effect of sodium butyrate and 5-Aza-2'-deoxycytidine on radiosensitivity in RKO colorectal cancer and MCF-7 breast cancer cell lines

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    Oh Seong

    2009-05-01

    Full Text Available Abstract Background The overall level of chromatin compaction is an important mechanism of radiosensitivity, and modification of DNA methylation and histone deacetylation may increase radiosensitivity by altering chromatin compaction. In this study, we investigated the effect of a demethylating agent, a histone deacetylase(HDAC inhibitor, and the two agents combined on radiosensitivity in human colon and breast cancer cell lines. Methods In this study, we used RKO colorectal cancer cell line and MCF-7 breast cancer cell lines and normal colon cell lines. On each of the cell lines, we used three different agents: the HDAC inhibitor sodium butyrate(SB, the demethylating agent 5-Aza-2'-deoxycytidine(5-aza-DC, and radiation. We then estimated the percentage of the cell survival using the XTT method and experimented to determine if there was an augmentation in the therapeutic effect by using different combinations of the two or three of the treatment methods. Results After treatment of each cell lines with 5-aza-DC, SB and 6 grays of radiation, we observed that the survival fraction was lower after the treatment with 5-aza-DC or SB than with radiation alone in RKO and MCF-7 cell lines(p Conclusion In conclusion, 5-aza-DC and SB can enhance radiosensitivity in both MCF-7 and RKO cell lines. The combination effect of a demethylating agent and an HDAC inhibitor is more effective than that of single agent treatment in both breast and colon cancer cell lines.

  14. Cytotoxic Effect on Cancerous Cell Lines by Biologically Synthesized Silver Nanoparticles

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    Balaji Kulandaivelu

    Full Text Available The biosynthesis of nanoparticles has been proposed as an environmental friendly and cost effective alternative to chemical and physical methods. Silver nanoparticles are biologically synthesized and characterized were used in the study. The invitro cytotoxic effect of biologically synthesized silver nanoparticles against MCF-7 cancer cell lines were assessed. The cytotoxic effects of the silver nanoparticles could significantly inhibited MCF-7 cancer cell lines proliferation in a time and concentration-dependent manner by MTT assay. Acridine orange, ethidium bromide (AO/EB dual staining, caspase-3 and DNA fragmentation assays were carried out using various concentrations of silver nanoparticles ranging from 1 to 100 μg/mL. At 100 μg/mL concentration, the silver nanoparticles exhibited significant cytotoxic effects and the apoptotic features were confirmed through caspase-3 activation and DNA fragmentation assays. Western blot analysis has revealed that nanoparticle was able to induce cytochrome c release from the mitochondria, which was initiated by the inhibition of Bcl-2 and activation of Bax. Thus, the results of the present study indicate that biologically synthesized silver nanoparticles might be used to treat breast cancer. The present studies suggest that these nanoparticles could be a new potential adjuvant chemotherapeutic and chemo preventive agent against cytotoxic cells. However, it necessitates clinical studies to ascertain their potential as anticancer agents.

  15. Extracellular Matrix Proteins Expression Profiling in Chemoresistant Variants of the A2780 Ovarian Cancer Cell Line

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    Radosław Januchowski

    2014-01-01

    Full Text Available Ovarian cancer is the leading cause of death among gynaecological malignancies. Extracellular matrix (ECM can affect drug resistance by preventing the penetration of the drug into cancer cells and increased resistance to apoptosis. This study demonstrates alterations in the expression levels of ECM components and related genes in cisplatin-, doxorubicin-, topotecan-, and paclitaxel-resistant variants of the A2780 ovarian cancer cell line. Affymetrix Gene Chip Human Genome Array Strips were used for hybridisations. The genes that had altered expression levels in drug-resistant sublines were selected and filtered by scatter plots. The genes that were up- or downregulated more than fivefold were selected and listed. Among the investigated genes, 28 genes were upregulated, 10 genes were downregulated, and two genes were down- or upregulated depending on the cell line. Between upregulated genes 12 were upregulated very significantly—over 20-fold. These genes included COL1A2, COL12A1, COL21A1, LOX, TGFBI, LAMB1, EFEMP1, GPC3, SDC2, MGP, MMP3, and TIMP3. Four genes were very significantly downregulated: COL11A1, LAMA2, GPC6, and LUM. The expression profiles of investigated genes provide a preliminary insight into the relationship between drug resistance and the expression of ECM components. Identifying correlations between investigated genes and drug resistance will require further analysis.

  16. Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line

    International Nuclear Information System (INIS)

    Terasaki, Takeo; Shimosato, Yukio; Wada, Makio; Yokota, Jun; Terada, Masaaki

    1990-01-01

    Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line. (author)

  17. Differential effects of a complex organochlorine mixture on the proliferation of breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Aube, Michel, E-mail: 4aubem@videotron.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Larochelle, Christian, E-mail: christian.larochelle@inspq.qc.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Ayotte, Pierre, E-mail: pierre.ayotte@inspq.qc.ca [Axe de recherche en sante des populations et environnementale, Centre de recherche du Centre hospitalier universitaire de Quebec and Universite Laval, 2875 Boulevard Laurier, Edifice Delta 2, bureau 600, Quebec, QC, Canada G1V 2M2 (Canada); Laboratoire de Toxicologie, Institut national de sante publique du Quebec, 945 avenue Wolfe, Quebec, QC, Canada G1V 5B3 (Canada)

    2011-04-15

    Organochlorine compounds (OCs) are a group of persistent chemicals that accumulate in fatty tissues with age. Although OCs has been tested individually for their capacity to induce breast cancer cell proliferation, few studies examined the effect of complex mixtures that comprise compounds frequently detected in the serum of women. We constituted such an OC mixture containing 15 different components in environmentally relevant proportions and assessed its proliferative effects in four breast cancer cell lines (MCF-7, T47D, CAMA-1, MDAMB231) and in non-cancerous CV-1 cells. We also determined the capacity of the mixture to modulate cell cycle stage of breast cancer cells and to induce estrogenic and antiandrogenic effects using gene reporter assays. We observed that low concentrations of the mixture (100x10{sup 3} and 50x10{sup 3} dilutions) stimulated the proliferation of MCF-7 cells while higher concentrations (10x10{sup 3} and 5x10{sup 3} dilutions) had the opposite effect. In contrast, the mixture inhibited the proliferation of non-hormone-dependent cell lines. The mixture significantly increased the number of MCF-7 cells entering the S phase, an effect that was blocked by the antiestrogen ICI 182,780. Low concentrations of the mixture also caused an increase in CAMA-1 cell proliferation but only in the presence estradiol and dihydrotestosterone (p<0.05 at the 50x10{sup 3} dilution). DDT analogs and polychlorinated biphenyls all had the capacity to stimulate the proliferation of CAMA-1 cells in the presence of sex steroids. Reporter gene assays further revealed that the mixture and several of its constituents (DDT analogs, aldrin, dieldrin, {beta}-hexachlorocyclohexane, toxaphene) induced estrogenic effects, whereas the mixture and several components (DDT analogs, aldrin, dieldrin and PCBs) inhibited the androgen signaling pathway. Our results indicate that the complex OC mixture increases the proliferation of MCF-7 cells due to its estrogenic potential. The

  18. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

    Science.gov (United States)

    Freedman, Rachel A; Gelman, Rebecca S; Wefel, Jeffrey S; Melisko, Michelle E; Hess, Kenneth R; Connolly, Roisin M; Van Poznak, Catherine H; Niravath, Polly A; Puhalla, Shannon L; Ibrahim, Nuhad; Blackwell, Kimberly L; Moy, Beverly; Herold, Christina; Liu, Minetta C; Lowe, Alarice; Agar, Nathalie Y R; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F; Krop, Ian E; Wolff, Antonio C; Winer, Eric P; Lin, Nancy U

    2016-03-20

    Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥ 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients

  19. Expression of Ku correlates with radiation sensitivities in the head and neck cancer cell lines

    International Nuclear Information System (INIS)

    Lee, Sang Wook; Yu, Eun Sil; Yi, So Lyoung; Son, Se Hee; Kim, Jong Hoon; Ahn, Seung Do; Shin, Seong Soo; Choi, Eun Kyung

    2004-01-01

    DNA-dependent protein kinase (DNA-PK) is a serine/threonine kinase consisting of a 470 kDa catalytic subunit (DNA-PKcs) and a heterodimeric regulatory complex, called Ku, which is composed of 70 kDa (Ku 70) and 86 kDa (Ku 80) proteins. The DNA-PK has been shown to play a pivotal role in rejoining DNA double-strand-breaks (dsb) in mammalian cells. The purpose of this study is to examine the relationship between the level of Ku expression and radiation sensitivity. Nine head and neck, cancer cell lines showed various intrinsic radiation sensitivities. Among the nine, AMC-HN-3 cell was the most sensitive for X-ray irradiation and AMC-HN-9 cell was the most resistance. The most sensitive and resistant cell lines were selected and the test sensitivity of radiation and expression of Ku were measured. Radiation sensitivity was obtained by colony forming assay and Ku protein expression using Western blot analysis. Ku80 increased expression by radiation, wheras Ku70 did not. Overexpression of Ku80 protein increased radiation resistance in AMC-HN9 cell line. There was a correlation between Ku80 expression and radiation resistance. Ku80 was shown to play an important role in radiation damage response. Induction of Ku80 expression had an important role in DNA damage repair by radiation. Ku80 expression may be an effective predictive assay of radiosensitivity on head and neck cancer

  20. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

    Science.gov (United States)

    Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

  1. LINE-1 methylation levels in leukocyte DNA and risk of renal cell cancer.

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    Linda M Liao

    Full Text Available Leukocyte global DNA methylation levels are currently being considered as biomarkers of cancer susceptibility and have been associated with risk of several cancers. In this study, we aimed to examine the association between long interspersed nuclear elements (LINE-1 methylation levels, as a biomarker of global DNA methylation in blood cell DNA, and renal cell cancer risk.LINE-1 methylation of bisulfite-converted genomic DNA isolated from leukocytes was quantified by pyrosequencing measured in triplicate, and averaged across 4 CpG sites. A total of 328 RCC cases and 654 controls frequency-matched(2∶1 on age(±5years, sex and study center, from a large case-control study conducted in Central and Eastern Europe were evaluated.LINE-1 methylation levels were significantly higher in RCC cases with a median of 81.97% (interquartile range[IQR]: 80.84-83.47 compared to 81.67% (IQR: 80.35-83.03 among controls (p = 0.003, Wilcoxon. Compared to the lowest LINE-1 methylation quartile(Q1, the adjusted ORs for increasing methylation quartiles were as follows: OR(Q2 = 1.84(1.20-2.81, OR(Q3 = 1.72(1.11-2.65 and OR(Q4 = 2.06(1.34-3.17, with a p-trend = 0.004. The association was stronger among current smokers (p-trend<0.001 than former or never smokers (p-interaction = 0.03. To eliminate the possibility of selection bias among controls, the relationship between LINE-1 methylation and smoking was evaluated and confirmed in a case-only analysis, as well.Higher levels of LINE-1 methylation appear to be positively associated with RCC risk, particularly among current smokers. Further investigations using both post- and pre-diagnostic genomic DNA is warranted to confirm findings and will be necessary to determine whether the observed differences occur prior to, or as a result of carcinogenesis.

  2. Pesticides and brain cancer linked in orchard farmers of Kashmir

    OpenAIRE

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A. R.; Raina, T. H.

    2010-01-01

    Background: The atmosphere of valley of Kashmir is ideal for fresh and dry fruit production. Millions of tons of pesticides, insecticides and fungicides (chemicals like chlorpyriphos, mancozeb, captan, dimethoate, phosalone, etc.) are being used by the orchard farmers to spray the plants, fruits and the leaves every year. The increasing trend in the incidence of primary malignant brain tumors in orchard farmers of Kashmir is alarming. Aim: To determine the relationship between the patients of...

  3. Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

    International Nuclear Information System (INIS)

    Ono, Makiko; Ando, Masashi; Yunokawa, Mayu

    2009-01-01

    Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Among the patients who received a trastuzumab-containing regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2-14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0-45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases. (author)

  4. TIMP-1 and CEA as biomarkers in third-line treatment with irinotecan and cetuximab for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2015-01-01

    in colorectal cancer (CRC). The aim of the present study was to investigate the clinical value of TIMP-1 in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. Patients with chemotherapy-resistant mCRC referred to third-line treatment with cetuximab (initial 400 mg/m(2...

  5. Mechanisms of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplicon

    NARCIS (Netherlands)

    Eijdems, E. W.; de Haas, M.; Coco-Martin, J. M.; Ottenheim, C. P.; Zaman, G. J.; Dauwerse, H. G.; Breuning, M. H.; Twentyman, P. R.; Borst, P.; Baas, F.

    1995-01-01

    Some multidrug resistant cell lines over-express the gene encoding the multidrug-resistance-associated protein (MRP). In all cell lines reported thus far, over-expression is associated with gene amplification. We have studied the predominant mechanisms of MRP over-expression in 4 human lung-cancer

  6. Advanced colorectal cancer, refractory to infusional fluorouracil treatment: efficacy of second line fluorouracil in combination with a different biochemical modulation

    NARCIS (Netherlands)

    van Halteren, H. K.; Wagener, D. J.; Vreugdenhil, G.; Punt, C. J.

    1997-01-01

    Currently there is no standard second line treatment for patients with advanced colorectal cancer (ACC). Previous reports have demonstrated that some patients may benefit from second line infusional 5-fluorouracil (5-FU) after failing 5-FU bolus treatment. We retrospectively studied the efficacy and

  7. The anti-cancer effect of octagon and spherical silver nanoparticles on MCF-7 breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Mehrdad Khatami

    2017-04-01

    Full Text Available Background: The modern science of nanotechnology is an interdisciplinary science that has contributed to advances in cancer treatment. This study was performed to evaluate the therapeutic effects of biosynthesized silver nanoparticles on breast cancer cell of line MCF-7 in vitro. Methods: This analytical study was performed in Kerman and Bam University of Medical Sciences, Bam City, Kerman Province, Iran from March 2015 to March 2016. Silver nanoparticles suspension was synthesized using palm kernel extract. The resulting silver nanoparticles were studied and characterized. The ultraviolet-visible spectroscopy and transmission electron microscopy used for screening of physicochemical properties. The average particle size of the biosynthesized silver nanoparticles was determined by transmission electron microscopy. The properties of different concentrations of synthesized silver nanoparticles (1 to 3 μg/ml and palm kernel extract (containing the same concentration of the extract was used for the synthesis of silver nanoparticles against MCF-7 human breast cancer cells were determined by MTT assay. MTT is used to assess cell viability as a function of redox potential. Actively respiring cells convert the water-soluble MTT to an insoluble purple formazan. Results: The ultraviolet-visible spectroscopy showed strong absorption peak at 429 nm. The X-ray diffraction (XRD and transmission electron microscopy (TEM images revealed the formation of silver nanoparticles with spherical and octagon shape and sizes in the range between 1-40 nm, with an average size approximately 17 nm. The anti-cancer effect of silver nanoparticles on cell viability was strongly depends on the concentration of silver nanoparticles and greatly decrease with increasing the concentration of silver nanoparticles. The IC50 amount of silver nanoparticle was 2 μg/ml. Conclusion: The biosynthesized silver nanoparticles showed a dose-dependent toxicity against MCF-7 human breast

  8. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  9. Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines

    Directory of Open Access Journals (Sweden)

    Zou Zhengyun

    2012-04-01

    Full Text Available Summary Background Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death. Methods MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR. Results Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells. Conclusions Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.

  10. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2013-10-01

    GFP – expressing MDA-MB-231/BR cells into immunocompromised mice. 5 weeks post tumor cell injection, animals were injected iv with PGN635, which binds...Center, Dallas, TX). These cell lines were maintained in RPMI-1640 supplemented with 10% v/v heat- inactivated FBS (Hyclone) without antibiotics . All cell

  11. Nitrates in drinking water and the risk of death from brain cancer: does hardness in drinking water matter?

    Science.gov (United States)

    Ho, Chi-Kung; Yang, Ya-Hui; Yang, Chun-Yuh

    2011-01-01

    The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from brain cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the influence of nitrates on development of brain cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death from brain cancer and exposure to nitrates in drinking water in Taiwan. All brain cancer deaths of Taiwan residents from 2003 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO₃-N), Ca, and Mg in drinking water was obtained from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO₃-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO₃-N exposure level was cancer occurrence was 1.04 (0.85-1.27) for individuals who resided in municipalities served by drinking water with a NO₃-N exposure ≥ 0.38 ppm. No marked effect modification was observed due to Ca and Mg intake via drinking water on brain cancer occurrence.

  12. DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line

    Directory of Open Access Journals (Sweden)

    Saeed Samarghandian

    2013-01-01

    Full Text Available Objectives: Apoptosis, an important mechanism that contributes to cell growth reduction, is reported to be induced by Crocus sativus (Saffron in different cancer types. However, limited effort has been made to correlate these effects to the active ingredients of saffron. The present study was designed to elucidate cytotoxic and apoptosis induction by safranal, the major coloring compound in saffron, in a human prostate cancer cell line (PC-3. Materials and Methods: PC-3 and human fetal lung fibroblast (MRC-5 cells were cultured and exposed to safranal (5, 10, 15, and 20 μg/ml. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay was performed to assess cytotoxicity. DNA fragmentation was assessed by gel electrophoresis. Cells were incubated with different concentrations of safranal, and cell morphologic changes and apoptosis were determined by the normal inverted microscope, Annexin V, and propidium iodide, followed by flow cytometric analysis, respectively. Results: MTT assay revealed a remarkable and concentration-dependent cytotoxic effect of safranal on PC-3 cells in comparison with non-malignant cell line. The morphologic alterations of the cells confirmed the MTT results. The IC 50 values against PC-3 cells were found to be 13.0 ΁ 0.07 and 6.4 ΁ 0.09 μg/ml at 48 and 72 h, respectively. Safranal induced an early and late apoptosis in the flow cytometry histogram of treated cells, indicating apoptosis is involved in this toxicity. DNA analysis revealed typical ladders as early as 48 and 72 h after treatment, indicative of apoptosis. Conclusions: Our preclinical study demonstrated a prostate cancer cell line to be highly sensitive to safranal-mediated growth inhibition and apoptotic cell death. Although the molecular mechanisms of safranal action are not clearly understood, it appears to have potential as a therapeutic agent.

  13. The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

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    Cheng CHEN

    2009-08-01

    Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

  14. A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

    Science.gov (United States)

    Zhu, Xiaofu; Ko, Yoo-Joung; Berry, Scott; Shah, Keya; Lee, Esther; Chan, Kelvin

    2017-07-01

    It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

  15. Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines.

    Science.gov (United States)

    Attia, Yasmin M; El-Abhar, Hanan S; Al Marzabani, Mahmoud M; Shouman, Samia A

    2015-11-03

    Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

  16. Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines

    International Nuclear Information System (INIS)

    Attia, Yasmin M.; EL-Abhar, Hanan S.; Al Marzabani, Mahmoud M.; Shouman, Samia A.

    2015-01-01

    Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment

  17. Paris Saponin I Sensitizes Gastric Cancer Cell Lines to Cisplatin via Cell Cycle Arrest and Apoptosis.

    Science.gov (United States)

    Song, Shuichuan; Du, Leiwen; Jiang, Hao; Zhu, Xinhai; Li, Jinhui; Xu, Ji

    2016-10-18

    BACKGROUND Dose-related toxicity is the major restriction of cisplatin and cisplatin-combination chemotherapy, and is a challenge for advanced gastric cancer treatment. We explored the possibility of using Paris saponin I as an agent to sensitize gastric cancer cells to cisplatin, and examined the underlying mechanism. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The cell cycle and apoptosis were detected using flow cytometry and Annexin V/PI staining. The P21waf1/cip1, Bcl-2, Bax, and caspase-3 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI sensitized gastric cancer cells to cisplatin, with low toxicity. The IC50 value of cisplatin in SGC-7901 cell lines was decreased when combined with PSI. PSI promoted cisplatin-induced G2/M phase arrest and apoptosis in a cisplatin concentration-dependent manner. Bcl-2 protein expression decreased, but Bax, caspase-3, and P21waf1/cip1 protein expression increased with PSI treatment. CONCLUSIONS The underlying mechanism of Paris saponin I may be related to targeting the apoptosis pathway and cell cycle blocking, which suggests that PSI is a potential therapeutic sensitizer for cisplatin in treating gastric cancer.

  18. Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

    Directory of Open Access Journals (Sweden)

    VandenBerg Scott R

    2010-04-01

    Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

  19. Nanotech revolution for the anti-cancer drug delivery through blood-brain barrier.

    Science.gov (United States)

    Caraglia, M; De Rosa, G; Salzano, G; Santini, D; Lamberti, M; Sperlongano, P; Lombardi, A; Abbruzzese, A; Addeo, R

    2012-03-01

    Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

  20. Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Møller, C; Bock, E

    1992-01-01

    characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were......Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

  1. pSv3neo transfection and radiosensitivity of human cancer cell lines

    International Nuclear Information System (INIS)

    Parris, C.N.; Masters, J.R.W.; Green, M.H.L.

    1990-01-01

    Immortalisation of human fibroblasts by transfection with a plasmid, pSV3neo, results in an increase in their radioresistance. The change in radiosensitivity may either be a consequence of transformation or due to expression of the SV40 T-antigen in pSV3neo. To investigate these two possibilities, we transfected pSV3neo into cells already transformed and immortalised. The radiosensitivies of three human bladder cancer cell lines were unaltered in clones expressing T-antigen, indicating that the changes observed in fibroblasts probably are a consequence of transformation, and not the presence of SV40 T-antigen. (author)

  2. Expression of myc family oncoproteins in small-cell lung-cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Vindeløv, L L; Spang-Thomsen, M

    1993-01-01

    A number of genes have altered activity in small-cell lung cancer (SCLC), but especially genes of the myc family (c-myc, L-myc and N-myc) are expressed at high levels in SCLC. Most studies have explored expression at the mRNA level, whereas studies of myc family oncoprotein expression are sparse....... WE examined the expression of myc proto-oncogenes at the mRNA and protein level in 23 cell lines or xenografts. In the cell lines, the doubling time and the cell-cycle distribution, as determined by flow-cytometric DNA analysis, were examined to establish whether the level of myc......-myc. In general, the level of expression of c-myc and N-myc was similar at the mRNA and the protein level. Expression of c-myc was positively correlated with the proliferative index (sum of S and G2+M phases) of cell lines, but not with the population doubling time. In general, L-myc-expressing cell lines had...

  3. Expression of the epidermal growth factor receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Damstrup, L; Rygaard, K; Spang-Thomsen, M

    1992-01-01

    of EGF receptor mRNA in all 10 cell lines that were found to be EGF receptor-positive and in one cell line that was found to be EGF receptor-negative in the radioreceptor assay and affinity labeling. Our results provide, for the first time, evidence that a large proportion of a broad panel of small cell......Epidermal growth factor (EGF) receptor expression was evaluated in a panel of 21 small cell lung cancer cell lines with radioreceptor assay, affinity labeling, and Northern blotting. We found high-affinity receptors to be expressed in 10 cell lines. Scatchard analysis of the binding data...... demonstrated that the cells bound between 3 and 52 fmol/mg protein with a KD ranging from 0.5 x 10(-10) to 2.7 x 10(-10) M. EGF binding to the receptor was confirmed by affinity-labeling EGF to the EGF receptor. The cross-linked complex had a M(r) of 170,000-180,000. Northern blotting showed the expression...

  4. Antiproliferative Evaluation of Isofuranodiene on Breast and Prostate Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Michela Buccioni

    2014-01-01

    Full Text Available The anticancer activity of isofuranodiene, extracted from Smyrnium olusatrum, was evaluated in human breast adenocarcinomas MDA-MB 231 and BT 474, and Caucasian prostate adenocarcinoma PC 3 cell lines by MTS assay. MTS assay showed a dose-dependent growth inhibition in the tumor cell lines after isofuranodiene treatment. The best antiproliferative activity of the isofuranodiene was found on PC 3 cells with an IC50 value of 29 μM, which was slightly less than the inhibition against the two breast adenocarcinoma cell lines with IC50 values of 59 and 55 μM on MDA-MB 231 and BT 474, respectively. Hoechst 33258 assay was performed in order to study the growth inhibition mechanism in prostate cancer cell line; the results indicate that isofuranodiene induces apoptosis. Overall, the understudy compound has a good anticancer activity especially towards the PC 3. On the contrary, it is less active on Chinese hamster ovary cells (CHO and human embryonic kidney (HEK 293 appearing as a good candidate as a potential natural anticancer drug with low side effects.

  5. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  6. Brain cancer and pesticide relationship in orchard farmers of Kashmir.

    Science.gov (United States)

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R

    2010-09-01

    The increasing trend in the incidence of primary malignant brain tumors in orchard farmers and their families in Kashmir. To determine the relationship between the patients of primary malignant brain tumors and their occupation. Retrospectively, case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases), admitted for treatment simultaneously over a period of 4 years from January 2005 to December 2008, to the Neurosurgery, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Kashmir, were studied. Follow-up and family interaction was established. Analysis revealed that 90.04% (389 out of 432) patients were orchard farm workers, orchard residents and orchard playing children exposed to the high levels of multiple types of neurotoxic and carcinogenic (chlorpyriphos, dimethoate, mancozeb and captan) chemicals for more than 10 years [relative risk (RR) = 10.6; odds ratio (OR) = >10; 95% confidence interval (CI) = >25-40]. The 9.96% (43 out of 432) patients were not exposed to pesticides. On the other hand, only 19 patients out of 457 controls had recorded history of pesticide exposure and 438 were unrelated to pesticides. Out of 389 patients, 71.7% (279 out of 389) were males and 28.3% (110 out of 389), including six members of three families, were females (one male child). All orchard-related 389 patients had high-grade tumors as compared to the non-pesticide tumors. Mortality in pesticide-exposed tumors was 12%. The higher or upper-normal levels of serum cholinesterase (AChE) were observed in 54.7% (213 out of 389) patients and decreased levels were found in only 45.3% (176 out of 389) orchard-related patients (RR = 19.4; OR = >5; 95% CI = >1-10). Although serum AChE levels were a routine investigation in malignant brain tumors, this was not a routine in other neurological conditions (hospitalized controls). The familial gliomas have shown an emerging trend in the orchard residents of

  7. Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

    International Nuclear Information System (INIS)

    Uchiyama, Bine; Satoh, Ken; Saijo, Yasuo

    1998-01-01

    Forty patients with metastatic brain tumors from primary lung cancer underwent radiosurgery (γ-knife). We retrospectively compared their prior treatment history, number of metastatic foci, and performance status, to evaluate the effects of, and indications for, γ-knife therapy. After both the primary and the metastatic tumors were controlled, performance status could be used as an index in the choice of γ-knife therapy. Our results demonstrate that repeated γ-knife radiosurgeries prolonged survival time. Gamma-knife radiosurgery improves quality of life and prognosis of patients with metastatic brain tumors. (author)

  8. Off-line data processing and display for computed tomographic images (EMI brain)

    International Nuclear Information System (INIS)

    Takizawa, Masaomi; Maruyama, Kiyoshi; Yano, Kesato; Takenaka, Eiichi.

    1978-01-01

    Processing and multi-format display for the CT (EMI) scan data have been tried by using an off-line small computer and an analog memory. Four or six CT images after processing are displayed on the CRT by a small computer with a 16 kilo-words core memory and an analog memory. Multi-format display of the CT image can be selected as follows; multi-slice display, continuative multi-window display, separate multi-window display, and multi-window level display. Electronic zooming for the real size viewing can give magnified CT image with one of displayed images if necessary. Image substraction, edge enhancement, smoothing, non-linear gray scale display, and synthesized image for the plane tomography reconstracted by the normal CT scan data, have been tried by the off-line data processing. A possibility for an effective application of the data base with CT image was obtained by these trials. (auth.)

  9. LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

    Science.gov (United States)

    Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

    2017-01-02

    Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

  10. Isolation and characterization of a new cell line from spontaneous mouse mammary tumour, MBL-6, for in vivo cancer studies

    Directory of Open Access Journals (Sweden)

    Ladan Langroudi

    2017-12-01

    Full Text Available In search for treatments against breast cancer, cell lines are one of the basic resources, particularly as in vitro models. Additionally, animal models of cancer are used as the successive step in therapeutics research. In this regard, human breast cancer cell lines provide fundamental models in vitro. However, in vivo studies require immunodeficient mice, which lack the influence of other in vivo factors such as the native microenvironment and the immune system. There are few standard models to study the pathogenic mechanism at molecular level and cell signaling pathway of breast cancer. In this study, a new mouse breast cancer cell line, MBL-6, was successfully established and characterized from tissues of a spontaneous mammary tumor. The cell line had epithelial morphology, formed adherent monolayer, maintained continuously in vitro and was able to form new tumors when injected subcutaneously in syngeneic mice. The growth pattern and metastasis evaluations revealed a considerable in situ duration before invading distant organs. Real time polymerase chain reaction (PCR analysis showed the expression of ER-, PR- and Her-2 receptors. The chromosome analysis showed numerous chromosomal abnormalities. Aggressive tumorigenecity in tumorigenesis test and the IC50 to cyclophosphamide (CTX, celecoxib (CLX and cisplatin (CPN was also evaluated. The numerous tests performed on the new MBL-6 cell line suggest that it is in good quality and may be used in animal models of breast cancer studies.

  11. Boron-neutron capture therapy for incurable cancer and inoperable brain tumors

    International Nuclear Information System (INIS)

    Hatanaka, Hiroshi

    1993-01-01

    Recent advances in cancer diagnosis and treatment have not yet improved the survival rate of patients with cancers of the brain, liver, etc. In these organs, an extirpation of the organ, which can be done for stomach, breast, cervix, lung, etc. is not allowed, and this fact is the cause of poor therapeutic results. Boron-neutron capture therapy (BNCT) utilizes the nuclear reaction which will take place between the boron-10 (loaded in the cancer cells artificially) and the thermal neutrons (delivered by reactors). The secondary radiations, helium and lithium hit the cancer cell itself and cause the death of the cancer cell while sparing the surrounding normal cells. BNCT is now being tried also by Oda of Kyoto University (9 cases) and by Nakagawa of Tokushima University (7 cases). It has been tried by Mishima (Kobe University) on 12 skin melanoma patients, proving satisfactory local control of the melanomas. Mercaptoundecahydrododecaborate (BHS) and boronophenylalanine (BPA) have been tried for brain tumors and for melanoma. For cancers of the liver and abdominal viscerae, antibody to the tumor specific antigen has been considered a good carrier of boron-10. Surgeons Takahashi, Fujii, Fujii, Yanagie, and Sekiguchi and immunologist Nariuchi of Tokyo University have been involved in the research and have obtained encouraging results in animals. Hatanaka has been proving good effect of BNCT upon giant cerebral arteriovenous malformation (AVM) and skull base meningioma. These diseases, although pathologically benign, have posed difficult problems in neurosurgery. It will be exciting good news to the patients. In conclusion, BNCT appears to be a good means to treat difficult lesions in the brain and other organs which defy sophisticated modern therapeutic means. (author)

  12. Neuropsychological profiles of breast cancer and brain tumor cohorts in Northeast Ontario, Canada.

    Science.gov (United States)

    Mariani, Matias; Collins, Mark William Glister

    2018-05-17

    As developments in cancer treatment have improved outcomes, research has increasingly focused on the role of cancer-related cognitive impairment (CRCI) in quality of life for cancer survivors. Impairment profiles have been heterogeneous across studies, necessitating the study of these effects across different cohorts. The purpose of this preliminary study is to compare the memory profiles of Northeast Ontario breast and CNS cancer patients, as there is no literature which exists for profiling CRCI within this largely rural region. Sixty-three outpatients with breast cancer (n = 32) or CNS tumors (n = 30) at the Northeast Cancer Centre in Sudbury, Canada, were administered a neuropsychological test battery as part of their clinical examination. Domains measured within this study included attention and concentration, processing speed, motor function, language skills, verbal and visual memory, and executive functioning. Participants with brain tumors scored poorer on most neuropsychological measures than participants with breast cancer. Initial verbal memory for individuals with breast cancer was lower than delayed recall and recognition trials. Trial 1 performance for this group was also negatively correlated with self-reported anxiety scores. Consistent with the literature, participants with breast cancer obtained higher scores on most test measures than participants with CNC tumors. Breast cancer participants had lower verbal memory scores on initial trials compared to delayed recall, potentially due to relationships with anxiety and attention. Further research into this cohort will strive to gain greater understanding of the patterns of deficits experienced and how these may inform individuals with cancer in other regions.

  13. Prostate cancer cell lines under hypoxia exhibit greater stem-like properties.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Ma

    Full Text Available Hypoxia is an important environmental change in many cancers. Hypoxic niches can be occupied by cancer stem/progenitor-like cells that are associated with tumor progression and resistance to radiotherapy and chemotherapy. However, it has not yet been fully elucidated how hypoxia influences the stem-like properties of prostate cancer cells. In this report, we investigated the effects of hypoxia on human prostate cancer cell lines, PC-3 and DU145. In comparison to normoxia (20% O(2, 7% O(2 induced higher expressions of HIF-1α and HIF-2α, which were associated with upregulation of Oct3/4 and Nanog; 1% O(2 induced even greater levels of these factors. The upregulated NANOG mRNA expression in hypoxia was confirmed to be predominantly retrogene NANOGP8. Similar growth rates were observed for cells cultivated under hypoxic and normoxic conditions for 48 hours; however, the colony formation assay revealed that 48 hours of hypoxic pretreatment resulted in the formation of more colonies. Treatment with 1% O(2 also extended the G(0/G(1 stage, resulting in more side population cells, and induced CD44 and ABCG2 expressions. Hypoxia also increased the number of cells positive for ABCG2 expression, which were predominantly found to be CD44(bright cells. Correspondingly, the sorted CD44(bright cells expressed higher levels of ABCG2, Oct3/4, and Nanog than CD44(dim cells, and hypoxic pretreatment significantly increased the expressions of these factors. CD44(bright cells under normoxia formed significantly more colonies and spheres compared with the CD44(dim cells, and hypoxic pretreatment even increased this effect. Our data indicate that prostate cancer cells under hypoxia possess greater stem-like properties.

  14. Sulforaphane modulates telomerase activity via epigenetic regulation in prostate cancer cell lines.

    Science.gov (United States)

    Abbas, Ata; Hall, J Adam; Patterson, William L; Ho, Emily; Hsu, Anna; Al-Mulla, Fahd; Georgel, Philippe T

    2016-02-01

    Epidemiologic studies have revealed that diets rich in sulforaphane (SFN), an isothiocyanate present in cruciferous vegetables, are associated with a marked decrease in prostate cancer incidence. The chemo-preventive role of SFN is associated with its histone de-acetylase inhibitor activity. However, the effect of SFN on chromatin composition and dynamic folding, especially in relation to HDAC inhibitor activity, remains poorly understood. In this study, we found that SFN can inhibit the expression and activity of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, in 2 prostate cancer cell lines. This decrease in gene expression is correlated with SFN-induced changes in chromatin structure and composition. The SFN-mediated changes in levels of histone post-translational modifications, more specifically acetylation of histone H3 lysine 18 and di-methylation of histone H3 lysine 4, 2 modifications linked with high risk of prostate cancer recurrence, were associated with regulatory elements within the hTERT promoter region. Chromatin condensation may also play a role in SFN-mediated hTERT repression, since expression and recruitment of MeCP2, a known chromatin compactor, were altered in SFN treated prostate cancer cells. Chromatin immuno-precipitation (ChIP) of MeCP2 showed enrichment over regions of the hTERT promoter with increased nucleosome density. These combined results strongly support a role for SFN in the mediation of epigenetic events leading to the repression of hTERT in prostate cancer cells. This ability of SFN to modify chromatin composition and structure associated with target gene expression provides a new model by which dietary phytochemicals may exert their chemoprevention activity.

  15. Generation of a Tph2 Conditional Knockout Mouse Line for Time- and Tissue-Specific Depletion of Brain Serotonin

    Science.gov (United States)

    Migliarini, Sara; Pacini, Giulia; Pasqualetti, Massimo

    2015-01-01

    Serotonin has been gaining increasing attention during the last two decades due to the dual function of this monoamine as key regulator during critical developmental events and as neurotransmitter. Importantly, unbalanced serotonergic levels during critical temporal phases might contribute to the onset of neuropsychiatric disorders, such as schizophrenia and autism. Despite increasing evidences from both animal models and human genetic studies have underpinned the importance of serotonin homeostasis maintenance during central nervous system development and adulthood, the precise role of this molecule in time-specific activities is only beginning to be elucidated. Serotonin synthesis is a 2-step process, the first step of which is mediated by the rate-limiting activity of Tph enzymes, belonging to the family of aromatic amino acid hydroxylases and existing in two isoforms, Tph1 and Tph2, responsible for the production of peripheral and brain serotonin, respectively. In the present study, we generated and validated a conditional knockout mouse line, Tph2 flox/flox, in which brain serotonin can be effectively ablated with time specificity. We demonstrated that the Cre-mediated excision of the third exon of Tph2 gene results in the production of a Tph2 null allele in which we observed the near-complete loss of brain serotonin, as well as the growth defects and perinatal lethality observed in serotonin conventional knockouts. We also revealed that in mice harbouring the Tph2 null allele, but not in wild-types, two distinct Tph2 mRNA isoforms are present, namely Tph2Δ3 and Tph2Δ3Δ4, with the latter showing an in-frame deletion of amino acids 84–178 and coding a protein that could potentially retain non-negligible enzymatic activity. As we could not detect Tph1 expression in the raphe, we made the hypothesis that the Tph2Δ3Δ4 isoform can be at the origin of the residual, sub-threshold amount of serotonin detected in the brain of Tph2 null/null mice. Finally, we set

  16. MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed antigen collection

    Science.gov (United States)

    Rozanov, Dmitri V.; Rozanov, Nikita D.; Chiotti, Kami; Reddy, Ashok; Wilmarth, Phillip A.; David, Larry L.; Cha, Seung W.; Woo, Sunghee; Pevzner, Pavel; Bafna, Vineet; Burrows, Gregory G.; Rantala, Juha K.; Levin, Trevor; Anur, Pavana; Johnson-Camacho, Katie; Tabatabaei, Shaadi; Munson, Daniel J.; Bruno, Tullia C.; Slansky, Jill E.; Kappler, John W.; Hirano, Naoto; Boegel, Sebastian; Fox, Bernard A.; Egelston, Colt; Simons, Diana L.; Jimenez, Grecia; Lee, Peter P.; Gray, Joe W.; Spellman, Paul T.

    2018-01-01

    Breast cancer therapy based on amplifying a patient’s antitumor immune response depends on the availability of appropriate MHC class I-restricted, breast cancer-specific epitopes. To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cell lines. We determined the sequence of 3,196 MHC class I-bound peptides representing 1,921 proteins from a panel of 20 breast cancer cell lines including basal, luminal, and claudin-low subtypes. The data has been deposited to the ProteomeXchange with identifier PXD006406. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2,740. Of the unique peptides eluted, more than 1,750 had been previously identified, and of these, sixteen have been shown to be immunogenic. Importantly, only 3 of these immunogenic peptides have been identified in breast cancer cells in earlier studies. MHC class I binding probability of eluted peptides was used to plot the distribution of MHC class I allele-specific peptides in accordance with the binding score for each breast cancer cell line. We also determined that the tested breast cancer cells presented 89 mutation-containing peptides and peptides derived from aberrantly translated genes, 7 of which were shared between four or two different cell lines. Overall, the high throughput identification of MHC class I-loaded peptides is an effective strategy for systematic characterization of cancer peptides, and could be employed for design of multi-peptide anticancer vaccines. PMID:29331515

  17. Exposure to magnetic field and brain cancer among child; Exposition au champ magnetique et cancer du cerveau chez l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Mir, L

    2008-09-15

    The risk of childhood brain cancer as a function of magnetic field exposure has been studied less than the risk of leukemia. this updated meta-analysis of thirteen epidemiologic studies thus provides an important contribution to the literature. No increased risk of brain cancer was found, and there were no differences by method of exposure assessment. Doubt remains only for the highest exposure levels, for which very limited data are available. (author)

  18. Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and İmmunity with Special Emphasis for Brain Tumors.

    Science.gov (United States)

    Altinoz, Meric Adil; Elmaci, Ilhan; Ince, Bahri; Ozpinar, Aysel; Sav, Aydin Murat

    2016-05-01

    In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS). HBs mediate coping with hypoxia and free radical stress in normal and tumor cells, and they are increased in certain tumors including breast, lung, colon, and squamous cell cancers. Recent studies showed HBs in meningioma, in the cyst fluid of craniopharyngioma, in the cerebrospinal fluid (CSF) of pediatric patients with posterior fossa tumors, and in glioblastoma cell lines. Hemorphins, abundant brain peptides formed via HB-chain cleavage, exert opioid activity and antiproliferative and immunomodifier effects. Hence mutations in HBs may modify brain tumorigenesis via influencing hemorphins and perturbing regulations of immune surveillance and cell growth in the neuroectodermal tissues. The β-globin gene cluster resides in the chromosome region 11p15.5, harboring important immunity genes and IGF2, H19, PHLDA2/TSSC3, TRIM3, and SLC22A18 genes associated with cancers and gliomas. 11p15.5 is a prominent region subject to epigenetic regulation. Thus the β-globin loci may exert haplotypal interactions with these. Some clues support this theory. It is well established that iron load induces liver cancer in thalassemia major; however iron load-independent associations also exist. Enhanced rates of hematologic malignancies are associated with HB Lepore, association of hemoglobin E with cholangiocarcinoma, and enhanced gastric cancer rates in the thalassemia trait. In

  19. Tumorigenicity and Validity of Fluorescence Labelled Mesenchymal and Epithelial Human Oral Cancer Cell Lines in Nude Mice

    Directory of Open Access Journals (Sweden)

    Wei Xin Cai

    2016-01-01

    Full Text Available Tumorigenicity and metastatic activity can be visually monitored in cancer cells that were labelled with stable fluorescence. The aim was to establish and validate local and distant spread of subcutaneously previously injected fluorescence transduced human tongue cancer cell lines of epithelial and mesenchymal phenotype in nude mice. A total of 32 four-week-old male athymic Balb/c nude mice were randomly allocated into 4 groups (n=8. A single dose of 0.3 mL PBS containing 1 × 107 of four different cancer cell-lines (UM1, UM1-GFP, UM2, and UM2-RFP was injected subcutaneously into the right side of their posterolateral back. Validity assessment of the labelled cancer cells’ tumorigenicity was assessed by physical examination, imaging, and histology four weeks after the injection. The tumor take rate of cancer cells was similar in animals injected with either parental or transduced cancer cells. Transduced cancer cells in mice were easily detectable in vivo and after cryosection using fluorescent imaging. UM1 cells showed increased tumor take rate and mean tumor volume, presenting with disorganized histopathological patterns. Fluorescence labelled epithelial and mesenchymal human tongue cancer cell lines do not change in tumorigenicity or cell phenotype after injection in vivo.

  20. Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

    International Nuclear Information System (INIS)

    Lee, Do Kyung; Jang, Seok; Kim, Mi Jin; Kim, Jung Hyun; Chung, Myung Jun; Kim, Kyung Jae; Ha, Nam Joo

    2008-01-01

    Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans. The anti-proliferative activity of B. adolescentis isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of B. adolescentis SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line. The butanol extract of B. adolescentis SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of B. adolescentis SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells. The butanol extract of B. adolescentis SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier

  1. Ebselen inhibits QSOX1 enzymatic activity and suppresses invasion of pancreatic and renal cancer cell lines.

    Science.gov (United States)

    Hanavan, Paul D; Borges, Chad R; Katchman, Benjamin A; Faigel, Douglas O; Ho, Thai H; Ma, Chen-Ting; Sergienko, Eduard A; Meurice, Nathalie; Petit, Joachim L; Lake, Douglas F

    2015-07-30

    Quiescin sulfhydryl oxidase 1 (QSOX1) is a highly conserved disulfide bond-generating enzyme that is overexpressed in diverse tumor types. Its enzymatic activity promotes the growth and invasion of tumor cells and alters extracellular matrix composition. In a nude mouse-human tumor xenograft model, tumors containing shRNA for QSOX1 grew significantly more slowly than controls, suggesting that QSOX1 supports a proliferative phenotype in vivo. High throughput screening experiments identified ebselen as an in vitro inhibitor of QSOX1 enzymatic activity. Ebselen treatment of pancreatic and renal cancer cell lines stalled tumor growth and inhibited invasion through Matrigel in vitro. Daily oral treatment with ebselen resulted in a 58% reduction in tumor growth in mice bearing human pancreatic tumor xenografts compared to controls. Mass spectrometric analysis of ebselen-treated QSOX1 mechanistically revealed that C165 and C237 of QSOX1 covalently bound to ebselen. This report details the anti-neoplastic properties of ebselen in pancreatic and renal cancer cell lines. The results here offer a "proof-of-principle" that enzymatic inhibition of QSOX1 may have clinical relevancy.

  2. In vitro radiosensitization by oxaliplatin and 5-fluorouracil in a human colon cancer cell line

    International Nuclear Information System (INIS)

    Kjellstroem, Johan; Kjellen, Elisabeth; Johnsson, Anders

    2005-01-01

    The current study was designed to compare the radiosensitizing effects of oxaliplatin and 5-fluorouracil (5FU) in a human colon cancer cell line. A human colon cancer cell line (S1) was treated with various doses of oxaliplatin, 5FU, radiation, and combinations thereof. Various clinically used schedules were mimicked. 5FU was either incubated during 1 h ('bolus') or 24 h ('continuous infusion'). When combining oxaliplatin and 5FU, an isobologram analysis revealed synergistic effects, regardless of 5FU schedule. The IC 10 and IC 50 -doses for the drugs where then combined with radiotherapy. With equitoxic drug doses (IC 50 ), radiosensitization was observed in the following order: oxaliplatin>5FU 24 h>5FU 1 h exposure. The degree of potentiation corresponded to approximately 0.8 Gy, 0.7 Gy, and 0.2 Gy, respectively. In this experimental setting, oxaliplatin seemed to be a better radiosensitizer than 5FU, and longer incubation time with 5FU was better than short exposure

  3. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  4. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer - brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  5. Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer.

    Science.gov (United States)

    Tsai, Yi-Fang; Tseng, Ling-Ming; Hsu, Chih-Yi; Yang, Muh-Hwa; Chiu, Jen-Hwey; Shyr, Yi-Ming

    2017-01-01

    There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples. The results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS. Our study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in

  6. Inclusion of brain in FDG PET/CT scanning techniques in cancer patients: Does it obviate the need for dedicated brain imaging?

    International Nuclear Information System (INIS)

    Purandare, Nilendu C.

    2011-01-01

    Metastases to the brain can affect about 10-20% cancer patients. Rising incidence of brain metastases in recent years is related to improved survival rates as a result of advances in cancer therapy and development of more sensitive diagnostic imaging techniques. In patients with extracranial malignancies detection of brain metastases is very important in deciding further diagnostic procedures, planning therapeutic strategies and also to ascertain prognosis. Computerized tomography (CT) and magnetic resonance imaging (MRI) are the modalities which have been traditionally used to assess metastatic disease to the central nervous system. It is generally accepted that MRI (contrast enhanced) is superior to CT scan (contrast enhanced) in the diagnosis of brain metastases. An inherently better soft tissue contrast resolution, stronger contrast enhancement, lack of bone artifacts and partial volume effects and direct multiplanar imaging enables MRI to pick up smaller sized as well as more number of metastases than a CT scan

  7. Inhibitory effects of 131I labeled 17-allylamino-17-demethoxygeldanamycin on breast cancer cell line

    International Nuclear Information System (INIS)

    Chen Daozhen; Liu Lu; Jiang Xinyu; Huang Ying; Yang Min; Yu Huixin; Luo Shineng; Lin Xiufeng

    2007-01-01

    Objective: 17-allylamino-17-demethoxygeldanamycin(17-AAG) is a less toxic analogue of geldanamycin (GA) that retains the tumoricidal features of GA. Same as its parent compound, 17-AAG inhibits several signaling pathways through binding to heat shock protein (HSP) 90, which results in destabilization of signaling complexes and degradation of client proteins in a variety of tumor cell growth. Treatment with 17-AAG was effective to inhibit tumor growth and induce apoptosis in colon cancer, glioblastoma, and breast cancer cell lines. This study aimed at exploring the anti-proliferation effects and mechanism of 131 I labeled 17-AAG on human breast cancer cell line MCF-7. Methods: 131 I-17-AAG was prepared by the reaction of 17-AAG with Na 131 I in the presence of hydrogen peroxide. The MCF-7 cells were divided into 5 groups with different additional drugs: group A, dimethyl sulfoxide (DMSO); group B, 370 kBq Na 131 I; group C, 2.5 mg/L 17-AAG; group D, 370 kBq 131 I-17-AAG; group E, 370 kBq 131 I-17-AAG + 2.5 mg/L 17-AAG. 3- (4,5-dimethylthiazol-2-yl)-2,5, diphenylte-trazolium bromide (MTT) assay was used to evaluate the effect of growth inhibition of MCF-7 cells. Cell cycle and apoptosis were analyzed by flow cytometry. The change of the expression of Akt2 mRNA in MCF-7 cells was examined by RT-PCR. Results: The labeling yield of 131 I-17-AAG was 83%. The radiochemical purity of 131 I-17-AAG after purification was 96.6%. The specific activity was 1.48 x 10 5 MBq/μmol. All drugs could significantly inhibit the growth of MCF-7 cells in vitro as the duration lasts longer, especially for group E. After 48 h, sub-G1 peaks detected by flow cytometry were(1.54±0.13)%, (5.72±1.05)%, (12.97±1.44)%, (20.65±1.36)%, (35.39±4.15)% for group A, B, C, D and E, respectively. The experimental groups (B-E) were all significantly higher than the control group (A, all P 131 I-17-AAG could suppress the growth of human breast cancer cell line MCF-7 and hasten the apoptosis. It could

  8. Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes

    Directory of Open Access Journals (Sweden)

    Chris L. Smith

    2016-06-01

    Full Text Available Glioblastoma multiforme is a heterogeneous and infiltrative cancer with dismal prognosis. Studying the migratory behavior of tumor-derived cell populations can be informative, but it places a high premium on the precision of in vitro methods and the relevance of in vivo conditions. In particular, the analysis of 2D cell migration may not reflect invasion into 3D extracellular matrices in vivo. Here, we describe a method that allows time-resolved studies of primary cell migration with single-cell resolution on a fibrillar surface that closely mimics in vivo 3D migration. We used this platform to screen 14 patient-derived glioblastoma samples. We observed that the migratory phenotype of a subset of cells in response to platelet-derived growth factor was highly predictive of tumor location and recurrence in the clinic. Therefore, migratory phenotypic classifiers analyzed at the single-cell level in a patient-specific way can provide high diagnostic and prognostic value for invasive cancers.

  9. Understanding the logics of pheromone processing in the honeybee brain: from labeled-lines to across-fiber patterns

    Directory of Open Access Journals (Sweden)

    Nina Deisig

    2007-12-01

    Full Text Available Honeybees employ a very rich repertoire of pheromones to ensure intraspecific communication in a wide range of behavioral contexts. This communication can be complex, since the same compounds can have a variety of physiological and behavioral effects depending on the receiver. Honeybees constitute an ideal model to study the neurobiological basis of pheromonal processing, as they are already one of the most infl uential animal models for the study of general odor processing and learning at behavioral, cellular and molecular levels. Accordingly, the anatomy of the bee brain is well characterized and electro- and opto-physiological recording techniques at different stages of the olfactory circuit are possible in the laboratory. Here we review pheromone communication in honeybees and analyze the different stages of olfactory processing in the honeybee brain, focusing on available data on pheromone detection, processing and representation at these different stages. In particular, we argue that the traditional distinction between labeled-line and across-fi ber pattern processing, attributed to pheromone and general odors respectively, may not be so clear in the case of honeybees, especially for social-pheromones. We propose new research avenues for stimulating future work in this area.

  10. Comparison between electric-field-navigated and line-navigated TMS for cortical motor mapping in patients with brain tumors.

    Science.gov (United States)

    Sollmann, Nico; Goblirsch-Kolb, Moritz F; Ille, Sebastian; Butenschoen, Vicki M; Boeckh-Behrens, Tobias; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2016-12-01

    For the navigation of transcranial magnetic stimulation (TMS), various techniques are available. Yet, there are two basic principles underlying them all: electric-field-navigated transcranial magnetic stimulation (En-TMS) and line-navigated transcranial magnetic stimulation (Ln-TMS). The current study was designed to compare both methods. To explore whether there is a difference in clinical applicability, workflow, and mapping results of both techniques, we systematically compared motor mapping via En-TMS and Ln-TMS in 12 patients suffering from brain tumors. The number of motor-positive stimulation spots and the ratio of positive spots per overall stimulation numbers were significantly higher for En-TMS (motor-positive spots: En-TMS vs. Ln-TMS: 128.3 ± 35.0 vs. 41.3 ± 26.8, p mapping in the neurosurgical context for the first time. Although both TMS systems tested in the present study are explicitly designed for application during motor mapping in patients with brain lesions, there are differences in applicability, workflow, and results between En-TMS and Ln-TMS, which should be distinctly considered during clinical use of the technique. However, to draw final conclusions about accuracy, confirmation of motor-positive Ln-TMS spots by intraoperative stimulation is crucial within the scope of upcoming investigations.

  11. The views of patients with brain cancer about palliative care: a qualitative study.

    Science.gov (United States)

    Vierhout, M; Daniels, M; Mazzotta, P; Vlahos, J; Mason, W P; Bernstein, M

    2017-12-01

    Palliative care, a specialty aimed at providing optimal care to patients with life-limiting and chronic conditions, has several benefits. Although palliative care is appropriate for neurosurgical conditions, including brain cancer, few studies have examined the views of brain cancer patients about palliative care. We aimed to explore the thoughts of brain cancer patients about palliative care, their opinions about early palliative care, and their preferred care setting. Semi-structured interviews and the qualitative research methodologies of grounded theory were used to explore perceptions of palliative care on the part of 39 brain cancer outpatients. Seven overarching actions emerged: ■Patients would prefer to receive palliative care in the home.■Increased time with caregivers and family are the main appeals of home care.■Patients express dissatisfaction with brief and superficial interactions with health care providers.■Patients believe that palliative care can contribute to their emotional well-being.■Patients are open to palliative care if they believe that it will not diminish optimism.■There is a preconceived idea that palliative care is directly linked to active dying, and that supposed link generates fear in some patients.■Patients prefer to be educated about palliative care as an option early in their illness, even if they are fearful of it. Overall, when educated about the true meaning of palliative care, most patients express interest in accessing palliative care services. Although the level of fear concerning palliative care varies in patients, most recognize the associated benefits.

  12. Brain cancer incidence trends in relation to cellular telephone use in the United States

    OpenAIRE

    Inskip, Peter D.; Hoover, Robert N.; Devesa, Susan S.

    2010-01-01

    The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this i...

  13. Brain metastasis from ovarian cancer: case report and review of the literature.

    Science.gov (United States)

    Hu, Xi-Quan; Imitola, Jaime; Kim, Ryan Y; Mahta, Ali; Kesari, Santosh

    2012-06-01

    We present an 80-year-old lady with a history of ovarian cancer, who manifested with seizure and left upper extremity weakness. The imaging revealed a multilobulated mass within right parietal lobe. She underwent surgical resection and the pathology was compatible with metastasis from ovarian adenocarcinoma. She received a whole brain radiation therapy and she has been in remission for more than 2 years.

  14. Cadmium telluride quantum dots induce apoptosis in human breast cancer cell lines.

    Science.gov (United States)

    Naderi, Saeed; Zare, Hakimeh; Taghavinia, Nima; Irajizad, Azam; Aghaei, Mahmoud; Panjehpour, Mojtaba

    2018-05-01

    Semiconductor quantum dots (QDs), especially those containing cadmium, have undergone marked improvements and are now widely used nanomaterials in applicable biological fields. However, great concerns exist regarding their toxicity in biomedical applications. Because of the lack of sufficient data regarding the toxicity mechanism of QDs, this study aimed to evaluate the cytotoxicity of three types of QDs: CdTe QDs, high yield CdTe QDs, and CdTe/CdS core/shell QDs on two human breast cancer cell lines MDA-MB468 and MCF-7. The breast cancer cells were treated with different concentrations of QDs, and cell viability was evaluated via MTT assay. Hoechst staining was applied for observation of morphological changes due to apoptosis. Apoptotic DNA fragmentation was visualized by the agarose gel electrophoresis assay. Flow cytometric annexin V/propidium iodide (PI) measurement was used for apoptosis detection. A significant decrease in cell viability was observed after QDs treatment ( p < 0.05). Apoptotic bodies and chromatin condensation was observed by Hoechst staining. DNA fragmentation assay demonstrated a DNA ladder profile in the exposed cells and also annexin V/PI flow cytometry confirmed apoptosis in a dose-dependent manner. Our results revealed that CdTe, high yield CdTe, and CdTe/CdS core/shell QDs induce apoptosis in breast cancer cell lines in a dose-dependent manner. This study would help realizing the underlying cytotoxicity mechanism, at least partly, of CdTe QDs and may provide information for the development of nanotoxicology and safe use of biological applications of QDs.

  15. Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

    Science.gov (United States)

    Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

    2015-01-01

    The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

  16. Selection of optimal treatment scheme for brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Dong Mingxin; Zhao Tong; Huang Jingzi; Yu Shukun; Ma Yan; Tian Zhongcheng; Jin Xiangshun; Quan Jizhong; Liu Jin; Wang Dongxu

    2006-01-01

    Objective: To select the optimal treatment scheme for brain metastases of non-small cell lung cancers (NSCLCs). Methods: Seventy-two NSCLC cases diagnosesd by pathology with brain metastases were randomly classified into three groups, Group I, 24 cases with whole brain conventional external fractioned irradiation of D T 36-41 Gy/4-5 w, Group II, 22 eases with y-knife treatment plus whole brain conventional external fractioned irradiation, and Group III, 26 cases with γ-knife plus whole brain conventional external fractioned irradiation in combination with chemotherapy of Vm-26. The surrounding area of tumor was strictly covered with 50% para-central-dosal curve in γ-knife treatment (D T 16-25 Gy with a mean of 16 Gy). The muirleaf collimator was selected according to the volume of tumors. Chemotherapy of Vm-26 (60 mg/m 2 d1-3) was applied during the treatment with whole brain conventional external fractioned irradiation (D T 19-29 Gy/2-3 w), 21 days in a period, 2 periods in total. Results: The median survival time was estimated to be 6.0 months (ranged from 1.2 to 19.0 months) in the Group I, 9.2 months (4.4-30 months) in the Group II, and 10.8 months (5.2-42.2 months) in the Group III. The 1-year and 2-year survival rates were 34.6% and 12.6% , 62.2% and 30.2%, and 70.8% and 35.6% respectively in Group I, Group II, and Group III, respectively. Conclusion: For brain metastases of NSCLC, γ-knife plus whole brain conventional external fractioned irradiation combined with treatment of Vm-26 had a significantly beneficial influence on improvement of the local control and 1-year and 2-year survival. There was no complaint about the side-effects of the treatment. (authors)

  17. Metabolic characterization of invaded cells of the pancreatic cancer cell line, PANC-1.

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    Fujita, Mayumi; Imadome, Kaori; Imai, Takashi

    2017-05-01

    We previously reported that about 0.4% of cells in the cultured human pancreatic cancer cell line, PANC-1, can invade matrigel during the transwell invasion assay, suggesting that these invaded PANC-1 cells may have specific characteristics to keep their invasive potential. To identify the metabolic characterization specific in the invaded PANC-1 cells, metabolome analysis of the invaded PANC-1 compared with the whole cultured PANC-1 was performed using CE-TOFMS, and concentrations of 110 metabolites were measured. In contrast to the whole cultured cells, the invaded PANC-1 was characterized as a population with reduced levels of amino acids and TCA cycle intermediates, and decreased and increased intermediates in glycolysis and nucleic acid metabolism. In particular, the ratio of both adenosine and guanosine energy charge was reduced in the invaded cells, revealing that the consumption of ATP and GTP was high in the invaded cells, and thus suggesting that ATP- or GTP-generating pathways are stimulated. In addition, the GSH/GSSG ratio was low in the invaded cells, but these cells had a higher surviving fraction after exposure to hydrogen peroxide. Thus, the invaded cells were the population resistant to oxidative stress. Furthermore, reduction in intracellular GSH content inhibited PANC-1 invasiveness, indicated that GSH has an important role in PANC-1 invasiveness. Overall, we propose the invaded cells have several unique metabolic profiles. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Release of volatile organic compounds (VOCs from the lung cancer cell line CALU-1 in vitro

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    Schubert Jochen

    2008-11-01

    Full Text Available Abstract Background The aim of this work was to confirm the existence of volatile organic compounds (VOCs specifically released or consumed by lung cancer cells. Methods 50 million cells of the human non-small cell lung cancer (NSCLC cell line CALU-1 were incubated in a sealed fermenter for 4 h or over night (18 hours. Then air samples from the headspace of the culture vessel were collected and preconcentrated by adsorption on solid sorbents with subsequent thermodesorption and analysis by means of gas chromatography mass spectrometry (GC-MS. Identification of altogether 60 compounds in GCMS measurement was done not only by spectral library match, but also by determination of retention times established with calibration mixtures of the respective pure compounds. Results The results showed a significant increase in the concentrations of 2,3,3-trimethylpentane, 2,3,5-trimethylhexane, 2,4-dimethylheptane and 4-methyloctane in the headspace of CALU-1 cell culture as compared to medium controls after 18 h. Decreased concentrations after 18 h of incubation were found for acetaldehyde, 3-methylbutanal, butyl acetate, acetonitrile, acrolein, methacrolein, 2-methylpropanal, 2-butanone, 2-methoxy-2-methylpropane, 2-ethoxy-2-methylpropane, and hexanal. Conclusion Our findings demonstrate that certain volatile compounds can be cancer-cell derived and thus indicative of the presence of a tumor, whereas other compounds are not released but seem to be consumed by CALU-1 cells.

  19. TASK-3 Downregulation Triggers Cellular Senescence and Growth Inhibition in Breast Cancer Cell Lines

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    Rafael Zúñiga

    2018-03-01

    Full Text Available TASK-3 potassium channels are believed to promote proliferation and survival of cancer cells, in part, by augmenting their resistance to both hypoxia and serum deprivation. While overexpression of TASK-3 is frequently observed in cancers, the understanding of its role and regulation during tumorigenesis remains incomplete. Here, we evaluated the effect of reducing the expression of TASK-3 in MDA-MB-231 and MCF-10F human mammary epithelial cell lines through small hairpin RNA (shRNA-mediated knockdown. Our results show that knocking down TASK-3 in fully transformed MDA-MB-231 cells reduces proliferation, which was accompanied by an induction of cellular senescence and cell cycle arrest, with an upregulation of cyclin-dependent kinase (CDK inhibitors p21 and p27. In non-tumorigenic MCF-10F cells, however, TASK-3 downregulation did not lead to senescence induction, although cell proliferation was impaired and an upregulation of CDK inhibitors was also evident. Our observations implicate TASK-3 as a critical factor in cell cycle progression and corroborate its potential as a therapeutic target in breast cancer treatment.

  20. 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.

  1. Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line

    International Nuclear Information System (INIS)

    Choi, Hyun-Jeung; Kim, Tae Yong; Ruiz-Llorente, Sergio; Jeon, Min Ji; Han, Ji Min; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2012-01-01

    Introduction: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. Methods: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. Results: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. Conclusions: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

  2. Establishment and characterization of a new cell line of canine inflammatory mammary cancer: IPC-366.

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    Sara Caceres

    Full Text Available Canine inflammatory mammary cancer (IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC. The aim of this study was to characterize a new cell line from IMC (IPC-366 for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The cells were grown under adherent conditions. The growth, cytological, ultrastructural and immunohistochemical (IHC characteristics of IPC-366 were evaluated. Ten female Balb/SCID mice were inoculated with IPC-366 cells to assess their tumorigenicity and metastatic potential. Chromosome aberration test and Karyotype revealed the presence of structural aberration, numerical and neutral rearrangements, demonstrating a chromosomal instability. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon that has been related to s vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2, E-cadherin, overexpressed COX-2 and high Ki-67 proliferation index (87.15 %. At 2 weeks after inoculating the IPC-366 cells, a tumor mass was found in 100 % of mice. At 4 weeks metastases in lung and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the

  3. Novel near-diploid ovarian cancer cell line derived from a highly aneuploid metastatic ovarian tumor.

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    Ester Rozenblum

    Full Text Available A new ovarian near-diploid cell line, OVDM1, was derived from a highly aneuploid serous ovarian metastatic adenocarcinoma. A metastatic tumor was obtained from a 47-year-old Ashkenazi Jewish patient three years after the first surgery removed the primary tumor, both ovaries, and the remaining reproductive organs. OVDM1 was characterized by cell morphology, genotyping, tumorigenic assay, mycoplasma testing, spectral karyotyping (SKY, and molecular profiling of the whole genome by aCGH and gene expression microarray. Targeted sequencing of a panel of cancer-related genes was also performed. Hierarchical clustering of gene expression data clearly confirmed the ovarian origin of the cell line. OVDM1 has a near-diploid karyotype with a low-level aneuploidy, but samples of the original metastatic tumor were grossly aneuploid. A number of single nucleotide variations (SNVs/mutations were detected in OVDM1 and the metastatic tumor samples. Some of them were cancer-related according to COSMIC and HGMD databases (no founder mutations in BRCA1 and BRCA2 have been found. A large number of focal copy number alterations (FCNAs were detected, including homozygous deletions (HDs targeting WWOX and GATA4. Progression of OVDM1 from early to late passages was accompanied by preservation of the near-diploid status, acquisition of only few additional large chromosomal rearrangements and more than 100 new small FCNAs. Most of newly acquired FCNAs seem to be related to localized but massive DNA fragmentation (chromothripsis-like rearrangements. Newly developed near-diploid OVDM1 cell line offers an opportunity to evaluate tumorigenesis pathways/events in a minor clone of metastatic ovarian adenocarcinoma as well as mechanisms of chromothripsis.

  4. Methylation associated transcriptional repression of ELOVL5 in novel colorectal cancer cell lines.

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    Arnoud Boot

    Full Text Available Genetic and epigenetic alterations mark colorectal cancer (CRC. Global hypomethylation is observed in nearly all CRC, but a distinct subset of CRC show the CpG Island Methylator Phenotype (CIMP. These tumors show DNA hypermethylation of a specific subset of CpG islands, resulting in transcriptional downregulation of nearby genes. Recently we reported the establishment of novel CRC cell lines derived from primary and metastatic CRC tissues. In this study we describe the DNA methylation profiling of these low passage CRC cell lines. We generated global DNA methylation profiles with Infinium HumanMethylation450 BeadChips and analysed them in conjunction with matching gene expression profiles. Multidimensional scaling of the DNA methylation and gene expression datasets showed that BRAF mutated cell lines form a distinct group. In this group we investigated the 706 loci which we have previously identified to be hypermethylated in BRAF mutant CRC. We validated the significant findings in the The Cancer Genome Atlas colon adenocarcinoma dataset. Our analysis identified ELOVL5, FAM127B, MTERF1, ZNF606 to be subject to transcriptional downregulation through DNA hypermethylation in CRC. We further investigated ELOVL5 with qPCR and immunohistochemical staining, validating our results, but did not find a clear relation between ELOVL5 expression and tumor stage or relapse free survival. ELOVL5, FAM127B, MTERF1, ZNF606 are involved in important cellular processes such as apoptosis, lipogenesis and the downstream transcriptional effect of the MAPK-pathway. We have identified a DNA methylation profile regulating key cellular processes in CRC, resulting in a growth advantage to the tumor cells.

  5. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

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    Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

    2012-01-01

    We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

  6. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  7. The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

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    Kimmelman Jonathan

    2007-11-01

    Full Text Available Abstract Background Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations. Methods We interviewed 29 individuals – 7 patients dying of a malignant brain tumor and 22 loved ones. One-on-one interviews were conducted according to a pre-designed interview guide. A combination of open-ended questions, as well as clinical scenarios was presented to participants in order to understand what is meaningful and valuable to them when determining treatment options and management approaches. The results were analyzed, coded, and interpreted using qualitative analytic techniques in order to arrive at several common overarching themes. Results Seven major themes were identified. In general, respondents were united in viewing brain cancer as unique amongst malignancies, due in large part to the premium placed on mental competence and cognitive functioning. Importantly, participants found their experiences, however difficult, led to the discovery of inner strength and resilience. Responses were usually framed within an interpersonal context, and participants were generally grateful for the opportunity to speak about their experiences. Attitudes towards religion, spirituality, and euthanasia were also probed. Conclusion Several important themes underlie the experiences of brain cancer patients and their caregivers. It is important to consider these when managing these patients and to respect not only their autonomy but also the complex interpersonal toll that a malignant diagnosis can have.

  8. Screening the Drug Sensitivity Genes Related to GEM and CDDP in the Lung Cancer Cell-lines

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    Chunyu YANG

    2009-10-01

    Full Text Available Background and objective Screening of small-cell lung cancer (SCLC and non-small cell lung cancer (NSCLC cell lines with gemcitabine hydrochloride (GEM and cisplatin (CDDP related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual. Methods The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized. Results There were 6 genes showing significant positive correlation (r≥0.632, P < 0.05 with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r≥± 0.4. Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules, Cathepsin B (Organization protease B and TIMP1 (Growth factor; the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories. Conclusion There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathepsin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.

  9. ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines.

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    Clément Chevalier

    Full Text Available The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.

  10. Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

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    Gerhard Hamilton

    2014-03-01

    Full Text Available Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4 inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose-Polymerase 1 (PARP1 inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS.

  11. Second-line combination therapies in nonsmall cell lung cancer without known driver mutations

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    Maria-Virginia Bluthgen

    2015-12-01

    Full Text Available In advanced nonsmall cell lung cancer (NSCLC patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies. In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.

  12. Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

    Science.gov (United States)

    Hamilton, Gerhard

    2014-01-01

    Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4) inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC) cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS) and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose)-Polymerase 1 (PARP1) inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS. PMID:24608973

  13. Widespread molecular patterns associated with drug sensitivity in breast cancer cell lines, with implications for human tumors.

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    Chad J Creighton

    Full Text Available BACKGROUND: Recent landmark studies have profiled cancer cell lines for molecular features, along with measuring the corresponding growth inhibitory effects for specific drug compounds. These data present a tool for determining which subsets of human cancer might be more responsive to particular drugs. To this end, the NCI-DREAM-sponsored DREAM7: Drug Sensitivity Prediction Challenge (sub-challenge 1 set out to predict the sensitivities of 18 breast cancer cell lines to 31 previously untested compounds, on the basis of molecular profiling data and a training subset of cell lines. METHODS AND RESULTS: With 47 teams submitting blinded predictions, team Creighton scored third in terms of overall accuracy. Team Creighton's method was simple and straightforward, incorporated multiple expression data types (RNA-seq, gene array, RPPA, and incorporated all profiled features (not only the "best" predictive ones. As an extension of the approach, cell line data, from public datasets of expression profiling coupled with drug sensitivities (Barretina, Garnett, Heiser were used to "predict" the drug sensitivities in human breast tumors (using data from The Cancer Genome Atlas. Drug sensitivity correlations within human breast tumors showed differences by expression-based subtype, with many associations in line with the expected (e.g. Lapatinib sensitivity in HER2-enriched cancers and others inviting further study (e.g. relative resistance to PI3K inhibitors in basal-like cancers. CONCLUSIONS: Molecular patterns associated with drug sensitivity are widespread, with potentially hundreds of genes that could be incorporated into making predictions, as well as offering biological clues as to the mechanisms involved. Applying the cell line patterns to human tumor data may help generate hypotheses on what tumor subsets might be more responsive to therapies, where multiple cell line datasets representing various drugs may be used, in order to assess consistency of

  14. Dual regulation of P-glycoprotein expression by Trichostatin A in cancer cell lines

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    Balaguer Trinidad

    2012-07-01

    Full Text Available Abstract Background It has been reported that the histone deacetylase inhibitor (iHDAc trichostatin A (TSA induces an increase in MDR1 gene transcription (ABCB1. This result would compromise the use of iHDACs in combination with other cytotoxic agents that are substrates of P-glycoprotein (Pgp. It has also been reported the use of alternative promoters by the ABCB1 gene and the existence of a translational control of Pgp protein. Finally, the ABCB1 gene is located in a genetic locus with the nested gene RUNDC3B in the complementary DNA strand, raising the possibility that RUNDC3B expression could interfere with ABCB1 alternative promoter regulation. Methods A combination of RT-PCR, real time RT-PCR, Western blot and drug accumulation assays by flow cytometry has been used in this study. Results The iHDACs-induced increase in MDR1 mRNA levels is not followed by a subsequent increase in Pgp protein levels or activity in several pancreatic and colon carcinoma cell lines, suggesting a translational control of Pgp in these cell lines. In addition, the MDR1 mRNA produced in these cell lines is shorter in its 5′ end that the Pgp mRNA produced in cell lines expressing Pgp protein. The different size of the Pgp mRNA is due to the use of alternative promoters. We also demonstrate that these promoters are differentially regulated by TSA. The translational blockade of Pgp mRNA in the pancreatic carcinoma cell lines could be related to alterations in the 5′ end of the MDR1 mRNA in the Pgp protein expressing cell lines. In addition, we demonstrate that the ABCB1 nested gene RUNDC3B expression although upregulated by TSA is independent of the ABCB1 alternative promoter used. Conclusions The results show that the increase in MDR1 mRNA expression after iHDACs treatment is clinically irrelevant since this mRNA does not render an active Pgp protein, at least in colon and pancreatic cancer cell lines. Furthermore, we demonstrate that TSA in fact, regulates

  15. Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer.

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    Vera L Silva

    Full Text Available The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line- 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 -CPTASNTSC and 4T1pep2-EVQSSKFPAHVS were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy.

  16. 2-DE analysis of breast cancer cell lines 1833 and 4175 with distinct metastatic organ-specific potentials: Comparison with parental cell line MDA-MB-231

    Czech Academy of Sciences Publication Activity Database

    Selicharová, Irena; Šanda, Miloslav; Mládková, Jana; Ohri, S. S.; Vashishta, A.; Fusek, M.; Jiráček, Jiří; Vetvicka, V.

    2008-01-01

    Roč. 19, č. 5 (2008), s. 1237-1244 ISSN 1021-335X R&D Projects: GA MZd NR8323 Grant - others:NIH(US) ROI CAA082159-03 Institutional research plan: CEZ:AV0Z40550506 Keywords : breast cancer * cell line * 2-DE * organ-specific metastases Subject RIV: CE - Biochemistry Impact factor: 1.524, year: 2008

  17. Development of a STAT3 reporter prostate cancer cell line for high throughput screening of STAT3 activators and inhibitors

    International Nuclear Information System (INIS)

    Chau, My N.; Banerjee, Partha P.

    2008-01-01

    STAT3 is constitutively activated in several cancers, including prostate cancer, and is therefore, a potential target for cancer therapy. DU-145 prostate cancer cells were stably co-transfected with STAT3 reporter and puromycin resistant plasmids to create a stable STAT3 reporter cell line that can be used for high throughput screening of STAT3 modulators. The applicability of this cell line was tested with two known activators and inhibitors of STAT3. As expected, EGF and IL-6 increased STAT3 reporter activity and enhanced the nuclear localization of phosphorylated STAT3 (pSTAT3); whereas Cucurbitacin I and AG490 decreased STAT3 reporter activity dose and time-dependently and reduced the localization of pSTAT3 in the nuclei of prostate cancer cells. Given the importance of STAT3 in cancer initiation and progression, the development of a stable STAT3 reporter cell line in prostate cancer cells provides a rapid, sensitive, and cost effective method for the screening of potential STAT3 modulators.

  18. SU-E-T-320: The Effect of Survivin Perturbation On the Radiation Response of Breast Cancer Cell Lines

    International Nuclear Information System (INIS)

    Smith, D; Debeb, B; Woodward, W

    2014-01-01

    Purpose: Survivin is the smallest member of the inhibitor of apoptosis protein family and is well-known for its universal over-expression in human cancers. Due to its role in apoptosis and cellular proliferation, survivin is implicated in the radiation response in several cancer types, and antisurvivin treatments have had success as a radiation sensitizer in many preclinical cancer models. As no studies to date have reported survivin as a factor affecting radiation resistance in breast cancer models, we sought to evaluate the synergistic relationship between survivin function and irradiation in breast cancer cell lines. Methods: Information regarding survivin protein expression in breast cancer was retrieved from three public databases: Oncomine, Kaplan-Meier Plotter, and GOBO. For the in vitro studies, survivin function was compromised by transducing a non-functional mutant form (survivin-DN) into two breast cancer cell lines, the estrogen receptor-positive MCF7 and the triple-negative, inflammatory SUM149. Cell growth was compared in the survivin-DN and control populations with colony-formation assays. To assess how survivin affects radiation response, clonogenic assays were performed by irradiating the cell lines up to 6 Gy. Results: From the public databases, survivin is more highly expressed in triple-negative breast cancer compared to all other subtypes, and is prognostic of poor survival in all breast cancer patients. In MCF7, the survivin-DN population had decreased colony-formation potential; the opposite was true in SUM149. In the clonogenic assays, abrogation of survivin function radio-protected MCF7 cells in monolayer and 3D growth conditions, while SUM149 survivin-DN cells were radiosensitized in monolayer conditions. Conclusion: We observed synergy between survivin function and radiation, although the results between the two cell lines were disparate. Further investigation is required to identify the mechanism of this discrepancy, including evaluation

  19. Human Cell Line-Derived Monoclonal IgA Antibodies for Cancer Immunotherapy

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    Felix Hart

    2017-05-01

    Full Text Available IgA antibodies have great potential to improve the functional diversity of current IgG antibody-based cancer immunotherapy options. However, IgA production and purification is not well established, which can at least in part be attributed to the more complex glycosylation as compared to IgG antibodies. IgA antibodies possess up to five N-glycosylation sites within their constant region of the heavy chain as compared to one site for IgG antibodies. The human GlycoExpress expression system was developed to produce biotherapeutics with optimized glycosylation and used here to generate a panel of IgA isotype antibodies directed against targets for solid (TA-mucin 1, Her2, EGFR, Thomsen–Friedenreich and hematological (CD20 cancer indications. The feasibility of good manufacturing practice was shown by the production of 11 g IgA within 35 days in a one liter perfusion bioreactor, and IgA antibodies in high purity were obtained after purification. The monoclonal IgA antibodies possessed a high sialylation degree, and no non-human glycan structures were detected. Kinetic analysis revealed increased avidity antigen binding for IgA dimers as compared to monomeric antibodies. The IgA antibodies exhibited potent Fab- and Fc-mediated functionalities against cancer cell lines, whereby especially granulocytes are recruited. Therefore, for patients who do not sufficiently benefit from therapeutic IgG antibodies, IgA antibodies may complement current regiment options and represent a promising strategy for cancer immunotherapy. In conclusion, a panel of novel biofunctional IgA antibodies with human glycosylation was successfully generated.

  20. Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Netchareonsirisuk, Ponsawan [Chulalongkorn University, Program in Biotechnology, Faculty of Science (Thailand); Puthong, Songchan [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand); Dubas, Stephan [Chulalongkorn University, Petroleum and Petrochemical College (Thailand); Palaga, Tanapat [Chulalongkorn University, Department of Microbiology, Faculty of Science (Thailand); Komolpis, Kittinan, E-mail: kittinan.k@chula.ac.th [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand)

    2016-11-15

    Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5–15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO{sub 3} alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC{sub 50}), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84–90 %) than necrosis (8–12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

  1. Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Fadi Kayali

    2011-02-01

    Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

  2. Prognostic factors of HER2-positive breast cancer patients who develop brain metastasis: a multicenter retrospective analysis.

    Science.gov (United States)

    Hayashi, Naoki; Niikura, Naoki; Masuda, Norikazu; Takashima, Seiki; Nakamura, Rikiya; Watanabe, Ken-ichi; Kanbayashi, Chizuko; Ishida, Mayumi; Hozumi, Yasuo; Tsuneizumi, Michiko; Kondo, Naoto; Naito, Yoichi; Honda, Yayoi; Matsui, Akira; Fujisawa, Tomomi; Oshitanai, Risa; Yasojima, Hiroyuki; Yamauchi, Hideko; Saji, Shigehira; Iwata, Hiroji

    2015-01-01

    The clinical course and prognostic factors of HER2-positive breast cancer patients with brain metastases are not well known because of the relatively small population. The aim of this study was to determine prognostic factors associated with HER2-positive patients who develop brain metastases. This retrospective study assessed the largest dataset to date of 432 HER2-positive patients who were diagnosed with brain metastases from 24 institutions of the Japan Clinical Oncology Group, Breast Cancer Study Group. The median age of the 432 patients was 54 years (range, 20-86 years). Of the patients, 162 patients (37.5 %) had ER-positive/HER2-positive (ER+HER2+) breast cancer, and 270 (62.5 %) had ER-negative/HER2-positive (ER-HER2+) breast cancer. The median brain metastasis-free survival period from primary breast cancer was 33.5 months in both groups. The median survival after developing brain metastasis was 16.5 and 11.5 months in the ER+HER2+ and ER-HER2+ groups, respectively, (p = 0.117). Patients with >3 brain metastases had significantly shorter overall survival in both ER+HER2+ (p developing brain metastases was not associated with survival duration after developing brain metastases (p = 0.571). However, patients treated with both trastuzumab and lapatinib after developing metastasis had significantly longer survival than patients treated with trastuzumab alone, lapatinib alone, or no HER2-targeting agent (p brain metastases, regardless of the use of trastuzumab before developing brain metastasis, treatment with both trastuzumab and lapatinib might improve survival.

  3. Transcriptome-wide studies of prostate cancer cell lines in the context of medical radiation

    International Nuclear Information System (INIS)

    Hammer, Paul

    2012-01-01

    The use of radiotherapy in addition to chemotherapy and surgical removal is the most powerful instrument in the fight against malignant tumors in cancer medicine. After cardiovascular diseases, cancer is the second leading cause of death in the western world, in which prostate cancer is the most frequent male cancer. Despite continuous technological improvements in radiological instruments and prognosis, it may occur a recurrence up to many years after radiotherapy due to a high resistance capability of individual malignant cells of the locally occurring tumor. Although modern radiation biology has studied many aspects of the resistance mechanisms, questions are largely unanswered especially in regards to prognostic terms and time response of tumor cells to ionizing radiation. As cellular models four prostate cancer cell lines with different radiation sensitivities (PC3, DuCaP, DU-145, RWPE-1) were cultured and tested for their ability to survive after exposure to ionizing radiation by a trypane blue and MTT viability assay. The proliferative capacity of the four cell lines was determined using a colony formation assay. The PC3 cell line (radiation-resistant) and the DuCaP cell line (radiation-sensitive) showed the maximal differences in terms of radiation sensitivity. Based on these results the two cell lines were selected to allow identification of potential prognostic marker for predicting the effectiveness of radiation therapy via their transcriptome-wide gene expression. Furthermore, a time series experiment with the radiation-resistant PC3 cell line was performed. At 8 different time points, during the period from 00:00 - 42:53 (hh:mm) after exposure with 1 Gy, the mRNA was quantified by next generation sequencing to investigate the dynamic behavior of time-delayed gene expression and to discover resistance mechanisms. Of 10,966 expressed genes 730 were significant differentially expressed, determined by setting a fold change threshold in conjunction with a P

  4. Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting

    International Nuclear Information System (INIS)

    Lekic, Mirko; Kovac, Viljem; Triller, Nadja; Knez, Lea; Sadikov, Aleksander; Cufer, Tanja

    2012-01-01

    Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis. All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4–6 cycles of

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

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

  7. Correlation between the parameters of radiosensitivity in human cancer cell lines

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Kim, Won Dong; Min, Kyung Soo

    1998-01-01

    We conducted clonogenic assay using human cancer cell lines (MKN-45, PC-14, Y-79, HeLa) to investigate a correlation between the parameters of radiosensitivity. Human cancer cell lines were irradiated with single doses of 1, 2, 3, 5, 7 and 10Gy for the study of radiosensitivity and sublethal damage repair capacity was assessed with two fractions of 5Gy separated with a time interval of 0, 1, 2, 3, 4, 6 and 24 hours. Surviving fraction was assessed with clonogenic assay using Sperman-Karber method and mathematical analysis of survival curves was done with linear-quadratic (LQ), multitarget-single hit(MS) model and mean inactivation dose(D). Surviving fractions at 2Gy(SF2) were variable among the cell lines, ranged from 0.174 to 0.85. The SF2 of Y-79 was lowest and that of PC-14 was highest(p<0.05, t-test). LQ model analysis showed that the values of α for Y-79, MKN-45, HeLa and PC-14 were 0.603, 0.356, 0.275 and 0.102 respectively, and those of β were 0.005, 0.016, 0.025 and 0.027 respectively. Fitting to MS model showed that the values of Do for Y-79, MKN-45, HeLa and PC-14 were 1.59, 1.84, 1.88 and 2.52 respectively, and those of n were 0.97, 1.46, 1.52 and 1.69 respectively. The Ds calculated by Gauss-Laguerre method were 1.62, 2.37, 2.61 and 3.95 respectively. So the SF2 was significantly correlated with α, Do and D. Their Pearson correlation coefficiencics were -0.953 and 0.993, 0.999 respectively(p<0.05). Sublethal damage repair was saturated around 4 hours and recovery ratios (RR) at plateau phase ranged from 2 to 3.79. But RR was not correlated with SF2, α, β, Do, D. The intrinsic radiosensitivity was very different among the tested human cell lines. Y-79 was the most sensitive and PC-14 was the least sensitive. SF2 was well correlated with α, Do, and D. RR was high for MKN-45 and HeLa but had nothing to do with radiosensitivity parameters. These basic parameters can be used as baseline data for various in vitro radiobiological experiments

  8. Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor

    Directory of Open Access Journals (Sweden)

    Vahideh Assadollahi

    2015-12-01

    Full Text Available Background: Genes are involved in the control of stem cell self-renewal as a new class of molecular markers of cancer. Objectives: In this study, the expression of Oct4, Nanog and Sox2 in cell lines MIA Paca-2, PA-TU-8902 and AsPC-1 and pancreatic cancer tissue were examined. Materials and Methods: In this experimental study, cell lines, MIA Paca-2, PA-TU-8902 and AsPC-1, were cultured in DMEM (Dulbecco’s Modified Eagles Medium and RPMI-1640 (Roswell Park Memorial Institute containing FBS 10% (fetal bovine serum in a 37°C incubator containing Co2 5% and humidity 90%. Samples of tumor and non-cancer pancreatic tumor were purchased Iran tumor bank. Extraction of RNA and synthesis of cDNA was performed. Expression levels of Oct4, Nanog and Sox2 were determined using Real-time PCR. The protein expression levels of target genes in the cell lines were studied by flow cytometry and immunocytochemistry. Results: The expression rate of Oct4, Nanog and Sox2 is more in the cancer cell lines than those in the control (normal tissue samples. The protein expression levels of target genes in the cell lines were confirmed by flow cytometry and immunocytochemistry. Conclusions: The genes are involved in stem cell self-renewal as a new class of molecular markers of cancer that detected in the pancreatic cell lines. Maybe, these genes play important role in the uncontrolled proliferation of cancer cells.

  9. Preliminary study of steep pulse irreversible electroporation technology in human large cell lung cancer cell lines L9981

    Directory of Open Access Journals (Sweden)

    Song Zuoqing

    2013-01-01

    Full Text Available Our aim was to validate the effectiveness of steep pulse irreversible electroporation technology in human large cell lung cancer cells and to screen the optimal treatment of parameters for human large cell lung cancer cells. Three different sets of steep pulse therapy parameters were applied on the lung cancer cell line L9981. The cell line L9981 inhibition rate and proliferation capacity were detected by Vi-Cell vitality analysis and MTT. Steep pulsed irreversible electroporation technology for large cell lung cancer L9981 presents killing effects with various therapy parameters. The optimal treatment parameters are at a voltage amplitude of 2000V/cm, pulse width of 100μs, pulse frequency of 1 Hz, pulse number 10. With this group of parameters, steep pulse could have the best tumor cell-killing effects.

  10. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    International Nuclear Information System (INIS)

    Martowicz, Agnieszka; Spizzo, Gilbert; Gastl, Guenther; Untergasser, Gerold

    2012-01-01

    The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAM high breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAM low breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAM high cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAM low cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

  11. Neurotensin is metabolized by endogenous proteases in prostate cancer cell lines.

    Science.gov (United States)

    Moody, T W; Mayr, C A; Gillespie, T J; Davis, T P

    1998-01-01

    The formation and processing of neurotensin (NT) by three prostate cancer cell lines was investigated. Neurotensin (NT) immunoreactivity was detected in conditioned media and extracts of LNCaP cells. Using HPLC techniques, the immunoreactivity extracted from LNCaP cells coeluted with synthetic NT standard. Metalloendopeptidase 3.4.24.15 activity was detected in PC-3, DU-145 and LNCaP cells, whereas high levels of neutral endopeptidase 3.4.24.1 1 activity was detected only in LNCaP cells. NT was relatively stable when incubated with PC-3 or D-145 cells but was rapidly degraded by LNCaP cells to NT1-11 and NT1-10. Phosphoramidon inhibited the metabolism of NT by LNCaP cells. These data suggest that NT is present in and metabolized by LNCaP cellular enzymes.

  12. Effect of NCAM-transfection on growth and invasion of a human cancer cell line

    DEFF Research Database (Denmark)

    Edvardsen, K; Bock, E; Jirus, S

    1997-01-01

    of modulating NCAM expression in vivo. In nude mice, NCAM-transfected cells developed tumors with longer latency periods and slower growth rates than tumors induced by NCAM-negative control cells, implying that NCAM may be involved not only in adhesive and motile behavior of tumor cells but also in their growth......-transfected cells. The fact that NCAM expression influences growth regulation attributes a pivotal role to this cell adhesion molecule during ontogenesis and tumor development.......A cDNA encoding the human transmembrane 140 kDa isoform of the neural cell adhesion molecule (NCAM) was transfected into the highly invasive MDA-MB-231 human breast cancer cell line. Transfectants with a homogeneous expression of NCAM showed a restricted capacity for penetration of an artificial...

  13. Reduction of the Earth's magnetic field inhibits growth rates of model cancer cell lines.

    Science.gov (United States)

    Martino, Carlos F; Portelli, Lucas; McCabe, Kevin; Hernandez, Mark; Barnes, Frank

    2010-12-01

    Small alterations in static magnetic fields have been shown to affect certain chemical reaction rates ex vivo. In this manuscript, we present data demonstrating that similar small changes in static magnetic fields between individual cell culture incubators results in significantly altered cell cycle rates for multiple cancer-derived cell lines. This change as assessed by cell number is not a result of apoptosis, necrosis, or cell cycle alterations. While the underlying mechanism is unclear, the implications for all cell culture experiments are clear; static magnetic field conditions within incubators must be considered and/or controlled just as one does for temperature, humidity, and carbon dioxide concentration. Copyright © 2010 Wiley-Liss, Inc.

  14. Dataset of curcumin derivatives for QSAR modeling of anti cancer against P388 cell line

    Directory of Open Access Journals (Sweden)

    Yum Eryanti

    2016-12-01

    Full Text Available The dataset of curcumin derivatives consists of 45 compounds (Table 1 with their anti cancer biological activity (IC50 against P388 cell line. 45 curcumin derivatives were used in the model development where 30 of these compounds were in the training set and the remaining 15 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA method. Based on the method, r2 value, r2 (CV value of 0.81, 0.67 were obtained. The QSAR model was also employed to predict the biological activity of compounds in the test set. Predictive correlation coefficient r2 values of 0.88 were obtained for the test set.

  15. Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle

    2015-01-01

    BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel...... with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient...

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

    Science.gov (United States)

    Sanchez-Martin, Manuel

    2008-09-01

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

  17. SU-F-T-678: Clotrimazole Sensitizes MCF-7 Breast Cancer Cell Line to Radiation

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    Garcia, L; Tambasco, M [San Diego State University, San Diego, CA (United States)

    2016-06-15

    Purpose: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. Methods: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT. Spectrophotometery was used to analyze the mitochondrial bound and soluble fraction of Hexokinase by means of relative enzymatic activity. Results: Our preliminary data have shown that CLT sensitizes MCF-7 cells to radiation in a dose and incubation time dependent manner up. We have also demonstrated that there are two radiosensitizing periods in MCF-7 cells with the first corresponding to the cycle arrest after 24 hours observed in other cell lines. The second radiosensitizing period occurs with incubation in CLT after irradiation which reaches maximum effect around 24 hours of incubation time. Preliminary data from our Hexokinase detachment assay show a factor of two increase in the ratio of unbound to bound Hexokinase when comparing incubation for 24 hours in media containing 0 and 20 µM CLT. Conclusion: This study and others indicate CLT as a possible radiosensitizing agent in cancer therapies. While CLT itself shows toxicity to the liver in high doses, this study further demonstrates that disruption of the Warburg Effect and unbinding of mitochondrial bound Hexokinase as a possible pathway for cancer treatment.

  18. Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line.

    Science.gov (United States)

    Goswamee, Priyodarshan; Pounardjian, Tamar; Giovannucci, David R

    2018-01-01

    Store-operated Ca 2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca 2+ entry that occurs in response to near-maximal depletion of Ca 2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca 2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca 2+ entry pathway in cancer cell migration has not been adequately assessed. The present study investigated the involvement of AA-induced Ca 2+ entry in migration in BON cells, a model gastro-enteropancreatic neuroendocrine tumor (GEPNET) cell line using pharmacological and gene knockdown methods in combination with live cell fluorescence imaging and standard migration assays. We showed that both the store-dependent and AA-induced Ca 2+ entry modes could be selectively activated and that exogenous administration of AA resulted in Ca 2+ entry that was pharmacologically distinct from SOCE. Also, whereas homomeric Orai1-containing channels appeared to largely underlie SOCE, the AA-induced Ca 2+ entry channel required the expression of Orai3 as well as Orai1. Moreover, we showed that AA treatment enhanced the migration of BON cells and that this migration could be abrogated by selective inhibition of the AA-induced Ca 2+ entry. Taken together, these data revealed that an alternative Orai3-dependent Ca 2+ entry pathway is an important signal for GEPNET cell migration.

  19. SU-F-T-678: Clotrimazole Sensitizes MCF-7 Breast Cancer Cell Line to Radiation

    International Nuclear Information System (INIS)

    Garcia, L; Tambasco, M

    2016-01-01

    Purpose: To study the effects of Clotrimazole (CLT) on radiosensitivity of MCF-7 Cells in correlation to detachment of Hexokinase II from the Voltage Dependent Anion Channel on the outer membrane of the mitochondria. Apoptotic fractions were also analyzed in relation to the detachment of Hexokinase. Methods: This study focused on the mammary adenocarcinoma cell line, MCF-7. Colony forming assays were used to analyze radiosensitization by CLT. Flow cytometry methods were used to analyze apoptotic vs necrotic fractions after treatment with CLT. Spectrophotometery was used to analyze the mitochondrial bound and soluble fraction of Hexokinase by means of relative enzymatic activity. Results: Our preliminary data have shown that CLT sensitizes MCF-7 cells to radiation in a dose and incubation time dependent manner up. We have also demonstrated that there are two radiosensitizing periods in MCF-7 cells with the first corresponding to the cycle arrest after 24 hours observed in other cell lines. The second radiosensitizing period occurs with incubation in CLT after irradiation which reaches maximum effect around 24 hours of incubation time. Preliminary data from our Hexokinase detachment assay show a factor of two increase in the ratio of unbound to bound Hexokinase when comparing incubation for 24 hours in media containing 0 and 20 µM CLT. Conclusion: This study and others indicate CLT as a possible radiosensitizing agent in cancer therapies. While CLT itself shows toxicity to the liver in high doses, this study further demonstrates that disruption of the Warburg Effect and unbinding of mitochondrial bound Hexokinase as a possible pathway for cancer treatment.

  20. The Apoptotic Effects of the P300 Activator on Breast Cancer and Lung Fibroblast Cell Lines

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Salahshoor

    2013-10-01

    Full Text Available Background: P300 is an enzyme that acetylates histones during stress. It alsoacetylates several non-histone proteins, including P53 which is the most important tumorsuppressor gene. P53 plays an important role in the apoptosis of tumor cells. Hereby,this study describes the potency of cholera toxin B subunit as a P300 activator to induceapoptosis in a breast cancer cell line (MCF-7 and a lung fibroblast cell line (MRC-5as a non-tumorigenic control sample. Methods: MCF-7 and MRC-5 were cultured in RPMI-1640 and treated with orwithout cholera toxin B subunit at the concentration of 85.43 μmol/L, based on the half-maximal inhibitory concentration index at different times (24, 48 and 72 h. Thepercentage of apoptotic cells was measured by flow cytometry. Real-time quantitativeRT-PCR was performed to estimate the mRNA expression of P300 in MCF-7 and MRC-5 with cholera toxin B subunit at different times. We used the ELISA and Bradford proteintechniques to detect levels of total and acetylated P53 protein generated in MCF-7 andMRC-5. Results: Our findings indicated that the cholera toxin B subunit effectively andsignificantly induced more apoptosis in MCF-7 compared to MRC-5. We showed thatexpression of P300 up-regulated by increasing the time of the cholera toxin B subunittreatment in MCF-7 but not in MRC-5. In addition, the acetylated and total P53protein levels increased more in MCF-7 cells than in MRC-5 cells.Conclusion: Cholera toxin B subunit induced significant cell death in MCF-7, butit could be well tolerated in MRC-5. Therefore, cholera toxin B subunit can besuggested as an anti-cancer agent.

  1. Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression.

    Science.gov (United States)

    Jehn, C F; Becker, B; Flath, B; Nogai, H; Vuong, L; Schmid, P; Lüftner, D

    2015-10-15

    Increased IL-6 and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. The objective was to assess the influence of BDNF and IL-6 on cognitive function and depression in patients with cancer. Serum BDNF and plasma IL-6 were measured in patients with metastatic cancer. Diagnosis of depression was established according to DSM-IV criteria. Cognitive function was assessed by the Verbal Learning and Memory Test (VLMT). A total of 59 patients were recruited in this study. Only IL-6 levels were significantly elevated in patients with clinical depression (35.7 vs. 6.9 pg/ml; pBDNF levels (p=0.16). Patients with clinical depression showed significant impairment of short-term memory (STM) (24.4 vs. 37.5; p=0.01), but not of long-term memory (LTM) (3.9 vs. 2.8; p=0.3). STM was dependent on the level of BDNF and younger age (b=0.60; p=0.001; b= -0.63; p=0.003, respectively). IL-6 was not only strongly associated with depression, but was an independent predictor of BDNF level as well (b= -0.50; p=0.01). LTM was associated only with a good KPS (b=0.47; p=0.037). Hemoglobin levels and the prior number of chemotherapy lines were not predictive of memory performance. Low BDNF is associated with cognitive impairment, STM, in patients with cancer, however no influence on depression could be found. IL-6 is strongly associated with depression and an independent predictor of BDNF levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Photodynamic effects of a novel pterin derivative on a pancreatic cancer cell line

    International Nuclear Information System (INIS)

    Yamada, Hiroko; Arai, Toshiyuki; Endo, Nobuyuki; Yamashita, Kouhei; Nonogawa, Mitsuru; Makino, Keisuke; Fukuda, Kazuhiko; Sasada, Masataka; Uchiyama, Takashi

    2005-01-01

    6-Formylpterin (6FP) has the potential to produce singlet oxygen ( 1 O 2 ) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the 1 O 2 generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate 1 O 2 to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable pterin derivatives has the potential for application in PDT

  3. Radiosensitization of C225 on human non-small cell lung cancer cell line H-520

    International Nuclear Information System (INIS)

    Zhang Yingdong; Wang Junjie; Liu Feng; Zhao Yong

    2008-01-01

    Objective: To investigate the efficacy of C225 (cetuximab), a chimeric human-mouse anti-epithelial growth factor receptor monoclonal antibody, combined with 60 Co gamma irradiation against human non-small cell lung cancer cell line H-520. Methods: H-520 cells were treated either with different dose of 60 Co irradiation (1,2,4,6,8 and 10 Gy)alone or together with C225 (100 nmol/L). Colony forming capacity was determined to create the survival curve 10 days after the treatment. Cells in different groups were harvested 72 hours after irradiation for apoptosis analysis or 48 hours after irradiation for cell cycle analysis by flow cytometry assay. Results: The clone number in combinational treatment group was less than that in irradiation only group, which suggested that the cell survival rate in the combinational treatment group was significantly decreased comparing with irradiation only group (F=6.36, P O + G 1 phases for C225 treatment, in G 2 + M phases for 60 Co irradiation, and in both G 0 + G 1 and G 2 + M phases for C225 in combination with 60 Co irradiation. Conclusions: C225 has radiosensitizing effects on H-520 cells, which may through the enhancement of 60 Co irradiation-induced cell death and cell cycle arrest. This study provides a supportive evidence for clinical treatment in non-small cell lung cancer. (authors)

  4. Effect of Evodiamine on Inducing Apoptosis of Human Gastric Cancer Cell Line SGC-7901 in Vitro

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    LIU Shao-ping

    2014-09-01

    Full Text Available Objective: To explore the proliferation inhibition and apoptosis-inducing effect of evodiamine in human gastric cancer SGC-7901 cells. Methods: After 48 or 24 h exposure to different concentrations of evodiamine, cell proliferation was analyzed using tetrazolium blue (MTT assay while apoptosis and cell-cycle phase distribution using flow cytometry. Results: In 0.01~30.00 μg/mL range of concentrations, evodiamine inhibited the proliferation of SGC-7901 cells in dose-dependent manner, and the overall mean IC50 was (3.79±0.16 μg/mL; the apoptosis rate was increased from 3.4% to 7.0%, 13.8% and 36.3% at concentrations of 0, 0.5, 1.5 and 30 μg/mL of evodiamine, respectively; the percentage of cells accumulated in G2/M phase was increased from 17.26% to 98.92% in the cells treated with evodiamine for 24 h in 0.01~30.00 μg/mL range of concentrations. Conclusion: Evodiamine can inhibit the proliferation, induce apoptosis in human gastric cancer cell line SGC-7901 in vitro and arrest the cell cycle at the G2/M phase.

  5. DNA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Yukihiro Furusawa

    Full Text Available Ultrasonic technologies pervade the medical field: as a long established imaging modality in clinical diagnostics; and, with the emergence of targeted high intensity focused ultrasound, as a means of thermally ablating tumours. In parallel, the potential of [non-thermal] intermediate intensity ultrasound as a minimally invasive therapy is also being rigorously assessed. Here, induction of apoptosis in cancer cells has been observed, although definitive identification of the underlying mechanism has thus far remained elusive. A likely candidate process has been suggested to involve sonochemical activity, where reactive oxygen species (ROS mediate the generation of DNA single-strand breaks. Here however, we provide compelling new evidence that strongly supports a purely mechanical mechanism. Moreover, by a combination of specific assays (neutral comet tail and staining for γH2AX foci formation we demonstrate for the first time that US exposure at even moderate intensities exhibits genotoxic potential, through its facility to generate DNA damage across multiple cancer lines. Notably, colocalization assays highlight that ionizing radiation and ultrasound have distinctly different signatures to their respective γH2AX foci formation patterns, likely reflecting the different stress distributions that initiated damage formation. Furthermore, parallel immuno-blotting suggests that DNA-PKcs have a preferential role in the repair of ultrasound-induced damage.

  6. Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line.

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    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.

  7. Cholesterol homeostasis in two commonly used human prostate cancer cell-lines, LNCaP and PC-3.

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    James Robert Krycer

    2009-12-01

    Full Text Available Recently, there has been renewed interest in the link between cholesterol and prostate cancer. It has been previously reported that in vitro, prostate cancer cells lack sterol-mediated feedback regulation of the major transcription factor in cholesterol homeostasis, sterol-regulatory element binding protein 2 (SREBP-2. This could explain the accumulation of cholesterol observed in clinical prostate cancers. Consequently, perturbed feedback regulation to increased sterol levels has become a pervasive concept in the prostate cancer setting. Here, we aimed to explore this in greater depth.After altering the cellular cholesterol status in LNCaP and PC-3 prostate cancer cells, we examined SREBP-2 processing, downstream effects on promoter activity and expression of SREBP-2 target genes, and functional activity (low-density lipoprotein uptake, cholesterol synthesis. In doing so, we observed that LNCaP and PC-3 cells were sensitive to increased sterol levels. In contrast, lowering cholesterol levels via statin treatment generated a greater response in LNCaP cells than PC-3 cells. This highlighted an important difference between these cell-lines: basal SREBP-2 activity appeared to be higher in PC-3 cells, reducing sensitivity to decreased cholesterol levels.Thus, prostate cancer cells are sensitive to changing sterol levels in vitro, but the extent of this regulation differs between prostate cancer cell-lines. These results shed new light on the regulation of cholesterol metabolism in two commonly used prostate cancer cell-lines, and emphasize the importance of establishing whether or not cholesterol homeostasis is perturbed in prostate cancer in vivo.

  8. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

    Science.gov (United States)

    Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

    2017-09-01

    For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit

  9. Non-Viral Transfection Methods Optimized for Gene Delivery to a Lung Cancer Cell Line

    Science.gov (United States)

    Salimzadeh, Loghman; Jaberipour, Mansooreh; Hosseini, Ahmad; Ghaderi, Abbas

    2013-01-01

    Background Mehr-80 is a newly established adherent human large cell lung cancer cell line that has not been transfected until now. This study aims to define the optimal transfection conditions and effects of some critical elements for enhancing gene delivery to this cell line by utilizing different non-viral transfection Procedures. Methods In the current study, calcium phosphate (CaP), DEAE-dextran, superfect, electroporation and lipofection transfection methods were used to optimize delivery of a plasmid construct that expressed Green Fluorescent Protein (GFP). Transgene expression was detected by fluorescent microscopy and flowcytometry. Toxicities of the methods were estimated by trypan blue staining. In order to evaluate the density of the transfected gene, we used a plasmid construct that expressed the Stromal cell-Derived Factor-1 (SDF-1) gene and measured its expression by real-time PCR. Results Mean levels of GFP-expressing cells 48 hr after transfection were 8.4% (CaP), 8.2% (DEAE-dextran), 4.9% (superfect), 34.1% (electroporation), and 40.1% (lipofection). Lipofection had the highest intense SDF-1 expression of the analyzed methods. Conclusion This study has shown that the lipofection and electroporation methods were more efficient at gene delivery to Mehr-80 cells. The quantity of DNA per transfection, reagent concentration, and incubation time were identified as essential factors for successful transfection in all of the studied methods. PMID:23799175

  10. Non-viral transfection methods optimized for gene delivery to a lung cancer cell line.

    Science.gov (United States)

    Salimzadeh, Loghman; Jaberipour, Mansooreh; Hosseini, Ahmad; Ghaderi, Abbas

    2013-04-01

    Mehr-80 is a newly established adherent human large cell lung cancer cell line that has not been transfected until now. This study aims to define the optimal transfection conditions and effects of some critical elements for enhancing gene delivery to this cell line by utilizing different non-viral transfection Procedures. In the current study, calcium phosphate (CaP), DEAE-dextran, superfect, electroporation and lipofection transfection methods were used to optimize delivery of a plasmid construct that expressed Green Fluorescent Protein (GFP). Transgene expression was detected by fluorescent microscopy and flowcytometry. Toxicities of the methods were estimated by trypan blue staining. In order to evaluate the density of the transfected gene, we used a plasmid construct that expressed the Stromal cell-Derived Factor-1 (SDF-1) gene and measured its expression by real-time PCR. Mean levels of GFP-expressing cells 48 hr after transfection were 8.4% (CaP), 8.2% (DEAE-dextran), 4.9% (superfect), 34.1% (electroporation), and 40.1% (lipofection). Lipofection had the highest intense SDF-1 expression of the analyzed methods. This study has shown that the lipofection and electroporation methods were more efficient at gene delivery to Mehr-80 cells. The quantity of DNA per transfection, reagent concentration, and incubation time were identified as essential factors for successful transfection in all of the studied methods.

  11. Effects of disulfiram on apoptosis in PANC-1 human pancreatic cancer cell line.

    Science.gov (United States)

    Dastjerdi, M Nikbakht; Babazadeh, Z; Rabbani, M; Gharagozloo, M; Esmaeili, A; Narimani, M

    2014-01-01

    Pancreatic carcinoma is currently considered as a rapidly progressive and fatal disease, and is typically diagnosed late in its natural course. It is characterized by a poor diagnosis and lack of response to conventional therapy. Recent studies have suggested that disulfiram (DSF), a member of the dithiocarbamate family, may have antitumor activity. This study aimed to evaluate the in vitro effect of DSF on apoptosis in human pancreatic cancerous cell line (PANC-1). PANC-1 cells were cultured and treated with DSF at doses of 5, 10, 13 μM for 24 h and apoptosis was measured. Methylation specific PCR (MS-PCR) and real-time quantitative PCR were carried out to detect the methylation pattern and to estimate the mRNA expression levels of RASSF1A, p21 and Bax. MS-PCR analysis demonstrated that no unmethylated band was apeared in PANC-1 cell line after DSF treatments. The real-time quantitative PCR results showed no significant mRNA expression for RASSF1A (p>0.05); whereas p21 and Bax expression were significantly (pPANC-1 through p21 and Bax pathway but not through RASSF1A.

  12. Experimental investigation of the cytotoxicity of medium-borne signals in human prostate cancer cell line

    International Nuclear Information System (INIS)

    Sjostedt, Svetlana; Bezak, Eva

    2012-01-01

    Introduction. Evidence exists that exposure of non-irradiated cells to Irradiated Cell Conditioned Medium (ICCM) can cause effects similar to those resulting from direct radiation damage. This study attempts to validate the stochastic model, relating absorbed dose to the emission and processing of cell death signals by non-irradiated cells, in vitro in PC3 human prostate cancer cell line. Methods. The recipient cell survival was measured after exposure of cells to ICMM derived from donor cells: a) exposed to radiation doses from 2 Gy to 8 Gy and b) of concentrations varying from 2 x 10 2 to 6 x 10 6 irradiated with 2 Gy. Results. Exposure to ICCM, irradiated with doses between 2-8 Gy, resulted in a significant (p 2 cells was significantly higher (p < 0.5) compared to the rest of donor cell concentrations, indicating that the toxicity of ICCM depends on the cellular concentration of donor cells. Non-linear regression data fitting provided reasonable agreement with the microdosimetric model for the induction of cell killing through medium-borne signals. Conclusion. For the given cell line and given experimental conditions, significant decreases in cell survival were observed in non-irradiated cells exposed to ICCM derived from donor cells of various concentrations and irradiated with different doses

  13. Tapirira guianensis Aubl. Extracts Inhibit Proliferation and Migration of Oral Cancer Cells Lines

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    Renato José Silva-Oliveira

    2016-11-01

    Full Text Available Cancer of the head and neck is a group of upper aerodigestive tract neoplasms in which aggressive treatments may cause harmful side effects to the patient. In the last decade, investigations on natural compounds have been particularly successful in the field of anticancer drug research. Our aim is to evaluate the antitumor effect of Tapirira guianensis Aubl. extracts on a panel of head and neck squamous cell carcinoma (HNSCC cell lines. Analysis of secondary metabolites classes in fractions of T. guianensis was performed using Nuclear Magnetic Resonance (NMR. Mutagenicity effect was evaluated by Ames mutagenicity assay. The cytotoxic effect, and migration and invasion inhibition were measured. Additionally, the expression level of apoptosis-related molecules (PARP, Caspases 3, and Fas and MMP-2 was detected using Western blot. Heterogeneous cytotoxicity response was observed for all fractions, which showed migration inhibition, reduced matrix degradation, and decreased cell invasion ability. Expression levels of MMP-2 decreased in all fractions, and particularly in the hexane fraction. Furthermore, overexpression of FAS and caspase-3, and increase of cleaved PARP indicates possible apoptosis extrinsic pathway activation. Antiproliferative activity of T. guianensis extract in HNSCC cells lines suggests the possibility of developing an anticancer agent or an additive with synergic activities associated with conventional anticancer therapy.

  14. Cytotoxic effects of new synthesis heterocyclic derivatives of Amoxicillin on some cancer cell lines

    Science.gov (United States)

    Al-Rawi, M. S.; Hussei, D. F.; Al-Taie, A. F.; Al-Halbosiy, M. M.; Hameed, B. A.

    2018-05-01

    A new Schiff base [I] was prepared by refluxing Amoxicillin trihydrate and 4-Hydroxy- 3,5-dimethoxybenzaldehyde in aqueous methanol solution using glacial acetic acid as a catalyst. The new 1,3-oxazepine derivative [II] was obtained by Diels- Alder reaction of Schiff base [I] with phthalic anhydride in dry benzene. The reaction of Schiff base [I] with thioglycolic acid in dry benzene led to the formation of thiazolidin-4-one derivative [III]. While the imidazolidin-4-one [IV] derivative was produced by reacting the mentioned Schiff base [I] with glycine and triethylamine in ethanol for 9 hrs. Tetrazole derivative [V] was synthesized by refluxing Schiff base [I] with sodium azide in dimethylformamid DMF. The structure of synthesized compounds[I-V] was characterized by their melting points, elemental analysis CHN-S and by their spectral data; FTIR and 1H NMR spectroscopy. Two cancer cell lines include: (RD) human pelvic rhabdomyosarcoma and (L20B) the mice intestines carcinoma cell line (which expresses the genes for human cellular receptor for Polio viruses) were used in this study. The cytotoxic effect of different concentrations of all the synthesized compounds for 48 hrs was examined. All compounds except [IV] and [V] showed less than 50% inhibition for (L20B), while these compounds exhibit inhibition more than 50% inhibition for (RD).

  15. Androgen responsiveness of the new human endometrial cancer cell line MFE-296.

    Science.gov (United States)

    Hackenberg, R; Beck, S; Filmer, A; Hushmand Nia, A; Kunzmann, R; Koch, M; Slater, E P; Schulz, K D

    1994-04-01

    MFE-296 endometrial cancer cells express androgen receptors in vitro. These cells, which are tumorigenic in nude mice, are derived from a moderately differentiated human endometrial adenocarcinoma. They express vimentin and the cytokeratins 7, 8, 18, and 19. Karyotyping revealed near-tetraploidy for most of the cells. No marker chromosomes were observed. DNA analyses confirmed the genetic identity of the cell line and the patient from whom the cell line was derived. Proliferation of MFE-296 cells was inhibited by the progestin R5020 and the androgen dihydrotestosterone (DHT). The inhibition of proliferation by DHT was antagonized by the antiandrogen Casodex, demonstrating the involvement of the androgen receptor. Androgen binding was determined at 22,000 binding sites per cell using a whole-cell assay (KD = 0.05 nM) and 30 fmol/mg protein with the dextran charcoal method; 7 fmol/mg protein of progesterone receptors were found, whereas estrogen receptors were below 5 fmol/mg protein. The androgen receptor was functionally intact, as demonstrated by transfection experiments with a reporter-gene construct, containing an androgen-responsive element. In MFE-296 cells the content of the androgen receptor was up-regulated by its own ligand.

  16. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines

    International Nuclear Information System (INIS)

    Bronzert, D.A.; Pantazis, P.; Antoniades, H.N.; Kasid, A.; Davidson, N.; Dickson, R.B.; Lippman, M.E.

    1987-01-01

    The authors report that human breast cancer cells secrete a growth factor that is biologically and immunologically similar to platelet-derived growth factor (PDGF). Serum-free medium conditioned by estrogen-independent MDA-MB-231 or estrogen-dependent MCF-7 cells contains a mitogenic or competence activity that is capable of inducing incorporation of [ 3 H] thymidine into quiescent Swiss 3T3 cells in the presence of platelet-poor plasma. Like authentic PDGF, the PDGF-like activity produced by breast cancer cells is stable after acid and heat treatment (95 0 C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of ≅30 kDa on NaDodSO 4 /polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO 4 /polyacrylamide gels identified proteins of 30 and 34 kDa. Upon reduction, the 30- and 34-kDa bands were converted to 15- and 16-kDa bands suggesting that the immunoprecipitated proteins were made up of two disulfide-linked polypeptides similar to PDGF. Hybridization studies with cDNA probes for the A chain PDGF and the B chain of PDGF/SIS identified transcripts for both PDGF chains in the MCF-7 and MDA-MB-231 cells. The data summarized above provide conclusive evidence for the synthesis and hormonally regulated secretion of a PDGF-like mitogen by breast carcinoma cells. Production of a PDGF-like growth factor by breast cancer cell lines may be important in mediating paracrine stimulation of tumor growth

  17. Uterine cervical cancer with brain metastasis as the initial site of presentation.

    Science.gov (United States)

    Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

    2015-07-01

    Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

  18. Irradiation effect on the apoptosis induction in the human cancer cell lines and the gingival fibroblast

    International Nuclear Information System (INIS)

    Park, Mu Soon; Lee, Sam Sun; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

    1998-01-01

    The radiation-induced apoptosis was studied for two human cancer cell lines (KB cells, RPMI 2650 cells) and the human gingival fibroblast cell line (HGF-1 cells). The single irradiation of 2, 10, 20 Gy was done with 241.5 cGy/min dose rate using the 137 Cs MK cell irradiator. The cell were stained with propidium iodide and examined under the fluoro-microscope and assayed with the flow cytometry a day after irradiation. Also, the LDH assay was done to determine the amount of necrotic cells. The obtained results were as follows : 1. On the fluoro-microscope, many fragmented nuclei were detected in the KB, RPMI 2650, and HGF-1 cells after irradiation. 2. On the DNA content histogram obtained from the flow cytometry, the percentages of the pre-G1 peak of the control and 2, 10 and 20 Gy irradiation group were 4.5, 55.0, 52.3, and 66.6% on KB cells, 2.7, 3.3, 31.8, and 32.6% on RPMI 2650 cells and 2.8, 21.8, 30.4, and 40.2% on HGF-1 cells respectively. 3. The number of G1-stage cells was abruptly decreased after 2 Gy irradiation on KB cells and 10 Gy irradiation on RPMI 2650 cells, But there was a slight decrease without regard to irradiation dose on HGF-1 cells. 4. There was no significantly different absorbance in extracellular LDH assay along the experimental cell lines

  19. Economic evaluation of first-line adjuvant chemotherapies for resectable gastric cancer patients in China.

    Science.gov (United States)

    Tan, Chongqing; Peng, Liubao; Zeng, Xiaohui; Li, Jianhe; Wan, Xiaomin; Chen, Gannong; Yi, Lidan; Luo, Xia; Zhao, Ziying

    2013-01-01

    First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown. The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer. A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed. For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%. Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

  20. Biologic characteristics of the side population of human small cell lung cancer cell line H446.

    Science.gov (United States)

    Wang, Bo; Yang, Huan; Huang, Yu-Zheng; Yan, Ru-Hong; Liu, Fen-Ju; Zhang, Jun-Ning

    2010-03-01

    Recently, the theory of cancer stem cells (CSCs) has presented new targets and orientations for tumor therapy. The major difficulties in researching CSCs include their isolation and purification. The aim of this study is to identify and characterize the side population (SP) cells in small cell lung cancer (SCLC) cell line H446, which lays the foundation for the isolation and purification of CSCs. Fluorescence-activated cell sorting (FACS) was used to sort SP and non-SP (NSP) cells from H446. Both subgroups were cultivated to survey the capacity to form into suspended tumor cell spheres. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR were used to evaluate the expression levels of the mRNA of CD133, ABCG2, and nucleostemin in both subgroups. The capacity of proliferation and the differences in drug resistance of both subgroups and unsorted cells were tested by the MTT method. The differentiation ability of both subgroups was determined by FACS. Proliferation was determined by subcutaneous tumor formation in nude mice. The percent of Hoechst 33342 negative cells was about (5.1 +/- 0.2)% in H446 by fluorescence microscopy. The percent of SP cells was (6.3 +/- 0.1)% by flow cytometry. SP cells had a stronger capability of forming into tumor spheres than NSP cells. The mRNA expression levels of ABCG2, CD133, and nucleostemin in SP cells were 21.60 +/- 0.26, 7.10 +/- 0.14, and 1.02 +/- 0.08 folds higher than that in NSP cells (P 0.05, respectively). In vivo, SP cells showed better proliferative ability and tougher viability when treated with drugs. SP cells can differentiate into NSP cells, but NSP cells cannot differentiate into SP cells. SP cells had a greater ability to form tumors. The H446 cell line contained some SP cells with stem cell properties. CD133 and ABCG2 may be cancer stem cell markers of SCLC.

  1. Comparison of lung cancer cell lines representing four histopathological subtypes with gene expression profiling using quantitative real-time PCR

    Directory of Open Access Journals (Sweden)

    Kawaguchi Makoto

    2010-01-01

    Full Text Available Abstract Background Lung cancers are the most common type of human malignancy and are intractable. Lung cancers are generally classified into four histopathological subtypes: adenocarcinoma (AD, squamous cell carcinoma (SQ, large cell carcinoma (LC, and small cell carcinoma (SC. Molecular biological characterization of these subtypes has been performed mainly using DNA microarrays. In this study, we compared the gene expression profiles of these four subtypes using twelve human lung cancer cell lines and the more reliable quantitative real-time PCR (qPCR. Results We selected 100 genes from public DNA microarray data and examined them by DNA microarray analysis in eight test cell lines (A549, ABC-1, EBC-1, LK-2, LU65, LU99, STC 1, RERF-LC-MA and a normal control lung cell line (MRC-9. From this, we extracted 19 candidate genes. We quantified the expression of the 19 genes and a housekeeping gene, GAPDH, with qPCR, using the same eight cell lines plus four additional validation lung cancer cell lines (RERF-LC-MS, LC-1/sq, 86-2, and MS-1-L. Finally, we characterized the four subtypes of lung cancer cell lines using principal component analysis (PCA of gene expression profiling for 12 of the 19 genes (AMY2A, CDH1, FOXG1, IGSF3, ISL1, MALL, PLAU, RAB25, S100P, SLCO4A1, STMN1, and TGM2. The combined PCA and gene pathway analyses suggested that these genes were related to cell adhesion, growth, and invasion. S100P in AD cells and CDH1 in AD and SQ cells were identified as candidate markers of these lung cancer subtypes based on their upregulation and the results of PCA analysis. Immunohistochemistry for S100P and RAB25 was closely correlated to gene expression. Conclusions These results show that the four subtypes, represented by 12 lung cancer cell lines, were well characterized using qPCR and PCA for the 12 genes examined. Certain genes, in particular S100P and CDH1, may be especially important for distinguishing the different subtypes. Our results

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

    Science.gov (United States)

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

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

  3. Monte Carlo calculations on efficiency of boron neutron capture therapy for brain cancer

    International Nuclear Information System (INIS)

    Awadalla, Galaleldin Mohamed Suliman

    2015-11-01

    The search for ways to treat cancer has led to many different treatments, including surgery, chemotherapy, and radiation therapy. Among these treatments, boron neutron capture therapy (BNCT) has shown promising results. BNCT is a radiotherapy treatment modality that has been proposed to treat brain cancer. In this technique, cancerous cells are being injected with 1 0B and irradiated by thermal neutrons to increase the probability of 1 0B (n, a)7 L i reaction to occur. This reaction can potentially deliver a high radiation dose sufficient to kill cancer cells by concentrating boron in them. The short rang of 1 0B (n, a) 7 L i reaction limits the damage to only cancerous cells without affecting healthy tissues. The effectiveness and safety of radiotherapy are dependent on the radiation dose delivered to the tumor and healthy tissues. In this thesis, after reviewing the basics and working principles of boron neutron capture therapy (BNCT), monte Carlo simulations were carried out to model a thermal neutron source suitable for BNCT and to examine the performance of proposed model when used to irradiate a sample of boron containing both 1 0B and 1 1B isotopes. MCNP5 code was used to examine the modeled neutron source through different shielding materials. The results were presented, analyzed and discussed at the end of the work. (author)

  4. Economic impact of simplified de Gramont regimen in first-line therapy in metastatic colorectal cancer.

    Science.gov (United States)

    Limat, Samuel; Bracco-Nolin, Claire-Hélène; Legat-Fagnoni, Christine; Chaigneau, Loic; Stein, Ulrich; Huchet, Bernard; Pivot, Xavier; Woronoff-Lemsi, Marie-Christine

    2006-06-01

    The cost of chemotherapy has dramatically increased in advanced colorectal cancer patients, and the schedule of fluorouracil administration appears to be a determining factor. This retrospective study compared direct medical costs related to two different de Gramont schedules (standard vs. simplified) given in first-line chemotherapy with oxaliplatin or irinotecan. This cost-minimization analysis was performed from the French Health System perspective. Consecutive unselected patients treated in first-line therapy by LV5FU2 de Gramont with oxaliplatin (Folfox regimen) or with irinotecan (Folfiri regimen) were enrolled. Hospital and outpatient resources related to chemotherapy and adverse events were collected from 1999 to 2004 in 87 patients. Overall cost was reduced in the simplified regimen. The major factor which explained cost saving was the lower need for admissions for chemotherapy. Amount of cost saving depended on the method for assessing hospital stay. In patients treated by the Folfox regimen the per diem and DRG methods found cost savings of Euro 1,997 and Euro 5,982 according to studied schedules; in patients treated by Folfiri regimen cost savings of Euro 4,773 and Euro 7,274 were observed, respectively. In addition, travel costs were also reduced by simplified regimens. The robustness of our results was showed by one-way sensitivity analyses. These findings demonstrate that the simplified de Gramont schedule reduces costs of current first-line chemotherapy in advanced colorectal cancer. Interestingly, our study showed several differences in costs between two costing approaches of hospital stay: average per diem and DRG costs. These results suggested that standard regimen may be considered a profitable strategy from the hospital perspective. The opposition between health system perspective and hospital perspective is worth examining and may affect daily practices. In conclusion, our study shows that the simplified de Gramont schedule in combination with

  5. SILENCING THE NUCLEOCYTOPLASMIC O-GLCNAC TRANSFERASE REDUCES PROLIFERATION, ADHESION AND MIGRATION OF CANCER AND FETAL HUMAN COLON CELL LINES

    Directory of Open Access Journals (Sweden)

    AGATA eSTEENACKERS

    2016-05-01

    Full Text Available The post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc is regulated by a unique couple of enzymes. O-GlcNAc transferase (OGT transfers the GlcNAc residue from UDP-GlcNAc, the final product of the hexosamine biosynthetic pathway (HBP, whereas O-GlcNAcase (OGA removes it. This study and others show that OGT and O-GlcNAcylation levels are increased in cancer cell lines. In that context we studied the effect of OGT silencing in the colon cancer cell lines HT29 and HCT116 and the primary colon cell line CCD841CoN. Herein we report that OGT silencing diminished proliferation, in vitro cell survival and adhesion of primary and cancer cell lines. SiOGT dramatically de-creased HT29 and CCD841CoN migration, CCD841CoN harboring high capabilities of mi-gration in Boyden chamber system when compared to HT29 and HCT116. The expression levels of actin and tubulin were unaffected by OGT knockdown but siOGT seemed to disor-ganize microfilament, microtubule and vinculin networks in CCD841CoN. While cancer cell lines harbor higher levels of OGT and O-GlcNAcylation to fulfill their proliferative and migra-tory properties, in agreement with their higher consumption of HBP main substrates glucose and glutamine, our data demonstrate that OGT expression is not only necessary for the biolog-ical properties of cancer cell lines but also for normal cells.

  6. Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.

    Directory of Open Access Journals (Sweden)

    Ivanna Ihnatovych

    Full Text Available Myosin IC is a single headed member of the myosin superfamily. We recently identified a novel isoform and showed that the MYOIC gene in mammalian cells encodes three isoforms (isoforms A, B, and C. Furthermore, we demonstrated that myosin IC isoform A but not isoform B exhibits a tissue specific expression pattern. In this study, we extended our analysis of myosin IC isoform expression patterns by analyzing the protein and mRNA expression in various mammalian cell lines and in various prostate specimens and tumor tissues from the transgenic mouse prostate (TRAMP model by immunoblotting, qRT-PCR, and by indirect immunohistochemical staining of paraffin embedded prostate specimen. Analysis of a panel of mammalian cell lines showed an increased mRNA and protein expression of specifically myosin IC isoform A in a panel of human and mouse prostate cancer cell lines but not in non-cancer prostate or other (non-prostate- cancer cell lines. Furthermore, we demonstrate that myosin IC isoform A expression is significantly increased in TRAMP mouse prostate samples with prostatic intraepithelial neoplasia (PIN lesions and in distant site metastases in lung and liver when compared to matched normal tissues. Our observations demonstrate specific changes in the expression of myosin IC isoform A that are concurrent with the occurrence of prostate cancer in the TRAMP mouse prostate cancer model that closely mimics clinical prostate cancer. These data suggest that elevated levels of myosin IC isoform A may be a potential marker for the detection of prostate cancer.

  7. Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Al-Asmari AK

    2016-10-01

    Full Text Available Abdulrahman Khazim Al-Asmari,1 Anvarbatcha Riyasdeen,1 Mohammad Hamed Al-Shahrani,2 Mozaffarul Islam1 1Research Center, 2Pediatric Hematology/Oncology and Bone Marrow Transplant Unit, Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia Abstract: Snake venom possesses various kinds of proteins and neurotoxic polypeptides, which can negatively interfere with the neurotransmitter signaling cascade. This phenomenon occurs mainly due to the blocking of ion channels in the body system. Envenomation prevents or severely interrupts nerve impulses from being transmitted, inhibition of adenosine triphosphate synthesis, and proper functioning of the cardiac muscles. However, some beneficial properties of venoms have also been reported. The aim of this study was to examine the snake venom as an anticancer agent due to its inhibitory effects on cancer progression such as cell motility, cell invasion, and colony formation. In this study, the effect of venoms on phenotypic changes and the change on molecular level in colorectal and breast cancer cell lines were examined. A reduction of 60%–90% in cell motility, colony formation, and cell invasion was observed when these cell lines were treated with different concentrations of snake venom. In addition, the increase in oxidative stress that results in an increase in the number of apoptotic cancer cells was significantly higher in the venom-treated cell lines. Further analysis showed that there was a decrease in the expression of pro-inflammatory cytokines and signaling proteins, strongly suggesting a promising role for snake venom against breast and colorectal cancer cell progression. In conclusion, the snake venoms used in this study showed significant anticancer properties against colorectal and breast cancer cell lines. Keywords: colorectal cancer, breast cancer, cell motility, colony formation, oxidative stress, apoptosis, IL-8, IL-6, RhoC, p-Erk1/2

  8. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

    2015-10-01

    The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: A case report

    Directory of Open Access Journals (Sweden)

    Wen-Chih Liu

    2012-05-01

    Full Text Available A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient’s neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.

  10. Brain Metastases from Breast Cancer and Response to Treatment with Eribulin: A Case Series

    Directory of Open Access Journals (Sweden)

    Alex Y. Chang

    2015-01-01

    Full Text Available Brain metastases are common in patients with advanced breast cancer (BC, causing considerable morbidity and mortality. Eribulin is a microtubule dynamics inhibitor approved for treating certain patients with metastatic BC, previously treated with an anthracycline and a taxane. In the 301 phase 3 study in 1102 women with advanced BC, eribulin and capecitabine treatments did not differ for co-primary endpoints (overall survival [OS]: 15.9 vs 14.5 months, P = 0.056; progression-free survival [PFS]: 4.1 vs 4.2 months, P = 0.30. Here, we report outcomes for six patients (eribulin, n = 3; capecitabine, n = 3 who had received treatment for brain metastases from BC (BCBM at baseline. All eribulin-treated patients experienced brain lesion shrinkage at some point during treatment, compared with one capecitabine-treated patient. Fewer patients in study 301 developed new BCBM with eribulin (13/544, 2.4% compared with capecitabine (25/546, 4.6%. Eribulin does not cross the healthy blood–brain barrier (BBB, but could have the potential to do so after cranial radiation therapy. Capecitabine may cross the BBB and has demonstrated activity in BCBM. Data from these patients and previous cases suggest that further investigation of eribulin for BCBM may be warranted.

  11. A delayed radiation necrosis of the brain in a patient with maxillary cancer

    International Nuclear Information System (INIS)

    Koike, Satoshi; Ogawa, Akihiro; Uno, Kinya; Okushi, Ikuyo; Inatsuki, Shinichi

    1987-01-01

    A 63-year-old male with maxillary cancer (T 4 N 0 M 0 ), who had been treated initially with 50 Gy of radiotherapy and 95 mg of Pepleomycin by intraarterial administration, was treated with 60 Gy of internal irradiation of Cesium source for the residual tumor. Furthermore, radical operation was performed to eradicate the tumor. A low density area (LDA) in the right temporal to occipital lobe of the brain was found by CT examination, when patient suffered from mental disturbance one year and 8 months postoperatively. Because a definite mass lesion could not be identified in the LDA, brain metastasis was ruled out. Patient was treated with a conservative medication using Glyceol, and his symptoms were successfully improved. (author)

  12. Next Generation Sequencing As an Aid to Diagnosis and Treatment of an Unusual Pediatric Brain Cancer

    Directory of Open Access Journals (Sweden)

    John Glod

    2014-07-01

    Full Text Available Classification of pediatric brain tumors with unusual histologic and clinical features may be a diagnostic challenge to the pathologist. We present a case of a 12-year-old girl with a primary intracranial tumor. The tumor classification was not certain initially, and the site of origin and clinical behavior were unusual. Genomic characterization of the tumor using a Clinical Laboratory Improvement Amendment (CLIA-certified next-generation sequencing assay assisted in the diagnosis and translated into patient benefit, albeit transient. Our case argues that next generation sequencing may play a role in the pathological classification of pediatric brain cancers and guiding targeted therapy, supporting additional studies of genetically targeted therapeutics.

  13. Urotensin-II receptor is over-expressed in colon cancer cell lines and in colon carcinoma in humans.

    Science.gov (United States)

    Federico, Alessandro; Zappavigna, Silvia; Romano, Marco; Grieco, Paolo; Luce, Amalia; Marra, Monica; Gravina, Antonietta Gerarda; Stiuso, Paola; D'Armiento, Francesco Paolo; Vitale, Giovanni; Tuccillo, Concetta; Novellino, Ettore; Loguercio, Carmela; Caraglia, Michele

    2014-01-01

    Urotensin (U)-II receptor (UTR) has been previously reported to be over-expressed in a number of tumours. Whether UTR-related pathway plays a role in colon carcinogenesis is unknown. We evaluated UTR protein and mRNA expression in human epithelial colon cancer cell lines and in normal colon tissue, adenomatous polyps and colon cancer. U-II protein expression was assessed in cancer cell lines. Moreover, we evaluated the effects of U-II(4-11) (an UTR agonist), antagonists and knockdown of UTR protein expression through a specific shRNA, on proliferation, invasion and motility of human colon cancer cells. Cancer cell lines expressed U-II protein and UTR protein and mRNA. By immunohistochemistry, UTR was expressed in 5-30% of epithelial cells in 45 normal controls, in 30-48% in 21 adenomatous polyps and in 65-90% in 48 colon adenocarcinomas. UTR mRNA expression was increased by threefold in adenomatous polyps and eightfold in colon cancer, compared with normal colon. U-II(4-11) induced a 20-40% increase in cell growth while the blockade of the receptor with specific antagonists caused growth inhibition of 20-40%. Moreover, the knock down of UTR with a shRNA or the inhibition of UTR with the antagonist urantide induced an approximately 50% inhibition of both motility and invasion. UTR appears to be involved in the regulation of colon cancer cell invasion and motility. These data suggest that UTR-related pathway may play a role in colon carcinogenesis and that UTR may function as a target for therapeutic intervention in colon cancer. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

  14. Carboplatin- and cisplatin-induced potentiation of moderate-dose radiation cytotoxicity in human lung cancer cell lines

    NARCIS (Netherlands)

    Groen, H. J.; Sleijfer, S.; Meijer, C.; Kampinga, H. H.; Konings, A. W. T.; de Vries, E. G. E.; Mulder, N. H.

    1995-01-01

    The interaction between moderate-dose radiation and cisplatin or carboplatin was studied in a cisplatin-sensitive (GLC(4)) and -resistant (GLC(4)-CDDP) human small-cell lung cancer cell line. Cellular toxicity was analysed under oxic conditions with the microculture tetrazolium assay. For the

  15. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

  16. Importance of blood cultures from peripheral veins in pediatric patients with cancer and a central venous line

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Møller, Jens Kjølseth; Rutkjaer, Cecilie

    2015-01-01

    When an infection is suspected in a child with cancer and a central venous line (CVL), cultures are often only obtained from the CVL and not from a peripheral vein (PV). This study was undertaken to evaluate the importance of concomitant blood cultures from the CVL and a PV....

  17. Correlation between live attenuated measles viral load and growth inhibition percentage in non-small cell lung cancer cell line

    Directory of Open Access Journals (Sweden)

    Rasha Fadhel Obaid

    2018-03-01

    Conclusion Live attenuated measles virus strain induced cytotoxic effect against human lung cancer cell line (A549 by induction of apoptosis as an important mechanism of anti-tumor activity, in addition, it indicates a correlation between the quantity of MV genomesand percentage of growth inhibition. This relation  has proved that measles virus had anticancer effect.

  18. Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology

    DEFF Research Database (Denmark)

    Popat, Sanjay; Mellemgaard, Anders; Reck, Martin

    2017-01-01

    PATIENTS & METHODS: We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer. RESULTS: Overall similarity of nintedanib + docetaxel versus ramucirumab + docetaxel...

  19. High hRFI expression correlates with resistance to Fluoro pyrimidines in human colon cancer cell lines and in xenografts

    International Nuclear Information System (INIS)

    Sasaki, S.; Tokyo Univ., Tokyo; Watanabe, T.; Konishi, T.; Kitayama, J.; Nagawa, H.; Kobunai, T.

    2005-01-01

    We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-α induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoro pyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue micro array consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy

  20. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Ge, Xiao-hui; Liu, Miao-ling; Lin, Qiang; Ren, Xiao-cang; Liu, Yue-e; Chen, Xue-ji; Wang, Dong-ying; Wang, Yong-qiang; Cao, Bin; Li, Zhi-gang

    2013-01-01

    Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ 2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ 2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ 2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent

  1. BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

    Science.gov (United States)

    Zavitsanos, Peter J; Wazer, David E; Hepel, Jaroslaw T; Wang, Yihong; Singh, Kamaljeet; Leonard, Kara L

    2018-05-18

    Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5