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Sample records for cancer growth influenced

  1. Insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth

    Institute of Scientific and Technical Information of China (English)

    Sarah K Johnson; Randy S Haun

    2009-01-01

    AIM: To investigate the functional significance of insulin-like growth factor binding protein-5 (IGFBP-5) overexpression in pancreatic cancer (PaC).METHODS: The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses.Changes in cell survival and signal transduction were evaluated after mitogen activated protein kinase and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.RESULTS: After serum depr ivat ion, IGFBP-5 expression increased both cell number and DNA synthesis in BxPC-3 cells, but reduced cell number in PANC-1 cells. Consistent with this observation, cell cycle analysis of IGFBP-5-expressing cells revealed accelerated cell cycle progression in BxPC-3 and G2/M arrest of PANC-1 cells. Signal transduction analysis revealed that Akt activation was increased in BxPC-3, but reduced in PANC-1 cells that express IGFBP-5. Inhibition of PI3K with LY294002 suppressed extracellular signal-regulated kinase-1 and -2 (ERK1/2) activation in BxPC-3, but enhanced ERK1/2 activation in PANC-1 cells that express IGFBP-5. When MEK1/2 was blocked, Akt activation remained elevated in IGFBP-5 expressing PaC cells; however, inhibition of PI3K or MEK1/2 abrogated IGFBP-5-mediated cell survival.CONCLUSION: These results indicate that IGFBP-5 expression affects the cell cycle and survival signal pathways and thus it may be an important mediator of PaC cell growth.

  2. Does growth hormone cause cancer?

    OpenAIRE

    Jenkins, P.J.; Mukherjee, A.; Shalet, S. M.

    2006-01-01

    KEYWORDS - CLASSIFICATION: adverse effects;Acromegaly;Adult;Animals;cancer epidemiology;complications;Child;Child Development;Colorectal Neoplasms;deficiency;epidemiology;etiology;Evaluation;Growth Hormone;Human Growth Hormone;Humans;Insulin-Like Growth Factor I;mechanisms of carcinogenesis;Neoplasm Recurrence,Local;Neoplasms;Neoplasms,Multiple Primary;physiology;physiopathology;Risk Factors;secretion;therapy. The ability of GH, via its mediator peptide IGF-1, to influence regulation of ce...

  3. Docetaxel Influences Autocrine of Transforming Growth Factors and Induces Apoptosis in Human Ovarian Cancer Cell Line AO

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Ya-li Hu; Yun-ying Cheng

    2006-01-01

    @@ Ovarian cancer is the second most common malignancy of female reproductive tract. Docetaxel shows good clinical efficacy against ovarian cancer.This present study was to investigate the role of docetaxel on apoptosis of ovarian cancer epithelial cell line AO as well as the secretion of transforming growth factor (TGF)-α and TGF-β1 during apoptosis.

  4. In vitro study of influence of raloxifene on the growth of human ovarian cancer cell line Skov 3

    Institute of Scientific and Technical Information of China (English)

    Wu Qin; Wu Yi-yong

    2004-01-01

    Objective: To study the effects of raloxifene on the growth of the human ovarian cancer cell line Skov3 and on the expression of cell proliferative antigen Ki-67 in vitro.Methods: The proliferative capacity of the ovarian cancer cell line Skov3 in the culture medium with raloxifene was evaluated by the microculture tetrazolium assay (MTT) and the expression of cell proliferation was appraised by the immunohistochemical staining of ki-67.Results: The growth of ovarian cancer cell line Skov3 was inhibited by raloxifene at high concentrations, while a trend of growth promotion at initial then followed by growth inhibition was found when raloxifene was at low concentrations. Raloxifene at high concentrations not only significantly reduced the expression of Ki-67 but also destroyed the cell structure.Conclusion: Raloxifene does not stimulate the growth of human ovarian cancer cell line Skov3significantly.

  5. Vascular endothelial growth factor, matrix metalloproteinases, and cyclooxygenase-2 influence prognosis of uterine cervical cancer in young women.

    Science.gov (United States)

    Noriyuki, Maiko; Sumi, Toshiyuki; Zhi, Xu; Misugi, Fumiko; Nobeyama, Hiroyuki; Yoshida, Hiroyuki; Matsumoto, Yoshinari; Yasui, Tomoyo; Honda, Ken-Ichi; Ishiko, Osamu

    2007-09-01

    Recent changes in the lifestyle of young women have led to an increase in the rate of uterine cervical cancer. We investigated the clinicopathological characteristics of uterine cervical cancer in young women, and examined the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). Tumor samples from 439 patients with uterine cervical cancer, who were initially treated at Osaka City University Medical School Hospital, Japan between 1995 and 2004, were stained immunohistochemically. The patients were classified into two groups according to age at onset: group Y included women aged or =36 years. Group Y had more cases of squamous cell carcinoma, while group O had more advanced cases (Pcervical cancer in young women.

  6. Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Cai ZX

    2016-06-01

    Full Text Available Zuxun Cai Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou City, People’s Republic of China Objective: To investigate the relationship between serum carcinoembryonic antigen (CEA level and epidermal growth factor receptor (EGFR gene mutations in non-small-cell lung cancer (NSCLC patients and to analyze the influence of CEA level on postoperative survival time in lung cancer patients. Methods: A total of 296 patients who were treated in Thoracic Surgery Department of Henan Provincial Chest Hospital from September 2011 to September 2013 were recruited. The level of tumor markers, such as CEA, was determined before the surgery, and EGFR gene mutations were detected after surgery. Thereby, the relationship between tumor makers, including CEA, and EGFR mutation and its influence on prognosis could be investigated. Results: Among 296 patients, the positive rate of EGFR gene mutation was 37.84% (112/296; the mutation occurred more frequently in nonsmokers, adenocarcinoma patients, women, and patients aged <60 years (P<0.05. Both tumor markers and chemosensitivity indicators were related to the profile of EGFR mutations. Elevated squamous cell carcinoma and Cyfra21-1 as well as positively expressed ERCC1 were more common in patients with wild-type EGFR (P<0.05, whereas increased CEA level was observed more frequently in patients with EGFR gene mutation (P=0.012. The positive rate of EGFR gene mutations was higher as the serum CEA level increased, that is, the positive rate in patients with serum CEA level <5, 5–20, and >20 µg/L was 39.81%, 45.32%, and 65.47%, respectively (P=0.004. Logistic regression analysis showed that CEA level was an independent factor in predicting EGFR gene mutations, and serum CEA level was also an independent factor in affecting the prognosis of NSCLC patients, as the overall 2-year survival rate was 73.86% in elevated CEA group and 86.43% in normal group (P<0.01. Conclusion: The prognosis of

  7. Escaping growth arrest in cancer

    NARCIS (Netherlands)

    Kortlever, R.M.

    2008-01-01

    We now have a general idea of which genes and cellular pathways are central in cancer development: uncontrolled growth governs establishment and spread of the disease. Nevertheless, to fully appreciate the consequences of the interplay of driver mutations in this genetic disease it is imperative we

  8. Influence of MSA on Cell Growth and Spontaneousn Metastasis of L9981-Luc Lung Cancer Transplanted Model in Nude Mice by Bioluminescence Imaging

    OpenAIRE

    Yuanrong REN; Wang, Yuli; Liu, Hongyu; YAN, HUIQIN; Chen, Jun; Hou, Mei; Li, Weimin; Yaguang FAN; Zhou, Qinghua

    2013-01-01

    Background and objective Methylseleninic acid (MSA) is an artificially developed selenium compound. It has been proven that MSA could inhibit growth and metastasis on many tumor cells. This study investigated whether MSA has an impact on the growth and metastasis of L9981-Luc lung cancer transplanted model in nude mice or not. Methods A transplantated tumor model was established in nude mice. Fifteen nude mice were randomly divided into three groups: the control group treated with normal sali...

  9. Leptin-Induced JAK/STAT Signaling and Cancer Growth

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    McKay Mullen

    2016-07-01

    Full Text Available Growth factor and cytokine signaling can influence the development of several cancer types. One of the key players in the development of cancer is the Janus kinas (JAK signal transducer of activators of transcription (STAT signaling pathway. The majority of growth factors and cytokine interactions with their membrane-bound receptors trigger JAK-STAT activation. The influential relationship between obesity and cancer is a fact. However, there is a complex sequence of events contributing to the regulation of this mechanism to promote tumor growth, yet to be fully elucidated. The JAK-STAT pathway is influenced by obesity-associated changes that have been shown to impact cancer growth and progression. This intricate process is highly regulated by a vast array of adipokines and cytokines that exert their pleiotropic effects on cancer cells to enhance metastasis to distant target sites. Leptin is a cytokine, or more precise, an adipokine secreted mainly by adipose tissue that requires JAK-STAT activation to exert its biological functions. Leptin is the central regulator of energy balance and appetite. Leptin binding to its receptor OB-R in turn activates JAK-STAT, which induces proliferation, angiogenesis, and anti-apoptotic events in normal cells and malignant cells expressing the receptor. Leptin also induces crosstalk with Notch and IL-1 (NILCO, which involves other angiogenic factors promoting tumor growth. Therefore, the existence of multiple novel classes of therapeutics that target the JAK/STAT pathway has significant clinical implications. Then, the identification of the signaling networks and factors that regulate the obesity-cancer link to which potential pharmacologic interventions can be implemented to inhibit tumor growth and metastasis. In this review, we will discuss the specific relationship between leptin-JAK-STAT signaling and cancer.

  10. Epidermal Growth Factor Receptor in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira-Cunha, Melissa, E-mail: melissacunha@doctors.org.uk [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Newman, William G. [Genetic Medicine, MAHSC, University of Manchester, St Mary' s Hospital, Oxford Road, Manchester, M13 9WL (United Kingdom); Siriwardena, Ajith K. [Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom)

    2011-03-24

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer.

  11. Growth of children with cancer

    NARCIS (Netherlands)

    Tamminga, Rienk Yde Johan

    1990-01-01

    The results of the present study indicate that it could be worthwhile for future researchers to study growth changes during very short periods of time using knemometry. This would enable them to differentiate more accurately the potentially adverse effect on growth of the separate components of the

  12. Norgestrel and gestodene stimulate breast cancer cell growth through an oestrogen receptor mediated mechanism.

    OpenAIRE

    Catherino, W. H.; Jeng, M. H.; Jordan, V.C.

    1993-01-01

    There is great concern over the long-term influence of oral contraceptives on the development of breast cancer in women. Oestrogens are known to stimulate the growth of human breast cancer cells, and this laboratory has previously reported (Jeng & Jordan, 1991) that the 19-norprogestin norethindrone could stimulate the proliferation of MCF-7 human breast cancer cells. We studied the influence of the 19-norprogestins norgestrel and gestodene compared to a 'non' 19-norprogestin medroxyprogester...

  13. Effect of acute exercise on prostate cancer cell growth.

    Science.gov (United States)

    Rundqvist, Helene; Augsten, Martin; Strömberg, Anna; Rullman, Eric; Mijwel, Sara; Kharaziha, Pedram; Panaretakis, Theocharis; Gustafsson, Thomas; Östman, Arne

    2013-01-01

    Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum) and after completed exercise (exercise serum). The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

  14. Effect of acute exercise on prostate cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Helene Rundqvist

    Full Text Available Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum and after completed exercise (exercise serum. The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

  15. Type 3 deiodinase: role in cancer growth, stemness and metabolism

    Directory of Open Access Journals (Sweden)

    Domenico eCiavardelli

    2014-12-01

    Full Text Available Deiodinases are selenoenzymes that catalyze thyroid hormones (THs activation (type 1 and type 2, D1 and D2 respectively or inactivation (type 3, D3. THs are essential for proper body development and cellular differentiation. Their intra- and extra-cellular concentrations are tightly regulated by deiodinases with a pre-receptorial control thus generating active or inactive form of THs. Changes in deiodinases expression are anatomically and temporally regulated and influence the downstream TH signaling. D3 overexpression is a feature of proliferative tissues such as embryo or cancer tissues. The enhanced TH degradation by D3 induces a local hypothyroidism thus inhibiting THs transcriptional activity. Of note, overexpression of D3 is a feature of several highly proliferative cancers. In this paper we review recent advances in the role of D3 in cancer growth, stemness and metabolic phenotype. In particular we focus on the main signalling pathways that result in the overexpression of D3 in cancer cells and are known to be relevant to cancer development, progression, and recurrence. We also discuss the potential role of D3 in cancer stem cells metabolic phenotype, an emerging topic in cancer research.

  16. Lifetime growth and risk of testicular cancer.

    Science.gov (United States)

    Richiardi, Lorenzo; Vizzini, Loredana; Pastore, Guido; Segnan, Nereo; Gillio-Tos, Anna; Fiano, Valentina; Grasso, Chiara; Ciuffreda, Libero; Lista, Patrizia; Pearce, Neil; Merletti, Franco

    2014-08-01

    Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (testicular cancer for tall (>180 cm) vs. short (testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence.

  17. Growth Laws in Cancer: Implications for Radiotherapy

    CERN Document Server

    Castorina, P; Gabriele, P; Guiot, C

    2006-01-01

    Comparing both, the more conventional Gompertz tumor growth law (GL) and the ``Universal'' law (UL), recently proposed and applied to cancer,we have investigated the growth law's implications on various radiotherapy regimen. According to GL, the surviving tumor cell fraction could be reduced 'ad libidum', independently of the initial tumor mass,simply by increasing the number of treatments. On the contrary, if tumor growth dynamics would indeed follow the Universal scaling law, there is a lower limit of the survival fraction that cannot be reduced any further regardless of the total number of treatments. This finding can explain the so called ``tumor size effect'' and re-emphasizes the importance of early diagnosis as it implies that radiotherapy may be successful provided the tumor mass at treatment onset is rather small. Taken together with our previous works, implications of these findings include revisiting standard radiotherapy regimen and overall treatment protocols.

  18. Polymorphisms in the insulin-like growth factor axis are associated with gastrointestinal cancer

    NARCIS (Netherlands)

    Ong, J.; Salomon, J.; Morsche, R.H.M. te; Roelofs, H.M.J.; Witteman, B.J.; Dura, P.; Lacko, M.; Peters, W.H.M.

    2014-01-01

    INTRODUCTION: Numerous factors influence the development of gastrointestinal (GI) cancer. The insulin-like growth factor (IGF) axis plays a role in embryonic and postnatal growth and tissue repair. Elevated levels of IGFs, low levels of IGF binding proteins (IGFBPs) and over-expression of IGF recept

  19. VEGF and colon cancer growth beyond angiogenesis: does VEGF directly mediate colon cancer growth via a non-angiogenic mechanism?

    Science.gov (United States)

    Ahluwalia, Amrita; Jones, Michael K; Matysiak-Budnik, Tamara; Tarnawski, Andrzej S

    2014-01-01

    In this article we review the role of vascular endothelial growth factor (VEGF) in colon cancer growth and the underlying mechanisms. Angiogenesis, the growth of new capillary blood vessels in the body, is critical for tissue injury healing and cancer growth. In 1971, Judah Folkman proposed the concept that tumor growth beyond 2 mm is critically dependent on angiogenesis. Tumors including colon cancers release angiogenic growth factors that stimulate blood vessels to grow into the tumors thus providing oxygen and nutrients that enable exponential growth. VEGF is the most potent angiogenic growth factor. Several studies have highlighted the role of VEGF in colon cancer, specifically in the stimulation of angiogenesis. This role of VEGF is strongly supported by studies showing that inhibition of VEGF using the blocking antibody, bevacizumab, results in decreased angiogenesis and abrogation of cancer growth. In the United States, bevacizumab in combination with chemotherapy is FDA approved for the treatment of metastatic colon cancer. However, the source of VEGF in colon cancer tissue, the mechanisms of VEGF generation in colon cancer cells and the molecular pathways involved in VEGF mediated angiogenesis in colon cancer are not fully known. The possibility that VEGF directly stimulates cancer cell growth in an autocrine manner has not been explored in depth.

  20. Genetic Influences on Growth Traits of BMI

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob V B; Fagnani, Corrado; Silventoinen, Karri;

    2008-01-01

    Objective:To investigate the interplay between genetic factors influencing baseline level and changes in BMI in adulthood.Methods and Procedures:A longitudinal twin study of the cohort of Finnish twins (N = 10,556 twin individuals) aged 20-46 years at baseline was conducted and followed up 15 years....... Data on weight and height were obtained from mailed surveys in 1975, 1981, and 1990.Results:Latent growth models revealed a substantial genetic influence on BMI level at baseline in males and females (heritability (h(2)) 80% (95% confidence interval 0.79-0.80) for males and h(2) = 82% (0.81, 0.......84) for females) and a moderate-to-high influence on rate of change in BMI (h(2) = 58% (0.50, 0.69) for males and h(2) = 64% (0.58, 0.69) for females). Only very weak evidence for genetic pleiotropy was observed; the genetic correlation between baseline and rate of change in BMI was very modest (-0.070 (-0.13, -0...

  1. Simulating cancer growth with multiscale agent-based modeling.

    Science.gov (United States)

    Wang, Zhihui; Butner, Joseph D; Kerketta, Romica; Cristini, Vittorio; Deisboeck, Thomas S

    2015-02-01

    There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models.

  2. Blood Type Influences Pancreatic Cancer Risk | Division of Cancer Prevention

    Science.gov (United States)

    A variation in the gene that determines ABO blood type influences the risk of pancreatic cancer, according to the results of the first genome-wide association study (GWAS) for this highly lethal disease. The genetic variation, a single nucleotide polymorphism (SNP), was discovered in a region of chromosome 9 that harbors the gene that determines blood type, the researchers reported August 2 online in Nature Genetics. |

  3. 水杨酸对人肝癌HepG2细胞体外生长的影响的研究*%Influence of Salicylic Acid on Human Hepatic Cancer HepG2 Cells Growth In-vitro

    Institute of Scientific and Technical Information of China (English)

    林冰; 郎锦义; 雷晴

    2014-01-01

    Objective: Salicylic acid ( SA) and its derivatives have been shown to induce apoptosis in a variety of cancer cells. The aim of this study is to investigate influence of SA on human hepatic cancer HepG2 cells growth in-vitro. Methods:MTT assay was used to determine the effect of SA on viability of HepG2 cells, EdU assay was used to detect the impact of SA on the proliferation activity of HepG2 cells, and the cell cycle progress altered and apoptosis of HepG2 cells induced by SA were determined using flow cytometry ( FCM) . Results:SA reduced significantly viability of hepatic cancer HepG2 cells in a concentration-dependent manner and had an IC50 value of (8. 92 ± 0. 45)mmol/L;EdU assay showed that the red fluorescence produced by incorporation of EdU decreased in HepG2 cells treated with SA for 24hr, thereby depress-ing the proliferation activity of HepG2 cells;FCM assay showed that compared to control, SA induced obviously cell cycle G0/G1-phase arrest ( 65. 5% ± 1. 21% vs. 34. 3% ± 0. 89%, P <0. 05 ) and delayed in entering S phase 24. 2% ± 0. 89% vs. 44. 0% ± 0. 64%, P<0. 05), and promoted apoptosis in HepG2 cells(24. 9% ± 0. 32% vs. 2. 3% ± 0. 11%, P<0. 05). Conclusion:SA would inhibits the growth of HepG2 cells by altering cell cycle progress, depressing prolifera-tion activity and promoting cell apoptosis.%目的:探讨水杨酸( salicylic acid, SA)对人肝癌HepG2细胞体外生长的影响。方法:利用MTT法测定SA对HepG2细胞存活性的作用;利用EdU法检测SA对HepG2细胞增殖活性的影响;利用流式细胞分析法测定SA诱导的HepG2细胞周期进程和凋亡。结果:SA显著且呈浓度依赖的降低人肝癌HepG2细胞的存活率,其半数抑制浓度(IC50)为(8.92±0.45)mmol/L;EdU分析显示,SA作用24hr,EdU掺入的红色荧光强度明显减弱,降低了HepG2细胞的增殖活性;FCM分析显示,与对照比较,SA诱导HepG2细胞周期阻滞于G0/G1期(65.5%±1.21%vs.34.3%±0.89%, P<0.05

  4. Pumpkin Fruit Influence on Calves’ Growth

    Directory of Open Access Journals (Sweden)

    A. SHIMKUS

    2014-07-01

    Full Text Available Pumpkin provides a valuable source of carotenoids and ascorbic acid which have major roles in nutrition as provitamin A and as an antioxidant respectively. Carotenoids are a source of vitamin A, and β-carotene present in pumpkin is converted to vitamin A in the body. Pumpkins’ biomass is distinguished for having antioxidant and phytobiotic characteristics.The aim of our research is to analyse pumpkin fruit (Cucurbita maxima D. flours’ influence upon calves growth, intestinal microflora, digestibility of rations’ nutrients and health. In pursuance of this aim two groups of 1-month-old Lithuanian Black and White breeds’ heifers were constituted, 10 animals per group: control and experimental. The heifers were fed by the same feeding plan and grown in equal conditions. Except for experimental groups’ animals, each of them was additionally given 120g of pumpkin fruits’ flour with their days’ ration.The results of this research showed that calves which were additionally given pumpkin fruits‘ flour had grown more rapidly. After six months of the research the weight of experimental groups‘ heifers was 9,2 kg or 5,34 pct. bigger than the weight of control groups‘ heifers. Pumpkin fruits‘ flour distinguished for phytobiotic activity in calves‘ intestine, it stimulated the increase of lacto- and bifidobacteria. After four months of the research there were 63,6 pct. (P<0,001 more lactobacteria and 19,3 pct. (P<0,01 more bifidobacteria in the faeces of heifers that were additionally given pumpkin fruits‘ flour comparing to heifers that were not given it. After 6 months of the research respectively there were 10,7 pct. and 34,0 pct. more of lacto- and bifidobacteria. Besides that, pumpkin fruits‘ flour improved digestibility of rations‘ nutrients. Digestibility of dry matter increased by 1,9 pct., organic matter – 2,3 pct., fat – 1,6 pct., proteins – 3,07 pct. (P>0,05. Morphological blood indexes of both calves groups

  5. [Do enkephalins and other endogenous opioids participate in regulation of cancer growth?].

    Science.gov (United States)

    Kajdaniuk, D; Marek, B; Buntner, B; Zwirska-Korczala, K

    2000-01-01

    Attempts are interesting exploratory trend to define precisely relations between endogenous opioid system and neoplastic process development. Mechanism in which enkephalins and other endogenous opioides could influence on cancer growth is not clear. Several hypothesis were put and presented in the paper.

  6. Endocrine fibroblast growth factor FGF19 promotes prostate cancer progression.

    Science.gov (United States)

    Feng, Shu; Dakhova, Olga; Creighton, Chad J; Ittmann, Michael

    2013-04-15

    Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require α-Klotho (KL) and/or β-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting.

  7. Notch pathway promotes ovarian cancer growth and migration via CXCR4/SDF1α chemokine system.

    Science.gov (United States)

    Chiaramonte, R; Colombo, M; Bulfamante, G; Falleni, M; Tosi, D; Garavelli, S; De Simone, D; Vigolo, E; Todoerti, K; Neri, A; Platonova, N

    2015-09-01

    Ovarian cancer is the most deadly gynecological malignancy. Understanding the molecular pathogenesis of ovarian cancer is critical to provide new targeted therapeutic strategies. Recent evidence supports a role for Notch in ovarian cancer progression and associates its dysregulation to poor overall survival. Similarly, CXCR4/SDF1α signalling correlates with ovarian cancer progression and metastasis. Recent findings indicate that Notch promotes CXCR4/SDF1α signalling and its effect on cell growth and migration; nonetheless, up to now, the association between Notch and CXCR4/SDFα in ovarian cancer has not been reported. Thereby, the aim of this study was to investigate if Notch and CXCR4/SDF1α cooperate in determining ovarian cancer growth, survival and migration. To address this issue, Notch signalling was inhibited by using γ-secretase inhibitors, or upregulated by forcing of Notch1 expression in ovarian cancer cell lines. Our results indicated that Notch activity influenced tumour cell growth and survival and positively regulated CXCR4 and SDF1α expression. CXCR4/SDF1α signalling mediated the effect of Notch pathway on ovarian cancer cell growth and SDF1α-driven migration. Additionally, for the first time, we demonstrated that Notch signalling activation can be detected in ovarian cancer specimens by immunohistochemistry analysis of the Notch transcriptional target, HES6 and is positively correlated with high expression levels of CXCR4 and SDF1α. Our results demonstrate that Notch affects ovarian cancer cell biology through the modulation of CXCR4/SDF1α signalling and suggest that Notch inhibition may be a rationale therapeutic approach to hamper ovarian cancer progression mediated by the CXCR4/SDF1α axis.

  8. The possible effect of diazepam on cancer development and growth.

    Science.gov (United States)

    Horrobin, D F; Trosko, J E

    1981-01-01

    Diazepam has the characteristics of a tumour promoter in a number of in vitro systems. The effect is apparent at concentrations of diazepam which are clinically relevant. Diazepam also accelerated tumour growth in two different experimental animal cancers. Tranquillizer use was found to be greater in women with metastatic breast cancer at the time of diagnosis than in those without metastases. Further evaluation of the possible effects of diazepam and related drugs on human and animal cancers is urgently required.

  9. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  10. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P; Barten, AD; Van Waarde, MAWH; Vujaskovic, Z; Van Tienhoven, G

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGF beta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and activ

  11. Embryonic morphogen nodal promotes breast cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Daniela F Quail

    Full Text Available Breast cancers expressing human embryonic stem cell (hESC-associated genes are more likely to progress than well-differentiated cancers and are thus associated with poor patient prognosis. Elevated proliferation and evasion of growth control are similarly associated with disease progression, and are classical hallmarks of cancer. In the current study we demonstrate that the hESC-associated factor Nodal promotes breast cancer growth. Specifically, we show that Nodal is elevated in aggressive MDA-MB-231, MDA-MB-468 and Hs578t human breast cancer cell lines, compared to poorly aggressive MCF-7 and T47D breast cancer cell lines. Nodal knockdown in aggressive breast cancer cells via shRNA reduces tumour incidence and significantly blunts tumour growth at primary sites. In vitro, using Trypan Blue exclusion assays, Western blot analysis of phosphorylated histone H3 and cleaved caspase-9, and real time RT-PCR analysis of BAX and BCL2 gene expression, we demonstrate that Nodal promotes expansion of breast cancer cells, likely via a combinatorial mechanism involving increased proliferation and decreased apopotosis. In an experimental model of metastasis using beta-glucuronidase (GUSB-deficient NOD/SCID/mucopolysaccharidosis type VII (MPSVII mice, we show that although Nodal is not required for the formation of small (<100 cells micrometastases at secondary sites, it supports an elevated proliferation:apoptosis ratio (Ki67:TUNEL in micrometastatic lesions. Indeed, at longer time points (8 weeks, we determined that Nodal is necessary for the subsequent development of macrometastatic lesions. Our findings demonstrate that Nodal supports tumour growth at primary and secondary sites by increasing the ratio of proliferation:apoptosis in breast cancer cells. As Nodal expression is relatively limited to embryonic systems and cancer, this study establishes Nodal as a potential tumour-specific target for the treatment of breast cancer.

  12. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk.

    Science.gov (United States)

    Clayton, Peter E; Banerjee, Indraneel; Murray, Philip G; Renehan, Andrew G

    2011-01-01

    Growth hormone (GH), insulin-like growth factor (IGF)-I and insulin have potent growth-promoting and anabolic actions. Their potential involvement in tumor promotion and progression has been of concern for several decades. The evidence that GH, IGF-I and insulin can promote and contribute to cancer progression comes from various sources, including transgenic and knockout mouse models and animal and human cell lines derived from cancers. Assessments of the GH-IGF axis in healthy individuals followed up to assess cancer incidence provide direct evidence of this risk; raised IGF-I levels in blood are associated with a slightly increased risk of some cancers. Studies of human diseases characterized by excess growth factor secretion or treated with growth factors have produced reassuring data, with no notable increases in de novo cancers in children treated with GH. Although follow-up for the vast majority of these children does not yet extend beyond young adulthood, a slight increase in cancers in those with long-standing excess GH secretion (as seen in patients with acromegaly) and no overall increase in cancer with insulin treatment, have been observed. Nevertheless, long-term surveillance for cancer incidence in all populations exposed to increased levels of GH is vitally important.

  13. Alpha2-Adrenergic Receptors and Breast Tumor Stroma: A Novel Pathway Driving Breast Cancer Growth and Metastasis

    Science.gov (United States)

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0439 TITLE: Alpha2-Adrenergic Receptors and Breast Tumor Stroma: A Novel Pathway Driving Breast Cancer Growth and...treatment of breast cancer often experience severe and chronic psychological stress. The sympathetic nervous system (SNS) is an important pathway by which...Sephton SE, McDonald PG, et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer . 2006;6:240-8. 3

  14. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Doherty, Jennifer A; Van Den Berg, David J

    2011-01-01

    The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial...... as an important gene for ovarian cancer; additional genotyping is warranted to further confirm these associations with IGF2 and to narrow down the region harboring the causal SNP....

  15. A computational model for cancer growth by using complex networks

    Science.gov (United States)

    Galvão, Viviane; Miranda, José G. V.

    2008-09-01

    In this work we propose a computational model to investigate the proliferation of cancerous cell by using complex networks. In our model the network represents the structure of available space in the cancer propagation. The computational scheme considers a cancerous cell randomly included in the complex network. When the system evolves the cells can assume three states: proliferative, non-proliferative, and necrotic. Our results were compared with experimental data obtained from three human lung carcinoma cell lines. The computational simulations show that the cancerous cells have a Gompertzian growth. Also, our model simulates the formation of necrosis, increase of density, and resources diffusion to regions of lower nutrient concentration. We obtain that the cancer growth is very similar in random and small-world networks. On the other hand, the topological structure of the small-world network is more affected. The scale-free network has the largest rates of cancer growth due to hub formation. Finally, our results indicate that for different average degrees the rate of cancer growth is related to the available space in the network.

  16. Factors Influencing Colorectal Cancer Screening Participation

    Directory of Open Access Journals (Sweden)

    Antonio Z. Gimeno García

    2012-01-01

    Full Text Available Colorectal cancer (CRC is a major health problem worldwide. Although population-based CRC screening is strongly recommended in average-risk population, compliance rates are still far from the desirable rates. High levels of screening uptake are necessary for the success of any screening program. Therefore, the investigation of factors influencing participation is crucial prior to design and launches a population-based organized screening campaign. Several studies have identified screening behaviour factors related to potential participants, providers, or health care system. These influencing factors can also be classified in non-modifiable (i.e., demographic factors, education, health insurance, or income and modifiable factors (i.e., knowledge about CRC and screening, patient and provider attitudes or structural barriers for screening. Modifiable determinants are of great interest as they are plausible targets for interventions. Interventions at different levels (patient, providers or health care system have been tested across the studies with different results. This paper analyzes factors related to CRC screening behaviour and potential interventions designed to improve screening uptake.

  17. Sulindac Sulfide, but Not Sulindac Sulfone, Inhibits Colorectal Cancer Growth

    Directory of Open Access Journals (Sweden)

    Christopher S. Williams

    1999-06-01

    Full Text Available Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

  18. FH535 inhibited migration and growth of breast cancer cells.

    Science.gov (United States)

    Iida, Joji; Dorchak, Jesse; Lehman, John R; Clancy, Rebecca; Luo, Chunqing; Chen, Yaqin; Somiari, Stella; Ellsworth, Rachel E; Hu, Hai; Mural, Richard J; Shriver, Craig D

    2012-01-01

    There is substantial evidence indicating that the WNT signaling pathway is activated in various cancer cell types including breast cancer. Previous studies reported that FH535, a small molecule inhibitor of the WNT signaling pathway, decreased growth of cancer cells but not normal fibroblasts, suggesting this pathway plays a role in tumor progression and metastasis. In this study, we tested FH535 as a potential inhibitor for malignant phenotypes of breast cancer cells including migration, invasion, and growth. FH535 significantly inhibited growth, migration, and invasion of triple negative (TN) breast cancer cell lines (MDA-MB231 and HCC38) in vitro. We demonstrate that FH535 was a potent growth inhibitor for TN breast cancer cell lines (HCC38 and MDA-MB-231) but not for other, non-TN breast cancer cell lines (MCF-7, T47D or SK-Br3) when cultured in three dimensional (3D) type I collagen gels. Western blotting analyses suggest that treatment of MDA-MB-231 cells with FH535 markedly inhibited the expression of NEDD9 but not activations of FAK, Src, or downstream targets such as p38 and Erk1/2. We demonstrated that NEDD9 was specifically associated with CSPG4 but not with β1 integrin or CD44 in MDA-MB-231 cells. Analyses of gene expression profiles in breast cancer tissues suggest that CSPG4 expression is higher in Basal-type breast cancers, many of which are TN, than any other subtypes. These results suggest not only a mechanism for migration and invasion involving the canonical WNT-signaling pathways but also novel strategies for treating patients who develop TN breast cancer.

  19. FH535 inhibited migration and growth of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Joji Iida

    Full Text Available There is substantial evidence indicating that the WNT signaling pathway is activated in various cancer cell types including breast cancer. Previous studies reported that FH535, a small molecule inhibitor of the WNT signaling pathway, decreased growth of cancer cells but not normal fibroblasts, suggesting this pathway plays a role in tumor progression and metastasis. In this study, we tested FH535 as a potential inhibitor for malignant phenotypes of breast cancer cells including migration, invasion, and growth. FH535 significantly inhibited growth, migration, and invasion of triple negative (TN breast cancer cell lines (MDA-MB231 and HCC38 in vitro. We demonstrate that FH535 was a potent growth inhibitor for TN breast cancer cell lines (HCC38 and MDA-MB-231 but not for other, non-TN breast cancer cell lines (MCF-7, T47D or SK-Br3 when cultured in three dimensional (3D type I collagen gels. Western blotting analyses suggest that treatment of MDA-MB-231 cells with FH535 markedly inhibited the expression of NEDD9 but not activations of FAK, Src, or downstream targets such as p38 and Erk1/2. We demonstrated that NEDD9 was specifically associated with CSPG4 but not with β1 integrin or CD44 in MDA-MB-231 cells. Analyses of gene expression profiles in breast cancer tissues suggest that CSPG4 expression is higher in Basal-type breast cancers, many of which are TN, than any other subtypes. These results suggest not only a mechanism for migration and invasion involving the canonical WNT-signaling pathways but also novel strategies for treating patients who develop TN breast cancer.

  20. Meaning Making and Psychological Adjustment following Cancer: The Mediating Roles of Growth, Life Meaning, and Restored Just-World Beliefs

    Science.gov (United States)

    Park, Crystal L.; Edmondson, Donald; Fenster, Juliane R.; Blank, Thomas O.

    2008-01-01

    Cancer survivors' efforts at meaning making may influence the extent to which they successfully make meaning from their experience (i.e., experience posttraumatic growth, find life meaningful, and restore beliefs in a just world), which may, in turn, influence their psychological adjustment. Previous research regarding both meaning making…

  1. Growth-stimulatory effect of resveratrol in human cancer cells.

    Science.gov (United States)

    Fukui, Masayuki; Yamabe, Noriko; Kang, Ki Sung; Zhu, Bao Ting

    2010-08-01

    Earlier studies have shown that resveratrol could induce death in several human cancer cell lines in culture. Here we report our observation that resveratrol can also promote the growth of certain human cancer cells when they are grown either in culture or in athymic nude mice as xenografts. At relatively low concentrations (cells, but this effect was not observed in several other human cell lines tested. Analysis of cell signaling molecules showed that resveratrol induced the activation of JNK, p38, Akt, and NF-kappaB signaling pathways in these cells. Further analysis using pharmacological inhibitors showed that only the NF-kappaB inhibitor (BAY11-7082) abrogated the growth-stimulatory effect of resveratrol in cultured cells. In athymic nude mice, resveratrol at 16.5 mg/kg body weight enhanced the growth of MDA-MB-435s xenografts compared to the control group, while resveratrol at the 33 mg/kg body weight dose did not have a similar effect. Additional analyses confirmed that resveratrol stimulated cancer cell growth in vivo through activation of the NF-kappaB signaling pathway. Taken together, these observations suggest that resveratrol at low concentrations could stimulate the growth of certain types of human cancer cells in vivo. This cell type-specific mitogenic effect of resveratrol may also partly contribute to the procarcinogenic effect of alcohol consumption (rich in resveratrol) in the development of certain human cancers.

  2. The influence of theobromine on angiogenic activity and proangiogenic cytokines production of human ovarian cancer cells.

    Science.gov (United States)

    Barcz, E; Sommer, E; Sokolnicka, I; Gawrychowski, K; Roszkowska-Purska, K; Janik, P; Skopinska-Rózewska, E

    1998-01-01

    Angiogenesis plays an important role in ovarian cancer growth and metastasis formation. Adenosine is one of the most potent stimulator of neovascularisation. The aim of present study was to determine if theobromine, adenosine receptor antagonist, influences angiogenic activity and proangiogenic cytokines production. Theobromine caused significant inhibition of angiogenic activity of ovarian cancer cells. In in vivo and in vitro cultures theobromine diminished vascular endothelial growth factor (VEGF) production. Production of basic fibroblast growth factor (bFGF) and interleukin-8 (IL-8) was not altered by the examined drug. These findings suggest that theobromine might be a potent inhibitor of angiogenesis induced by ovarian cancer cells and its mechanism of action is related to inhibition of VEGF production.

  3. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio

    2009-01-01

    PURPOSE: MicroRNA (miRNA) expression profiles improve classification, diagnosis, and prognostic information of malignancies, including lung cancer. This study uncovered unique growth-suppressive miRNAs in lung cancer. EXPERIMENTAL DESIGN: miRNA arrays were done on normal lung tissues...... and adenocarcinomas from wild-type and proteasome degradation-resistant cyclin E transgenic mice to reveal repressed miRNAs in lung cancer. Real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays validated these findings. Lung cancer cell lines were derived from each...... transgenic line (designated as ED-1 and ED-2 cells, respectively). Each highlighted miRNA was independently transfected into these cells. Growth-suppressive mechanisms were explored. Expression of a computationally predicted miRNA target was examined. These miRNAs were studied in a paired normal...

  4. Childhood BMI growth trajectories and endometrial cancer risk

    DEFF Research Database (Denmark)

    Aarestrup, Julie; Gamborg, Michael; Tilling, Kate;

    2017-01-01

    cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6 to 14 years and born 1930-89 formed the analytical population. BMI was transformed to age-specific z-scores. Using linear spline multilevel models......Previously, we found that excess weight already in childhood has positive associations with endometrial cancer, however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial......, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain...

  5. DNA Walker-Regulated Cancer Cell Growth Inhibition.

    Science.gov (United States)

    Li, Feiran; Cha, Tae-Gon; Pan, Jing; Ozcelikkale, Altug; Han, Bumsoo; Choi, Jong Hyun

    2016-06-16

    We demonstrate a DNAzyme-based walker system as a controlled oligonucleotide drug AS1411 release platform for breast cancer treatment. In this system, AS1411 strands are released from fuel strands as a walker moves along its carbon nanotube track. The release rate and amount of anticancer oligonucleotides are controlled by the walker operation. With a walker system embedded within the collagen extracellular matrix, we show that this drug release system can be used for in situ cancer cell growth inhibition.

  6. A Gompertzian model with random effects to cervical cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Mazlan, Mazma Syahidatul Ayuni; Rosli, Norhayati [Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, 26300 Gambang, Pahang (Malaysia)

    2015-05-15

    In this paper, a Gompertzian model with random effects is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via maximum likehood estimation. We apply 4-stage Runge-Kutta (SRK4) for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of the cervical cancer growth. Low values of root mean-square error (RMSE) of Gompertzian model with random effect indicate good fits.

  7. Gompertzian stochastic model with delay effect to cervical cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti [Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, 26300 Gambang, Pahang (Malaysia); Bahar, Arifah [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor and UTM Centre for Industrial and Applied Mathematics (UTM-CIAM), Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia)

    2015-02-03

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  8. Gompertzian stochastic model with delay effect to cervical cancer growth

    Science.gov (United States)

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

    2015-02-01

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  9. The influence of the CHIEF pathway on colorectal cancer-specific mortality.

    Science.gov (United States)

    Slattery, Martha L; Lundgreen, Abbie

    2014-01-01

    Many components of the CHIEF (Convergence of Hormones, Inflammation, and Energy Related Factors) pathway could influence survival given their involvement in cell growth, apoptosis, angiogenesis, and tumor invasion stimulation. We used ARTP (Adaptive Rank Truncation Product) to test if genes in the pathway were associated with colorectal cancer-specific mortality. Colon cancer (n = 1555) and rectal cancer (n = 754) cases were followed over five years. Age, center, stage at diagnosis, and tumor molecular phenotype were considered when calculating ARTP p values. A polygenic risk score was used to summarize the magnitude of risk associated with this pathway. The JAK/STAT/SOC was significant for colon cancer survival (PARTP = 0.035). Fifteen genes (DUSP2, INFGR1, IL6, IRF2, JAK2, MAP3K10, MMP1, NFkB1A, NOS2A, PIK3CA, SEPX1, SMAD3, TLR2, TYK2, and VDR) were associated with colon cancer mortality (PARTP cancer (PARTP cancer-specific mortality among colon cancer cases in the upper at-risk alleles group was 11.81 (95% CI 7.07, 19. 74) and was 10.99 (95% CI 5.30, 22.78) for rectal cancer. These results suggest that several genes in the CHIEF pathway are important for colorectal cancer survival; the risk associated with the pathway merits validation in other studies.

  10. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

    Directory of Open Access Journals (Sweden)

    Barbara Marengo

    2016-01-01

    Full Text Available Reactive oxygen species (ROS and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy.

  11. Interacting inflammatory and growth factor signals underlie the obesity-cancer link.

    Science.gov (United States)

    Lashinger, Laura M; Ford, Nikki A; Hursting, Stephen D

    2014-02-01

    The prevalence of obesity, an established risk factor for many chronic diseases (including diabetes, cardiovascular disease, stroke, and several types of cancer), has risen steadily for the past several decades in the United States and many parts of the world. Today, ∼70% of U.S. adults and 30% of children are at an unhealthy weight. The evidence on key biologic mechanisms underlying the obesity-cancer link, with an emphasis on local and systemic inflammatory processes and their crosstalk with energy-sensing growth factor signaling pathways, will be discussed. Understanding the influence and underlying mechanisms of obesity on chronic inflammation and cancer will identify promising mechanistic targets and strategies for disrupting the obesity-cancer link and provide important lessons regarding the associations between obesity, inflammation, and other chronic diseases.

  12. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy.

    Science.gov (United States)

    Marengo, Barbara; Nitti, Mariapaola; Furfaro, Anna Lisa; Colla, Renata; Ciucis, Chiara De; Marinari, Umberto Maria; Pronzato, Maria Adelaide; Traverso, Nicola; Domenicotti, Cinzia

    2016-01-01

    Reactive oxygen species (ROS) and their products are components of cell signaling pathways and play important roles in cellular physiology and pathophysiology. Under physiological conditions, cells control ROS levels by the use of scavenging systems such as superoxide dismutases, peroxiredoxins, and glutathione that balance ROS generation and elimination. Under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids, and DNA, leading to cell damage that may contribute to carcinogenesis. Several studies have shown that cancer cells display an adaptive response to oxidative stress by increasing expression of antioxidant enzymes and molecules. As a double-edged sword, ROS influence signaling pathways determining beneficial or detrimental outcomes in cancer therapy. In this review, we address the role of redox homeostasis in cancer growth and therapy and examine the current literature regarding the redox regulatory systems that become upregulated in cancer and their role in promoting tumor progression and resistance to chemotherapy.

  13. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.

    Science.gov (United States)

    Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Reiter, Michael; Tsaur, Igor; Bartsch, Georg; Haferkamp, Axel; Blaheta, Roman A

    2014-01-01

    Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

  14. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP. Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

  15. Colloid's influences on microalgae growth as a potential environmental factor

    Institute of Scientific and Technical Information of China (English)

    赵新淮; 张正斌; 刘莲生

    2003-01-01

    The role of colloid as "colloid pump" in the ocean is well known. The important influence of colloid in seawater on the growth of microalga was found in our 1999-2000 study. Colloid concentrates were obtained by employing a cross-flow filtration systen to ultrafilter seawater (which had been pre-filtrated by 0.45 μm acetate cellulose membrane) successively with different membranes. Ultrafiltration retentions (we called them colloid concentrates ) together with control sample ( seawater without colloid) were then inoculated with two species of microalgae and cultivated in selected conditions. Monitoring of microalgae growth during cultivation showed that all colloid concentrates had obvious influence on the growth of the microalgae studied. Addition of Fe(OH)3 colloid or organic colloid (protein or carbohydrate) to the control sample enhanced the microalgae's growth.

  16. NIM: A Node Influence Based Method for Cancer Classification

    Directory of Open Access Journals (Sweden)

    Yiwen Wang

    2014-01-01

    Full Text Available The classification of different cancer types owns great significance in the medical field. However, the great majority of existing cancer classification methods are clinical-based and have relatively weak diagnostic ability. With the rapid development of gene expression technology, it is able to classify different kinds of cancers using DNA microarray. Our main idea is to confront the problem of cancer classification using gene expression data from a graph-based view. Based on a new node influence model we proposed, this paper presents a novel high accuracy method for cancer classification, which is composed of four parts: the first is to calculate the similarity matrix of all samples, the second is to compute the node influence of training samples, the third is to obtain the similarity between every test sample and each class using weighted sum of node influence and similarity matrix, and the last is to classify each test sample based on its similarity between every class. The data sets used in our experiments are breast cancer, central nervous system, colon tumor, prostate cancer, acute lymphoblastic leukemia, and lung cancer. experimental results showed that our node influence based method (NIM is more efficient and robust than the support vector machine, K-nearest neighbor, C4.5, naive Bayes, and CART.

  17. NIM: a node influence based method for cancer classification.

    Science.gov (United States)

    Wang, Yiwen; Yao, Min; Yang, Jianhua

    2014-01-01

    The classification of different cancer types owns great significance in the medical field. However, the great majority of existing cancer classification methods are clinical-based and have relatively weak diagnostic ability. With the rapid development of gene expression technology, it is able to classify different kinds of cancers using DNA microarray. Our main idea is to confront the problem of cancer classification using gene expression data from a graph-based view. Based on a new node influence model we proposed, this paper presents a novel high accuracy method for cancer classification, which is composed of four parts: the first is to calculate the similarity matrix of all samples, the second is to compute the node influence of training samples, the third is to obtain the similarity between every test sample and each class using weighted sum of node influence and similarity matrix, and the last is to classify each test sample based on its similarity between every class. The data sets used in our experiments are breast cancer, central nervous system, colon tumor, prostate cancer, acute lymphoblastic leukemia, and lung cancer. experimental results showed that our node influence based method (NIM) is more efficient and robust than the support vector machine, K-nearest neighbor, C4.5, naive Bayes, and CART.

  18. Influence of low molecular weight heparin on cancer patients’ survival

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2014-07-01

    Full Text Available There is an evidence of interaction between the hemostasis system and tumor progression factors. It is known that in addition to the fibrin formation and platelets activation, thrombin can influence many cells function interacting with protease-activating receptors including tumor cells. These receptors are involved in the malignant cell phenotype formation (adhesion, proliferation, proteolysis. Thrombin can also affect angiogenesis by stimulating endothelial cells penetration through basal membrane and its migration with new vessels formation. Furthermore, it can cause the release of main neoangiogenesis promoter – vascular endothelial growth factor. All of the above and many other linkages of coagulation and tumor create a theoretical background of possible affecting tumor by regulation of the coagulation activity. Thepromise of this approach is controversial, but there is some clinical and experimental evidence of their effectiveness. The most used group ofdrugs for this purpose was heparins. Several retrospective studies have shown a benefit of low molecular weight heparins (LMWH over unfractionated heparin in cancer patient survival. The appearance of a new heparins group – ultra LMWH are of interest from this point ofview and their possible use in cancer patients. To date bemiparin and semuloparin are used in clinic. Both (bemiparin about 3600 kDa,semuloparin 3000 kDa have substancially reduced molecular weight as compared with the smallest of LMWH – enoxaparin (4600 kDa.Use of bemiparin in patients with small cell lung cancer receiving chemotherapy resulted in increased of 2-year survival rate compared to the control group (68.6 % vs. 29.4 %, p = 0.0042.

  19. The influence of growth hormone on bone and adipose programming.

    Science.gov (United States)

    Oberbauer, Anita M

    2014-01-01

    In utero growth hormone exposure is associated with distinct immediate growth responses and long term impacts on adult physiological parameters that include obesity, insulin resistance, and bone function. Growth hormone accelerates cellular proliferation in many tissues but is exemplified by increases in the number of cells within the cartilaginous growth plate of bone. In some cases growth hormone also potentiates differentiation as seen in the differentiation of adipocytes that rapidly fill upon withdrawal of growth hormone. Growth hormone provokes these changes either by direct action or through intermediaries such as insulin-like growth factor-I and other downstream effector molecules. The specific mechanism used by growth hormone in programming tissues is not yet fully characterized and likely represents a multipronged approach involving DNA modification, altered adult hormonal milieu, and the development of an augmented stem cell pool capable of future engagement as is seen in adipose accrual. This review summarizes findings of growth hormone's influence on in utero and neonatal cellular and metabolic profiles related to bone and adipose tissue.

  20. [Psychopharmaceuticals and cancer. Modification of tumor growth by psychoactive drugs].

    Science.gov (United States)

    Jäger, H

    1984-02-23

    Psychotropic agents can promote tumors and inhibit neoplastic cell growth. Diazepam which is cancerogenic in some animal models has no such potency in large epidemiologic studies. Neuroleptics increase serumprolactine but psychiatric patients treated with these agents are not of higher risk for breast cancer.

  1. Cancer Cells Hijack Gluconeogenic Enzymes to Fuel Cell Growth.

    Science.gov (United States)

    Balsa-Martinez, Eduardo; Puigserver, Pere

    2015-11-19

    In this issue and the October 15th issue of Molecular Cell, studies by Montal et al. (2015) and Vincent et al. (2015) report that certain types of cancer cells utilize the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxykinase 2 (PCK2) to reprogram anabolic metabolism and support cell growth.

  2. Beclin 1 regulates growth factor receptor signaling in breast cancer.

    Science.gov (United States)

    Rohatgi, R A; Janusis, J; Leonard, D; Bellvé, K D; Fogarty, K E; Baehrecke, E H; Corvera, S; Shaw, L M

    2015-10-16

    Beclin 1 is a haploinsufficient tumor suppressor that is decreased in many human tumors. The function of beclin 1 in cancer has been attributed primarily to its role in the degradative process of macroautophagy. However, beclin 1 is a core component of the vacuolar protein sorting 34 (Vps34)/class III phosphatidylinositoI-3 kinase (PI3KC3) and Vps15/p150 complex that regulates multiple membrane-trafficking events. In the current study, we describe an alternative mechanism of action for beclin 1 in breast cancer involving its control of growth factor receptor signaling. We identify a specific stage of early endosome maturation that is regulated by beclin 1, the transition of APPL1-containing phosphatidyIinositol 3-phosphate-negative (PI3P(-)) endosomes to PI3P(+) endosomes. Beclin 1 regulates PI3P production in response to growth factor stimulation to control the residency time of growth factor receptors in the PI3P(-)/APPL(+)-signaling-competent compartment. As a result, suppression of BECN1 sustains growth factor-stimulated AKT and ERK activation resulting in increased breast carcinoma cell invasion. In human breast tumors, beclin 1 expression is inversely correlated with AKT and ERK phosphorylation. Our data identify a novel role for beclin 1 in regulating growth factor signaling and reveal a mechanism by which loss of beclin 1 expression would enhance breast cancer progression.

  3. The influence of hormone therapies on colon and rectal cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels;

    2016-01-01

    followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression...... analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0......Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were...

  4. Liver acid sphingomyelinase inhibits growth of metastatic colon cancer.

    Science.gov (United States)

    Osawa, Yosuke; Suetsugu, Atsushi; Matsushima-Nishiwaki, Rie; Yasuda, Ichiro; Saibara, Toshiji; Moriwaki, Hisataka; Seishima, Mitsuru; Kozawa, Osamu

    2013-02-01

    Acid sphingomyelinase (ASM) regulates the homeostasis of sphingolipids, including ceramides and sphingosine-1-phosphate (S1P). These sphingolipids regulate carcinogenesis and proliferation, survival, and apoptosis of cancer cells. However, the role of ASM in host defense against liver metastasis remains unclear. In this study, the involvement of ASM in liver metastasis of colon cancer was examined using Asm-/- and Asm+/+ mice that were inoculated with SL4 colon cancer cells to produce metastatic liver tumors. Asm-/- mice demonstrated enhanced tumor growth and reduced macrophage accumulation in the tumor, accompanied by decreased numbers of hepatic myofibroblasts (hMFs), which express tissue inhibitor of metalloproteinase 1 (TIMP1), around the tumor margin. Tumor growth was increased by macrophage depletion or by Timp1 deficiency, but was decreased by hepatocyte-specific ASM overexpression, which was associated with increased S1P production. S1P stimulated macrophage migration and TIMP1 expression in hMFs in vitro. These findings indicate that ASM in the liver inhibits tumor growth through cytotoxic macrophage accumulation and TIMP1 production by hMFs in response to S1P. Targeting ASM may represent a new therapeutic strategy for treating liver metastasis of colon cancer.

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

    Science.gov (United States)

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

    2016-10-01

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

  6. Tyrosine Kinase Domain Gene Polymorphism of Epidermal Growth Factor Receptor in Gastric Cancer in Northern Iran

    Directory of Open Access Journals (Sweden)

    Jeivad F

    2012-01-01

    Full Text Available Background: Gastric cancer is one of the most common diseases of digestive system with a low 5-year survival rate and metastasis is the main cause of death. Multi-factors, such as changes in molecular pathways and deregulation of cells are involved in the disease development. Epidermal growth factor receptor pathway (EGFR which is associated with cell proliferation and survival can influence cancer development. EGFR function is governed by its genetic polymorphism; thus, we aimed to study the tyrosine kinase domain gene mutations of the receptor in patients with gastric cancer.Methods : In this experimental study, 123 subjects (83 patients with gastric cancer and 40 normal subjects were investigated in north of Iran for EGFR gene polymorphisms during 1 year. Genomic DNA was extracted by DNA extraction kit according to the manufacture's protocol. Polymerase chain reaction single-stranded conformation polymorphism (PCR-SSCP and silver staining were performed for investigating EGFR gene polymorphisms. Results : The participants included 72 men and 44 women. Gene polymorphism in exon 18 was present in 10% of the study population but SSCP pattern in exon 19 did not show different migrate bands neither in patients nor in normal subjects.Conclusion: It seems that screening for tyrosine kinas gene polymorphism of epidermal growth factor receptor in patients with gastric cancer and use of tyrosine kinas inhibitors could be useful in the prevention of disease progress and improvement of treatment process for a better quality of life in these patients.

  7. Mathematical modelling of the influence of heat shock proteins on cancer invasion of tissue.

    Science.gov (United States)

    Szymańska, Zuzanna; Urbański, Jakub; Marciniak-Czochra, Anna

    2009-04-01

    Tumour cell invasion is crucial for cancer metastasis, which is the main cause of cancer mortality. An important group of proteins involved in cancer invasion are the Heat Shock Proteins (HSPs). According to experimental data, inhibition of one of these proteins, Hsp90, slows down cancer cells while they are invading tissue, but does not affect the synthesis of matrix metalloproteinases (MMP2 and MMP9), which are very important for cancer metastasis, acting as extracellular matrix (ECM) degrading enzymes. To test different biological hypotheses regarding how precisely Hsp90 influences tumour invasion, in this paper we use a model of solid tumour growth which accounts for the interactions between Hsp90 dynamics and the migration of cancer cells and, alternatively, between Hsp90 dynamics and the synthesis of matrix degrading enzymes (MDEs). The model consists of a system of reaction-diffusion-taxis partial differential equations describing interactions between cancer cells, MDE, and the host tissue (ECM). Using numerical simulations we investigate the effects of the administration of Hsp90 inhibitors on the dynamics of tumour invasion. Alternative mechanisms of reduction of cancer invasiveness result in different simulated patterns of the invading tumour cells. Therefore, predictions of the model suggest experiments which might be performed to develop a deeper understanding of the tumour invasion process.

  8. Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1.

    Science.gov (United States)

    Zhang, Tong-Han; Liang, Li-Zhong; Liu, Xiao-Ling; Wu, Ji-Nan; Su, Kui; Chen, Jue-Yao; Zheng, Qiao-Yi; Huang, Hong-Zhang; Liao, Gui-Qing

    2017-04-01

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), was the earliest discovered to be correlated with cancer and contributes to the initiation and development of several types of tumors. Dysregulation of MALAT1 expression is frequently observed in many types of cancer such as gastric cancer, esophageal squamous cell carcinoma and glioma. To date, the role of MALAT1 and the underlying mechanisms in tongue cancer development remain unclear. In the present study, we studied the influence of MALAT1 on tongue cancer cell lines and clinical tongue cancer samples so as to detect its function and the underlying mechanism. In the present study, lncRNA-MALAT1 was specifically upregulated in tongue cancer cell lines and overexpression promoted tongue cancer cell growth by targeting miR-124. Knockdown of MALAT1 suppressed the growth and invasion of human tongue cancer cells and inhibited metastasis in vitro and in vivo. In addition, miR-124-dependent jagged1 (JAG1) regulation was required for MALAT1-induced tongue cancer cell growth. Our data revealed that MALAT1 inhibited tongue cancer cell growth and metastasis through miR-124-dependent JAG1 regulation. In conclusion, we revealed that MALAT1 may play an oncogenic role by increasing proliferation and metastasis of tongue cancer and is a potential therapeutic target in human tongue cancer.

  9. Cyclooxygenase 2 genotypes influence prostate cancer susceptibility in Japanese Men.

    Science.gov (United States)

    Sugie, Satoru; Tsukino, Hiromasa; Mukai, Shoichiro; Akioka, Takahiro; Shibata, Norihiko; Nagano, Masafumi; Kamoto, Toshiyuki

    2014-03-01

    This study aims to evaluate the relationship between the cyclooxygenase 2 (COX2) G1195A (rs689465) polymorphism and the risk of prostate cancer in a Japanese population and the associations between COX2 polymorphisms and clinicopathological characteristics, including Gleason grade and prostate-specific antigen (PSA) grade. We recruited 134 patients with prostate cancer and 86 healthy controls matched for age and smoking status. The COX2 G1195A polymorphism status was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. Genotype distributions (p = 0.028) and allelic frequencies (p = 0.014) differed significantly between prostate cancer and control groups in terms of the COX2 G1195A polymorphism (Pearson's χ (2) test). Logistic regression analysis of case and control outcomes showed an odds ratio between the GG and AA genotypes of 3.15 (95% confidence interval = 1.27-8.08, p = 0.014), indicating an increased risk of prostate cancer associated with the AA genotype. Subset analysis revealed no significant associations between this polymorphism and clinicopathological characteristics of prostate cancer. This study demonstrated a relationship between the COX2 G1195A variant and prostate cancer risk. This polymorphism may merit further investigation as a potential genomic marker for the early detection of prostate cancer. Our results support the hypothesis that rs689465 influences susceptibility to prostate cancer; however, prostate cancer progression was not associated with rs689465 in a Japanese population.

  10. Smoking, Green Tea Consumption, Genetic Polymorphisms in the Insulin-Like Growth Factors and Lung Cancer Risk

    OpenAIRE

    I-Hsin Lin; Ming-Lin Ho; Hsuan-Yu Chen; Hong-Shen Lee; Chia-Chen Huang; Yin-Hung Chu; Shiau-Yun Lin; Ya-Ru Deng; Yu-Hao He; Yu-Hui Lien; Chi-Wen Hsu; Ruey-Hong Wong

    2012-01-01

    Insulin-like growth factors (IGFs) are mediators of growth hormones; they have an influence on cell proliferation and differentiation. In addition, IGF-binding protein (IGFBP)-3 could suppress the mitogenic action of IGFs. Interestingly, tea polyphenols could substantially reduce IGF1 and increase IGFBP3. In this study, we evaluated the effects of smoking, green tea consumption, as well as IGF1, IGF2, and IGFBP3 polymorphisms, on lung cancer risk. Questionnaires were administered to obtain th...

  11. Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.

    Science.gov (United States)

    Wang, Tao; Xie, Zi-ping; Huang, Zhan-sen; Li, Hao; Wei, An-yang; Di, Jin-ming; Xiao, Heng-jun; Zhang, Zhi-gang; Cai, Liu-hong; Tao, Xin; Qi, Tao; Chen, Di-ling; Chen, Jun

    2015-10-01

    In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

  12. Growth hormone and cancer: GH production and action in glioma?

    Science.gov (United States)

    Lea, Robert W; Dawson, Timothy; Martinez-Moreno, Carlos G; El-Abry, Nasra; Harvey, Steve

    2015-09-01

    The hypersecretion of pituitary growth hormone (GH) is associated with an increased risk of cancer, while reducing pituitary GH signaling reduces this risk. Roles for pituitary GH in cancer are therefore well established. The expression of the GH gene is, however, not confined to the pituitary gland and it is now known to occur in many extrapituitary tissues, in which it has local autocrine or paracrine actions, rather than endocrine function. It is, for instance, expressed in cancers of the prostate, lung, skin, endometrium and colon. The oncogenicity of autocrine GH may also be greater than that induced by endocrine or exogenous GH, as higher concentrations of GHR antagonists are required to inhibit its actions. This may reflect the fact that autocrine GH is thought to act at intracellular receptors directly after synthesis, in compartments not readily accessible to endocrine (or exogenous) GH. The roles and actions of extrapituitary GH in cancer may therefore differ from those of pituitary GH. The possibility that GH may be expressed and act in glioma tumors was therefore examined by immunohistochemistry. These results demonstrate, for the first time, the presence of abundant GH- and GH receptor (GHR-) immunoreactivity in glioma, in which they were co-localized in cytoplasmic but not nuclear compartments. These results demonstrate that glioma differs from most cancers in lacking nuclear GHRs, but GH is nevertheless likely to have autocrine or paracrine actions in the induction and progression of glioma.

  13. Growth Analysis of Cancer Biology Research, 2000-2011

    Directory of Open Access Journals (Sweden)

    Keshava,

    2015-09-01

    Full Text Available Methods and Material: The PubMed database was used for retrieving data on 'cancer biology.' Articles were downloaded from the years 2000 to 2011. The articles were classified chronologically and transferred to a spreadsheet application for analysis of the data as per the objectives of the study. Statistical Method: To investigate the nature of growth of articles via exponential, linear, and logistics tests. Result: The year wise analysis of the growth of articles output shows that for the years 2000 to 2005 and later there is a sudden increase in output, during the years 2006 to 2007 and 2008 to 2011. The high productivity of articles during these years may be due to their significance in cancer biology literature, having received prominence in research. Conclusion: There is an obvious need for better compilations of statistics on numbers of publications in the years from 2000 to 2011 on various disciplines on a worldwide scale, for informed critical assessments of the amount of new knowledge contributed by these publications, and for enhancements and refinements of present Scientometric techniques (citation and publication counts, so that valid measures of knowledge growth may be obtained. Only then will Scientometrics be able to provide accurate, useful descriptions and predictions of knowledge growth.

  14. Adipose-derived stems cells and their role in human cancer development, growth, progression, and metastasis: a systematic review.

    Science.gov (United States)

    Freese, Kyle E; Kokai, Lauren; Edwards, Robert P; Philips, Brian J; Sheikh, M Aamir; Kelley, Joseph; Comerci, John; Marra, Kacey G; Rubin, J Peter; Linkov, Faina

    2015-04-01

    Obesity is a well recognized risk factor for several types of cancers, many of which occur solely or disproportionately in women. Adipose tissue is a rich source of adipose-derived stem cells (ASC), which have received attention for their role in cancer behavior. The purpose of this systematic review is to present the existing literature on the role of ASCs in the growth, development, progression, and metastasis of cancer, with an emphasis on malignancies that primarily affect women. To accomplish this goal, the bibliographic database PubMed was systematically searched for articles published between 2001 and 2014 that address ASCs' relationship to human cancer. Thirty-seven articles on ASCs' role in human cancer were reviewed. Literature suggests that ASCs exhibit cancer-promoting properties, influence/are influenced by the tumor microenvironment, promote angiogenesis, and may be associated with pathogenic processes through a variety of mechanisms, such as playing a role in hypoxic tumor microenvironment. ASCs appear to be important contributors to tumor behavior, but research in areas specific to women's cancers, specifically endometrial cancer, is scarce. Also, because obesity continues to be a major health concern, it is important to continue research in this area to improve understanding of the impact adiposity has on cancer incidence.

  15. [Immunohistochemical and histopathological study of expression of epidermal growth factor receptors in gastric cancer].

    Science.gov (United States)

    Kikkawa, K; Kato, M; Saitoh, Y

    1993-12-01

    To evaluate the importance of epidermal growth factor receptors (EGFR) in the growth and progression of human gastric cancer, we immunohistochemically stained EGFR in specimens of gastric cancer and compared the results with histopathological findings. Fresh frozen sections obtained from 65 cases of gastric cancer were stained by indirect immunostaining technique using Oncogene Scince Inc. Cat. No. GR01 (528 IgG reported by Kawamoto et al.) as anti-EGFR monoclonal antibody. Of the 65 cases of gastric cancer, 17 (26.2%) were EGFR-positive. In differentiated cancer, EGFR was positive in 15 of 28 cases (53.6%) of advanced cancer, and 1 of 14 (7.1%) of early stage cancer. In undifferentiated cancer, 1 of 15 cases (6.7%) of advanced cancer was positive, but all 8 cases of early stage cancer were negative. In differentiated cancer, EGFR was more frequently positive in cases of advanced cancer than in those of early stage cancer (p < 0.05). These results suggest that EGFR are expressed or increase in the transition process from early to advanced stage cancer in differentiated gastric cancer. In addition, the lower EGFR-positive rate in cases of undifferentiated cancer than in those of differentiated cancer suggests that an increase in EGFR is not needed for cancer growth in most cases of undifferentiated cancer.

  16. The influence of the CHIEF pathway on colorectal cancer-specific mortality.

    Directory of Open Access Journals (Sweden)

    Martha L Slattery

    Full Text Available Many components of the CHIEF (Convergence of Hormones, Inflammation, and Energy Related Factors pathway could influence survival given their involvement in cell growth, apoptosis, angiogenesis, and tumor invasion stimulation. We used ARTP (Adaptive Rank Truncation Product to test if genes in the pathway were associated with colorectal cancer-specific mortality. Colon cancer (n = 1555 and rectal cancer (n = 754 cases were followed over five years. Age, center, stage at diagnosis, and tumor molecular phenotype were considered when calculating ARTP p values. A polygenic risk score was used to summarize the magnitude of risk associated with this pathway. The JAK/STAT/SOC was significant for colon cancer survival (PARTP = 0.035. Fifteen genes (DUSP2, INFGR1, IL6, IRF2, JAK2, MAP3K10, MMP1, NFkB1A, NOS2A, PIK3CA, SEPX1, SMAD3, TLR2, TYK2, and VDR were associated with colon cancer mortality (PARTP < 0.05; JAK2 (PARTP  = 0.0086, PIK3CA (PARTP = 0.0098, and SMAD3 (PARTP = 0.0059 had the strongest associations. Over 40 SNPs were significantly associated with survival within the 15 significant genes (PARTP < 0.05. SMAD3 had the strongest association with survival (HRGG 2.46 95% CI 1.44,4.21 PTtrnd = 0.0002. Seven genes (IL2RA, IL8RA, IL8RB, IRF2, RAF1, RUNX3, and SEPX1 were significantly associated with rectal cancer (PARTP < 0.05. The HR for colorectal cancer-specific mortality among colon cancer cases in the upper at-risk alleles group was 11.81 (95% CI 7.07, 19. 74 and was 10.99 (95% CI 5.30, 22.78 for rectal cancer. These results suggest that several genes in the CHIEF pathway are important for colorectal cancer survival; the risk associated with the pathway merits validation in other studies.

  17. Polymorphisms of Insulin-Like Growth Factor 1 Pathway Genes and Breast Cancer Risk.

    Science.gov (United States)

    Shi, Joy; Aronson, Kristan J; Grundy, Anne; Kobayashi, Lindsay C; Burstyn, Igor; Schuetz, Johanna M; Lohrisch, Caroline A; SenGupta, Sandip K; Lai, Agnes S; Brooks-Wilson, Angela; Spinelli, John J; Richardson, Harriet

    2016-01-01

    Genetic variants of insulin-like growth factor 1 (IGF1) pathway genes have been shown to be associated with breast density and IGF1 levels and, therefore, may also influence breast cancer risk via pro-survival signaling cascades. The aim of this study was to investigate associations between IGF1 pathway single nucleotide polymorphisms (SNPs) and breast cancer risk among European and East Asian women, and potential interactions with menopausal status and breast tumor subtype. Stratified analyses of 1,037 cases and 1,050 controls from a population-based case-control study were conducted to assess associations with breast cancer for 22 SNPs across 5 IGF1 pathway genes in European and East Asian women. Odds ratios were calculated using logistic regression in additive genetic models. Polytomous logistic regression was used to assess heterogeneity by breast tumor subtype. Two SNPs of the IGF1 gene (rs1019731 and rs12821878) were associated with breast cancer risk among European women. Four highly linked IGF1 SNPs (rs2288378, rs17727841, rs7136446, and rs7956547) were modified by menopausal status among East Asian women only and associated with postmenopausal breast cancers. The association between rs2288378 and breast cancer risk was also modified by breast tumor subtype among East Asian women. Several IGF1 polymorphisms were found to be associated with breast cancer risk and some of these associations were modified by menopausal status or breast tumor subtype. Such interactions should be considered when assessing the role of these variants in breast cancer etiology.

  18. A Possible Link Between the Pubertal Growth of Girls and Prostate Cancer in Their Sons

    Science.gov (United States)

    BARKER, DAVID J.P.; OSMOND, CLIVE; THORNBURG, KENT L.; KAJANTIE, EERO; ERIKSSON, JOHAN G.

    2012-01-01

    Objectives Among women attending antenatal clinics during 1934–1944 a large intercristal diameter, the maximum distance between the pelvic iliac crests, was associated with a raised incidence of breast and ovarian cancer in the daughters in later life. At puberty, the intercristal diameter of girls enlarges rapidly under the influence of estrogen. We speculated that high maternal estrogen concentrations during pregnancy initiate hormonal cancers in their daughters. Here, we examine the association between the mothers’ intercristal diameters and prostate cancer in their sons. Methods Using the national cancer registry we identified 221 cases of prostate cancer among 6,975 men born during 1934–1944 in Helsinki, Finland. Four thousand four hundred and one of these men had their mother’s bony pelvic measurements recorded: there were 149 cases among them. Results Hazard ratios for prostate cancer rose as the mother’s intercristal diameter increased; but this association was restricted to men who were born before 40 weeks of gestation. Among these men the hazard ratio was 1.27 (95% CI 1.09–1.48; P = 0.002). The hazard ratio was 2.2 (1.3–3.7; P < 0.001) in men whose mothers weighed more than 80 kg in late pregnancy compared with those whose mothers weighed 60 kg or less. Conclusions These findings are consistent with a conceptual framework for the origins of hormonally dependent cancers that invokes exposure of embryonic tissue to maternal sex hormones followed by resetting of the fetal hypothalamic-gonadotropin axis in late gestation. We hypothesize that compensatory prepubertal growth among girls is associated with hormonal cancers in the next generation. PMID:22287160

  19. The Theaflavin Monomers Inhibit the Cancer Cells Growth in Vitro

    Institute of Scientific and Technical Information of China (English)

    You-Ying TU; An-Bin TANG; Naoharu WATANABE

    2004-01-01

    The inhibition effects of tea theaflavins complex (TFs), theaflavin-3-3 '-digallate (TFDG),theaflavin-3'-gallate (TF2B), and an unidentified compound (UC) on the growth of human liver cancer BEL-7402 cells, gastric cancer MKN-28 cells and acute promyelocytic leukemia LH-60 cells were investigated.TFs was obtained through the catalysis of catechins with immobilized polyphenols oxidase. TFDG, TF2B and UC were isolated from TFs with high speed countercurrent chromatography (HSCCC). The results showed that TF2B significantly inhibited the growth of all three kinds of cancer cells, TFs, TFDG and UC had some effect on BEL-7402 and MKN-28, but little activity on LH-60. The inhibition effects of TF2B, TFDG, and UC on BEL-7402 and MKN-28 were stronger than TFs. The relationship coefficients between monomer concentration and its inhibition rate against MKN-28 and BEL-7402 were 0.87 and 0.98 for TF2B, 0.96 and 0.98 for UC, respectively. The IC50 values ofTFs, TF2B, and TFDG were 0.18, 0.11, and 0.16 mM on BEL-7402 cells, and 1.11, 0.22, and 0.25 mM on MKN-28 cells respectively.

  20. Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth

    Directory of Open Access Journals (Sweden)

    Claudia Ceci

    2016-11-01

    Full Text Available Ellagic acid (EA is a polyphenolic compound that can be found as a naturally occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes, green tea and nuts. Previous studies have reported the antitumor properties of EA mainly using in vitro models. No data are available about EA influence on bladder cancer cell invasion of the extracellular matrix triggered by vascular endothelial growth factor-A (VEGF-A, an angiogenic factor associated with disease progression and recurrence, and tumor growth in vivo. In this study, we have investigated EA activity against four different human bladder cancer cell lines (i.e., T24, UM-UC-3, 5637 and HT-1376 by in vitro proliferation tests (measuring metabolic and foci forming activity, invasion and chemotactic assays in response to VEGF-A and in vivo preclinical models in nude mice. Results indicate that EA exerts anti-proliferative effects as a single agent and enhances the antitumor activity of mitomycin C, which is commonly used for the treatment of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates the expression of programmed cell death ligand 1 (PD-L1, an immune checkpoint involved in immune escape. EA in vitro activity was confirmed by the results of in vivo studies showing a significant reduction of the growth rate, infiltrative behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In conclusion, these results suggest that EA may have a potential role as an adjunct therapy for bladder cancer.

  1. Fibroblast Growth Factor 2: An Epithelial Ductal Cell Growth Inhibitor That Drops Out in Breast Cancer

    Science.gov (United States)

    2011-10-01

    analyzed data on tumor progression in these genetically modified animals and completed the staining of different markers of tumor growth (FGF/ FGFR ...H) . Original magnifications: X400 (A-H) 6. FGF, FGFRs and markers differentiating normal and mammary tumor cells We also continued to...oncogene or the absence of FGF2. Figure 5 Immunohistochemistry (IHC) of FGFR in mammary cancer. Staining confirmed the presence of FGFR1

  2. Key variables influencing patterns of lava dome growth and collapse

    Science.gov (United States)

    Husain, T.; Elsworth, D.; Voight, B.; Mattioli, G. S.; Jansma, P. E.

    2013-12-01

    transition in the growth pattern, while a decrease in infusion rate results in larger crystals causing the material to stiffen leading to formation of spines. Material stiffness controls the growth direction of the viscous plug in the lava dome interior. Material strength and stiffness controled by rate of infusion influence lava dome growth more significantly than coefficient of frictional of the talus.

  3. Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients.

    Science.gov (United States)

    Rozman, Ales; Silar, Mira; Kosnik, Mitja

    2012-12-01

    BACKGROUND.: Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. PATIENTS AND METHODS.: Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. RESULTS.: We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. CONCLUSION.: Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF.

  4. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.

    Science.gov (United States)

    Kim-Fuchs, Corina; Le, Caroline P; Pimentel, Matthew A; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K

    2014-08-01

    Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

  5. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    Energy Technology Data Exchange (ETDEWEB)

    De Veirman, Kim, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Rao, Luigia [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); De Bruyne, Elke; Menu, Eline; Van Valckenborgh, Els [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Van Riet, Ivan [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium); Stem Cell Laboratory, Division of Clinical Hematology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels 1090 (Belgium); Frassanito, Maria Antonia [Department of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari Medical School, Bari I-70124 (Italy); Di Marzo, Lucia; Vacca, Angelo [Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine, University of Bari Medical School, Bari I-70124 (Italy); Vanderkerken, Karin, E-mail: kdeveirm@vub.ac.be [Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels 1090 (Belgium)

    2014-06-27

    Cancer associated fibroblasts (CAFs) comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease.

  6. Cancer Associated Fibroblasts and Tumor Growth: Focus on Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Kim De Veirman

    2014-06-01

    Full Text Available Cancer associated fibroblasts (CAFs comprise a heterogeneous population that resides within the tumor microenvironment. They actively participate in tumor growth and metastasis by production of cytokines and chemokines, and the release of pro-inflammatory and pro-angiogenic factors, creating a more supportive microenvironment. The aim of the current review is to summarize the origin and characteristics of CAFs, and to describe the role of CAFs in tumor progression and metastasis. Furthermore, we focus on the presence of CAFs in hypoxic conditions in relation to multiple myeloma disease.

  7. Inhibition of Breast Cancer Growth by IGFBP-3

    Science.gov (United States)

    1998-10-01

    interacting proteins including putative IGFBP-3 receptor in human breast cancer cells by employing the yeast two-hybrid system. Two cDNA clones matched sequences in the GenBank database: (1) Eps8 - epidermal growth factor receptor kinase substrate, and (2) GRP78/BiP - glucose regulated stress protein, or human immunoglobulin heavy chain binding protein. The third cDNA, designated clone 4-33, was not identified in the database and represents a novel gene / protein. I have thus far concentrated my efforts on this novel cDNA clone: (1) synthesis of recombinant human

  8. Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer.

    Science.gov (United States)

    Harding, Thomas C; Long, Li; Palencia, Servando; Zhang, Hongbing; Sadra, Ali; Hestir, Kevin; Patil, Namrata; Levin, Anita; Hsu, Amy W; Charych, Deborah; Brennan, Thomas; Zanghi, James; Halenbeck, Robert; Marshall, Shannon A; Qin, Minmin; Doberstein, Stephen K; Hollenbaugh, Diane; Kavanaugh, W Michael; Williams, Lewis T; Baker, Kevin P

    2013-03-27

    The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis in many solid tumors. Although there has long been interest in FGF pathway inhibitors, development has been complicated: An effective FGF inhibitor must block the activity of multiple mitogenic FGF ligands but must spare the metabolic hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To achieve these design requirements, we engineered a soluble FGF receptor 1 Fc fusion protein, FP-1039. FP-1039 binds tightly to all of the mitogenic FGF ligands, inhibits FGF-stimulated cell proliferation in vitro, blocks FGF- and vascular endothelial growth factor (VEGF)-induced angiogenesis in vivo, and inhibits in vivo growth of a broad range of tumor types. FP-1039 antitumor response is positively correlated with RNA levels of FGF2, FGF18, FGFR1c, FGFR3c, and ETV4; models with genetic aberrations in the FGF pathway, including FGFR1-amplified lung cancer and FGFR2-mutated endometrial cancer, are particularly sensitive to FP-1039-mediated tumor inhibition. FP-1039 does not appreciably bind the hormonal FGFs, because these ligands require a cell surface co-receptor, klotho or β-klotho, for high-affinity binding and signaling. Serum calcium and phosphate levels, which are regulated by FGF-23, are not altered by administration of FP-1039. By selectively blocking nonhormonal FGFs, FP-1039 treatment confers antitumor efficacy without the toxicities associated with other FGF pathway inhibitors.

  9. Growth Inhibition of Breast Cancer in Rat by AAV Mediated Angiostatin Gene

    Institute of Scientific and Technical Information of China (English)

    LI Ran; CHEN Hong; REN Chang-shan

    2007-01-01

    Objective: To observe growth inhibition effect of adeno-associated viral vectors (AAV) mediated angiostatin (ANG) gene on implanted breast cancer in rat and its mechanism. Methods: Gene transfer technique was used to transfer AAV-ANG to the tumor. Growth curves were drawn to observe the growth of breast cancer implanted in rat, and immunohistochemical method was used to detect the effects of angiostatin on microvesel density (MVD) of breast cancer implanted in rat. Results: Angiostatin inhibited the growth of breast cancer implanted in rat and decreased the microvessel density of tumor. Conclusion: Expression of an angiostatin transgene can suppress the growth of breast cancer implanted in rat through the inhibition of the growth of microvessels, surggesting that angiostatin gene transfer technique may be effective against breast cancer.

  10. Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Berasain, Carmen, E-mail: cberasain@unav.es; Latasa, María Ujue; Urtasun, Raquel; Goñi, Saioa; Elizalde, María; Garcia-Irigoyen, Oihane; Azcona, María [Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008 (Spain); Prieto, Jesús [Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008 (Spain); CIBERehd, University Clinic, University of Navarra, Pamplona 31080 (Spain); Ávila, Matías A. [Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Pamplona 31008 (Spain)

    2011-05-18

    Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a “signaling hub” where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment.

  11. THE INFLUENCE OF GLOBALIZATION ON ECONOMIC GROWTH IN ROMANIA

    Directory of Open Access Journals (Sweden)

    PAUL BOGDAN ZAMFIR

    2015-12-01

    Full Text Available In this paper we propose to emphasize the structural changes involved by globalization process who generate a semnificative influence on the economic growth in Romania. Thus, on this background it is important to point out that even though the phenomenon of globalization represents manny opportunities for Romanian economic growth, nevertheles, our country must regard at the same time all the systemic risks that are involved in this process. From this perspective, an important role has the activity of romanian small and medium sized enterprises that through its specific creates jobs and contributes substantially to growth in Romania. In terms of risks, for our country is necessary to develop effective mechanisms of self-defense against involved economic dangers. Also, should not be ignored that the quality of European Union member offers for Romania a strong base and in the same time the chance to benefit from the positive effects of the single market and the opportunities offered by the global market. In this framework, Romanian economy is not exempted from stiff competition in the field of trade in goods and services from countries like China or India who succeed through competition, to "break down trade barriers" of economic blocs. More than that, Romanian high tech industry can take advantage for themselves from the positive effects of globalization process by penetrating on third country markets.

  12. An investigation on different factors influencing growth of banking deposits

    Directory of Open Access Journals (Sweden)

    Zahra Houshmand Neghabi

    2013-01-01

    Full Text Available Banking deposit is the primary source of contributing to economy and it is important to understand what factors influence such deposits. In this paper, we present an empirical study to find the relationship between banking deposit and other important factors such as capital market, money market, commodity market, foreign exchange rates such as US dollar and Euro exchange rates to local currency (Rials. We gather the data over the period of 2010-2012 and using ordinary least square technique study different hypotheses. All t-student values are statistically meaningful when the level of significance is ten percent and some of the parameters are even meaningful when the level of significance is five percent. The results indicate that the rate of bank deposit is negatively associated with commodity market growth rate (-.001995, US dollar exchange rate (-0.004167, banking industry growth rate (-0.278826 and moving average (-0.940418. In addition, dependent variable is positively associated with Euro exchange growth rate (0.005676.

  13. Dickkopf3 overexpression inhibits pancreatic cancer cell growth in vitro

    Institute of Scientific and Technical Information of China (English)

    Yu-Mei Gu; Yi-Hui Ma; Wu-Gan Zhao; Jie Chen

    2011-01-01

    AIM: To elucidate the role of dickkopf3 (Dkk3) in human pancreatic cancer cell growth.METHODS: Dkk3 mRNA and protein expression in human pancreatic cancer cell lines were detected by real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blotting and immunofluorescence. Methylation of the Dkk3 promoter sequence was examined by methylation-specific polymerase chain reaction (MSP) and Dkk3 mRNA expression was determined by real-time RT-PCR after 5-aza-2'-deoxycytidine (5-aza-dC) treatment. The effects of Dkk3 on cancer cell proliferation and in vitro sensitivity to gemcitabine were investigated by CellTiter 96. AQueous One Solution Cell Proliferation Assay (MTS) after transfecting the Dkk3 expression plasmid into human pancreatic cancer cells. The expression of β-catenin, phosphorylated extracellular signal-regulated protein kinases (pERK) and extracellular signal-regulated protein kinases (ERK) was also examined by real-time RT-PCR and Western blotting after upregulating Dkk3 expression in human pancreatic cancer cells.RESULTS: The results show that the expression levels of both Dkk3 mRNA and protein were low in all pancreatic cancer cell lines tested. The Dkk3 promoter sequence was methylated in the MIA PaCa-2 and AsPC-1 cell lines, which showed reduced Dkk3 expression. These two cell lines, which initially had a methylated Dkk3 promoter, showed increased Dkk3 mRNA expression that was dependent upon the dosage and timing of the DNA demethylating agent, 5-aza-dC, treatment (P < 0.05 or P < 0.01). When Dkk3 expression was upregulated following the transfection of a Dkk3 expression plasmid into MIA PaCa-2 cells, the ability of cells to proliferate decreased (P < 0.01), and the expression of β-catenin and pERK was downregulated (P < 0.01). Sensitivity to gemcitabine was enhanced in Dkk3 expression plasmid-transfected cells.CONCLUSION: Our findings, for the first time, implicate Dkk3 as a tumor suppressor in human pancreatic cancer

  14. S-Adenosylmethionine Inhibits the Growth of Cancer Cells by Reversing the Hypomethylation Status of c-myc and H-ras in Human Gastric Cancer and Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jin Luo, Yan-Ni Li, Fei Wang, Wei-Ming Zhang, Xin Geng

    2010-01-01

    Full Text Available A global DNA hypomethylation might activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-Adenosylmethionine (SAM serves as a major methyl donor in biological transmethylation events. The object of this study is to explore the influence of SAM on the status of methylation at the promoter of the oncogenes c-myc, H-ras and tumor-suppressor gene p16 (INK4a, as well as its inhibitory effect on cancer cells. The results indicated that SAM treatment inhibited cell growth in gastric cancer cells and colon cancer cells, and the inhibition efficiency was significantly higher than that in the normal cells. Under standard growth conditions, C-myc and H-ras promoters were hypomethylated in gastric cancer cells and colon cancer cells. SAM treatment resulted in a heavy methylation of these promoters, which consequently downregulated mRNA and protein levels. In contrast, there was no significant difference in mRNA and protein levels of p16 (INK4a with and without SAM treatment. SAM can effectively inhibit the tumor cells growth by reversing the DNA hypomethylation on promoters of oncogenes, thus down-regulating their expression. With no influence on the expression of the tumor suppressor genes, such as P16, SAM could be used as a potential drug for cancer therapy.

  15. Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival.

    Science.gov (United States)

    Tiong, Kai Hung; Tan, Boon Shing; Choo, Heng Lungh; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Tan, Si Hoey; Khor, Nelson Tze Woei; Wong, Shew Fung; See, Sze-Jia; Tan, Yuen-Fen; Rosli, Rozita; Cheong, Soon-Keng; Leong, Chee-Onn

    2016-09-06

    Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.

  16. SRPK2 promotes the growth and migration of the colon cancer cells.

    Science.gov (United States)

    Wang, Jian; Wu, Hai-Feng; Shen, Wei; Xu, Dong-Yan; Ruan, Ting-Yan; Tao, Guo-Qing; Lu, Pei-Hua

    2016-07-15

    Colon cancer is one of the major causes of cancer-related death in the world. Understanding the molecular mechanism underlying this malignancy will facilitate the diagnosis and treatment. Serine-arginine protein kinase 2 (SRPK2) has been reported to be upregulated in several cancer types. However, its expression and functions in colon cancer remains unknown. In this study, it was found that the expression of SRPK2 was up-regulated in the clinical colon cancer samples. Overexpression of SRPK2 promoted the growth and migration of colon cancer cells, while knocking down the expression of SRPK2 inhibited the growth, migration and tumorigenecity of colon cancer cells. Molecular mechanism studies revealed that SRPK2 activated ERK signaling in colon cancer cells. Taken together, our study demonstrated the tumor promoting roles of SRPK2 in colon cancer cells and SRPK2 might be a promising therapeutic target for colon cancer.

  17. The Inuit cancer pattern--the influence of migration

    DEFF Research Database (Denmark)

    Boysen, T.; Friborg, J.; Andersen, Allan;

    2008-01-01

    in Greenland we investigated whether migration to Denmark influenced their risk of cancer. Greenland is part of the Danish Kingdom, and population-based registries cover both countries. Using rates for Denmark as reference, sex-specific standardized incidence ratios (SIR) were calculated for Inuit who never...... [31.7 (CI 22.0-45.5)] and salivary glands [3.1 (CI 1.4-6.9)] observed among Inuit migrating to Denmark were comparable to those observed among Inuit never living in Denmark. Significant higher risk of cancer of the bladder, breast, prostate gland, skin, brain and stomach was observed among Inuit...... following migration to Denmark. The SIR was not generally influenced by duration of stay. The high risk of carcinoma of the nasopharynx and salivary glands observed in Inuit populations is maintained after migration to a low incidence area. This indicates that genetic factors or environmental factors acting...

  18. Matrix rigidity regulates cancer cell growth and cellular phenotype.

    Directory of Open Access Journals (Sweden)

    Robert W Tilghman

    Full Text Available BACKGROUND: The mechanical properties of the extracellular matrix have an important role in cell growth and differentiation. However, it is unclear as to what extent cancer cells respond to changes in the mechanical properties (rigidity/stiffness of the microenvironment and how this response varies among cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: In this study we used a recently developed 96-well plate system that arrays extracellular matrix-conjugated polyacrylamide gels that increase in stiffness by at least 50-fold across the plate. This plate was used to determine how changes in the rigidity of the extracellular matrix modulate the biological properties of tumor cells. The cell lines tested fall into one of two categories based on their proliferation on substrates of differing stiffness: "rigidity dependent" (those which show an increase in cell growth as extracellular rigidity is increased, and "rigidity independent" (those which grow equally on both soft and stiff substrates. Cells which grew poorly on soft gels also showed decreased spreading and migration under these conditions. More importantly, seeding the cell lines into the lungs of nude mice revealed that the ability of cells to grow on soft gels in vitro correlated with their ability to grow in a soft tissue environment in vivo. The lung carcinoma line A549 responded to culture on soft gels by expressing the differentiated epithelial marker E-cadherin and decreasing the expression of the mesenchymal transcription factor Slug. CONCLUSIONS/SIGNIFICANCE: These observations suggest that the mechanical properties of the matrix environment play a significant role in regulating the proliferation and the morphological properties of cancer cells. Further, the multiwell format of the soft-plate assay is a useful and effective adjunct to established 3-dimensional cell culture models.

  19. Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors.

    Science.gov (United States)

    Wright, Marilyn; Bryans, Angie; Gray, Kaylin; Skinner, Leah; Verhoeve, Amanda

    2013-01-01

    The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a "mixed methods" design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale-Adolescents, and the Amherst Health and Activity Study-Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer.

  20. Physical Activity in Adolescents following Treatment for Cancer: Influencing Factors

    Directory of Open Access Journals (Sweden)

    Marilyn Wright

    2013-01-01

    Full Text Available The purpose of this study was to examine physical activity levels and influencing individual and environmental factors in a group of adolescent survivors of cancer and a comparison group. Methods. The study was conducted using a “mixed methods” design. Quantitative data was collected from 48 adolescent survivors of cancer and 48 comparison adolescents using the Godin Leisure-Time Exercise Questionnaire, the Fatigue Scale—Adolescents, and the Amherst Health and Activity Study—Student Survey. Qualitative data was collected in individual semistructured interviews. Results. Reported leisure-time physical activity total scores were not significantly different between groups. Physical activity levels were positively correlated with adult social support factors in the group of adolescent survivors of cancer, but not in the comparison group. Time was the primary barrier to physical activity in both groups. Fatigue scores were higher for the comparison but were not associated with physical activity levels in either group. The qualitative data further supported these findings. Conclusions. Barriers to physical activity were common between adolescent survivors of cancer and a comparative group. Increased knowledge of the motivators and barriers to physical activity may help health care providers and families provide more effective health promotion strategies to adolescent survivors of pediatric cancer.

  1. Influence of nuclei segmentation on breast cancer malignancy classification

    Science.gov (United States)

    Jelen, Lukasz; Fevens, Thomas; Krzyzak, Adam

    2009-02-01

    Breast Cancer is one of the most deadly cancers affecting middle-aged women. Accurate diagnosis and prognosis are crucial to reduce the high death rate. Nowadays there are numerous diagnostic tools for breast cancer diagnosis. In this paper we discuss a role of nuclear segmentation from fine needle aspiration biopsy (FNA) slides and its influence on malignancy classification. Classification of malignancy plays a very important role during the diagnosis process of breast cancer. Out of all cancer diagnostic tools, FNA slides provide the most valuable information about the cancer malignancy grade which helps to choose an appropriate treatment. This process involves assessing numerous nuclear features and therefore precise segmentation of nuclei is very important. In this work we compare three powerful segmentation approaches and test their impact on the classification of breast cancer malignancy. The studied approaches involve level set segmentation, fuzzy c-means segmentation and textural segmentation based on co-occurrence matrix. Segmented nuclei were used to extract nuclear features for malignancy classification. For classification purposes four different classifiers were trained and tested with previously extracted features. The compared classifiers are Multilayer Perceptron (MLP), Self-Organizing Maps (SOM), Principal Component-based Neural Network (PCA) and Support Vector Machines (SVM). The presented results show that level set segmentation yields the best results over the three compared approaches and leads to a good feature extraction with a lowest average error rate of 6.51% over four different classifiers. The best performance was recorded for multilayer perceptron with an error rate of 3.07% using fuzzy c-means segmentation.

  2. MicroRNA-181b expression in prostate cancer tissues and its influence on the biological behavior of the prostate cancer cell line PC-3.

    Science.gov (United States)

    He, L; Yao, H; Fan, L H; Liu, L; Qiu, S; Li, X; Gao, J P; Hao, C Q

    2013-04-02

    We examined microRNA-181b (miRNA) expression in prostate cancer tissues and its effect on the prostate cancer cell line PC-3. Tissues from 27 cases of prostate cancer and 30 samples of normal human prostate were collected by surgical removal. Total miRNA was extracted, and the relative expression of miR-181b was quantified using RT-PCR. miR-181b ASO was transfected into prostate cancer PC-3 cells. miR-181b expression in transfected and non-transfected cells was measured using RT-PCR. Changes in cell apoptosis were measured using flow cytometry. MTT and cell growth curve methods were used to assess the influence of miR-181b expression on cell proliferation. The changes in cell invasive ability in vitro were detected using the Transwell chamber method. miR-181b was up-regulated in the prostate cancer tissues compared with the normal prostate samples. It was down-regulated after miR-181b ASO transfection into the prostate cancer PC-3 cells. Down-regulation of miR-181b in the PC-3 cell induced apoptosis, inhibited proliferation, and depressed invasion of PC-3 cells in vitro. As miR-181b is over-expressed in prostate cancer, its down-regulation could have potential as gene therapy for prostate cancer by inducing apoptosis, inhibiting proliferation and depressing invasion by cancer cells.

  3. Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer

    Institute of Scientific and Technical Information of China (English)

    Bing-Feng Chu; Yi-Yu Qin; Sheng-Lai Zhang; Zhi-Wei Quan; Ming-Di Zhang; Jian-Wei Bi

    2016-01-01

    Background:The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells.The role of NRARP in carcinogenesis deserves extensive investigations.This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation,apoptosis,cell cycle,and invasion in thyroid cancer.Methods:Thirty-four cases with thyroid cancer were collected from the Department of General Surgery,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine between 2011 and 2012.Immunohistochemistry was used to detect the level of NRARP in cancer tissues.Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression.Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay.Apoptosis and cell cycle distribution were determined by flow cytometry.Cell invasion was tested using Transwell invasion assay.In addition,expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection.Student's t-test,one-way analysis of variance (ANOVA),or Kaplan-Meier were used to analyze the differences between two group or three groups.Results:NRARP was highly expressed in thyroid cancer tissues.Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05).Lenti-NRARP-shRNA-induced G1 arrest (BHT 101:72.57% ± 5.32%;8305C:75.45% ± 5.26%) by promoting p21 expression,induced apoptosis by promoting bax expression and suppressing bcl-2 expression,and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression.Conclusion:Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer,that suggests a potential role of NRARP in thyroid cancer targeted

  4. THE INFLUENCE OF THE ECONOMIC GROWTH ON THE BIRTH RATE

    Directory of Open Access Journals (Sweden)

    SAVU MIHAELA

    2013-02-01

    Full Text Available The changes occurred over time in the population have effects on the economy, especially the reductions in thebirth rate which may lead to disturbances in the population structure. The relationship between the economic growthand the birth rate in Romania is analysed over an 11-year period, in order to see its intensity. The presentation of theevolution of the gross domestic product and of the birth rate is completed by the calculation of the Spearmancoefficient for determining the intensity of the relationship between the two indicators. The decrease of the birth rate isdetermined, to a modest extent, by the economic growth, with a wide range of factors that influence it. In this situation,the establishment and implementation of a birth rate recovery strategy is highly necessary to reduce the imbalancecreated in the population structure.

  5. Fostering Growth in the Survivorship Experience: Investigating Breast Cancer Survivors' Lived Experiences Scaling Mt. Kilimanjaro from a Posttraumatic Growth Perspective

    Science.gov (United States)

    Burke, Shaunna M.; Sabiston, Catherine M.

    2012-01-01

    The aim of this study was to use an ethnographic case study approach to explore breast cancer survivors' experiences scaling Mt. Kilimanjaro from a posttraumatic growth perspective. Three breast cancer survivors who participated in interviews and observations during a nine-day climb on the mountain were included in this study. Findings are…

  6. Tubulin binding cofactor C (TBCC suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Laurier Jean-Fabien

    2010-04-01

    Full Text Available Abstract Background Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC, a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers. Methods We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. In vivo growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. In vitro sensitivity to antimicrotubule agents was studied by flow cytometry. In vivo chemosensitivity was assayed by treatment of mice implanted with tumor cells. Results TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation in vitro, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts in vivo. TBCC overexpressing variants displayed enhanced sensitivity to

  7. Feather growth influences blood mercury level of young songbirds.

    Science.gov (United States)

    Condon, Anne M; Cristol, Daniel A

    2009-02-01

    Dynamics of mercury in feathers and blood of free-living songbirds is poorly understood. Nestling eastern bluebirds (Sialia sialis) living along the mercury-contaminated South River (Virginia, USA) had blood mercury levels an order of magnitude lower than their parents (nestling: 0.09 +/- 0.06 mg/kg [mean +/- standard deviation], n = 156; adult: 1.21 +/- 0.57 mg/kg, n = 86). To test whether this low blood mercury was the result of mercury sequestration in rapidly growing feathers, we repeatedly sampled free-living juveniles throughout the period of feather growth and molt. Mean blood mercury concentrations increased to 0.52 +/- 0.36 mg/kg (n = 44) after the completion of feather growth. Some individuals had reached adult blood mercury levels within three months of leaving the nest, but levels dropped to 0.20 +/- 0.09 mg/kg (n = 11) once the autumn molt had begun. Most studies of mercury contamination in juvenile birds have focused on recently hatched young with thousands of rapidly growing feathers. However, the highest risk period for mercury intoxication in young birds may be during the vulnerable period after fledging, when feathers no longer serve as a buffer against dietary mercury. We found that nestling blood mercury levels were not indicative of the extent of contamination because a large portion of the ingested mercury ended up in feathers. The present study demonstrates unequivocally that in songbirds blood mercury level is influenced strongly by the growth and molt of feathers.

  8. Amygdalin influences bladder cancer cell adhesion and invasion in vitro.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK and total and activated focal adhesion kinase (FAK were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines may depend upon the cancer cell type.

  9. Amygdalin influences bladder cancer cell adhesion and invasion in vitro.

    Science.gov (United States)

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

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.

  10. Influence of continental growth on mid-ocean ridge depth

    Science.gov (United States)

    Sim, Shi J.; Stegman, Dave R.; Coltice, Nicolas

    2016-11-01

    The interconnectedness of life, water, and plate tectonics is strikingly apparent along mid-ocean ridges (MOR) where communities of organisms flourish off the disequilibrium of chemical potentials created by circulation of hydrothermal fluids driven by Earth's heat. Moreover, submarine hydrothermal environments may be critical for the emergence of life on Earth. Oceans were likely present in the Hadean but questions remain about early Earth's global tectonics, including when seafloor spreading began and whether mid-oceanic ridges were deep enough for maximum hydrothermal activities. For example, plate tectonics influences global sea level by driving secular variations in the volume of ocean basins due to continental growth. Similarly, variations in the distribution of seafloor age and associated subsidence, due to assembly and dispersal of supercontinents, explain the largest sea level variation over the past 140 Myr. Using synthetic plate configurations derived from numerical models of mantle convection appropriate for early Earth, we show that MOR have remained submerged and their depths potentially constant over geologic time. Thus, conditions in the early Earth existed for hydrothermal vents at similar depths as today, providing environments conducive for the development of life and allowing for processes such as hydrothermal alteration of oceanic crust to influence the mantle's geochemical evolution.

  11. The report of posttraumatic growth in Malaysian cancer patients : relationships with psychological distress and coping strategies

    NARCIS (Netherlands)

    Schroevers, Maya J.; Teo, Irene

    2008-01-01

    Objective: The challenge of a cancer diagnosis may eventually lead to the experience of positive psychological changes, also referred to as posttraumatic growth. As most research on posttraumatic growth in cancer patients has been conducted in Western countries, little is known about the experience

  12. Regulation of endometrial cancer cell growth by luteinizing hormone (LH) and follicle stimulating hormone (FSH)

    OpenAIRE

    Davies, S.; Bax, C M R; Chatzaki, E; Chard, Tim; Iles, Ray K.

    2000-01-01

    Gonadotrophin releasing hormone analogues (GnRHa) have been used to treat recurrent endometrial cancer. However, the mode of action is uncertain. Our previous studies showed no direct effect of GnRHa on endometrial cancer cell growth in vitro. We have now examined the effect of luteinizing hormone (LH) and follicle stimulating hormone (FSH) on endometrial cancer cell growth. The aim was to determine whether suppression of pituitary LH and FSH by GnRHa could explain the tumour regression seen ...

  13. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Zhang Hong-Yan

    2011-09-01

    Full Text Available Abstract Background Connective tissue growth factor (CTGF has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P 1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  14. Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression

    Science.gov (United States)

    Nahta, Rita; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Andrade-Vieira, Rafaela; Bay, Sarah; G. Brown, Dustin; Calaf, Gloria M.; Castellino, Robert C.; Cohen-Solal, Karine A.; Colacci, Annamaria; Cruickshanks, Nichola; Dent, Paul; Di Fiore, Riccardo; Forte, Stefano; Goldberg, Gary S.; Hamid, Roslida A.; Krishnan, Harini; Laird, Dale W.; Lasfar, Ahmed; Marignani, Paola A.; Memeo, Lorenzo; Mondello, Chiara; Naus, Christian C.; Ponce-Cusi, Richard; Raju, Jayadev; Roy, Debasish; Roy, Rabindra; P. Ryan, Elizabeth; Salem, Hosni K.; Scovassi, A. Ivana; Singh, Neetu; Vaccari, Monica; Vento, Renza; Vondráček, Jan; Wade, Mark; Woodrick, Jordan; Bisson, William H.

    2015-01-01

    As part of the Halifax Project, this review brings attention to the potential effects of environmental chemicals on important molecular and cellular regulators of the cancer hallmark of evading growth suppression. Specifically, we review the mechanisms by which cancer cells escape the growth-inhibitory signals of p53, retinoblastoma protein, transforming growth factor-beta, gap junctions and contact inhibition. We discuss the effects of selected environmental chemicals on these mechanisms of growth inhibition and cross-reference the effects of these chemicals in other classical cancer hallmarks. PMID:26106139

  15. The influence of curcumin combined with irinotecan on the growth of colorectal cancer Lovo cells in vitro%姜黄素联合伊立替康对大肠癌Lovo细胞体外生长的影响

    Institute of Scientific and Technical Information of China (English)

    王家智; 陈小伍; 朱达坚; 剧永乐

    2013-01-01

    目的 探讨姜黄素、伊立替康对大肠癌Lovo细胞的单药作用、协同作用及联合给药方式.方法 不同浓度姜黄素和伊立替康、不同联合给药方式、不同作用时间作用于Lovo细胞,噻唑蓝(MTT)比色法、流式细胞仪分别检测Lovo细胞增殖、凋亡率.结果 姜黄素、伊立替康均呈时间、剂量依赖性抑制Lovo细胞增殖.混合给药中联合用药组Lovo细胞凋亡率比单药组显著增加(P<0.01);贯序给药中2个实验组Lovo细胞凋亡率比对照组显著增加(P<0.05);贯序给药Lovo细胞凋亡率显著高于混合给药(P<0.05).结论 姜黄素及伊立替康呈时间、剂量依赖抑制Lovo细胞增殖,两者具有协同作用,贯序给药比混合给药更有效提高两者对Lovo细胞抑制作用.%Objective To investigate the effect of curcumin and irinotecan on colorectal cancer Lovo cells.Methods Methyl thiazol tetrazolium (MTT) assay and flow cytometry were used to detect the proliferation activity and apoptosis rate of Lovo cells treated by different concentrations of curcumin and irinotecan alone or in combination at different time points.Results Curcumin and irinotecan inhibited the proliferation of Lovo cells both in time-and dose-dependent manner.The inhibition rate of Lovo cells in curcumin + irinotecan combined group with mixed administration was significantly higher than in curcumin group or irinotecan group (P < 0.01),and that in two experimental groups with sequential administration was significantly higher than in control group (P < 0.05).As compared with the mixed administration group,the apoptosis rate of Lovo cells was increased significantly in the sequential administration groups.Conclusion Both curcumin and irinotecan can inhibit the proliferation of Lovo cells time-dose dependently,and exert the synergic effects.Compared to the mixed administration,the sequential administration can enhance the inhibitory effect on Lovo cells.

  16. A growth model for primary cancer (II). New rules, progress curves and morphology transitions

    Science.gov (United States)

    Jr, S. C. Ferreira; Martins, M. L.; Vilela, M. J.

    1999-10-01

    In the present paper we extend the analysis of another model recently proposed to simulate the growth of carcinoma “in situ”, which includes cell proliferation, motility and death, as well as chemotactic interactions among cells. The tumour patterns generated by two distinct growth rules are characterised by its gyration radius, surface roughness, total number of cancer cells, and number of cells on tumour periphery. Our results indicate that very distinct morphological patterns follow Gompertz growth curves and their gyration radii increase linearly in time and scale, in the asymptotic limit, as a square root of the total number of tumour cells. In contrast, these distinct tumour patterns exhibit different scaling laws for their surfaces. Thus, some biological features of malignant behaviour seem to influence particularly the structure of the tumour border, while its gyration radius and progress curve are described by more robust functions. Finally, for both rules used, morphology transitions as well as a transient behaviour up to the onset of the phase of rapid growth in the Gompertz curves are observed.

  17. Methylselenol, a selenium metabolite, inhibits colon cancer cell growth and cancer xenografts in C57BL/6 mice

    Science.gov (United States)

    Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo but its role in colon cancer prevention remains to be characterized. This study tested the hypothesis that methylselenol inhibits the growth of colon cancer cells and tumors. We found that submicr...

  18. Human recombinant erythropoietin does not promote cancer growth in presence of functional receptors expressed in cancer cells.

    Science.gov (United States)

    Belda-Iniesta, Cristóbal; Perona, Rosario; Carpeño, Javier de Castro; Cejas, Paloma; Casado, Enrique; Manguan-García, Cristina; Ibanez de Caceres, Inmaculada; Sanchez-Perez, Isabel; Andreu, Francisco Bernabeu; Ferreira, Javier Alves; Aguilera, Alfredo; de la Peña, Javier; Perez-Sánchez, Elia; Madero, Rosario; Feliu, Jaime; Sereno, María; González-Barón, Manuel

    2007-10-01

    Human recombinant erythropoietin (hrEPO) therapy might be associated with tumor progression and death. This effect has been suggested to be secondary to rhEPO binding to its receptor (EPOR) expressed on cancer cells. However, there are several concerns about EPOR functionality when expressed on cancer cells. In this paper we have provided evidence that EPOR expressed in cancer cells could be implicated in proliferation events because a transfection of EPOR siRNA to EPOR-expressing bladder cancer cells resulted in a marked reduction in cell growth. However, these cell lines do not grow in the presence of hrEPO. Furthermore, bladder cancer patients that expressed EPOR in tumor samples had a reduced survival in absence of rhEPO treatment. Therefore, EPOR is implicated in bladder cancer growth but this effect appears to be independent from rhEPO supplementation. Reports which suggest that rhEPO promotes cancer growth due to the expression of EPOR in cancer cells must be observed with caution since in the presence of functional EPOR rhEPO does not promote growth.

  19. Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations

    Directory of Open Access Journals (Sweden)

    Lamond NW

    2014-05-01

    Full Text Available Nathan WD Lamond, Tallal YounisDepartment of Medicine, Dalhousie University at the Queen Elizabeth II Health Sciences Centre, Halifax, NS, CanadaAbstract: In the absence of specific therapy, the 15%–20% of breast cancers demonstrating human epidermal growth-factor receptor 2 (HER2 protein overexpression and/or gene amplification are characterized by a more aggressive phenotype and poorer prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin, the first anti-HER2-targeted therapy, has been associated with improved survival outcomes in HER2-positive breast cancer. However, many patients with early stage disease continue to relapse, and metastatic disease remains incurable. In order to further improve these outcomes, several novel HER2-targeted agents have recently been developed. Pertuzumab (Perjeta, a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease. This review briefly summarizes pertuzumab's clinical development as well as the published evidence supporting its use, and highlights some of the currently unanswered questions that will influence pertuzumab’s incorporation into clinical practice.Keywords: HER2/neu, clinical trials, drug development, novel therapies, targeted anticancer therapy

  20. Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth.

    Science.gov (United States)

    Shukla, Surendra K; Dasgupta, Aneesha; Mehla, Kamiya; Gunda, Venugopal; Vernucci, Enza; Souchek, Joshua; Goode, Gennifer; King, Ryan; Mishra, Anusha; Rai, Ibha; Nagarajan, Sangeetha; Chaika, Nina V; Yu, Fang; Singh, Pankaj K

    2015-12-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models.

  1. Choline Phospholipid Metabolites of Human Vascular Endothelial Cells Altered by Cyclooxygenase Inhibition, Growth Factor Depletion, and Paracrine Factors Secreted by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Noriko Mori

    2003-04-01

    Full Text Available Magnetic resonance studies have previously shown that solid tumors and cancer cells in culture typically exhibit high phosphocholine and total choline. Treatment of cancer cells with the anti-inflammatory agent, indomethacin (INDO, reverted the phenotype of choline phospholipid metabolites in cancer cells towards a less malignant phenotype. Since endothelial cells form a key component of tumor vasculature, in this study, we used MR spectroscopy to characterize the phenotype of choline phospholipid metabolites in human umbilical vein endothelial cells (HUVECs. We determined the effect of growth factors, the anti-inflammatory agent INDO, and conditioned media obtained from a malignant cell line, on choline phospholipid metabolites. Growth factor depletion or treatment with INDO induced similar changes in the choline phospholipid metabolites of HUVECs. Treatment with conditioned medium obtained from MDA-MB-231 cancer cells induced changes similar to the presence of growth factor supplements. These results suggest that cancer cells secrete growth factors and/or other molecules that influence the choline phospholipid metabolism of HUVECs. The ability of INDO to alter choline phospholipid metabolism in the presence of growth factor supplements suggests that the inflammatory response pathways of HUVECs may play a role in cancer cell-HUVEC interaction and in the response of HUVECs to growth factors.

  2. Nonsmall Cell Lung Cancer Therapy: Insight into Multitargeted Small-Molecule Growth Factor Receptor Inhibitors

    Directory of Open Access Journals (Sweden)

    Mridul Roy

    2013-01-01

    Full Text Available To date, lung cancer is the leading cause of cancer-related death worldwide, among which nonsmall cell lung cancer (NSCLC comprises about 85%. Taking into account the side effects of surgery, radiation, platinum-based doublet chemotherapy, and the growth self-sufficiency characteristic of cancer cells, drugs have been discovered toward growth factor receptor (GFR to treat NSCLC. As expected, these drugs provide a greater benefit. To increase the efficacy of such growth factor receptor tyrosine kinase inhibitors (RTKIs, coinhibition of GFR signaling pathways and combination of inhibitors along with radiation or chemotherapy have drew intense insight. Although clinical trials about single-agent RTKIs or their combination strategies suggest their increase potency against cancer, they are not beyond adverse effects, and sometimes the effects are more deadly than chemotherapy. Nevertheless the hope for RTKIs may be proved true by further researches and digging deep into cancer therapeutics.

  3. Impairments that Influence Physical Function among Survivors of Childhood Cancer

    Directory of Open Access Journals (Sweden)

    Carmen L. Wilson

    2015-01-01

    Full Text Available Children treated for cancer are at increased risk of developing chronic health conditions, some of which may manifest during or soon after treatment while others emerge many years after therapy. These health problems may limit physical performance and functional capacity, interfering with participation in work, social, and recreational activities. In this review, we discuss treatment-induced impairments in the endocrine, musculoskeletal, neurological, and cardiopulmonary systems and their influence on mobility and physical function. We found that cranial radiation at a young age was associated with a broad range of chronic conditions including obesity, short stature, low bone mineral density and neuromotor impairments. Anthracyclines and chest radiation are associated with both short and long-term cardiotoxicity. Although numerous chronic conditions are documented among individuals treated for childhood cancer, the impact of these conditions on mobility and function are not well characterized, with most studies limited to survivors of acute lymphoblastic leukemia and brain tumors. Moving forward, further research assessing the impact of chronic conditions on participation in work and social activities is required. Moreover, interventions to prevent or ameliorate the loss of physical function among children treated for cancer are likely to become an important area of survivorship research.

  4. Modeling cancer growth and its treatment by means of statistical mechanics entropy

    Science.gov (United States)

    Khordad, R.; Rastegar Sedehi, H. R.

    2016-08-01

    In this paper, we have modeled cancer growth and its treatment based on nonextensive entropies. To this end, five nonextensive entropies are employed to model the cancer growth. The used entropies are Tsallis, Rényi, Landsberg-Vedral, Abe and Escort. First, we have proposed the growth of cancer tumor as a function of time for all the entropies with different nonextensive parameter q. When the time passes, the entropies show a bounded growth for cancer tumor size. The speed of tumor size growth is different for all the entropies. The Tsallis and Escort ones have highest and lowest speed, respectively. For q>1, the Escort entropy cannot predict a bounded growth for cancer tumor size. Then, we have investigated the cancer tumor treatment by adding a cell-kill function to the evolution equation. For q1, a cell-kill term is a suitable case. According to the results, it is found that the nonextensive parameter q, type of entropy, and cell-kill function are important factors for modeling the cancer growth and its treatment.

  5. Post-traumatic growth among elderly women with breast cancer compared to breast cancer-free women

    DEFF Research Database (Denmark)

    Brix, Sofie Andersen; Bidstrup, Pernille Envold; Christensen, Jane

    2013-01-01

    Although breast cancer (BC) may have negative psychological sequelae, it may also be experienced as an existential challenge, which can derive personal growth. Only one study has been conducted, however, on whether women with BC experience more post-traumatic growth (PTG) than BC-free women. We...

  6. beta-Sitosterol inhibits HT-29 human colon cancer cell growth and alters membrane lipids.

    Science.gov (United States)

    Awad, A B; Chen, Y C; Fink, C S; Hennessey, T

    1996-01-01

    The purpose of the present study was to examine the effect of beta-sitosterol, the main dietary phytosterol on the growth of HT-29 cells, a human colon cancer cell line. In addition, the incorporation of this phytosterol into cellular membranes and how this might influence the lipid composition of the membranes were investigated. Tumor cells were grown in DMEM containing 10% FBS and supplemented with sterols (cholesterol or beta-sitosterol) at final concentrations up to 16 microM. The sterols were supplied to the media in the form of sterol cyclodextrin complexes. The cyclodextrin used was 2-hydroxypropyl-beta-cyclodextrin. The sterol to cyclodextrin molar ratio was maintained at 1:300. The study indicated that 8 and 16 microM beta-sitosterol were effective at cel growth inhibition as compared to cholesterol or to the control (no sterol supplementation). After supplementation with 16 microM beta-sitosterol for 9 days, cell growth was only one-third that of cells supplemented with equimolar concentration of cholesterol. No effect was observed on total membrane phospholipid concentration. At 16 microM beta-sitosterol supplementation, membrane cholesterol was reduced by 26%. Cholesterol supplementation resulted in a significant increase in the cholesterol/phospholipid ratio compared to either beta-sitosterol supplemented cells or controls. There was a 50% reduction in membrane sphingomyelin (SM) of cells grown in 16 microM beta-sitosterol. Additional changes were observed in the fatty acid composition of minor phospholipids of beta-sitosterol supplemented cells, such as SM, phosphatidylserine (PS), and phosphatidylinositol (PI). Only in the case of PI, was there an effect of these fatty acid changes on the unsaturation index, beta-sitosterol incorporation resulted in an increase in the U.I. It is possible that the observed growth inhibition by beta-sitosterol may be mediated through the influence of signal transduction pathways that involve membrane phospholipids.

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

  8. Transforming growth factor-β signaling and cancer: the 28th Sapporo Cancer Seminar, 25-27 June 2008.

    Science.gov (United States)

    Miyazono, Kohei

    2009-02-01

    The Sapporo Cancer Seminars have been held annually since 1981. The 28th Sapporo Cancer Seminar was held on 26-27 June 2008 at the Hokkaido University Conference Hall, focusing on transforming growth factor (TGF)-β signaling and cancer. More than 150 scientists participated in the seminar, and it provided a great deal of information on the role of TGF-β signaling in carcinogenesis and tumor metastasis. The possible use of TGF-β antagonists for treatment of cancers was also discussed at the seminar.

  9. Dynamic response of cancer under the influence of immunological activity and therapy

    NARCIS (Netherlands)

    De Vladar, H.P.; Gonzalez, J.A.

    2004-01-01

    The dynamical basis of tumoral growth has been controversial. Many models have been proposed to explain cancer development. The descriptions employ exponential, potential, logistic or Gompertzian growth laws. Some of these models are concerned with the interaction between cancer and the immunologica

  10. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes.

    Directory of Open Access Journals (Sweden)

    Geetanjali Kharmate

    Full Text Available Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa. However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it is unknown whether exosomes derived from PCa cells or PCa patient serum contains EGFR. The aim of this study was to detect and characterize EGFR in exosomes derived from PCa cells, LNCaP xenograft and PCa patient serum. Exosomes were isolated from conditioned media of different PCa cell lines; LNCaP xenograft serum as well as patient plasma/serum by differential centrifugation and ultracentrifugation on a sucrose density gradient. Exosomes were confirmed by electron microscopy, expression of exosomal markers and NanoSight™ analysis. EGFR expression was determined by western blot analysis and ELISA. This study demonstrates that exosomes may easily be derived from PCa cell lines, serum obtained from PCa xenograft bearing mice and clinical samples derived from PCa patients. Presence of exosomal EGFR in PCa patient exosomes may present a novel approach for measuring of the disease state. Our work will allow to build on this finding for future understanding of PCa exosomes and their potential role in PCa progression and as minimal invasive biomarkers for PCa.

  11. Inhibition of Androgen-Independent Growth of Prostate Cancer by siRNA- Mediated Androgen Receptor Gene Silencing

    Science.gov (United States)

    2008-02-01

    Center, Kansas City, KS 66160, USA Introduction Prostate cancer is the most common cancer diagnosed after skin cancers and the... cancer cell growth: androgen regulation of CDK2, CDK4 , and CKI p16 genes. Cancer Res. 1997; 57:4511-4516. 109. Gregory CW, Hamil KG, Kim D, Hall SH...the most diagnosed non- skin cancer and the second leading cause of cancer -related death [2]. Currently, prostate-specific antigen (PSA) is the most

  12. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    Science.gov (United States)

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer.

  13. Cancer Secretome May Influence BSP and DSP Expression in Human Salivary Gland Cells.

    Science.gov (United States)

    Hamilton, Samantha Lynn; Ferando, Blake; Eapen, Asha Sarah; Yu, Jennifer Chian; Joy, Anita Rose

    2017-03-01

    One of the biggest challenges in managing head and neck cancers, especially salivary gland cancers, is the identification of secreted biomarkers of the disease that can be evaluated noninvasively. A relevant source of enriched tumor markers could potentially be found in the tumor secretome. Although numerous studies have evaluated secretomes from various cancers, the influence of the cancer secretome derived from salivary gland cancers on the behavior of normal cells has not yet been elucidated. Our data indicate that secretome derived from salivary gland cancer cells can influence the expression of two potential biomarkers of oral cancer-namely, bone sialoprotein (BSP) and dentin sialoprotein (DSP)-in normal salivary gland cells. Using routine immunohistochemistry, immunofluorescence, and immunoblotting techniques, we demonstrate an enrichment of BSP and DSP in human salivary gland (HSG) cancer tissue, unique localizations of BSP and DSP in HSG cancer cells, and enriched expression of BSP and DSP in normal salivary gland cells exposed to a cancer secretome. The secretome domain of the cancer microenvironment could alter signaling cascades responsible for normal cell proliferation, migration, and invasion, thus enhancing cancer cell survival and the potential for cancer progression. The cancer secretome may be critical in maintaining and stimulating "cancer-ness," thus potentially promoting specific hallmarks of metastasis.

  14. Knockdown of cullin 4A inhibits growth and increases chemosensitivity in lung cancer cells.

    Science.gov (United States)

    Hung, Ming-Szu; Chen, I-Chuan; You, Liang; Jablons, David M; Li, Ya-Chin; Mao, Jian-Hua; Xu, Zhidong; Lung, Jr-Hau; Yang, Cheng-Ta; Liu, Shih-Tung

    2016-07-01

    Cullin 4A (Cul4A) has been observed to be overexpressed in various cancers. In this study, the role of Cul4A in the growth and chemosensitivity in lung cancer cells were studied. We showed that Cul4A is overexpressed in lung cancer cells and tissues. Knockdown of the Cul4A expression by shRNA in lung cancer cells resulted in decreased cellular proliferation and growth in lung cancer cells. Increased sensitivity to gemcitabine, a chemotherapy drug, was also noted in those Cul4A knockdown lung cancer cells. Moreover, increased expression of p21, transforming growth factor (TGF)-β inducible early gene-1 (TIEG1) and TGF beta-induced (TGFBI) was observed in lung cancer cells after Cul4A knockdown, which may be partially related to increased chemosensitivity to gemcitabine. G0/G1 cell cycle arrest was also noted after Cul4A knockdown. Notably, decreased tumour growth and increased chemosensitivity to gemcitabine were also noted after Cul4A knockdown in lung cancer xenograft nude mice models. In summary, our study showed that targeting Cul4A with RNAi or other techniques may provide a possible insight to the development of lung cancer therapy in the future.

  15. Factors influencing the attitudes of Chinese cancer patients and their families toward the disclosure of a cancer diagnosis.

    Science.gov (United States)

    Sun, Wenwen; Wang, Zhehai; Fang, Shu; Li, Minmin

    2015-03-01

    The disclosure of a cancer diagnosis to patients has been a core topic in oncology departments. Previous studies have demonstrated that Chinese cancer patients and their families differ in their attitudes toward cancer diagnosis disclosure. However, the influencing factors regarding their different attitudes remain unknown. In the present study, a questionnaire was delivered to 266 cancer patients and 266 matched family members. The results showed that cancer patients were more likely to desire to be informed of their condition than family members (85 vs. 18%, P cancer, 16.5% expected to reduce the severity of their condition, and 4.9% expected to lengthen their lives. Therefore, physicians have a responsibility to appropriately provide knowledge regarding cancer to the patients' families if their educational level is lower and if they have no knowledge of recent treatments, which may improve their acceptability of a cancer diagnosis for patients.

  16. Smoking, green tea consumption, genetic polymorphisms in the insulin-like growth factors and lung cancer risk.

    Science.gov (United States)

    Lin, I-Hsin; Ho, Ming-Lin; Chen, Hsuan-Yu; Lee, Hong-Shen; Huang, Chia-Chen; Chu, Yin-Hung; Lin, Shiau-Yun; Deng, Ya-Ru; He, Yu-Hao; Lien, Yu-Hui; Hsu, Chi-Wen; Wong, Ruey-Hong

    2012-01-01

    Insulin-like growth factors (IGFs) are mediators of growth hormones; they have an influence on cell proliferation and differentiation. In addition, IGF-binding protein (IGFBP)-3 could suppress the mitogenic action of IGFs. Interestingly, tea polyphenols could substantially reduce IGF1 and increase IGFBP3. In this study, we evaluated the effects of smoking, green tea consumption, as well as IGF1, IGF2, and IGFBP3 polymorphisms, on lung cancer risk. Questionnaires were administered to obtain the subjects' characteristics, including smoking habits and green tea consumption from 170 primary lung cancer cases and 340 healthy controls. Genotypes for IGF1, IGF2, and IGFBP3 were identified by polymerase chain reaction. Lung cancer cases had a higher proportion of smoking, green tea consumption of less than one cup per day, exposure to cooking fumes, and family history of lung cancer than controls. After adjusting the confounding effect, an elevated risk was observed in smokers who never drank green tea, as compared to smokers who drank green tea more than one cup per day (odds ratio (OR) = 13.16, 95% confidence interval (CI) = 2.96-58.51). Interaction between smoking and green tea consumption on lung cancer risk was also observed. Among green tea drinkers who drank more than one cup per day, IGF1 (CA)(19)/(CA)(19) and (CA)(19)/X genotypes carriers had a significantly reduced risk of lung cancer (OR = 0.06, 95% CI = 0.01-0.44) compared with IGF1 X/X carriers. Smoking-induced pulmonary carcinogenesis could be modulated by green tea consumption and their growth factor environment.

  17. Smoking, green tea consumption, genetic polymorphisms in the insulin-like growth factors and lung cancer risk.

    Directory of Open Access Journals (Sweden)

    I-Hsin Lin

    Full Text Available Insulin-like growth factors (IGFs are mediators of growth hormones; they have an influence on cell proliferation and differentiation. In addition, IGF-binding protein (IGFBP-3 could suppress the mitogenic action of IGFs. Interestingly, tea polyphenols could substantially reduce IGF1 and increase IGFBP3. In this study, we evaluated the effects of smoking, green tea consumption, as well as IGF1, IGF2, and IGFBP3 polymorphisms, on lung cancer risk. Questionnaires were administered to obtain the subjects' characteristics, including smoking habits and green tea consumption from 170 primary lung cancer cases and 340 healthy controls. Genotypes for IGF1, IGF2, and IGFBP3 were identified by polymerase chain reaction. Lung cancer cases had a higher proportion of smoking, green tea consumption of less than one cup per day, exposure to cooking fumes, and family history of lung cancer than controls. After adjusting the confounding effect, an elevated risk was observed in smokers who never drank green tea, as compared to smokers who drank green tea more than one cup per day (odds ratio (OR = 13.16, 95% confidence interval (CI = 2.96-58.51. Interaction between smoking and green tea consumption on lung cancer risk was also observed. Among green tea drinkers who drank more than one cup per day, IGF1 (CA(19/(CA(19 and (CA(19/X genotypes carriers had a significantly reduced risk of lung cancer (OR = 0.06, 95% CI = 0.01-0.44 compared with IGF1 X/X carriers. Smoking-induced pulmonary carcinogenesis could be modulated by green tea consumption and their growth factor environment.

  18. Surface Relief Influence on Rheed Oscillations Shape During MBE Growth

    Science.gov (United States)

    1998-06-01

    During MBE Growth DISTRIBUTION: Approved for public release, distribution unlimited Availability: Hard copy only. This paper is part of the following...during MBE growth 1. G. Neizvestny, N L. Shwartz and Z. Sh. Yanovitskaya Institute of Semiconductor Physics RAS, Russia, Novosibirsk 90, pr...microrelief of growing film is demonstrated. Simulation of MBE growth process was carried out by Monte Carlo method in assumption of the SOS deposition on the

  19. Cell motility and ECM proteolysis regulate tumor growth and tumor relapse by altering the fraction of cancer stem cells and their spatial scattering

    Science.gov (United States)

    Kumar, Sandeep; Kulkarni, Rahul; Sen, Shamik

    2016-06-01

    Tumors consist of multiple cell sub-populations including cancer stem cells (CSCs), transiently amplifying cells and terminally differentiated cells (TDCs), with the CSC fraction dictating the aggressiveness of the tumor and drug sensitivity. In epithelial cancers, tumor growth is influenced greatly by properties of the extracellular matrix (ECM), with cancer progression associated with an increase in ECM density. However, the extent to which increased ECM confinement induced by an increase in ECM density influences tumor growth and post treatment relapse dynamics remains incompletely understood. In this study, we use a cellular automata-based discrete modeling approach to study the collective influence of ECM density, cell motility and ECM proteolysis on tumor growth, tumor heterogeneity, and tumor relapse after drug treatment. We show that while increased confinement suppresses tumor growth and the spatial scattering of CSCs, this effect can be reversed when cells become more motile and proteolytically active. Our results further suggest that, in addition to the absolute number of CSCs, their spatial positioning also plays an important role in driving tumor growth. In a nutshell, our study suggests that, in confined environments, cell motility and ECM proteolysis are two key factors that regulate tumor growth and tumor relapse dynamics by altering the number and spatial distribution of CSCs.

  20. Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development.

    Science.gov (United States)

    Mueller, Kristina M; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P; Moriggl, Richard

    2012-09-25

    Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5-GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development.

  1. Type 1 insulin-like growth factor receptor monoclonal antibody (HX-1162 treatment for liver cancer

    Directory of Open Access Journals (Sweden)

    Chen XH

    2013-05-01

    Full Text Available Xue-Hui Chen, Zhi-Qiang Li, Hua Peng, Su-Mei Jin, Hui-Qing Fu, Tie-Chui Zhu, Xiao-Gang WengThe First Affiliated Hospital of Xinxiang Medical University, Weihui, People's Republic of ChinaAbstract: One of the most important molecules mediating the proliferation, growth, and metastasis of cancer cells is insulin-like growth factor (IGF, with its receptor IGF-R1. Here, we describe the potential of an IGF-1R monoclonal antibody, HX-1162, on liver cancer apoptosis in vitro and in vivo. We found that HX-1162 could induce the apoptosis of cultured liver cancer cells. Additionally, HX-1162 treatment inhibited the tumor growth after cancer cell grafting and enhanced the cell apoptosis inside the tumor tissue. We conclude that IGF-R1 targeting therapy provides a new avenue toward treating liver cancer.Keywords: IGF, IGF-R1, apoptosis, hepatocellular carcinoma

  2. Development of a growth-hormone-conjugated nanodiamond complex for cancer therapy.

    Science.gov (United States)

    Chu, Hsueh-Liang; Chen, Hung-Wei; Tseng, Shin-Hua; Hsu, Ming-Hua; Ho, Li-Ping; Chou, Fu-Hsuan; Li, Md Phd Hsing-Yuan; Chang, Yu-Chuan; Chen, Pei-Hsin; Tsai, Li-Yun; Chou, Ching-Chung; Chen, Jyh Shin; Cheng, Tsai-Mu; Chang, Chia-Ching

    2014-05-01

    It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH-nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a "nanoblast" and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.

  3. Sonic hedgehog pathway contributes to gastric cancer cell growth and proliferation.

    Science.gov (United States)

    Wan, Jianhua; Zhou, Ji; Zhao, Hailong; Wang, Mei; Wei, Zhuanqin; Gao, Hongyan; Wang, Yongzhong; Cui, Hongjuan

    2014-04-01

    The Sonic Hedgehog (Shh) signaling pathway is commonly activated in gastrointestinal cancer. However, our understanding of the Shh pathway in gastric cancer remains limited. Here we examined the effects of cyclopamine, a specific inhibitor of the Shh signaling pathway, on cell growth and proliferation in gastric primary cancer cells GAM-016 and the MKN-45 cell line. The results showed that the Shh signaling molecules SHH, PTCH, SMO, GLI1, and GLI2 were intact and activated in both types of cells. Furthermore, we observed that cyclopamine inhibited gastric cancer cell proliferation through cell cycle arrest and apoptosis. An in vivo study using NOD/SCID mouse xenografts demonstrated that cyclopamine significantly prevented tumor growth and development. Our study indicated that Shh signaling pathway could promote gastric cancer cell proliferation and tumor development, and blocking this pathway may be a potential strategy in gastric cancer treatment.

  4. Association between thyroid cancer and epidermal growth factor receptor mutation in female with nonsmall cell lung cancer

    Science.gov (United States)

    Kim, Seo Yun; Kim, Hye-Ryoun; Kim, Cheol Hyeon; Koh, Jae Soo; Baek, Hee Jong; Choi, Chang-Min; Song, Joon Seon; Lee, Jae Cheol; Na, Im II

    2017-01-01

    BACKGROUND: The aim of this study was to investigate the association between epidermal growth factor receptor (EGFR) mutation and thyroid cancer in female patients with nonsmall-cell lung cancer (NSCLC). METHODS: In a retrospective study, we examined 835 female patients who were diagnosed with NSCLC and underwent an EGFR mutation test between June 2003 and August 2013. The associations of EGFR mutation with thyroid cancer and a family history of thyroid cancer were evaluated using logistic regression models. RESULTS: EGFR mutation was found in 378 of 835 patients. In addition to adenocarcinoma (P cancer (5.8% versus 2.6%; P = 0.020), while showing a trend toward inverse association with a personal history of nonthyroid cancer (5.8% vs. 9.0%; P = 0.086). Likewise, the incidence of EGFR mutations was associated with a family history of thyroid cancer (2.9% vs. 0.9%; P = 0.028), while showing a trend toward inverse association with a family history of nonthyroid cancer (27.8% vs. 33.7%; P = 0.066). Multivariate logistic regression showed that the incidence of EGFR mutations was different in women with thyroid or nonthyroid cancer (P = 0.035) and in women with a family history of thyroid or nonthyroid cancer (P = 0.023). CONCLUSIONS: Our data suggest that thyroid cancer and a family history of thyroid cancer are associated with EGFR-mutated NSCLC in female patients. The differences in the incidence of thyroid cancer and a family history of thyroid cancer by EGFR mutational status provide new insight into pathogenesis of this genetic change.

  5. TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

    Science.gov (United States)

    Haricharan, Svasti; Brown, Powel

    2015-06-23

    Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

  6. Increased concentrations of growth factors and activation of the EGFR system in breast cancer

    DEFF Research Database (Denmark)

    Aalund Olsen, Dorte; Bechmann, Troels; Østergaard, Birthe;

    2012-01-01

    In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values.......In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values....

  7. The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread

    Science.gov (United States)

    2014-12-01

    home to tissue injury. Monocyte polarization into the classically activated pro- inflam - matory macrophages (M1) occurs early on in tissue repair, whereas...AWARD NUMBER: W81XWH-12-1-0438 TITLE: The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread PRINCIPAL INVESTIGATOR...SUBTITLE The Role of Mesenchymal Stem Cells in Promoting Ovarian Cancer Growth and Spread 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0438 5c

  8. Novel Tissue‐Specific Mechanism of Regulation of Angiogenesis and Cancer Growth in Response to Hyperglycemia

    OpenAIRE

    Bhattacharyya, Sanghamitra; Sul, Kristina; Krukovets, Irene; Nestor, Carla; Li, Jianbo; Adognravi, Olga Stenina

    2012-01-01

    Background Hyperglycemia is an independent risk factor for the development of vascular diabetic complications, which are characterized by endothelial dysfunction and tissue‐specific aberrant angiogenesis. Tumor growth is also dependent on angiogenesis. Diabetes affects several cancers in a tissue‐specific way. For example, it positively correlates with the incidence of breast cancer but negatively correlates with the incidence of prostate cancer. The tissue‐specific molecular mechanisms activ...

  9. Alternate Splicing of CD44 Messenger RNA in Prostate Cancer Growth

    Science.gov (United States)

    2009-10-01

    and found them to act somewhat differently in prostate cancer . 5. Because of the interest at Univ. of Colorado in the nutritional chemoprevention...growth and invasion [1-6]. Silibinin is a nutritional supplement that has gained attention as intervention to prevent or treat cancer ...pathways. [12] matrix [13] 1 protein in gastric epithelial [14] tate cancer cell invasion. [15] . [17] erson AS, Agarwal R, [18] [19] on of

  10. Cross-cultural correlations of childhood growth and adult breast cancer.

    Science.gov (United States)

    Micozzi, M S

    1987-08-01

    International differences in breast cancer incidence and mortality, and studies on Japanese migrants to the United States, point to the importance of environmental factors, including diet and nutrition, in the etiology of breast cancer. Some studies have suggested that dietary patterns in early life are important to the long-term risk of breast cancer. Given that human growth is partially a function of early dietary intake, cross-cultural correlations between breast cancer rates and anthropometric variables measured at different times in childhood provide additional information about the association of early nutrition and cancer. In this study, the associations between food consumption and anthropometric variables, and childhood growth patterns (attained size at age) and adult breast cancer rates, were considered. Data from cross-sectional growth studies conducted during the years 1956-1971 on children aged 6-18 years were obtained for age-specific stature, sitting height, weight, triceps skinfold thickness, arm and chest circumferences, and biacromial and biiliac diameters. National food consumption data were obtained from the United Nations Food and Agriculture Organization (FAO) and socioeconomic status indicators from the United Nations Children's Fund (UNICEF). Cancer incidence data for the years 1972-1977 were obtained from regional cancer registries reported by the International Agency for Research on Cancer (IARC), and mortality data for 1978 were obtained from national cancer registries around the world. Significant correlations were seen between national food consumption data and childhood growth (attained size at age); between cancer incidence and age-specific stature (r = 0.68), weight (r = 0.59), triceps skinfold thickness (r = 0.78), and biacromial width (r = 0.84); and between mortality and age-specific stature (r = 0.77), weight (r = 0.75), and biacromial width (r = 0.78). In general, the correlation coefficients of the observed anthropometric

  11. Complement-mediated tumour growth: implications for cancer nanotechnology and nanomedicines

    DEFF Research Database (Denmark)

    Moghimi, S. M.; Andresen, Thomas Lars

    2009-01-01

    The recent unexpected observation that complement activation helps turnout growth and progression has an important bearing on the future development of cancer nanomedicines for site-specific tumour targeting as these entities are capable of triggering complement. These issues are discussed...... and suggestions are provided for future design and development of safer and effective cancer nanomedicines....

  12. Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Szlachcic A

    2016-08-01

    Full Text Available Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Abstract: Fibroblast growth factor receptors (FGFRs are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V, was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE, and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The FGF1V–valine–citrulline–MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V–vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. Keywords: fibroblast growth factor 1, FGF receptor, targeted cancer therapy, cytotoxic conjugates, FGFR-dependent cancer, MMAE, auristatin

  13. Empirical analysis of influence on economic growth of China by income distribution difference

    Institute of Scientific and Technical Information of China (English)

    LIU Zhen-biao; CHEN Xiao-hong

    2005-01-01

    Based on a theoretic hypothesis that income inequality has both positive and negative effect on economic growth, this paper analyzes the influence of income distribution differences on economic growth of China by establishing a multivariate linear regression model. The influence of income distribution difference on the economic growth of China changes with the change of time. During a short period immediately after China implemented reform and opening up policy, income inequality has a positive influence on the economic growth of China. However, along with the passing of time, such positive influence has become weaker and weaker and even convertes into negative effective. This paper proposes several advices with policy to restrain the difference of income distribution from expanding and weaken its negative effect on economic growth of China.

  14. [Influence endophytic bacteria to promote plants growth in stress conditions].

    Science.gov (United States)

    Napora, Anna; Kacprzak, Małgorzata; Nowak, Kamil; Grobelak, Anna

    2015-01-01

    The growth of plants under stress conditions is often assisted by microorganisms colonizing the rhizosphere (the root zone of the highest microbial activity). One of the most important bacterial groups to encourage the growth of plants (PGPB) are endophytes. These microorganisms penetrate living cells of plants and there they lead the microbiological activity as endosymbionts. These microorganisms can effectively promote the growth of plants under stress conditions and stimulate biochemical activities: nitrogen fixation, production of growth hormones (auxins, cytokinins and gibberellins), reduction of the high concentration of ethylene as well as facilitation of the collection plant minerals and water. This paper is an attempt to summarize the current state of knowledge about the biochemical activity of bacterial endophytes.

  15. Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate.

    Science.gov (United States)

    Murray, Onika T; Wong, Chi C; Vrankova, Kvetoslava; Rigas, Basil

    2014-02-01

    Phospho-sulindac (P-S), a promising anticancer agent, is efficacious in pre-clinical models of human cancer and is apparently safe. Here, we studied the effect of P-S on pancreatic cancer growth. We found that P-S strongly inhibits the growth of human pancreatic cancer cells in vitro, is efficacious in inhibiting the growth of pancreatic xenografts in nude mice, and has an excellent safety profile. Microarray analysis revealed that P-S induced the expression of nuclear factor of activated T-cells, isoform c1 (NFATc1) gene. NFATc1, a calcineurin-responsive transcription factor associated with aggressive pancreatic cancer. The role of increased NFATc1 expression on the growth inhibitory effect of P-S on cancer growth was evaluated by silencing or by overexpressing it both in vitro and in vivo. We found that when the expression of NFATc1 was abrogated by RNAi, pancreatic cancer cells were more responsive to treatment with P-S. Conversely, overexpressing the NFATc1 gene made the pancreatic cancer cells less responsive to treatment with P-S. NFATc1 likely mediates drug resistance to P-S and is an unfavorable prognostic factor that predicts poor tumor response. We also demonstrated that NFATc1-mediated resistance can be overcome by cyclosporin A (CsA), an NFAT inhibitor, and that the combination of P-S and CsA synergistically inhibited pancreatic cancer cell growth. In conclusion, our preclinical data establish P-S as an efficacious drug for pancreatic cancer in preclinical models, which merits further evaluation.

  16. Influence of Acetylene on Growth of Sulfate-Respiring Bacteria

    OpenAIRE

    Payne, W J; Grant, M. A.

    1982-01-01

    At a concentration of 20% of the atmosphere of the culture flasks, acetylene inhibited growth and carbon dioxide production by Desulfovibrio desulfuricans and Desulfovibrio gigas. The bacteria did not reduce acetylene to ethylene, and neither acetylene dicarboxylic acid nor ethylene was inhibitory. At 10%, acetylene was partially inhibitory for the desulfovibrios. At 5%, acetylene impeded the rate but did not limit the extent of growth and catabolism of the desulfovibrios. Desulfotomaculum ru...

  17. Influence of hydrogen environments on crack growth in Inconel 718

    Science.gov (United States)

    Walter, R. J.; Chandler, W. T.

    1978-01-01

    The effect of hydrogen environments on sustained-load and cyclic-load crack growth in Inconel 718 was investigated using fracture-mechanics-type specimens. The sustained-load crack growth was determined to be a function of heat-treatment condition, temperature, and hydrogen pressure. The threshold stress intensity for subcritical crack growth was independent of hydrogen pressure at pressures greater than 21 MN/sq m (3000 psi). The cyclic-load crack growth rate in Inconel 718 at low and moderate stress intensity ranges increased with increasing hydrogen pressure. Decreasing the cyclic frequency from 1.0 to 0.1 Hz considerably increased the cyclic crack growth rate at 0.069 MN/sq m (10 psi) and at 68.9 MN/sq m (10,000 psi) hydrogen pressure. A series of measurements performed between 1.0 and 0.1 Hz showed that the crack growth rate increased as a complex function of the time per cycle.

  18. Tree growth and competition in an old-growth Picea abies forest of boreal Sweden: influence of tree spatial patterning

    Science.gov (United States)

    Fraver, Shawn; D'Amato, Anthony W.; Bradford, John B.; Jonsson, Bengt Gunnar; Jönsson, Mari; Esseen, Per-Anders

    2013-01-01

    Question: What factors best characterize tree competitive environments in this structurally diverse old-growth forest, and do these factors vary spatially within and among stands? Location: Old-growth Picea abies forest of boreal Sweden. Methods: Using long-term, mapped permanent plot data augmented with dendrochronological analyses, we evaluated the effect of neighbourhood competition on focal tree growth by means of standard competition indices, each modified to include various metrics of trees size, neighbour mortality weighting (for neighbours that died during the inventory period), and within-neighbourhood tree clustering. Candidate models were evaluated using mixed-model linear regression analyses, with mean basal area increment as the response variable. We then analysed stand-level spatial patterns of competition indices and growth rates (via kriging) to determine if the relationship between these patterns could further elucidate factors influencing tree growth. Results: Inter-tree competition clearly affected growth rates, with crown volume being the size metric most strongly influencing the neighbourhood competitive environment. Including neighbour tree mortality weightings in models only slightly improved descriptions of competitive interactions. Although the within-neighbourhood clustering index did not improve model predictions, competition intensity was influenced by the underlying stand-level tree spatial arrangement: stand-level clustering locally intensified competition and reduced tree growth, whereas in the absence of such clustering, inter-tree competition played a lesser role in constraining tree growth. Conclusions: Our findings demonstrate that competition continues to influence forest processes and structures in an old-growth system that has not experienced major disturbances for at least two centuries. The finding that the underlying tree spatial pattern influenced the competitive environment suggests caution in interpreting traditional tree

  19. Survivin gene silencing sensitizes prostate cancer cells to selenium growth inhibition

    Directory of Open Access Journals (Sweden)

    Liu Xichun

    2010-08-01

    Full Text Available Abstract Background Prostate cancer is a leading cause of cancer-related death in men worldwide. Survivin is a member of the inhibitor of apoptosis (IAP protein family that is expressed in the majority of human tumors including prostate cancer, but is barely detectable in terminally differentiated normal cells. Downregulation of survivin could sensitize prostate cancer cells to chemotherapeutic agents in vitro and in vivo. Selenium is an essential trace element. Several studies have shown that selenium compounds inhibit the growth of prostate cancer cells. The objective of this study is to investigate whether survivin gene silencing in conjunction with selenium treatment could enhance the therapeutic efficacy for prostate cancer and to elucidate the underlying mechanisms. Methods Expression of survivin was analyzed in a collection of normal and malignant prostatic tissues by immunohistochemical staining. In vitro studies were conducted in PC-3M, C4-2B, and 22Rv1 prostate cancer cells. The effect of selenium on survivin expression was analyzed by Western blotting and semi-quantitative RT-PCR. Survivin gene knockdown was carried out by transfecting cells with a short hairpin RNA (shRNA designed against survivin. Cell proliferation was quantitated by the 3-(4,5-Dimethylthiazol-2-yl- 2,5-Diphenyltetrazolium Bromide (MTT assay and apoptosis by propidium iodide staining followed by flow cytometry analysis. Finally, in vivo tumor growth assay was performed by establishing PC-3M xenograft in nude mice and monitoring tumor growth following transfection and treatment. Results We found that survivin was undetectable in normal prostatic tissues but was highly expressed in prostate cancers. Survivin knockdown or selenium treatment inhibited the growth of prostate cancer cells, but the selenium effect was modest. In contrast to what have been observed in other cell lines, selenium treatment had little or no effect on survivin expression in several androgen

  20. Do signal transduction cascades influence survival in triple-negative breast cancer? A preliminary study

    Science.gov (United States)

    Mumm, Jan-Niclas; Kölbl, Alexandra C; Jeschke, Udo; Andergassen, Ulrich

    2016-01-01

    Background Triple-negative breast cancer (TNBC) is a rather aggressive form of breast cancer, comprised by early metastasis formation and reduced overall survival of the affected patients. Steroid hormone receptors and the human epidermal growth factor receptor 2 are not overexpressed, limiting therapeutic options. Therefore, new treatment options have to be investigated. The aim of our preliminary study was to detect coherences between some molecules of intracellular signal transduction pathways and survival of patients with TNBC, in order to obtain some hints for new therapeutical solutions. Methods Thirty-one paraffin-embedded tumor tissue samples, which were determined to be negative for steroid hormone receptors as well as human epidermal growth factor receptor 2, were immunohistochemically stained for a number of signal transduction molecules from several signaling pathways. β-Catenin, HIF1α, MCL, Notch1, LRP6, XBP1, and FOXP3 were stained with specific antibodies, and their staining was correlated with patient survival by Kaplan–Meier analyses. Results Only two of the investigated molecules have shown correlation with overall survival. Cytoplasmic staining of HIF1α and centro-tumoral lymphocyte FOXP3 staining showed statistically significant correlations with survival. Conclusion The coherence of signal transduction molecules with survival of patients with TNBC is still controversially discussed in the literature. Our study comprises one more mosaic stone in the elucidation of these intracellular processes and their influences on patient outcome. Lots of research still has to be done in this field, but it would be worthwhile as it may offer new therapeutic targets for a group of patients with breast cancer, which is still hard to treat. PMID:27307757

  1. Integrative modelling of the influence of MAPK network on cancer cell fate decision.

    Directory of Open Access Journals (Sweden)

    Luca Grieco

    2013-10-01

    Full Text Available The Mitogen-Activated Protein Kinase (MAPK network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3 activating mutations.

  2. Bioactive food components, cancer cell growth limitation and reversal of glycolytic metabolism.

    Science.gov (United States)

    Keijer, Jaap; Bekkenkamp-Grovenstein, Melissa; Venema, Dini; Dommels, Yvonne E M

    2011-06-01

    Cancer cells are resistant to apoptosis and show a shift in energy production from mitochondrial oxidative phosphorylation to cytosolic glycolysis. Apoptosis resistance and metabolic reprogramming are linked in many cancer cells and both processes center on mitochondria. Clearly, mutated cancer cells escape surveillance and turn into selfish cells. However, many of the mechanisms that operate cellular metabolic control still function in cancer cells. This review describes the metabolic importance of glucose and glutamine, glycolytic enzymes, oxygen, growth cofactors and mitochondria and focuses on the potential role of bioactive food components, including micronutrients. The role of B- and A-vitamin cofactors in (mitochondrial) metabolism is highlighted and the cancer protective potential of omega-3 fatty acids and several polyphenols is discussed in relation to metabolic reprogramming, including the mechanisms that may be involved. Furthermore, it is shown that cancer cell growth reduction by limiting the growth cofactor folic acid seems to be associated with reversal of metabolic reprogramming. Altogether, reversal of metabolic reprogramming may be an attractive strategy to increase susceptibility to apoptotic surveillance. Food bioactive components that affect various aspects of metabolism may be important tools to reverse glycolytic to oxidative metabolism and enhance sensitivity to apoptosis. The success of such a strategy may depend on several actors, acting in concert. Growth cofactors may be one of these, which call for careful (re)evaluation of their function in normal and in cancer metabolism.

  3. Growth-inhibitory Effects of Curcumin on Ovary Cancer Cells and Its Mechanisms

    Institute of Scientific and Technical Information of China (English)

    郑丽端; 童强松; 吴翠环

    2004-01-01

    Summary: To study the growth-inhibitory ettects ot curcumin on human ovary cancer A2780 cells in vitro and its molecular mechanisms, the growth inhibition rates of A2780 cancer cells, after being treated with 10 μmol/L-50 μmol/L curcumin for 6-24 h, were examined by MTT method. The morphological changes of cancer cells were observed under inversion microscopy. Cellular apoptotic rates were determined by using TUNEL. The protein expression levels of bcl-2, p53 and MDM2 in cancer cells were examined by SP immunohistochemistry. After being treated by various concentrations of curcumin, the growth of cancer cells was inhibited significantly. Some cancer cells presented characteristic morphological changes of apoptosis. The rates of apoptosis were 6.41% -28.48% (P<0.01). The expression of bcl-2 and p53 was decreased, which depended on the action time (P<0.01). There were no obvious changes in MDM2 expression. It was concluded that curcumin could significantly inhibit the growth of ovary cancer cells. The induction of apoptosis by down-regulating the expression of bcl-2 and p53 was probably one of its molecular mechanisms.

  4. Growth of ZnO nanostructures on Au-coated Si: Influence of growth temperature on growth mechanism and morphology

    DEFF Research Database (Denmark)

    Kumar, Rajendra; McGlynn, E.; Biswas, M.;

    2008-01-01

    ZnO nanostructures were grown on Au-catalyzed Si silicon substrates using vapor phase transport at growth temperatures from 800 to 1150 degrees C. The sample location ensured a low Zn vapor supersaturation during growth. Nanostructures grown at 800 and 850 degrees C showed a faceted rodlike...... growth tended to dominate resulting in the formation of a porous, nanostructured morphology. In all cases growth was seen only on the Au-coated region. Our results show that the majority of the nanostructures grow via a vapor-solid mechanism at low growth temperatures with no evidence of Au nanoparticles...... morphology with mainly one-dimensional (1D) growth along the nanorod axis. Samples grown at intermediate temperatures (900, 950, and 1050 degrees C) in all cases showed significant three dimensional (3D) growth at the base of 1D nanostructures. At higher growth temperatures (1100 and 1150 degrees C) 3D...

  5. GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis.

    Science.gov (United States)

    Agarwal, Neeraj; Dancik, Garrett M; Goodspeed, Andrew; Costello, James C; Owens, Charles; Duex, Jason E; Theodorescu, Dan

    2016-09-01

    In principle, the inhibition of candidate gain-of-function genes defined through genomic analyses of large patient cohorts offers an attractive therapeutic strategy. In this study, we focused on changes in expression of CD24, a well-validated clinical biomarker of poor prognosis and a driver of tumor growth and metastasis, as a benchmark to assess functional relevance. Through this approach, we identified GON4L as a regulator of CD24 from screening a pooled shRNA library of 176 candidate gain-of-function genes. GON4L depletion reduced CD24 expression in human bladder cancer cells and blocked cell proliferation in vitro and tumor xenograft growth in vivo Mechanistically, GON4L interacted with transcription factor YY1, promoting its association with the androgen receptor to drive CD24 expression and cell growth. In clinical bladder cancer specimens, expression of GON4L, YY1, and CD24 was elevated compared with normal bladder urothelium. This pathway is biologically relevant in other cancer types as well, where CD24 and the androgen receptor are clinically prognostic, given that silencing of GON4L and YY1 suppressed CD24 expression and growth of human lung, prostate, and breast cancer cells. Overall, our results define GON4L as a novel driver of cancer growth, offering new biomarker and therapeutic opportunities. Cancer Res; 76(17); 5175-85. ©2016 AACR.

  6. Dabigatran Potentiates Gemcitabine-Induced Growth Inhibition of Pancreatic Cancer in Mice

    Science.gov (United States)

    Shi, Kun; Damhofer, Helene; Daalhuisen, Joost; ten Brink, Marieke; Richel, Dick J; Spek, C Arnold

    2017-01-01

    Pancreatic cancer is one of the most lethal solid malignancies, with few treatment options. We have recently shown that expression of protease activated receptor (PAR)-1 in the tumor microenvironment drives the progression and induces the chemoresistance of pancreatic cancer. As thrombin is the prototypical PAR-1 agonist, here we address the effects of the direct thrombin inhibitor dabigatran on pancreatic cancer growth and drug resistance in an orthotropic pancreatic cancer model. We show that dabigatran treatment did not affect primary tumor growth, whereas it significantly increased tumor dissemination throughout the peritoneal cavity. Increased dissemination was accompanied by intratumoral bleeding and increased numbers of aberrant and/or collapsed blood vessels in the primary tumors. In combination with gemcitabine, dabigatran treatment limited primary tumor growth, did not induce bleeding complications and prevented tumor cell dissemination. Dabigatran was, however, not as efficient as genetic ablation of PAR-1 in our previous study, suggesting that thrombin is not the main PAR-1 agonist in the setting of pancreatic cancer. Overall, we show that dabigatran potentiates gemcitabine-induced growth inhibition of pancreatic cancer but does not affect primary tumor growth when used as monotherapy. PMID:28182192

  7. Optimal control on bladder cancer growth model with BCG immunotherapy and chemotherapy

    Science.gov (United States)

    Dewi, C.; Trisilowati

    2015-03-01

    In this paper, an optimal control model of the growth of bladder cancer with BCG (Basil Calmate Guerin) immunotherapy and chemotherapy is discussed. The purpose of this optimal control is to determine the number of BCG vaccine and drug should be given during treatment such that the growth of bladder cancer cells can be suppressed. Optimal control is obtained by applying Pontryagin principle. Furthermore, the optimal control problem is solved numerically using Forward-Backward Sweep method. Numerical simulations show the effectiveness of the vaccine and drug in controlling the growth of cancer cells. Hence, it can reduce the number of cancer cells that is not infected with BCG as well as minimize the cost of the treatment.

  8. Anti-IL-20 Monoclonal Antibody Suppresses Prostate Cancer Growth and Bone Osteolysis in Murine Models.

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Hsu

    Full Text Available Interleukin (IL-20 is a proinflammatory cytokine in the IL-10 family. IL-20 is associated with tumor promotion in the pathogenesis of oral, bladder, and breast cancer. However, little is known about the role of IL-20 in prostate cancer. We hypothesize that IL-20 promotes the growth of prostate cancer cells. Immunohistochemical staining showed that IL-20 and its receptors were expressed in human PC-3 and LNCaP prostate cancer cell lines and in prostate tumor tissue from 40 patients. In vitro, IL-20 upregulated N-cadherin, STAT3, vimentin, fibronectin, RANKL, cathepsin G, and cathepsin K, and increased the migration and colony formation of prostate cancer cells via activated p38, ERK1/2, AKT, and NF-κB signals in PC-3 cells. We investigated the effects of anti-IL-20 monoclonal antibody 7E on prostate tumor growth in vivo using SCID mouse subcutaneous and intratibial xenograft tumor models. In vivo, 7E reduced tumor growth, suppressed tumor-mediated osteolysis, and protected bone mineral density after intratibial injection of prostate cancer cells. We conclude that IL-20 is involved in the cell migration, colony formation, and tumor-induced osteolysis of prostate cancer. Therefore, IL-20 might be a novel target for treating prostate cancer.

  9. Observation of dendritic growth under the influence of forced convection

    Science.gov (United States)

    Roshchupkina, O.; Shevchenko, N.; Eckert, S.

    2015-06-01

    The directional solidification of Ga-25wt%In alloys within a Hele-Shaw cell was visualized by X-ray radioscopy. The investigations are focused on the impact of melt convection on the dendritic growth. Natural convection occurs during a bottom up solidification because lighter solute is rejected during crystallization. Forced convection was produced by a specific electromagnetic pump. The direction of forced melt flow is almost horizontal at the solidification front. Melt flow induces various effects on grain morphology primarily caused by convective transport of solute, such as a facilitation of the growth of primary trunks or lateral branches, dendrite remelting, fragmentation or freckle formation depending on the dendrite orientation, the flow direction and intensity. Forced flow eliminates solutal plumes and damps local fluctuations of solute. A preferential growth of the secondary arms occurs at the upstream side of the dendrites, whereas high solute concentration at the downstream side inhibits the formation of secondary branches.

  10. Influence of corruption on economic growth rate and foreign investment

    Science.gov (United States)

    Podobnik, Boris; Shao, Jia; Njavro, Djuro; Ivanov, Plamen Ch.; Stanley, H. E.

    2008-06-01

    We analyze the dependence of the Gross Domestic Product ( GDP) per capita growth rates on changes in the Corruption Perceptions Index ( CPI). For the period 1999 2004 for all countries in the world, we find on average that an increase of CPI by one unit leads to an increase of the annual GDP per capita growth rate by 1.7%. By regressing only the European countries with transition economies, we find that an increase of CPI by one unit generates an increase of the annual GDP per capita growth rate by 2.4%. We also analyze the relation between foreign direct investments received by different countries and CPI, and we find a statistically significant power-law functional dependence between foreign direct investment per capita and the country corruption level measured by the CPI. We introduce a new measure to quantify the relative corruption between countries based on their respective wealth as measured by GDP per capita.

  11. ROLE OF RAC-1 DEPENDENT NADPH OXIDASE IN THE GROWTH OF PANCREATIC CANCER

    OpenAIRE

    2010-01-01

    K-ras mutations occur in as high as 95% of patients with pancreatic cancer. K-ras activates Rac1-dependent NADPH oxidase, a key source of superoxide. Superoxide plays an important role in pancreatic cancer cell proliferation and scavenging or decreasing the levels of superoxide inhibits pancreatic cancer cell growth both in vitro and in vivo. DNA microarray analysis and RT-PCR has demonstrated that Rac1 is also upregulated in pancreatic cancer. The aim of this study was to determine if inhibi...

  12. Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance.

    Science.gov (United States)

    Bhirde, Ashwinkumar A; Chikkaveeraiah, Bhaskara V; Srivatsan, Avinash; Niu, Gang; Jin, Albert J; Kapoor, Ankur; Wang, Zhe; Patel, Sachin; Patel, Vyomesh; Gorbach, Alexander M; Leapman, Richard D; Gutkind, J Silvio; Hight Walker, Angela R; Chen, Xiaoyuan

    2014-05-27

    Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells. The novel nanoformula with a cholanic acid-derivatized hyaluronic acid (CAHA) biopolymer wrapped around a sSWCNT and loaded with doxorubicin (DOX), CAHA-sSWCNT-DOX, is much more effective in killing drug-resistant cancer cells compared to the free DOX and phospholipid PEG (PL-PEG)-modified sSWCNT formula, PEG-sSWCNT-DOX. The CAHA-sSWCNT-DOX affects the viscoelastic property more than free DOX and PL-PEG-sSWCNT-DOX, which in turn allows more drug molecules to be internalized. Intravenous injection of CAHA-sSWCNT-DOX (12 mg/kg DOX equivalent) followed by 808 nm laser irradiation (1 W/cm(2), 90 s) led to complete tumor eradication in a subcutaneous OVCAR8/ADR drug-resistant xenograft model, while free DOX alone failed to delay tumor growth. Our newly developed CAHA-sSWCNT-DOX nanoformula, which delivers therapeutics and acts as a sensitizer to influence drug uptake and induce apoptosis with minimal resistance factor, provides a novel effective means of counteracting the phenomenon of multidrug resistance.

  13. Glycone-rich Soy Isoflavone Extracts Promote Estrogen Receptor Positive Breast Cancer Cell Growth.

    Science.gov (United States)

    Johnson, Kailee A; Vemuri, Sravan; Alsahafi, Sameerh; Castillo, Rudy; Cheriyath, Venugopalan

    2016-01-01

    Due to the association of hormone replacement therapy (HRT) with breast cancer risk, estrogenically active soy isoflavones are considered as an HRT alternative to alleviate menopausal symptoms. However, several recent reports challenged the health benefits of soy isoflavones and associated them with breast cancer promotion. While glyconic isoflavones are the major constituents of soybean seeds, due to their low cell permeability, they are considered to be biologically inactive. The glyconic isoflavones may exert their effects on membrane-bound estrogen receptors or could be converted to aglycones by extracellular β-glucosidases. Therefore, we hypothesized that despite their low cell permeability, soybean cultivars with high glyconic isoflavones may promote breast cancer cell growth. To test this, composition and estrogenic activity of isoflavones from 54 commercial soybean cultivars were determined. Soybean seeds produced in identical climate and growth conditions were used to minimize the effects of extraneous factors on isoflavone profile and concentrations. The glyconic daidzin concentration negatively correlated with genistin and with other aglycones. Relative to control, isoflavone extracts from 51 cultivars were estrogenic and promoted the growth of estrogen receptor positive (ER+) breast cancer cell line MCF-7 from 1.14 to 4.59 folds and other three cultivars slightly reduced the growth. Among these, extracts from three cultivars were highly estrogenic and promoted MCF-7 cell growth by 2.59-4.64 folds (Psoy isoflavone extracts may exert estrogenic effects and promote ER+ breast cancer growth.

  14. Urban Growth Areas, sphere of influence, truckee meadows service area, Published in 2006, Washoe County.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Urban Growth Areas dataset, was produced all or in part from Published Reports/Deeds information as of 2006. It is described as 'sphere of influence, truckee...

  15. Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer

    Science.gov (United States)

    Feng, Ming-Xuan; Wang, Ya-Hui; Yang, Xiao-Mei; He, Ping; Tian, Guang-Ang; Zhang, Xiao-Xin; Li, Qing; Cao, Xiao-Yan; Huo, Yan-Miao; Yang, Min-Wei; Fu, Xue-Liang; Li, Jiao; Liu, De-Jun; Dai, Miao; Wen, Shan-Yun; Gu, Jian-Ren; Hong, Jie; Hua, Rong; Zhang, Zhi-Gang; Sun, Yong-Wei

    2016-01-01

    Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein associated with vascular morphogenesis and remodeling, is commonly upregulated in multiple types of human cancers and correlates with tumor progression. However, its expression pattern and underlying cellular functions in pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. In current study, we observed that expression of EDIL3 was significantly up-regulated in PDAC compared with normal controls in both cell lines and clinical specimens. In addition, elevated EDIL3 expression was positively correlated with patients’ TNM stage and T classification. Kaplan-Meier analysis indicated that high EDIL3 expression was significantly associated with shorter overall survival times in PDAC patients. Multivariate Cox regression analysis confirmed EDIL3 expression, age, lymph node metastasis and histological differentiation as independent prognostic factors in PDAC. Knockdown of EDIL3 showed no significant influence on cell viability, migration, invasion and starvation-induced apoptosis, but compromised anoikis resistance and anchorage independent tumor growth of PDAC cells. Meanwhile, treatment with recombinant EDIL3 protein markedly promoted anoikis resistance and anchorage independent tumor growth. Mechanistically, we demonstrated that altered protein expression of Bcl-2 family might contribute to the oncogenic activities of EDIL3. In conclusion, this study provides evidences that EDIL3 is a potential predictor and plays an important role in anchorage independent tumor growth of PDAC and EDIL3-related pathways might represent a novel therapeutic strategy for treatment of pancreatic cancer. PMID:26735172

  16. Influence of maternal folate status on human fetal growth parameters

    NARCIS (Netherlands)

    van Uitert, Evelyne M.; Steegers-Theunissen, Regine P. M.

    2013-01-01

    Worldwide periconceptional folic acid supplement use is recommended to prevent neural tube defects. This also stimulated research on maternal folate status in association with fetal growth, an important predictor of perinatal and future development and health. We provide an overview of literature on

  17. Molecular mobility of scaffolds' biopolymers influences cell growth.

    Science.gov (United States)

    Podlipec, Rok; Gorgieva, Selestina; Jurašin, Darija; Urbančič, Iztok; Kokol, Vanja; Strancar, Janez

    2014-09-24

    Understanding biocompatibility of materials and scaffolds is one of the main challenges in the field of tissue engineering and regeneration. The complex nature of cell-biomaterial interaction requires extensive preclinical functionality testing by studying specific cell responses to different biomaterial properties, from morphology and mechanics to surface characteristics at the molecular level. Despite constant improvements, a more general picture of biocompatibility is still lacking and tailormade scaffolds are not yet available. The scope of our study was thus the investigation of the correlation of fibroblast cell growth on different gelatin scaffolds with their morphological, mechanical as well as surface molecular properties. The latter were thoroughly investigated via polymer molecular mobility studied by site-directed spin labeling and electron paramagnetic resonance spectroscopy (EPR) for the first time. Anisotropy of the rotational motion of the gelatin side chain mobility was identified as the most correlated quantity with cell growth in the first days after adhesion, while weaker correlations were found with scaffold viscoelasticity and no correlations with scaffold morphology. Namely, the scaffolds with highly mobile or unrestricted polymers identified with the cell growth being five times less efficient (N(cells) = 60 ± 25 mm(-2)) as compared to cell growth on the scaffolds with considerable part of polymers with the restricted rotational motion (N(cells) = 290 ± 25 mm(-2)). This suggests that molecular mobility of scaffold components could play an important role in cell response to medical devices, reflecting a new aspect of the biocompatibility concept.

  18. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Ryuta Tobe

    2011-09-01

    Full Text Available Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins. Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15 may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G0/G1 phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.

  19. Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yallapu Murali M

    2010-04-01

    Full Text Available Abstract Background Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. Methods Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid (PLGA nanoparticle formulation of curcumin (Nano-CUR was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. Results Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre

  20. Cancer targeted gene therapy of BikDD inhibits orthotopic lung cancer growth and improves long-term survival.

    Science.gov (United States)

    Sher, Y-P; Tzeng, T-F; Kan, S-F; Hsu, J; Xie, X; Han, Z; Lin, W-C; Li, L-Y; Hung, M-C

    2009-09-17

    Lung cancer is a leading cause of cancer death due to the high incidence of metastasis; therefore, novel and effective treatments are urgently needed. A current strategy is cancer-specific targeted gene therapy. Although many identified that cancer-specific promoters are highly specific, they tend to have low activity compared with the ubiquitous cytomegalovirus (CMV) promoter, limiting their application. We developed a targeted gene therapy expression system for lung cancer that is highly specific with strong activity. Our expression vector uses the survivin promoter, highly expressed in many cancers but not normal adult tissues. We enhanced the survivin promoter activity comparable to the CMV promoter in lung cancer cell lines using an established platform technology, whereas the survivin promoter remained weak in normal cells. In mouse models, the transgene was specifically expressed in the lung tumor tissue, compared with the CMV promoter that was expressed in both normal and tumor tissues. In addition, the therapeutic gene BikDD, a mutant form of pro-apoptotic Bcl2 interacting killer, induced cell killing in vitro, and inhibited cell growth and prolonged mouse survival in vivo. Importantly, there was virtually no toxicity when BikDD was expressed with our expression system. Thus, the current report provides a therapeutic efficacy and safe strategy worthy of development in clinical trials treating lung cancer.

  1. Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

    Directory of Open Access Journals (Sweden)

    Ashraf Soliman

    2014-01-01

    Full Text Available Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS. The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS.

  2. Roxatidine- and cimetidine-induced angiogenesis inhibition suppresses growth of colon cancer implants in syngeneic mice.

    Science.gov (United States)

    Tomita, Kazuyoshi; Izumi, Kazuki; Okabe, Susumu

    2003-11-01

    Cimetidine is known to suppress the growth of several tumors, including gastrointestinal cancer, in humans and animals. Nonetheless, whether other histamine H(2)-receptor antagonists exert such tumor suppressive effects remains unclear. The effect of roxatidine acetate hydrochloride (roxatidine), an H(2)-receptor antagonist, on the growth of colon cancer implanted in mice was examined and compared with that of cimetidine. Drugs were orally delivered for 26 - 29 days beginning before or after implantation of syngeneic colon cancer (Colon 38) in C57BL/6 mice. Tumor volume was determined throughout and histochemical analysis was also performed. Tumor tissue and serum vascular endothelial growth factor (VEGF) levels were measured. In vitro cell growth was assessed by the MTT assay. Both roxatidine and cimetidine significantly suppressed the growth of Colon 38 tumor implants. Histologic analysis revealed that such antagonists markedly increased necrotic areas and decreased the density of microvessels in tumor tissue. Both H(2)-receptor antagonists suppressed VEGF levels in tumor tissue and significantly decreased serum VEGF levels in Colon 38-bearing mice. Such drugs, however, failed to suppress in vitro growth of the cell line. In conclusion, both roxatidine and cimetidine were found to exert suppressive effects on the growth of colon cancer implants in mice by inhibiting angiogenesis via reducing VEGF expression.

  3. Growth and nutrition of cacao seedlings influenced by zinc application in soil

    Science.gov (United States)

    Levels of Zn in tropical soils profoundly influences growth and nutrition of tree crops . Research was undertaken to assess the effect of soil Zn on growth and nutrition of clonal cacao tree seedlings of PH 16. Three acidic Oxisol soils differing in texture were used with nine doses of Zn (0, 1, 2, ...

  4. Nitrogen forms and levels influence on growth and nutrition of cacao

    Science.gov (United States)

    Ammonium and nitrate are the major forms of N present in tropical soils. A climatically controlled growth chamber experiment was conducted to assess the influence of forms (NO3-, NH4+, and mix of NO3- + NH4+) and levels (1.5 to 12.0 mM) of N on the growth and nutrition of cacao (Theobroma cacao L). ...

  5. An alternative model of cancer cell growth and metastasis.

    Science.gov (United States)

    Vaidya, Jayant S

    2007-04-01

    I propose an alternative model of cancer in which metastasis need not all arise out of spread from the "original" tumour. The model assumes that cancer cells arise from stem cells that best grow in the organ of their differentiation. When the internal milieu allows it they also grow at other sites as well, thus complementing the conventional (spreading) metastatic process. Several phenomena in the natural history of cancer, especially breast cancer, that challenge the conventional model, fit well after inclusion of the new model. These are (a) a very modest benefit of screening (b) frequent sparing of lungs from haematogenous metastasis (c) presence of occult cancers in autopsy studies (d) only a modest effect of local treatment (e) relative ineffectiveness of high-dose chemotherapy (f) constant time between surgery and peak of hazard of relapse irrespective of stage of the tumour. All these phenomena are much easier to explain when one rejects the dogma that all metastasis arise only from the primary tumour. This paper is aimed only to suggest an alternative perspective of natural history of solid tumours--to stimulate research on the complex internal milieu that allows cancer cells to develop in new light.

  6. Enriched environment inhibits mouse pancreatic cancer growth and down-regulates the expression of mitochondria-related genes in cancer cells.

    Science.gov (United States)

    Li, Guohua; Gan, Yu; Fan, Yingchao; Wu, Yufeng; Lin, Hechun; Song, Yanfang; Cai, Xiaojin; Yu, Xiang; Pan, Weihong; Yao, Ming; Gu, Jianren; Tu, Hong

    2015-01-19

    Psycho-social stress has been suggested to influence the development of cancer, but it remains poorly defined with regard to pancreatic cancer, a lethal malignancy with few effective treatment modalities. In this study, we sought to investigate the impacts of enriched environment (EE) housing, a rodent model of "eustress", on the growth of mouse pancreatic cancer, and to explore the potential underlying mechanisms through gene expression profiling. The EE mice showed significantly reduced tumor weights in both subcutaneous (53%) and orthotopic (41%) models, while each single component of EE (inanimate stimulation, social stimulation or physical exercise) was not profound enough to achieve comparative anti-tumor effects as EE. The integrative transcriptomic and proteomic analysis revealed that in response to EE, a total of 129 genes in the tumors showed differential expression at both the mRNA and protein levels. The differentially expressed genes were mostly localized to the mitochondria and enriched in the citrate cycle and oxidative phosphorylation pathways. Interestingly, nearly all of the mitochondria-related genes were down-regulated by EE. Our data have provided experimental evidence in favor of the application of positive stress or of benign environmental stimulation in pancreatic cancer therapy.

  7. 15d-PGJ2 inhibits cell growth and induces apoptosis of MCG-803 human gastric cancer cell line

    Institute of Scientific and Technical Information of China (English)

    Yun-Xian Chen; Xue-Yun Zhong; Yan-Fang Qin; Wang Bing; Li-Zhen He

    2003-01-01

    AIM: To investigate the influence of peroxisome proliferator activated receptor γ (PPARγ) ligand, 15-deoxy-△12, 14-prostaglandin J2 (15dPGJ2) on the proliferation and apoptosis of MCG-803 human gastric cancer cell lines.METHODS: Cell proliferation was measured by 3H-TdR assay. Apoptosis was determined by ELISA and TUNEL staining. Protein and mRNA level of bcl-2 family and COXs were measured by Western blotting and Northern blotting respectively. PGE2 production was examined by RIA.RESULTS: 15dPGJ2 inhibited cell growth and induced apoptosis of MlCG-803 cells. The COX-2 and bcl-2/bax ratios were decreased following 15dPGJ2 treatment. The PGE2production in supernatants was also decreased. These changes were in a dose-dependent manner.CONCLUSION: 15dPGJ2 may be a useful therapeutic agent for the treatment of gastric cancer.

  8. Mechanistic basis and clinical relevance of the role of transforming growth factor-βin cancer

    Institute of Scientific and Technical Information of China (English)

    Run-Long Lin; Lu-Jun Zhao

    2015-01-01

    Transforming growth factor-β(TGF-β) is a key factor in cancer development and progression. TGF-βcan suppress tumorigenesis by inhibiting cell cycle progression and stimulating apoptosis in early stages of cancer progression. However, TGF-βcan modulate cancer-related processes, such as cell invasion, distant metastasis, and microenvironment modiifcation that may be used by cancer cells to their advantage in late stages. Corresponding mechanisms include angiogenesis promotion, anti-tumor immunity suppression, and epithelial-to-mesenchymal transition (EMT) induction. hTe correlation between TGF-βexpression and cancer prognosis has also been extensively investigated. Results suggest that TGF-βpathway can be targeted to treat cancer;as such, the feasibility of this treatment is investigated in clinical trials.

  9. [Influence of seedling assortment on Panax notoginseng growth and yield].

    Science.gov (United States)

    Cui, X; Wang, C; Chen, Z

    1998-02-01

    Making Panax notoginseng seedling assortment according to seedling size before transplanting, the result shows that the influence is better, the yield of root tuber and fruit is higher. Culturing good seedling is the fundamental measure to increase yield of P. notoginseng.

  10. Influence of lead tetraethyl on the growth of Funaria hygrometrica L. and Marchantia polymorpha L.

    Directory of Open Access Journals (Sweden)

    Irena Krupińska

    2015-05-01

    Full Text Available The influence of various lead tetraethyl concentrations (mixture added to petrol as antiknock agent on the growth and development of Funaria hygrometrica L. spores and of Marchantia polymorpha L. gemmulae was investigated. An inhibitory effect of the concentration applied was noted on germination and growth of spores and gemmulae development. Lead tetraethyl produces disturbances In the development of these plants, gradual degeneration of chloroplasts occurs and inhibition of growth leading to profusely branched "dwarf" forms. The disturbances are largely reversible.

  11. Genetic Influences on Temporomandibular Joint Development and Growth.

    Science.gov (United States)

    Hinton, Robert J; Jing, Junjun; Feng, Jian Q

    2015-01-01

    The temporomandibular joint (TMJ) is a small synovial joint at which the mandible articulates with the skull during movements involved in speaking and mastication. However, the secondary cartilage lining its joint surfaces is indicative of a very different developmental history than limb cartilages. This review summarizes our current knowledge of genes that regulate the formation of primary components of the TMJ, as well as genes that regulate postnatal growth of the TMJ. Although the TMJ is regulated by some of the same genes that are important in limb joints, others appear unique to the TMJ or have different actions. Runx2, Sox9, and members of the TGF-β/BMP family are critical drivers of chondrogenesis during condylar cartilage morphogenesis, and Indian hedgehog (Ihh) is important for formation of the articular disc and cavitation. Osterix (Osx) is a critical regulator of endochondral bone formation during postnatal TMJ growth.

  12. Growth Inhibition and Apoptosis Inducing Mechanisms of Curcumin on Human Ovarian Cancer Cell Line A2780

    Institute of Scientific and Technical Information of China (English)

    ZHENG Li-duan; TONG Qiang-song; WU Cui-huan

    2006-01-01

    Objective: To explore the growth inhibition effects and apoptosis inducing mechanisms of curcumin on human ovarian cancer cell line A2780. Methods: After treatment with 10-50 μmol/L curcumin for 6-24 h, the growth activity of A2780 cancer cells were studied by [ 4, 5-dimethylthiazol-2-yl]-2, 5-diphenyItetrazolium bromide (MTT) colorimetry. Cellular apoptosis was inspected by flow cytometery and acridine orange-ethidium bromide fluorescent staining methods. The fragmentation of cellular chromosome DNA was detected by DNA ladder, the ultrastructural change was observed under a transmission electron microscope,and the protein levels of nuclear factor-kappa B (NF-κB, P65) and cysteinyl aspartate specific protease-3 (Caspase-3) in ovarian cancer cells were measured by immunohistochemistry. Results: After treatment with various concentrations of curcumin, the growth inhibition rates of cancer cells reached 62.05%- 89.24%,with sub-G1 peaks appearing on histogram. Part of the cancer cells showed characteristic morphological changes of apoptosis under fluorescence and electron microscopes, and the rate of apoptosis was 21.5 % -33.5%. The protein expression of NF-κB was decreased, while that of Caspase-3 was increased in a timedependent manner. Conclusion: Curcumin could significantly inhibit the growth of human ovarian cancer cells;inducing apoptosis through up-regulating Caspase-3 and down-regulating gene expression of NF-κB is probably one of its molecular mechanisms.

  13. Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor growth

    Institute of Scientific and Technical Information of China (English)

    Gang Zhao; Li-Li Guo; Jing-Yong Xu; Hua Yang; Mei-Xiong Huang; Gang Xiao

    2011-01-01

    AIM: To investigate the effects of integrin-linked kinase (ILK) on gastric cancer cells both in vitro and in vivo . METHODS: ILK small interfering RNA (siRNA) was transfected into human gastric cancer BGC-823 cells and ILK expression was monitored by real-time quantitative polymerase chain reaction, Western blotting analysis and immunocytochemistry. Cell attachment, proliferation, invasion, microfilament dynamics and the secretion of vascular endothelial growth factor (VEGF) were also measured. Gastric cancer cells treated with ILK siRNA were subcutaneously transplanted into nude mice and tumor growth was assessed. RESULTS: Both ILK mRNA and protein levels were significantly down-regulated by ILK siRNA in human gastric cancer cells. This significantly inhibited cell attachment, proliferation and invasion. The knockdown of ILK also disturbed F-actin assembly and reduced VEGF secretion in conditioned medium by 40% (P < 0.05). Four weeks after injection of ILK siRNA-transfected gastric cancer cells into nude mice, tumor volume and weight were significantly reduced compared with that of tumors induced by cells treated with non-silencing siRNA or by untreated cells (P < 0.05). CONCLUSION: Targeting ILK with siRNA suppresses the growth of gastric cancer cells both in vitro and in vivo . ILK plays an important role in gastric cancer progression.

  14. Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk?

    Science.gov (United States)

    Tentori, Lucio; Graziani, Grazia

    2007-05-01

    Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.

  15. Morpholino-Mediated Isoform Modulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) Reduces Colon Cancer Xenograft Growth

    Energy Technology Data Exchange (ETDEWEB)

    Stagg, Brian C., E-mail: briancstagg@gmail.com; Uehara, Hironori; Lambert, Nathan; Rai, Ruju; Gupta, Isha; Radmall, Bryce; Bates, Taylor; Ambati, Balamurali K. [John A Moran Eye Center, University of Utah, Salt Lake City, UT, 65 Mario Capecchi Drive, Salt Lake City, UT 84132 (United States)

    2014-11-26

    Angiogenesis plays a key role in tumor growth. Vascular endothelial growth factor (VEGF) is a pro-angiogenic that is involved in tumor angiogenesis. When VEGF binds to membrane-bound vascular endothelial growth factor receptor 2 (mVEGFR2), it promotes angiogenesis. Through alternative polyadenylation, VEGFR2 is also expressed in a soluble form (sVEGFR2). sVEGFR2 sequesters VEGF and is therefore anti-angiogenic. The aim of this study was to show that treatment with a previously developed and reported antisense morpholino oligomer that shifts expression from mVEGFR2 to sVEGFR2 would lead to reduced tumor vascularization and growth in a murine colon cancer xenograft model. Xenografts were generated by implanting human HCT-116 colon cancer cells into the flanks of NMRI nu/nu mice. Treatment with the therapeutic morpholino reduced both tumor growth and tumor vascularization. Because the HCT-116 cells used for the experiments did not express VEGFR2 and because the treatment morpholino targeted mouse rather than human VEGFR2, it is likely that treatment morpholino was acting on the mouse endothelial cells rather than directly on the tumor cells.

  16. Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton.

    Science.gov (United States)

    Qin, Juan; Li, Dengwen; Zhou, Yunqiang; Xie, Songbo; Du, Xin; Hao, Ziwei; Liu, Ruming; Liu, Xinqi; Liu, Min; Zhou, Jun

    2017-01-10

    Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy. Our data further show that ALG-2 stimulates breast cancer growth and metastasis in mice. ALG-2 also promotes breast cancer cell proliferation, survival, and motility in vitro. Mechanistic data reveal that ALG-2 disrupts the localization of centrosome proteins, resulting in spindle multipolarity and chromosome missegregation. In addition, ALG-2 drives the polarization and migration of breast cancer cells by facilitating the rearrangement of microtubules and microfilaments. These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy.

  17. Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis.

    Science.gov (United States)

    Dang, Qiang; Song, Wenbin; Xu, Defeng; Ma, Yanmin; Li, Feng; Zeng, Jin; Zhu, Guodong; Wang, Xinyang; Chang, Luke S; He, Dalin; Li, Lei

    2015-09-01

    The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.

  18. An Embryonic Growth Pathway is Reactivated in Human Prostate Cancer

    Science.gov (United States)

    2005-06-01

    increased tumor growth results from an Ectopic activation of Sonic hedgehog signaling is a keyincrease in tumor cell proliferation. The striking contrast...inducer of growth in development of the limbs, central ner- vous system, lungs, craniofacial skeleton, hair, teeth , gastro- Accepted for publication May 17

  19. Correlation of microRNA-124 expression in cervical cancer tissue with cancer cell growth and invasion

    Institute of Scientific and Technical Information of China (English)

    Yi Zhu

    2016-01-01

    Objective:To study the correlation of microRNA-124 expression in cervical cancer tissue with cancer cell growth and invasion.Methods: A total of 56 cases of cervical cancer tissue samples and 60 cases of normal cervical tissue samples were selected for study, and microRNA-124 expression levels as well as protein content of proliferation, apoptosis and invasion genes in cervical tissue samples were determined.Results: The relative expression level of miR-124 in cervical cancer tissue was significantly lower than that in normal cervical tissue and the higher the FIGO staging, the lower the relative expression level of miR-124; cervical cancer tissue with different miR-124 expression was divided into group A-D according to quartile, there were differences in the protein content of cyclinD1, CDK4, CDK6, Prdx4, TNFAIP8, Piwil2, p16, p27, Caspase-3, Ezrin, CD44v6, E-cadherin andβ-catenin in cervical cancer tissue of group A, B, C and D, and the lower the relative expression level of miR-124, the higher the protein content of cyclinD1, CDK4, CDK6, Prdx4, TNFAIP8, Piwil2 as well as Ezrin and CD44v6, and the lower the protein content of p16, p27, Caspase-3 as well as E-cadherin andβ-catenin.Conclusions: microRNA-124 shows a trend of lower expression in cervical cancer tissue and is closely related to the excessive proliferation, insufficient apoptosis and invasive growth of cancer cells.

  20. Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer

    Energy Technology Data Exchange (ETDEWEB)

    Chitcholtan, Kenny, E-mail: kenny.chitcholtan@otago.ac.nz [Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand); Asselin, Eric, E-mail: Eric.Asselin@uqtr.ca [Department of Chemistry and Biology, University of Quebec, at Trois-Rivières, C.P. 500, Trois-Rivières, Quebec, Canada G9A 5H7 (Canada); Parent, Sophie, E-mail: Sophie.Parent@uqtr.ca [Department of Chemistry and Biology, University of Quebec, at Trois-Rivières, C.P. 500, Trois-Rivières, Quebec, Canada G9A 5H7 (Canada); Sykes, Peter H., E-mail: peter.sykes@otago.ac.nz [Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand); Evans, John J., E-mail: john.evans@otago.ac.nz [Department of Obstetrics and Gynaecology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand); Centre of Neuroendocrinology and The MacDiarmid Institute of Advanced Materials and Nanotechnology, University of Otago, Christchurch, 2 Riccarton Avenue, Christchurch 8011 (New Zealand)

    2013-01-01

    Three-dimensional (3D) in vitro models have an invaluable role in understanding the behaviour of tumour cells in a well defined microenvironment. This is because some aspects of tumour characteristics cannot be fully recapitulated in a cell monolayer (2D). In the present study, we compared growth patterns, expression of signalling molecules, and metabolism-associated proteins of endometrial cancer cell lines in 3D and 2D cell cultures. Cancer cells formed spherical structures in 3D reconstituted basement membrane (3D rBM), and the morphological appearance was cell line dependent. Cell differentiation was observed after 8 days in the 3D rBM. There was reduced proliferation, detected by less expression of PCNA in 3D rBM than in 2D cell monolayers. The addition of exogenous epidermal growth factor (EGF) to cancer cells induced phosphorylation of EGFR and Akt in both cell culture conditions. The uptake of glucose was selectively altered in the 3D rBM, but there was a lack of association with Glut-1 expression. The secretion of vascular endothelial growth factor (VEGF) and prostaglandin E{sub 2} (PGE{sub 2}) was selectively altered in 3D rBM, and it was cell line dependent. Our data demonstrated that 3D rBM as an in vitro model can influence proliferation and metabolism of endometrial cancer cell behaviour compared to 2D cell monolayer. Changes are specific to individual cell types. The use of 3D rBM is, therefore, important in the in vitro study of targeted anticancer therapies.

  1. Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF - opioid growth factor receptor (OGFr axis

    Directory of Open Access Journals (Sweden)

    Donahue Renee N

    2009-10-01

    Full Text Available Abstract Background Carcinoma of the thyroid gland is an uncommon cancer, but the most frequent malignancy of the endocrine system. Most thyroid cancers are derived from the follicular cell. Follicular carcinoma (FTC is considered more malignant than papillary thyroid carcinoma (PTC, and anaplastic thyroid cancer (ATC is one of the most lethal human cancers. Opioid Growth Factor (OGF; chemical term - [Met5]-enkephalin and its receptor, OGFr, form an inhibitory axis regulating cell proliferation. Both the peptide and receptor have been detected in a wide variety of cancers, and OGF is currently used clinically as a biotherapy for some non-thyroid neoplasias. This study addressed the question of whether the OGF-OGFr axis is present and functional in human thyroid follicular cell - derived cancer. Methods Utilizing human ATC (KAT-18, PTC (KTC-1, and FTC (WRO 82-1 cell lines, immunohistochemistry was employed to ascertain the presence and location of OGF and OGFr. The growth characteristics in the presence of OGF or the opioid antagonist naltrexone (NTX, and the specificity of opioid peptides for proliferation of ATC, were established in KAT-18 cells. Dependence on peptide and receptor were investigated using neutralization studies with antibodies and siRNA experiments, respectively. The mechanism of peptide action on DNA synthesis and cell survival was ascertained. The ubiquity of the OGF-OGFr axis in thyroid follicular cell-derived cancer was assessed in KTC-1 (PTC and WRO 82-1 (FTC tumor cells. Results OGF and OGFr were present in KAT-18 cells. Concentrations of 10-6 M OGF inhibited cell replication up to 30%, whereas NTX increased cell growth up to 35% relative to cultures treated with sterile water. OGF treatment reduced cell number by as much as 38% in KAT-18 ATC in a dose-dependent and receptor-mediated manner. OGF antibodies neutralized the inhibitory effects of OGF, and siRNA knockdown of OGFr negated growth inhibition by OGF. Cell survival

  2. Influence of Boron doping on micro crystalline silicon growth

    Institute of Scientific and Technical Information of China (English)

    Li Xin-Li; Wang Guo; Chen Yong-Sheng; Yang Shi-E; Gu Jin-Hua; Lu Jing-Xiao; Gao Xiao-Yong; Li Rui; Jiao Yue-Chao; Gao Hai-Bo

    2011-01-01

    Microcrystalline silicon (Ftc-Si:H) thin films with and without boron doping are deposited using the radio-frequency plasmsrenhanced chemical vapour deposition method. The surface roughness evolutions of the silicon thin films are investigated using ex situ spectroscopic ellipsometry and an atomic force microscope. It is shown that the growth exponent β and the roughness exponent a are about 0.369 and 0.95 for the undoped thin film,respectively. Whereas,for the boron-doped pc-Si:H thin film,βincreases to 0.534 and a decreases to 0.46 due to the shadowing effect.

  3. Growth inhibition of human breast cancer cells and down-regulation of ODC1 and ADA genes by Nepeta binaloudensis

    Directory of Open Access Journals (Sweden)

    Akbar Safipour Afshar

    Full Text Available ABSTRACT Nepeta binaloudensis Jamzad, Lamiaceae, is a rare medicinal plant endemic to Iran. In spite of many studies about the chemical constituents and antibacterial effects of this species, no report has been provided about its cytotoxic and anticancer activities. In this study we have evaluated the effects of EtOH 70%, hexane and aqueous extracts of N. binaloudensis on the cell proliferation and n-hexane extract on the expression of adenosine deaminase and ornithine decarboxylase 1 genes in breast cancer cell lines (MCF-7, MDA-MB-231 compared to non-cancer line (MCF-10A. The cell lines were subjected to increasing doses of the extracts ranging from 10 to 320 µg/ml. Cell viability was quantified by MTS assay. Expression of adenosine deaminase and ornithine decarboxylase 1 genes was analyzed by real time PCR. N. binaloudensis inhibited the growth of malignant cells in a time and dose-dependent manner. Among extracts of N. binaloudensis, the hexane extract was found to be more toxic compared to other extracts. Results showed a marked decrease in the expression of ornithine decarboxylase 1 and adenosine deaminase genes in cancer cell lines. At 60 µg/ml concentration of N. binaloudensis hexane extract ornithine decarboxylase 1 and adenosine deaminase mRNA expression were reduced 4.9 fold and 3.5 fold in MCF-7 cell line and 3.6 fold and 2.6 fold in MDA-MB-231 cell line compared to control, respectively. The result of our study highlights the potential influences of N. binaloudensis hexane extract on ornithine decarboxylase 1 and adenosine deaminase genes expression in breast cancer cells and its relation to inhibition of cancer cell growth.

  4. Inhibitory effects of antagonists of growth hormone-releasing hormone on growth and invasiveness of PC3 human prostate cancer.

    Science.gov (United States)

    Muñoz-Moreno, Laura; Arenas, M Isabel; Schally, Andrew V; Fernández-Martínez, Ana B; Zarka, Elías; González-Santander, Marta; Carmena, María J; Vacas, Eva; Prieto, Juan C; Bajo, Ana M

    2013-02-15

    New approaches are needed to the therapy of advanced prostate cancer. This study determined the effect of growth hormone-releasing hormone (GHRH) antagonists, JMR-132 and JV-1-38 on growth of PC3 tumors as well as on angiogenesis and metastasis through the evaluation of various factors that contribute largely to the progression of prostate cancer. Human PC3 androgen-independent prostate cancer cells were injected subcutaneously into nude mice. The treatment with JMR-132 (10 μg/day) or JV-1-38 (20 μg/day) lasted 41 days. We also evaluated the effects of JMR-132 and JV-1-38 on proliferation, cell adhesion and migration in PC-3 cells in vitro. Several techniques (Western blot, reverse transcription polymerase chain reaction, immunohistochemistry, ELISA and zymography) were used to evaluate the expression levels of GHRH receptors and its splice variants, GHRH, vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF)-1α, metalloproteinases (MMPs) -2 and -9, β-catenin and E-cadherin. GHRH antagonists suppressed the proliferation of PC-3 cells in vitro and significantly inhibited growth of PC3 tumors. After treatment with these analogues, we found an increase in expression of GHRH receptor accompanied by a decrease of GHRH levels, a reduction in both VEGF and HIF-1α expression and in active forms of MMP-2 and MMP-9, a significant increase in levels of membrane-associated β-catenin and a significant decline in E-cadherin. These results support that the blockade of GHRH receptors can modulate elements involved in angiogenesis and metastasis. Consequently, GHRH antagonists could be considered as suitable candidates for therapeutic trials in the management of androgen-independent prostate cancer.

  5. Influence of mycorrhiza and organic ferlitizer to the growth of matoa (Pometia pinnata seedling

    Directory of Open Access Journals (Sweden)

    EDWI MAHAJOENO

    2013-11-01

    Full Text Available Sugiyarto, Wardani PK, Setyono P, Mahajoeno E, Sunarto. 2013. Influence of mycorrhiza and organic ferlitizer to the growth of matoa (Pometia pinnata seedling. Nusantara Bioscience 5: 57-62. The purpose of this research was to find out the influence of mycorrhiza, organic fertilizer and their combination to the growth of seedlings matoa. The reseach was arranged on Completely Randomized design with two treatments factor; i.e. giving mycorrhiza (0 g, 5 g, 10 g/polybag and giving organic fertilizer (0 mL, 1 mL, 2 mL/polybag respectively each in 6 replications. The observed treatments were plant height, leaf number and plant biomass. The observation datas were analyzed by multivariate analysis level of 5 %, continued with LSD test. The result showed that there was no significant influence on given mycorrhiza for matoa seedling growth for all of the growth parameters. There was no influence of organic fertilizer for plant height parameter, but significantly influence for the number of leaf and biomass. The best increase of the number of leaf and biomass was on organic fertilizer treatment at 2 mL dosage. There were no influence in the growth of matoa by the combination treatments betwen mycorrhyza and organik fertilizer.

  6. Control of cancer growth using single input autonomous fuzzy Nano-particles

    Directory of Open Access Journals (Sweden)

    Fahimeh Razmi

    2015-04-01

    Full Text Available In this paper a single input fuzzy controller is applied on autonomous drug-encapsulated nanoparticles (ADENPs to restrict the cancer growth. The proposed ADENPs, swarmly release the drug in local cancerous tissue and effectively decreases the destruction of normal tissue. The amount of released drug is defined considering to feed backed values of tumor growth rate and the used drug. Some significant characteristics of Nano particles compared to Nano-robots is their ability to recognize the cancerous tissue from the normal one and their simple structure. Nano particles became an attractive topic in Nano science and many efforts have been done to manufacture these particles. Simulation results show that the proposed controlling method not only decreases the cancerous tissue effectively but also reduces the side effects of drug impressively.

  7. Growth signals, inflammation, and vascular perturbations: mechanistic links between obesity, metabolic syndrome, and cancer.

    Science.gov (United States)

    Hursting, Stephen D; Hursting, Marcie J

    2012-08-01

    Nearly 35% of adults and 20% of children in the United States are obese, defined as a body mass index ≥ 30 kg/m(2). Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and progression. This review synthesizes the evidence on key biological mechanisms underlying the obesity-cancer link, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and vascular integrity processes. These interrelated pathways represent possible mechanistic targets for disrupting the obesity-cancer link.

  8. Implication of platelet-derived growth factor receptor alpha in prostate cancer skeletal metastasis

    Institute of Scientific and Technical Information of China (English)

    Qingxin Liu; Danielle Jernigan; Yun Zhang; Alessandro Fatatis

    2011-01-01

    Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients.The skeleton is frequently targeted by disseminated cancer cells andrepresents the sole site of spread in more than 80% of prostate cancer cases.Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells.Here,we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion.Finally,we offer pre-clinical evidence that this receptor is a viable target for therapy.

  9. Understanding and Targeting Cell Growth Networks in Breast Cancer

    Science.gov (United States)

    2013-04-01

    pathology  187(1):112-­‐126.   2.   Sherr  CJ  &  Weber  JD  (2000)  The  ARF/p53  pathway.  Current...J,  Solimini  NL,  &  Elledge  SJ  (2009)  Principles  of  cancer  therapy:  oncogene  and  non-­‐oncogene   addiction ...Cancer Res 2010; 70: 4749–4758. 32 Diederichs S, Haber DA. Dual role for argonautes in microRNA processing and posttranscriptional regulation of

  10. The Mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and Epithelial Mesenchymal Transition (EMT in human lung cancer.

    Directory of Open Access Journals (Sweden)

    Frances E Lennon

    Full Text Available Recent epidemiologic studies implying differences in cancer recurrence based on anesthetic regimens raise the possibility that the mu opioid receptor (MOR can influence cancer progression. Based on our previous observations that overexpression of MOR in human non-small cell lung cancer (NSCLC cells increased tumor growth and metastasis, this study examined whether MOR regulates growth factor receptor signaling and epithelial mesenchymal transition (EMT in human NSCLC cells. We utilized specific siRNA, shRNA, chemical inhibitors and overexpression vectors in human H358 NSCLC cells that were either untreated or treated with various concentrations of DAMGO, morphine, fentanyl, EGF or IGF. Cell function assays, immunoblot and immunoprecipitation assays were then performed. Our results indicate MOR regulates opioid and growth factor-induced EGF receptor signaling (Src, Gab-1, PI3K, Akt and STAT3 activation which is crucial for consequent human NSCLC cell proliferation and migration. In addition, human NSCLC cells treated with opioids, growth factors or MOR overexpression exhibited an increase in snail, slug and vimentin and decrease ZO-1 and claudin-1 protein levels, results consistent with an EMT phenotype. Further, these effects were reversed with silencing (shRNA or chemical inhibition of MOR, Src, Gab-1, PI3K, Akt and STAT3 (p<0.05. Our data suggest a possible direct effect of MOR on opioid and growth factor-signaling and consequent proliferation, migration and EMT transition during lung cancer progression. Such an effect provides a plausible explanation for the epidemiologic findings.

  11. EXPRESSION OF MATRIX METALLOPROTEINASE-7 INVOLVING IN GROWTH, INVASION, METASTASIS AND ANGIOGENESIS OF GASTRIC CANCER

    Institute of Scientific and Technical Information of China (English)

    郑华川; 李晓晗; 孙晋民; 曹乾; 辛彦; 张荫昌

    2003-01-01

    Objective. To investigate the role of matrix metalloproteinase-7 (MMP-7) expression in caricinogenesisand progression of gastric cancer.Methods. We studied MMP-7 expression and microvessel density (MVD) in adjacent mucosa and pri-mary foci of 113 cases of gastric cancer by streptavidin-biotin-immunoperoxidase method using anti-MMP-7 and anti-CD34 antibodies. MMP-7 expression and mean MVD were compared with clinicopatholog-ical features of gastric cancer, with the relationship between MMP-7 expression and MVD concerned in gastric cancer.Results. MMP-7 showed positive expression in adjacent mucosa of gastric cancer (29.20%, 33/113),less than that in gastric cancer (69.03%, 78/113). MMP-7 expression in primary foci of gastric cancerwas positively correlated with tumor size, invasive depth, metastasis and TNM staging (P<0.05), but notwith differentiation or growth pattern of gastric cancer (P>0.05). Positive correlation of mean MVD withtumor size, invasive depth, metastasis and TNM staging was found (P<0.05), despite no relationshipbetween mean MVD and differentiation of gastric cancer (P>0.05). Mean MVD was dependent on MMP-7expression in gastric cancer (P<0.05).Conclusion. Up-regulated expression of MMP-7 played an important role in carcinogenesis and pro-gression by participating in growth, invasion, metastasis and angiogenesis of gastric cancer. MMP-7 ex-pression could be regarded as an effective and objective marker to reflect the biological behaviors of gas-tric cancer.

  12. Risk of thrombosis in cancer and the role of supportive care (transfusion, catheters, and growth factors).

    Science.gov (United States)

    Castaman, Giancarlo

    2016-04-01

    Thrombosis in cancer patients is a well-known, frequent complication which can adversely influence treatment outcome and mortality rate. Several cancer-related or patient-related factors may contribute in modulating the magnitude of the risk. Among the treatment-related factors, the use of blood transfusions, erythropoiesis stimulating agents and central venous catheters play a significant role in influencing the epidemiology of thromboembolism in cancer patients. Red cell transfusions may influence the risk of both arterial and venous thromboembolism (VTE), although the mechanisms of causal relationship have not clearly elucidated. A judicious use should be considered, especially for active bleeding with the risk of significant anemia and the presence of cardiovascular risk factors. The use of erythropoiesis stimulating agents carries a definite risk of thrombosis in cancer patients and there is still a debate on whether they can also influence cancer biology and thus clinical outcome. Their use should be carefully weighed considering the duration of chemotherapy courses and the possible short-term benefits of these agents. Catheter-related thrombosis may be present in about 1-5% of cancer patients but asymptomatic cases detected by close ultrasound monitoring may be by far higher. Tailored anti-thrombotic treatment should be undertaken according to the presence of risk of bleeding (e.g., thrombocytopenia). Thrombophylaxis should be considered in patients with a high-risk prothrombotic profile.

  13. Influence of environmental factors on growth and pigment synthesis by purple thiobacteria

    Directory of Open Access Journals (Sweden)

    Y. О. Pavlova

    2007-12-01

    Full Text Available The influence of different environmental factors on growth and pigment biosynthesis by particular strains of purple thiobacteria was investigated. These strains belong to the genus Chromatium, Thiocystis, Thiocapsa and Lamprocystis and were isolated from Yavoriv sulphur mine. Calcium, magnesium, manganese, iron and sodium chloride should be included in the medium for optimal growth of these bacteria. Addition of these elements entails increasing the biomass production and synthesis of carotenoids and bacteriochlorophyll a. Initial concentration of inoculum and electron donor has essential influence on growth of purple thiobacteria. Early in the development of culture, sulphide was oxidized, and then the growth impairment and destruction of cells under exposure of light were observed. For the optimization of bacteria growth the electron donor (sulphide must be added many times during the cultivation process in the concentration, which is not exceed an inhibition dose. The additional bringing of the electron donor in the medium promotes the raise of cells’ biomass. The acetate introduction in the medium has positive influence on the pigments’ biosynthesis. The essential factor of growth and pigments’ biosynthesis is the light intensity. Peak gain of the culture growth was observed under 400 lx. The amplification of light exposure is accompanied by the decrease of growth and content of pigments in cells. Oxygen inhibits the synthesis of pigments in all strains

  14. Evaluation of trade influence on economic growth rate by computational intelligence approach

    Science.gov (United States)

    Sokolov-Mladenović, Svetlana; Milovančević, Milos; Mladenović, Igor

    2017-01-01

    In this study was analyzed the influence of trade parameters on the economic growth forecasting accuracy. Computational intelligence method was used for the analyzing since the method can handle highly nonlinear data. It is known that the economic growth could be modeled based on the different trade parameters. In this study five input parameters were considered. These input parameters were: trade in services, exports of goods and services, imports of goods and services, trade and merchandise trade. All these parameters were calculated as added percentages in gross domestic product (GDP). The main goal was to select which parameters are the most impactful on the economic growth percentage. GDP was used as economic growth indicator. Results show that the imports of goods and services has the highest influence on the economic growth forecasting accuracy.

  15. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yihui [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Tang, Qingchao [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China); Li, Mingqi; Jiang, Shixiong [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Wang, Xishan, E-mail: wxshan12081@163.com [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China)

    2014-02-07

    Highlights: • miR-375 is downregulated in colorectal cancer cell lines and tissues. • miR-375 inhibits colorectal cancer cell growth by targeting PIK3CA. • miR-375 inhibits colorectal cancer cell growth in xenograft nude mice model. - Abstract: Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3′-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.

  16. Salinomycin inhibits growth of pancreatic cancer and cancer cell migration by disruption of actin stress fiber integrity.

    Science.gov (United States)

    Schenk, Miriam; Aykut, Berk; Teske, Christian; Giese, Nathalia A; Weitz, Juergen; Welsch, Thilo

    2015-03-28

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth, early metastasis and high resistance to chemotherapy. Salinomycin is a promising compound eliminating cancer stem cells and retarding cancer cell migration. The present study investigated the effectiveness of salinomycin against PDAC in vivo and elucidated the mechanism of PDAC growth inhibition. Salinomycin treatment was well tolerated by the mice and significantly reduced tumor growth after 19 days compared to the control group (each n = 16). There was a trend that salinomycin also impeded metastatic spread to the liver and peritoneum. Whereas salinomycin moderately induced apoptosis and retarded proliferation at 5-10 µM, it strongly inhibited cancer cell migration that was accompanied by a marked loss of actin stress fibers after 6-9 h. Salinomycin silenced RhoA activity, and loss of stress fibers could be reversed by Rho activation. Moreover, salinomycin dislocated fascin from filopodia and stimulated Rac-associated circular dorsal ruffle formation. In conclusion, salinomycin is an effective and promising compound against PDAC. Besides its known stem cell-specific cytotoxic effects, salinomycin blocks cancer cell migration by disrupting stress fiber integrity and affecting the mutual Rho-GTPase balance.

  17. Influence of static magnetic fields on S. cerevisae biomass growth

    Directory of Open Access Journals (Sweden)

    João B. Muniz

    2007-05-01

    Full Text Available Biomass growth of Saccharomyces cerevisiae DAUFPE-1012 was studied in eight batch fermentations exposed to steady magnetic fields (SMF running at 23ºC (± 1ºC, for 24 h in a double cylindrical tube reactor with synchronic agitation. For every batch, one tube was exposed to 220mT flow intensity SMF, produced by NdFeB rod magnets attached diametrically opposed (N to S magnets on one tube. In the other tube, without magnets, the fermentation occurred in the same conditions. The biomass growth in culture (yeast extract + glucose 2% was monitored by spectrometry to obtain the absorbance and later, the corresponding cell dry weight. The culture glucose concentration was monitored every two hours so as the pH, which was maintained between 4 and 5. As a result, the biomass (g/L increment was 2.5 times greater in magnetized cultures (n=8 as compared with SMF non-exposed cultures (n=8. The differential (SMF-control biomass growth rate (135% was slightly higher than the glucose consumption rate (130 % leading to increased biomass production of the magnetized cells.O crescimento da biomassa da Saccharomyces cerevisiae DAUFPE-1012 foi estudado em oito bateladas de fermentação, cada uma exposta aos campos magnéticos contínuos (CMC, à 23ºC (± 1ºC, durante um período de 24 horas em um reator duplo com agitação sincrônica. Em cada batelada,um tubo foi exposto ao CMC, com 220mT de intensidade de fluxo, produzidos por imãs de NdFeB fixados diametralmente opostos (N para S em um tubo do reator de fermentação. Em outro tubo, sem imãs, a fermentação ocorreu nas mesmas condições. O crescimento da biomassa nas culturas (extrato de fermento + glicose 2% foi monitorado através de espectrometria e correlacionado ao peso seco de levedura. A concentração de glicose nas culturas foi monitorada a cada duas horas e o pH foi mantido entre 4 e 5. Como resultado, a biomassa (g/L aumentou 2,5 vezes nas culturas magnetizadas (n=8 quando comparadas com as

  18. Enhanced invasion and tumor growth of fibroblast growth factor 8b-overexpressing MCF-7 human breast cancer cells.

    Science.gov (United States)

    Ruohola, J K; Viitanen, T P; Valve, E M; Seppänen, J A; Loponen, N T; Keskitalo, J J; Lakkakorpi, P T; Härkönen, P L

    2001-05-15

    Fibroblast growth factor 8 (FGF-8) is a secreted heparin-binding protein, which has mitogenic and transforming activity. Increased expression of FGF-8 has been found in human breast cancer, and it has a potential autocrine role in its progression. Human FGF-8 is alternatively spliced to generate four protein isoforms (a, b, e, and f). Isoform b has been shown to be the most transforming. In this work, we studied the role of FGF-8b in the growth (in vitro and in vivo) of MCF-7 human breast cancer cells, which proliferate in an estrogen-dependent manner. Constitutive overexpression of FGF-8b in MCF-7 cells down-regulated FGF-8b-binding receptors FGF receptor (FGFR) 1IIIc, FGFR2IIIc, and FGFR4 found to be expressed in these cells. FGF-8b overexpression led to an increase in the anchorage-independent proliferation rate in suspension culture and colony formation in soft agar, when MCF-7 cells were cultured with or without estradiol. FGF-8b also provided an additional growth advantage for cells stimulated with estradiol. In addition, FGF-8b-transfected cells invaded more actively through Matrigel than did control cells. This was possibly due to the increased secretion of matrix metalloproteinase 9. In vivo, FGF-8b-transfected MCF-7 cells formed faster growing tumors than vector-only-transfected cells when xenografted into nude mice. The tumors formed by FGF-8b-transfected cells were more vascular than the tumors formed by vector-only-transfected cells. In conclusion, FGF-8b expression confers a growth advantage to MCF-7 breast carcinoma cells, both in vitro and in vivo. In addition to stimulation of proliferation, this growth advantage probably arises from increased invasion and tumor vascularization induced by FGF-8b. The results suggest that FGF-8b signaling may be an important factor in the regulation of tumorigenesis and progression of human breast cancer.

  19. Exosomes secreted from human colon cancer cells influence the adhesion of neighboring metastatic cells: Role of microRNA-210

    Science.gov (United States)

    Bigagli, Elisabetta; Luceri, Cristina; Guasti, Daniele; Cinci, Lorenzo

    2016-01-01

    ABSTRACT Cancer-secreted exosomes influence tumor microenvironment and support cancer growth and metastasis. MiR-210 is frequently up-regulated in colorectal cancer tissues and correlates with metastatic disease. We investigated whether exosomes are actively released by HCT-8 colon cancer cells, the role of exosomal miR-210 in the cross-talk between primary cancer cells and neighboring metastatic cells and its contribution in regulating epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). After 7 d of culture, a subpopulation of viable HCT-8 cells detached the monolayer and started to grow in suspension, suggesting anoikis resistance and a metastatic potential. The expression of key proteins of EMT revealed that these cells were E-cadherin negative and vimentin positive further confirming their metastatic phenotype and the acquisition of anoikis resistance. Metastatic cells, in the presence of adherently growing HCT-8, continued to grow in suspension whereas only if seeded in cell-free wells, were able to adhere again and to form E-cadherin positive and vimentin negative new colonies, suggesting the occurrence of MET. The chemosensitivity to 5 fluorouracil and to FOLFOX-like treatment of metastatic cells was significantly diminished compared to adherent HCT-8 cells. Of note, adherent new colonies undergoing MET, were insensitive to both chemotherapeutic strategies. Electron microscopy analysis demonstrated that adherently growing HCT-8, actually secreted exosomes and that exosomes in turn were taken up by metastatic cells. When exosomes secreted by adherently growing HCT-8 were administered to metastatic cells, MET was significantly inhibited. miR-210 was significantly upregulated in exosomes compared to its intracellular levels in adherently growing HCT-8 cells and correlated to anoikis resistance and EMT markers. Exosomes containing miR-210 might be considered as EMT promoting signals that preserve the local cancer-growth

  20. [Conformity of cancerous diagnosis of serum-fluorimetry under the influence of carotenoid fluorescence].

    Science.gov (United States)

    Meng, J; Zhang, Y; Ren, X; Ma, H; Ren, W; Xu, X; Cao, B; Li, W

    2000-08-01

    We observed that carotenoid had sensitization for fluorescence of porphyrin as cancerous diagnostic technology was applied in clinic by serum-fluorimetry. The Forster theory was used in order to analyse sensitized fluorescence between carotenoid and porphyrin in this paper. Transfer characteristic between energy donor and energy acceptor was calculated and discussed its influence on cancerous diagnosis.

  1. Dynamic tracing for epidermal growth factor receptor mutations in urinary circulating DNA in gastric cancer patients.

    Science.gov (United States)

    Shi, Xiu-Qin; Xue, Wen-Hua; Zhao, Song-Feng; Zhang, Xiao-Jian; Sun, Wukong

    2017-02-01

    The mutations of epidermal growth factor receptor are detected in gastric cancer, indicating its suitability as a target for receptor tyrosine kinase inhibitors, as well as a marker for clinical outcome of chemotherapeutic treatments. However, extraction of quality tumor tissue for molecular processes remains challenging. Here, we aimed to examine the clinical relevance of urinary cell-free DNA as an alternative tumor material source used specifically for monitoring epidermal growth factor receptor mutations. Therefore, 120 gastric cancer patients with epidermal growth factor receptor mutations and 100 healthy controls were recruited for the study. The gastric patients also received epidermal growth factor receptor inhibitor treatment for a serial monitoring study. Paired primary tumor specimens were obtained with blood and urine samples, which were taken at a 1-month interval for a duration of 12 months. We found that urinary cell-free DNA yielded a close agreement of 92% on epidermal growth factor receptor mutation status when compared to primary tissue at baseline, and of 99% epidermal growth factor receptor mutation status when compared to plasma samples at different time points. Thus, our data suggest that urinary cell-free DNA may be a reliable source for screening and monitoring epidermal growth factor receptor mutations in the primary gastric cancer.

  2. Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth.

    Science.gov (United States)

    Shi, Ying; Chen, Guo-Bin; Huang, Xiao-Xiao; Xiao, Chuan-Xing; Wang, Huan-Huan; Li, Ye-Sen; Zhang, Jin-Fang; Li, Shao; Xia, Yin; Ren, Jian-Lin; Guleng, Bayasi

    2015-08-21

    Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment.

  3. Application of chemokine receptor antagonist with stents reduces local inflammation and suppresses cancer growth.

    Science.gov (United States)

    Mao, Ai-Wu; Jiang, Ting-Hui; Sun, Xian-Jun; Peng, Jian

    2015-11-01

    Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients' condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth.

  4. Suppression of gastric cancer growth by adenovirus-mediated transfer of the PTEN gene

    Institute of Scientific and Technical Information of China (English)

    Ying Hang; Yong-Chen Zheng; Yan Cao; Qing-Shan Li; Yu-Jie Sui

    2005-01-01

    AIM: To investigate the tumor-suppressive effect of the phosphatase and tensin homologue deleted from chromosome (PTEN) in human gastric cancer cells th atwere wild type for PTEN.METHODS: Adenoviruses expressing PTEN or luciferase as a control were introduced into gastric cancer cells.The effect of exogenous PTEN gene on the growth and apoptosis of gastric cancer cells that are wtPTEN were examined in vitro and in vivo.RESULTS: Adenovirus-mediated transfer of PTEN (AdPTEN) suppressed cell growth and induced apoptosis significantly in gastric cancer cells (MGC-803, SGC-7901)carrying wtPTEN in comparison with that in normal gastric epithelial cells (GES-1) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase and mitogen-activated protein kinase and cell-cycle arrest at the G2/M phase but not at the G1 phase. Furthermore,treatment of human gastric tumor xenografts (MGC-803,SGC-7901) with Ad-PTEN resulted in a significant (P<0.01)suppression of tumor growth.CONCLUSION: These results indicate a significant tumorsuppressive effect of Ad-PTEN against human gastric cancer cells. Thus, Ad-PTEN may be used as a potential therapeutic strategy for treatment of gastric cancers.

  5. PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

    Energy Technology Data Exchange (ETDEWEB)

    Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

    2014-09-05

    Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

  6. Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer

    Institute of Scientific and Technical Information of China (English)

    Michael Hopfner; Detlef Schuppan; Hans Scherübl

    2008-01-01

    Growth factors and their corresponding receptors are commonly overexpressed and/or dysregulated in many cancers including hepatocellular cancer (HCC). Clinical trials indicate that growth factor receptors and their related signalling pathways play important roles in HCC cancer etiology and progression, thus providing rational targets for innovative cancer therapies. A number of strategies including monoclonal antibodies, tyrosine kinase inhibitors ("small molecule inhibitors") and antisense oligonucleotides have already been evaluated for their potency to inhibit the activity and downstream signalling cascades of these receptors in HCC. First clinical trials have also shown that multi-kinase inhibition is an effective novel treatment strategy in HCC. In this respect sorafenib, an inhibitor of Raf-, VEGF- and PDGF-signalling, is the first multi-kinase inhibitor that has been approved by the FDA for the treatment of advanced HCC. Moreover, the serine-threonine kinase of mammalian target of rapamycin (mTOR) upon which the signalling of several growth factor receptors converge plays a central role in cancer cell proliferation, mTOR inhibition of HCC is currently also being studied in preclinical trials. As HCCs represent hypervascularized neoplasms, inhibition of tumour vessel formation via interfering with the VEGF/VEGFR system is another promising approach in HCC treatment. This review will summarize the current status of the various growth factor receptor-based treatment strategies and in view of the multitude of novel targeted approaches, the rationale for combination therapies for advanced HCC treatment will also be taken into account.

  7. Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Dan PU

    2013-11-01

    Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

  8. Cancer Stem Cell Plasticity as Tumor Growth Promoter and Catalyst of Population Collapse

    Directory of Open Access Journals (Sweden)

    Jan Poleszczuk

    2016-01-01

    Full Text Available It is increasingly argued that cancer stem cells are not a cellular phenotype but rather a transient state that cells can acquire, either through intrinsic signaling cascades or in response to environmental cues. While cancer stem cell plasticity is generally associated with increased aggressiveness and treatment resistance, we set out to thoroughly investigate the impact of different rates of plasticity on early and late tumor growth dynamics and the response to therapy. We develop an agent-based model of cancer stem cell driven tumor growth, in which plasticity is defined as a spontaneous transition between stem and nonstem cancer cell states. Simulations of the model show that plasticity can substantially increase tumor growth rate and invasion. At high rates of plasticity, however, the cells get exhausted and the tumor will undergo spontaneous remission in the long term. In a series of in silico trials, we show that such remission can be facilitated through radiotherapy. The presented study suggests that stem cell plasticity has rather complex, nonintuitive implications on tumor growth and treatment response. Further theoretical, experimental, and integrated studies are needed to fully decipher cancer stem cell plasticity and how it can be harnessed for novel therapeutic approaches.

  9. Lifestyle influences on the association between pre-diagnostic hormone replacement therapy and breast cancer prognosis - results from The Danish 'Diet, Cancer and Health' prospective cohort

    DEFF Research Database (Denmark)

    Holm, Marianne; Olsen, Anja; Kroman, Niels

    2014-01-01

    OBJECTIVES: The association between pre-diagnostic hormone replacement therapy (HRT) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated. STUDY DESIGN: Female participants from the prospective cohort "Diet, Cancer...

  10. Effect of soy saponin on the growth of human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Cheng-Yu; Tsai; Yue-Hwa; Chen; Yi-Wen; Chien; Wen-Hsuan; Huang; Shyh-Hsiang; Lin

    2010-01-01

    AIM:To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells.METHODS:WiDr human colon cancer cells were treated with 150,300,600 or 1200 ppm of soy saponin to determine the effect on cell growth,cell morphology,alkaline phosphatase(AP) and protein kinase C(PKC) activities,and P53 protein,c-Fos and c-Jun gene expression.RESULTS:Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-Otetradecanol-phorbol-13-acetate-stimulated PKC ...

  11. A novel HDAC inhibitor, CG200745, inhibits pancreatic cancer cell growth and overcomes gemcitabine resistance

    Science.gov (United States)

    Lee, Hee Seung; Park, Soo Been; Kim, Sun A; Kwon, Sool Ki; Cha, Hyunju; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Song, Si Young

    2017-01-01

    Pancreatic cancer is predominantly lethal, and is primarily treated using gemcitabine, with increasing resistance. Therefore, novel agents that increase tumor sensitivity to gemcitabine are needed. Histone deacetylase (HDAC) inhibitors are emerging therapeutic agents, since HDAC plays an important role in cancer initiation and progression. We evaluated the antitumor effect of a novel HDAC inhibitor, CG200745, combined with gemcitabine/erlotinib on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells. Three pancreatic cancer-cell lines were used to evaluate the antitumor effect of CG200745 combined with gemcitabine/erlotinib. CG200745 induced the expression of apoptotic proteins (PARP and caspase-3) and increased the levels of acetylated histone H3. CG200745 with gemcitabine/erlotinib showed significant growth inhibition and synergistic antitumor effects in vitro. In vivo, gemcitabine/erlotinib and CG200745 reduced tumor size up to 50%. CG200745 enhanced the sensitivity of gemcitabine-resistant pancreatic cancer cells to gemcitabine, and decreased the level of ATP-binding cassette-transporter genes, especially multidrug resistance protein 3 (MRP3) and MRP4. The novel HDAC inhibitor, CG200745, with gemcitabine/erlotinib had a synergistic anti-tumor effect on pancreatic cancer cells. CG200745 significantly improved pancreatic cancer sensitivity to gemcitabine, with a prominent antitumor effect on gemcitabine-resistant pancreatic cancer cells. Therefore, improved clinical outcome is expected in the future. PMID:28134290

  12. Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer

    Science.gov (United States)

    Shiozawa, Yusuke; Havens, Aaron M.; Jung, Younghun; Ziegler, Anne M.; Pedersen, Elisabeth A.; Wang, Jingcheng; Wang, Jianhua; Lu, Ganwei; Roodman, G. David; Loberg, Robert D.; Pienta, Kenneth J.; Taichman, Russell S.

    2013-01-01

    One of the most life-threatening complications of prostate cancer is skeletal metastasis. In order to develop treatment for metastasis, it is important to understand its molecular mechanisms. Our work in this field has drawn parallels between hematopoietic stem cell and prostate cancer homing to the marrow. Our recent work demonstrated that annexin II expressed by osteoblasts and endothelial cells plays a critical role in niche selection. In this study, we demonstrate that annexin II and its receptor play a crucial role in establishing metastasis of prostate cancer. Prostate cancer cell lines migrate toward annexin II and the adhesion of prostate cancer to osteoblasts and endothelial cells was inhibited by annexin II. By blocking annexin II or its receptor in animal models, short-term and long-term localization of prostate cancers are limited. Annexin II may also facilitate the growth of prostate cancer in vitro and in vivo by the MAPK pathway. These data strongly suggest annexin II and its receptor axis plays a central role in prostate cancer metastasis, and that prostate cancer utilize the hematopoietic stem cell homing mechanisms to gain access to the niche. PMID:18636554

  13. Over-Expression of Platelet-Derived Growth Factor-D Promotes Tumor Growth and Invasion in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Yuan Wang

    2014-03-01

    Full Text Available The platelet-derived growth factor-D (PDGF-D was demonstrated to be able to promote tumor growth and invasion in human malignancies. However, little is known about its roles in endometrial cancer. In the present study, we investigated the expression and functions of PDGF-D in human endometrial cancer. Alterations of PDGF-D mRNA and protein were determined by real time PCR, western blot and immunohistochemical staining. Up-regulation of PDGF-D was achieved by stably transfecting the pcDNA3-PDGF-D plasmids into ECC-1 cells; and knockdown of PDGF-D was achieved by transient transfection with siRNA-PDGF-D into Ishikawa cells. The MTT assay, colony formation assay and Transwell assay were used to detect the effects of PDGF-D on cellular proliferation and invasion. The xenograft assay was used to investigate the functions of PDGF-D in vivo. Compared to normal endometrium, more than 50% cancer samples showed over-expression of PDGF-D (p < 0.001, and high level of PDGF-D was correlated with late stage (p = 0.003, deep myometrium invasion (p < 0.001 and lympha vascular space invasion (p = 0.006. In vitro, over-expressing PDGF-D in ECC-1 cells significantly accelerated tumor growth and promoted cellular invasion by increasing the level of MMP2 and MMP9; while silencing PDGF-D in Ishikawa cells impaired cell proliferation and inhibited the invasion, through suppressing the expression of MMP2 and MMP9. Moreover, we also demonstrated that over-expressed PDGF-D could induce EMT and knockdown of PDGF-D blocked the EMT transition. Consistently, in xenografts assay, PDGF-D over-expression significantly promoted tumor growth and tumor weights. We demonstrated that PDGF-D was commonly over-expressed in endometrial cancer, which was associated with late stage deep myometrium invasion and lympha vascular space invasion. Both in vitro and in vivo experiments showed PDGF-D could promote tumor growth and invasion through up-regulating MMP2/9 and inducing EMT. Thus, we

  14. Influence of picosecond pulse electric field to invasive ability of cervical cancer

    Directory of Open Access Journals (Sweden)

    Li-mei WU

    2015-10-01

    Full Text Available Objective To investigate the influence of picosecond pulse electric field (psPEF to the invasive ability of cervical cancer. Methods The model of cervical cancer was reproduced in BALB/c nude mice (n=24, and they were randomly divided into four groups (n=6 when the xenografts had grown reaching a diameter of 0.8-1.0cm: control group (psPEF was not given, low field intensity group (50kV/cm, moderate field intensity group (60kV/cm and high field intensity group (70kV/cm. Seven days after the psPEF treatment, the histomorphological changes were observed with HE staining and transmission electron microscopy (TEM, the expressions of vascular endothelial growth factor (VEGF and matrix metalloproteinases-9 (MMP-9 were determined with immunohistochemical (IHC staining, and the changes in protein level of VEGF and MMP-9 were assessed with Western blotting. Results After psPEF treatment, the area of necrosis was found to be increased with an increase in psPEF intensity. With TEM different degrees of apoptosis and necrosis in tumor cells with an increase of psPEF intensity were found. IHC showed that the number of VEGF and MMP-9 positive cells in cancer tissue was decreased with an increase in psPEF intensity. The average optical density (AOD of VEGF and MMP-9 proteins decreased significantly in psPEF treatment groups compared with that in control group, and the AOD values in psPEF treatment groups decreased with an increase in psPEF intensity, and the decrease was statistically significant (P<0.05. Western blotting showed the expressive levels of VEGF and MMP-9 proteins declined gradually with an increase in psPEF intensity, and the difference between groups was statistically significant (P<0.05. Conclusion psPEF may have anti-cervical cancer effects by inhibiting the secretion of VEGF and MMP-9 and reducing the invasive ability of cervical cancer cells. DOI: 10.11855/j.issn.0577-7402.2015.09.03

  15. Kaempferol inhibits cancer cell growth by antagonizing estrogen-related receptor α and γ activities.

    Science.gov (United States)

    Wang, Haibin; Gao, Minghui; Wang, Junjian

    2013-11-01

    Kaempferol is a dietary flavonoid that can function as a selective estrogen receptor modulator (SERM). Estrogen-related receptors alpha and gamma (ERRα and ERRγ) are orphan nuclear receptors that play important roles in mitochondrial biogenesis and cancer development. We have shown that kaempferol can functionally antagonize the activities of ERRs based on both response element reporter systems and target gene analysis. Kaempferol modulation of mitochondrial function and suppression cancer cell growth has been confirmed. These findings suggest that kaempferol may exert their anti-cancer activities through antagonizing ERRs activities.

  16. Programmable models of growth and mutation of cancer-cell populations

    CERN Document Server

    Bortolussi, Luca; 10.4204/EPTCS.67.4

    2011-01-01

    In this paper we propose a systematic approach to construct mathematical models describing populations of cancer-cells at different stages of disease development. The methodology we propose is based on stochastic Concurrent Constraint Programming, a flexible stochastic modelling language. The methodology is tested on (and partially motivated by) the study of prostate cancer. In particular, we prove how our method is suitable to systematically reconstruct different mathematical models of prostate cancer growth - together with interactions with different kinds of hormone therapy - at different levels of refinement.

  17. Cloning of WWOX Gene and Its Growth-inhibiting Effects on Ovarian Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    熊宙芳; 胡沙; 王泽华

    2010-01-01

    The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase(WWOX) gene on ovarian cancer cell line A2780 were investigated.The full length cDNA of human WWOX gene was amplified from normal human ovary tissues.The correct cDNA of full length WWOX was subcloned into eukaryocytic expression vector pCMV.After introduction of WWOX gene into cancer cells with liposome,the WWOX mRNA and protein level in the cancer cells were detected by reverse transcription polymerase chain reactio...

  18. Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the anti-tumor effects of paeonol in gastric cancer cell proliferation and apoptosis in vitro and in vivo.METHODS:Murine gastric cancer cell line mouse forestomach carcinoma(MFC) or human gastric cancer cell line SGC-7901 was cultured in the presence or absence of paeonol.Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,and cell cycle and apoptosis by flow cytometry and TUNEL staining.Tumor growth after subcutaneous implantation of MF...

  19. The Inhibitory Effect of Oridonin on the Growth of Fifteen Human Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Junhui Chen; Shaobin Wang; Dongyang Chen; Guisheng Chang; Qingfeng Xin; Shoujun Yuan; Zhongying Shen

    2007-01-01

    OBJECTIVE To study the inhibitory effect of oridonin on the growth of cancer cells.METHODS Fifteen human cancer cell lines were subjected to various concentrations of oridonin in culture medium.The inhibitory rate of cell growth was measured by the MTT assay.and compared with a negative control and 5-Fu-positive control.RESULTS The 50% inhibiting concentration (IC50) and maximal inhibi tion (Imax) of oridonin shown by studying the growth of the cancer cell lines were as follows:leukemias (HL60 cells:3.9 μg/ml and 73.8%.K562 cells:4.3 μg/ml and 76.2%):esophageal cancers (SHEEC cells:15.4 μg/ml and 99.2%,Eca109 cells:15.1 μg/ml and 84.6%,TE1 cells:4.0 μg/ml and 70.2%):gastric cancers (BGC823 cells:7.6 μg/ml and 98.7%,SGC7901 cells:12.3 μg/ml and 85.7%):colon cancers (HT29 cells:13.6 μg/ml and 97.2%,HCT cells:14.5 μg/ml and 96.5%):liver cancers (Bel7402 cells:15.2 μg/ml and 89.2%,HepG2 cells:7.1 μg/ml and 88.3%):pancreatic cancer (PC3 cells:11.3 μg/ml and 68.4%):lung cancer (A549 cells:18.6 μg/ml and 98.0%):breast cancer (MCF7 cells:18.4 μg/ml and 84.7%):uterine cervix cancer (Hela cells:13.7μg/ml and 98.5%).CONCLUSION Oridonin had a relatively wide anti-tumor spectrum,and a relatively strong inhibitory effect on the growth of the 15 human cancer cells.Inhibitory effects were concentration dependent.

  20. Altered Fibroblast Growth Factor Receptor 4 Stability Promotes Prostate Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jianghua Wang

    2008-08-01

    Full Text Available Fibroblast growth factor receptor 4 (FGFR-4 is expressed at significant levels in almost all human prostate cancers, and expression of its ligands is ubiquitous. A common polymorphism of FGFR-4 in which arginine (Arg388 replaces glycine (Gly388 at amino acid 388 is associated with progression in human prostate cancer. We show that the FGFR-4 Arg388 polymorphism, which is present in most prostate cancer patients, results in increased receptor stability and sustained receptor activation. In patients bearing the FGFR-4 Gly388 variant, expression of Huntingtin-interacting protein 1 (HIP1, which occurs in more than half of human prostate cancers, also results in FGFR-4 stabilization. This is associated with enhanced proliferation and anchorage-independent growth in vitro. Our findings indicate that increased receptor stability and sustained FGFR-4 signaling occur in most human prostate cancers due to either the presence of a common genetic polymorphism or the expression of a protein that stabilizes FGFR-4. Both of these alterations are associated with clinical progression in patients with prostate cancer. Thus, FGFR-4 signaling and receptor turnover are important potential therapeutic targets in prostate cancer.

  1. CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ishan Roy

    Full Text Available Pancreatic ductal adenocarcinoma is an unsolved health problem with nearly 75% of patients diagnosed with advanced disease and an overall 5-year survival rate near 5%. Despite the strong link between mortality and malignancy, the mechanisms behind pancreatic cancer dissemination and metastasis are poorly understood. Correlative pathological and cell culture analyses suggest the chemokine receptor CXCR4 plays a biological role in pancreatic cancer progression. In vivo roles for the CXCR4 ligand CXCL12 in pancreatic cancer malignancy were investigated. CXCR4 and CXCR7 were consistently expressed in normal and cancerous pancreatic ductal epithelium, established cell lines, and patient-derived primary cancer cells. Relative to healthy exocrine ducts, CXCL12 expression was pathologically repressed in pancreatic cancer tissue specimens and patient-derived cell lines. To test the functional consequences of CXCL12 silencing, pancreatic cancer cell lines stably expressingthe chemokine were engineered. Consistent with a role for CXCL12 as a tumor suppressor, cells producing the chemokine wereincreasingly adherent and migration deficient in vitro and poorly metastatic in vivo, compared to control cells. Further, CXCL12 reintroduction significantly reduced tumor growth in vitro, with significantly smaller tumors in vivo, leading to a pronounced survival advantage in a preclinical model. Together, these data demonstrate a functional tumor suppressive role for the normal expression of CXCL12 in pancreatic ducts, regulating both tumor growth andcellulardissemination to metastatic sites.

  2. IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells.

    Science.gov (United States)

    Long, Jun; Zhang, Xulong; Wen, Mingjie; Kong, Qingli; Lv, Zhe; An, Yunqing; Wei, Xiao-Qing

    2013-01-01

    Interleukin (IL)-35 is a novel heterodimeric cytokine in the IL-12 family and is composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. IL-35 is expressed in T regulatory (Treg) cells and contributes to the immune suppression function of these cells. In contrast, we found that both IL-35 subunits were expressed concurrently in most human cancer cell lines compared to normal cell lines. In addition, we found that TNF-α and IFN-γ stimulation led to increased IL-35 expression in human cancer cells. Furthermore, over-expression of IL-35 in human cancer cells suppressed cell growth in vitro, induced cell cycle arrest at the G1 phase, and mediated robust apoptosis induced by serum starvation, TNF-α, and IFN-γ stimulation through the up-regulation of Fas and concurrent down-regulation of cyclinD1, survivin, and Bcl-2 expression. In conclusion, our results reveal a novel functional role for IL-35 in suppressing cancer activity, inhibiting cancer cell growth, and increasing the apoptosis sensitivity of human cancer cells through the regulation of genes related to the cell cycle and apoptosis. Thus, this research provides new insights into IL-35 function and presents a possible target for the development of novel cancer therapies.

  3. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Torben F., E-mail: torben.hansen@slb.regionsyddanmark.dk; Spindler, Karen-Lise G. [Department of Oncology, Vejle Hospital, Vejle (Denmark); Andersen, Rikke F. [Department of Biochemistry, Vejle Hospital, Vejle (Denmark); Lindebjerg, Jan [Department of Clinical Pathology, Vejle Hospital, Vejle (Denmark); Kølvraa, Steen [Department of Clinical Genetics, Vejle Hospital, Vejle (Denmark); Brandslund, Ivan [Department of Biochemistry, Vejle Hospital, Vejle (Denmark); Jakobsen, Anders [Department of Oncology, Vejle Hospital, Vejle (Denmark)

    2010-06-28

    New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study was to investigate the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC. The study included 486 patients surgically resected for stage II and III CRC, divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed by polymerase chain reaction. Haplotypes were estimated using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49–4.06), p < 0.001. Validation was provided by consistent findings in a second and independent cohort. Haplotype combinations call for further investigation.

  4. NFkB signaling is important for growth of antiestrogen resistant breast cancer cells

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Emdal, Kristina Bennet; Guerra, Barbara;

    2012-01-01

    resistant cell growth and a potential target for re-sensitizing resistant cells to endocrine therapy. We used an MCF-7-derived cell model for antiestrogen resistant breast cancer to investigate dependence on NF¿B signaling for antiestrogen resistant cell growth. We found that targeting NF¿B preferentially...... inhibited resistant cell growth. Antiestrogen resistant cells expressed increased p50 and RelB, and displayed increased phosphorylation of p65 at Ser529 and Ser536. Moreover, transcriptional activity of NF¿B after stimulation with tumor necrosis factor a was enhanced in antiestrogen resistant cell lines...... resistant cells increased sensitivity to tamoxifen treatment. Our data provide evidence that NF¿B signaling is enhanced in antiestrogen resistant breast cancer cells and plays an important role for antiestrogen resistant cell growth and for sensitivity to tamoxifen treatment in resistant cells. Our results...

  5. The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta.

    OpenAIRE

    Colletta, A. A.; Wakefield, L M; Howell, F. V.; Danielpour, D; Baum, M.; Sporn, M B

    1991-01-01

    Recent experimental work has identified a novel intracellular binding site for the synthetic progestin, Gestodene, that appears to be uniquely expressed in human breast cancer cells. Gestodene is shown here to inhibit the growth of human breast cancer cells in a dose-dependent fashion, but has no effect on endocrine-responsive human endometrial cancer cells. Gestodene induced a 90-fold increase in the secretion of transforming growth factor-beta (TGF-beta) by T47D human breast cancer cells. O...

  6. Polypeptide Chirality Influences Multilayer Thin Film Growth and Structure

    Science.gov (United States)

    Bell, Zephra; Khadka, Dhan; Haynie, Donald

    2011-03-01

    Polypeptide multilayer thin films are being developed for a variety of applications.These include coatings for implant devices and systems for drug delivery in thebiomedical sciences, and optical coatings. Subsequent polymer adsorption steps involve polymers of opposite polarity. Here, the polymers were polypeptides. This project compared the consequences of changing polypeptide chirality on film growth and structure. The peptides were poly(L-glutamic acid), its right-handed counterpart, poly(D-glutamic acid), and poly(lysine-tyrosine). The first two are negatively charged at neutral pH, the third one is positively charged. Poly(lysine-tyrosine)/poly(L-glutamic acid) films and poly(lysine-tyrosine)/poly(D-glutamic acid) films werefabricated on 1 mm-thick quartz plates. In one experiment, films were grown to 34layers. The UV absorption spectrum was taken after each layer deposited to determinethe rate of polymer self-assembly. Separately, UV or visible wavelength spectra wereobtained for films stained with a dye cooled/heated in the range 4-65 °C. In anotherexperiment, a mixture of poly-L-glutamic acid and poly-D-glutamic acid was used as thepolyanion for film buildup. The data show that poly(lysine-tyrosine)/poly(L-glutamicacid) films built up at a higher rate than the corresponding right-handed films.

  7. KLF5 expression in prostate cancer tissue and effect of KLF5 knockdown on prostate cancer cell growth

    Institute of Scientific and Technical Information of China (English)

    Chong-Jun Shi; Wei-Zhong Yang; Yuan-Rong Kong; Wen-Guang Zhou

    2016-01-01

    Objective:To study the KLF5 expression in prostate cancer tissue and the effect of KLF5 knockdown on prostate cancer cell growth.Methods:Prostate cancer and benign prostatic hyperplasia tissue were collected to extract RNA and determine the mRNA levels ofKLF5as well as proliferation and epithelial-mesenchymal transition-related genes; DU145 cells were cultured and transfected with KLF5 siRNA and negative control siRNA, and then RNA was extracted to determine the mRNA levels of proliferation and epithelial-mesenchymal transition-related genes.Results:KLF5, SRSF1, Survivin, MACC1, c-Met, N-cadherinand Vimentin mRNA levels in prostate cancer tissue were significantly higher than those in benign prostatic hyperplasia tissue whileTGF-β,E-cadherinandβ-catenin mRNA levels were significantly lower than those in benign prostatic hyperplasia tissue;SRSF1, Survivin, MACC1, c-Met, TGF-β,N-cadherin andVimentinmRNA levels in si-KLF5 group were significantly lower than those in si-NC group while E-cadherin andβ-cateninmRNA levels were significantly higher than those in si-NC group.Conclusions: KLF5 expression levels are unusually high in prostate cancer tissue, and targeted knockdown of KLF5 expression can inhibit the prostate cancer cell proliferation and epithelial-mesenchymal transition.

  8. EphrinA5 suppresses colon cancer development by negatively regulating epidermal growth factor receptor stability.

    Science.gov (United States)

    Wang, Tong-Hong; Chang, Junn-Liang; Ho, Jar-Yi; Wu, Hsiao-Chun; Chen, Tse-Ching

    2012-01-01

    Colon cancer is one of the most common human cancers worldwide. Owing to its aggressiveness and lethality, it is necessary to determine the mechanisms regulating the carcinogenesis of colon cancer. EphrinA5 has been reported to act as a putative tumor suppressor in glioma; however, little is known concerning the role of this protein in the context of colon cancer. To elucidate the biological significance of ephrinA5 in colon cancer, we examined ephrinA5 and epidermal growth factor receptor (EGFR) expression profiles in both colon cancer and normal tissues, using immunohistochemistry on a 96-spot tissue microarray. Gain-of-function and loss-of-function experiments were performed on the human colon cancer cell lines SW480 and WiDr to determine the biological effects of ephrinA5 in relation to cell proliferation, survival, and migration. It was found that ephrinA5 mRNA and protein levels were significantly reduced in colon cancer as compared with normal colon tissue specimens. EphrinA5 expression was also negatively associated with tumor differentiation and clinical stage. In colon cancer cell line models, ephrinA5 exerted an inhibitory effect on EGFR by promoting c-Cbl-mediated EGFR ubiquitination and degradation. EphrinA5 did not affect the transcriptional regulation of EGFR mRNA expression in colon cancer cells. Expression of ephrinA5 suppressed colon cancer cell proliferation, migration, and chemotherapeutic resistance. In conclusion, ephrinA5 inhibited colon cancer progression by promoting c-Cbl-mediated EGFR degradation. Our findings identify a novel mechanism that could be utilized to improve the therapeutic efficiency of EGFR-targeting strategies.

  9. Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone

    Science.gov (United States)

    2007-03-01

    red channels or (b) green/red channels . Arrows, translocated chromosome. Cancer Research Cancer Res 2006; 66: (16). August 15, 2006 8276...Administration of nRHa drugs, such as leuprorelin acetate (LA) and triptore- in (TR), results in an initial increase in serum luteinizing ormone (LH) and

  10. Epidermal growth factor receptor analyses in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Lindebjerg, Jan; Nielsen, Jens Nederby;

    2006-01-01

    equivalent EGFR status (28/34). There was a tendency to higher median protein level (by ELISA) in IHC positive patients compared to IHC negative patients (p=0.086). The median EGFR gene expression level was significantly lower in tumours than in the normal colon with no difference according to IHC status......EGFR immunohistochemistry (IHC) status is not a reliable predictive marker for response to EGFR-targeted therapies. The present study compares the EGFR status at DNA, RNA and protein level. Blood samples, corresponding normal colon and colorectal cancer tissue were collected from 199 colorectal...... cancer (CRC) patients. EGFR status was evaluated by FISH analysis, real-time RT-PCR, ELISA and IHC. A polymorphism in the EGFR promoter was evaluated by PCR analysis. The EGFR levels by different methods were mutually compared. Seventy-eight percent of primary tumours and corresponding lymph nodes had...

  11. Influence of electrolytes on growth, phototropism, nutation and surface potential in etiolated cucumber seedlings

    Science.gov (United States)

    Spalding, E. P.; Cosgrove, D. J.

    1993-01-01

    A variety of electrolytes (10-30 mol m-3) increased the relative growth rate of etiolated cucumber (Cucumis sativus L. cv. Burpee's Pickler) hypocotyls by 20-50% relative to water-only controls. The nonelectrolyte mannitol inhibited growth by 10%. All salts tested were effective, regardless of chemical composition or valence. Measurements of cell-sap osmolality ruled out an osmotic mechanism for the growth stimulation by electrolytes. This, and the nonspecificity of the response, indicate that an electrical property of the solutions was responsible for their growth-stimulating activity. Measurements of surface electrical potential supported this reasoning. Treatment with electrolytes also enhanced nutation and altered the pattern of phototropic curvature development. A novel analytical method for quantitating these effects on growth was developed. The evidence indicates that electrolytes influence an electrophysiological parameter that is involved in the control of cell expansion and the coordination of growth underlying tropisms and nutations.

  12. Influence of growth regulators on plant growth, yield, and skin color of specialty potatoes

    Science.gov (United States)

    2,4-D has been used since the 1950’s to enhance color in red-skinned potatoes, but there is little research on the potential use of other plant growth regulators to improve tuber skin color in the wide range of specialty potatoes now available on the market. Field trials conducted at Parma, ID in 20...

  13. Exosomes in tumor microenvironment influence cancer progression and metastasis.

    Science.gov (United States)

    Kahlert, Christoph; Kalluri, Raghu

    2013-04-01

    Exosomes are small membrane vesicles of endocytic origin with a size of 50-100 nm. They can contain microRNAs, mRNAs, DNA fragments, and proteins, which are shuttled from a donor cell to recipient cells. Many different cell types including immune cells, mesenchymal cells, and cancer cells release exosomes. There is emerging evidence that cancer-derived exosomes contribute to the recruitment and reprogramming of constituents associated with tumor environment. Here, we discuss different mechanisms associated with biogenesis, payload, and transport of exosomes. We highlight the functional relevance of exosomes in cancer, as related to tumor microenvironment, tumor immunology, angiogenesis, and metastasis. Exosomes may exert an immunosuppressive function as well as trigger an anti-tumor response by presenting tumor antigens to dendritic cells. Exosomes may serve as cancer biomarkers and aid in the treatment of cancer.

  14. Men, food, and prostate cancer: gender influences on men's diets.

    Science.gov (United States)

    Mróz, Lawrence W; Chapman, Gwen E; Oliffe, John L; Bottorff, Joan L

    2011-03-01

    Although healthy eating might enhance long-term survival, few men with prostate cancer make diet changes to advance their well-being. Men's typically poor diets and uninterest in self-health may impede nutrition interventions and diet change. Food choice behavior is complex involving many determinants, including gender, which can shape men's health practices, diets, and prostate cancer experiences. Developing men-centered prostate cancer nutrition interventions to engage men (and where appropriate their partners) in promoting healthy diets can afford health benefits. This article presents an overview and synthesis of current knowledge about men's food practices and provides an analysis of diet and diet change behaviors for men with prostate cancer. Masculinity and gender relations theory are discussed in the context of men's food practices, and suggestions for future applications to nutrition and prostate cancer research and diet interventions are made.

  15. GROWTH INHIBITION OF HUMAN LARYNGEAL CANCER CELL WITH THE ADENOVIRUS-MEDIATED p53 GENE

    Institute of Scientific and Technical Information of China (English)

    WANG Qi; HAN De-min; WANG Wen-ge; WU Zu-ze; ZHANG Wei

    1999-01-01

    Objective: In most laryngeal cancers, the function of p53 gene is down regulated. To explore the potential use of p53 in gene therapy of laryngeal cancer, by introducing wild-type p53 into laryngeal cancer cell line via a recombinant adenoviral vector, Ad5CMV-p53 and analyzing its effects on cell and tumor growth. Methods: A human laryngeal cancer cell line Hep-2 was used.Recombinant cytomegalovirus-promoted adenoviruses containing human wild-type p53 cDNA was transiently introduced into Hep-2 line. The growth suppression of the Hep-2 cells and established s.c. squamous carcinoma model was examined. The p53 protein expression was detected using immunohistochemical analysis. Results: The transduction efficiencies of Hep-2 cell line were 100% at a multiplicity of 100 or greater. The p53 protein expression peaked on day 2 after infection and lasted far 5 days. In vitro growth assays revealed cell death following Ad5CMV-p53 infected. In vivo studies, Ad5CMV-p53 inhibited the tumorigenicity of Hep-2 cell, and in nude mice with established s.c. squamous carcinoma nodules showed that tumor volumes were significantly reduced in mice that received peritumoral infiltration of Ad5CMV-p53. Conclusion: Adenovirus-mediated antitumor therapy carrying the p53 gene is an efficient method to inhibit laryngeal cancer growth. Transfection of laryngeal cancer cells with the wild-type p53 gene via Ad5CMV-p53 is a potential novel approach to the therapy of laryngeal cancer.

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

    OpenAIRE

    2011-01-01

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

  17. Growth conditions influence melanization of Brazilian clinical Sporothrix schenckii isolates.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Frases, Susana; Fialho Monteiro, Paulo Cezar; Gutierrez-Galhardo, Maria Clara; Zancopé-Oliveira, Rosely Maria; Nosanchuk, Joshua D

    2009-04-01

    Sporothrix schenckii is known to produce DHN melanin on both conidial and yeast cells, however little information is available regarding the factors inducing fungal melanization. We evaluated whether culture conditions influenced melanization of 25 Brazilian S. schenckii strains and one control strain (ATCC 10212). Tested conditions included different media, pH, temperature, incubation time, glucose concentrations, and presence or absence of tricyclazole or L-DOPA. Melanization was reduced on Sabouraud compared to defined chemical medium. The majority of strains produced small amounts of melanin at 37 degrees C and none melanized at basic pH. Increased glucose concentrations did not inhibit melanization, rather increasing glucose enhanced pigment production in 27% of strains. Melanin synthesis was also enhanced by the addition of L-DOPA and its addition to medium with tricyclazole, an inhibitor of melanin synthesis, resulted in fungal melanization, including hyphal melanin production. Our results suggest that different S. schenckii strains have distinct control of melanization and that this fungus can use phenolic compounds to enhance melanization in vitro.

  18. Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

    Science.gov (United States)

    Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

    2016-12-01

    Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

  19. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  20. Insulin-like growth factor-I, soy protein intake, and breast cancer risk.

    Science.gov (United States)

    Sanderson, Maureen; Shu, Xiao Ou; Yu, Herbert; Dai, Qi; Malin, Alecia S; Gao, Yu-Tang; Zheng, Wei

    2004-01-01

    Previous studies have found that estrogen enhances the effect of insulin-like growth factor-I (IGF-I) levels on breast cancer cell growth. Participants in the Shanghai Breast Cancer Study (SBCS) consumed large amounts of soy that was high in isoflavones, which act as weak estrogens and as anti-estrogens. We assessed whether soy protein intake modified the effect of IGF-I levels on breast cancer risk. The SBCS is a population-based case-control study of breast cancer among women aged 25-64 conducted between 1996 and 1998 in urban Shanghai. In-person interviews were completed with 1,459 incident breast cancer cases ascertained through a population-based cancer registry and 1,556 controls randomly selected from the general population (with respective response rates of 91% and 90%). This analysis is restricted to the 397 cases and 397 matched controls for whom information on IGF-I levels was available. For premenopausal breast cancer, we found nearly significant interactions between soy protein intake and IGF-I levels (P = 0.080) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels (P = 0.057). The direction of the interaction appeared to be negative for IGF-I levels but was positive for IGFBP-3 levels. No interaction was evident between soy protein intake and IGF-I or IGFBP-3 levels among postmenopausal women. Our results suggest that soy protein intake may negatively modulate the effect of IGF-I and may positively modulate the effect of IGFBP-3 levels on premenopausal breast cancer risk. Further studies are needed to confirm our finding and to understand the biological mechanisms of these potential interactions.

  1. Biology of cancer and aging.

    Science.gov (United States)

    Holmes, F F; Wilson, J; Blesch, K S; Kaesberg, P R; Miller, R; Sprott, R

    1991-12-01

    The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development.

  2. Oxygen tension during biofilm growth influences the efficacy antimicrobial agents

    Directory of Open Access Journals (Sweden)

    Raquel Pippi ANTONIAZZI

    Full Text Available Abstract Objective To compare the antimicrobial efficacy of a 0.12% chlorhexidine (CHX and herbal green tea (Camellia sinensis solution on established biofilms formed at different oxygen tensions in an in situ model. Method Twenty-five dental students were eligible for the study. In situ devices with standardized enamel specimens (ES facing the palatal and buccal sides were inserted in the mouths of volunteers for a 7 day period. No agent was applied during the first four days. From the fifth day onward, both agents were applied to the test ES group and no agent was applied to the control ES group. After 7 days the ES fragments were removed from the devices, sonicated, plated on agar, and incubated for 24 h at 37 °C to determine and quantify the colony forming units (CFUs. Result CHX had significantly higher efficacy compared to green tea on the buccal (1330 vs. 2170 CFU/µL and palatal (2250 vs. 2520 CFU/µL ES. In addition, intragroup comparisons showed significantly higher efficacy in buccal ES over palatal ES (1330 vs. 2250 CFU/µL for CHX and 2170 vs, 2520 CFU/µL for CV for both solutions. Analysis of the ES controls showed significantly higher biofilm formation in palatal ES compared to buccal ES. Conclusion CHX has higher efficacy than green tea on 4-day biofilms. The efficacy of both agents was reduced for biofilms grown in a low oxygen tension environment. Therefore, the oxygen tension environment seems to influence the efficacy of the tested agents.

  3. Influence of arsenic trioxide on the growth activity and apoptosis of gastric cancer cell during hypoxia%三氧化二砷对低氧下人胃癌细胞SGC-7901生长活性及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    王彬; 王树庆

    2009-01-01

    目的 探讨三氧化二砷(As2O3)在低氧条件下对体外培养的人胃癌细胞SGC-7901生长的抑制及凋亡影响.方法 用氯化钴(CoCl2)制作低氧模型, 设常氧组、低氧组、低氧加药物组,分别取0.5、1.0、2.0、5.0、10.0 μmol/L五个不同浓度的As2O3作用于胃癌细胞,用细胞活力测定(MTT)法检测药物作用后的细胞活力,HOECHST33258染色试剂盒测细胞凋亡.结果 ①低氧加药物组As2O3对SGC-7901 细胞生长有抑制作用,与常氧对照组比较差异有统计学意义(P<0.05),并呈剂量-时间-效应关系.②低氧加药物组中,随着As2O3浓度的升高,胃癌细胞凋亡率也逐渐升高(P<0.05).结论 低氧下As2O3对人胃癌细胞SGC-7901生长有抑制和诱导凋亡作用,这种作用可能是As2O3发挥抗肿瘤的生物学基础.%Objective To investigate the effect of arsenic trioxide (As2O3) on the inhibition and apoptosis of gastric cancer cell SGC-7901 during hypoxia. Methods The environment of hypoxia was established by CoCl2 method. The gastric cancer cell were divided into three groups:normal group, hypoxia group and hypoxia combined arsenic trioxide group. The gastric cancer cell SGC-7901was stimulated respectivly 0.5,1.0,2.0,5.0 μmol/L and 10.0 μmol/L of arsenic trioxide.The growth activity of the gastric caner cell of As2O3 was determined by MTT ,and the apoptosis of the gastric caner cell by arsenict rioxide were examined with HOECHST33258 of gastric cancer cell SGC-7901, there was a significant difference rate gradually increased with higher concentration of As2O3 in hypoxia combined arsenic trioxide groups(P<0.05). Conclusion The growth of human gastric cancer cell SGC-7901 were suppressed, and apoptosis of human gastric cancer cell SGC-7901were induced by As2O3 during hypoxia,it may be biological basic of anti-tumor of As2O3.

  4. The influence of gibberellic acid and kinetin on the growth of Scenedesmus quadricauda (Turp. Breb.

    Directory of Open Access Journals (Sweden)

    J. Buczek

    2015-01-01

    Full Text Available The influence of gibberellic acid (GA3 and of kinetin (6-furfurylamino purine on the increment of cell number increase in dry weight and upon protein level in Scenedesmus quadricauda (Turp. Bréb. was studied. It was found that 10-7 M GA3 stimulates at the same time cell growth and dry weight increase of the algae. No influence of GA3 upon the protein content was observed. Kinetin of 10- M concentration stimulates in the initial growth phase cell multiplication and increases the protein level. This substance promotes the increment in dry weight however in the later phase of growth. Furthermore kinetin prolongs the viability of algae, extending the growth phase.

  5. Gastric cancer screening compliance is influenced by the weight status.

    Science.gov (United States)

    Park, Jin Joo; Park, Hyun Ah

    2013-07-01

    Obesity is associated with decreased compliance with cancer screening, but with an increased risk for cancer development. However, the relationship between weight status and compliance with stomach cancer screening has not been not studied as yet. We examined men and women aged between 40 and 80 years from the 4th Korea National Health and Nutrition Examination Survey from 2007 to 2009. BMI was classified into ≤18.4 kg/m (underweight), 18.5-22.9 kg/m (normal), 23-24.9 kg/m (overweight), 25.0-29.9 kg/m (moderate obesity), and ≥30.0 kg/m (severe obesity). Screening compliance was defined as undergoing stomach cancer screening every 2 years with either gastroscopy or upper gastrointestinal series. The overall screening rates of stomach cancer were 43.2 (0.9)% for men and 43.4 (0.8)% for women. After adjustment for covariates, the screening rates were higher in overweight men (adjusted odds ratio, 1.19; 95% confidence interval, 0.98-1.44), with a marginal significance, and significantly lower in women with severe obesity (adjusted odds ratio, 0.55; 95% confidence interval, 0.40-0.76). The difference was mainly driven by the lower acceptance of gastroscopy rather than upper gastrointestinal series. In conclusion, obesity is associated with lower compliance with stomach cancer screening in Korean women. Therefore, new strategies need to be developed to improve the cancer screening compliance in obese women.

  6. Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells.

    Science.gov (United States)

    Hung, Ming-Szu; Chen, I-Chuan; Lung, Jr-Hau; Lin, Paul-Yann; Li, Ya-Chin; Tsai, Ying-Huang

    2016-01-01

    Epidermal growth factor receptor (EGFR) activation has been shown to play a critical role in tumor angiogenesis. In this study, we investigate the correlation between EGFR mutations and cadherin-5 (CDH5), which is an angiogenic factor, in lung cancer cells. Increased expression CDH5 is observed in lung cancer cells with EGFR mutations. Stable lung cancer cell lines expressing mutant (exon 19 deletion E746-A750, and exon 21 missense mutation L858R) and wild type EGFR genes are established. A significantly higher expression of CDH5 is observed in exon 19 deletion stable lung cancer cells and mouse xenografts. Further studies show that expression of CDH5 is decreased after the inhibition of EGFR and downstream Akt pathways in lung cancer cells with EGFR mutation. In addition, mutant EGFR genes potentiates angiogenesis in lung cancer cells, which is inhibited by CDH5 siRNA, and potentiates migration and invasion in lung cancer cells. Our study shows that mutant EGFR genes are associated with overexpression of CDH5 through increased phosphorylation of EGFR and downstream Akt pathways. Our result may provide an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future.

  7. Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion

    Directory of Open Access Journals (Sweden)

    Liu Jinsong

    2005-02-01

    Full Text Available Abstract Background Insulin-like growth factor binding protein 2 (IGFBP2 is overexpressed in ovarian malignant tissues and in the serum and cystic fluid of ovarian cancer patients, suggesting an important role of IGFBP2 in the biology of ovarian cancer. The purpose of this study was to assess the role of increased IGFBP2 in ovarian cancer cells. Results Using western blotting and tissue microarray analyses, we showed that IGFBP2 was frequently overexpressed in ovarian carcinomas compared with normal ovarian tissues. Furthermore, IGFBP2 was significantly overexpressed in invasive serous ovarian carcinomas compared with borderline serous ovarian tumors. To test whether increased IGFBP2 contributes to the highly invasive nature of ovarian cancer cells, we generated IGFBP2-overexpressing cells from an SKOV3 ovarian cancer cell line, which has a very low level of endogenous IGFBP2. A Matrigel invasion assay showed that these IGFBP2-overexpressing cells were more invasive than the control cells. We then designed small interference RNA (siRNA molecules that attenuated IGFBP2 expression in PA-1 ovarian cancer cells, which have a high level of endogenous IGFBP2. The Matrigel invasion assay showed that the attenuation of IGFBP2 expression indeed decreased the invasiveness of PA-1 cells. Conclusions We therefore showed that IGFBP2 enhances the invasion capacity of ovarian cancer cells. Blockage of IGFBP2 may thus constitute a viable strategy for targeted cancer therapy.

  8. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Rizwani, Wasia [Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007 (India); Allen, Amanda E.; Trevino, Jose G., E-mail: Jose.Trevino@surgery.ufl.edu [Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610 (United States)

    2015-09-03

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  9. Continuous and low-energy 125I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth

    Directory of Open Access Journals (Sweden)

    Gong Yan-fang

    2011-04-01

    Full Text Available Abstract Background Iodine 125 (125I seed irradiation is an effective treatment for unresectable pancreatic cancers. However, the radiobiological mechanisms underlying brachytherapy remain unclear. Therefore, we investigated the influence of continuous and low-energy 125I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs and cell growth in pancreatic cancers. Materials and methods For in vitro 125I seed irradiation, SW-1990 cells were divided into three groups: control (0 Gy, 2 Gy, and 4 Gy. To create an animal model of pancreatic cancer, the SW 1990 cells were surgically implanted into the mouse pancreas. At 10 d post-implantation, the 30 mice with pancreatic cancer underwent 125I seed implantation and were separated into three groups: 0 Gy, 2 Gy, and 4 Gy group. At 48 or 72 h after irradiation, apoptosis was detected by flow cytometry; changes in DNMTs mRNA and protein expression were assessed by real-time PCR and western blotting analysis, respectively. At 28 d after 125I seed implantation, in vivo apoptosis was evaluated with TUNEL staining, while DNMTs protein expression was detected with immunohistochemical staining. The tumor volume was measured 0 and 28 d after 125I seed implantation. Results 125I seed irradiation induced significant apoptosis, especially at 4 Gy. DNMT1 and DNMT3b mRNA and protein expression were substantially higher in the 2 Gy group than in the control group. Conversely, the 4 Gy cell group exhibited significantly decreased DNMT3b mRNA and protein expression relative to the control group. There were substantially more TUNEL positive in the 125I seed implantation treatment group than in the control group, especially at 4 Gy. The 4 Gy seed implantation group showed weaker staining for DNMT1 and DNMT3b protein relative to the control group. Consequently, 125I seed implantation inhibited cancer growth and reduced cancer volume. Conclusion 125I seed implantation kills pancreatic cancer cells, especially

  10. Genomic and genetic alterations influence the progression of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Stefania Nobili; Lorenzo Bruno; Ida Landini; Cristina Napoli; Paolo Bechi; Francesco Tonelli; Carlos A Rubio; Enrico Mini; Gabriella Nesi

    2011-01-01

    Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Twomain gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.

  11. Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

    Directory of Open Access Journals (Sweden)

    Dietmar Abraham

    2013-09-01

    Full Text Available The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF. PlGF is a member of the vascular endothelial growth factor (VEGF family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.

  12. Targeting SPARC by lentivirus-mediated RNA interference inhibits cervical cancer cell growth and metastasis

    Directory of Open Access Journals (Sweden)

    Chen Jie

    2012-10-01

    Full Text Available Abstract Background Secreted protein acidic and rich in cysteine (SPARC, a calcium-binding matricellular glycoprotein, is implicated in the progressions of some cancers. However, no information has been available to date regarding the function of SPARC in cervical cancer cell growth and metastasis. Methods In this study, we isolated and established high invasive subclones and low invasive subclones from human cervical cancer cell lines HeLa and SiHa by the limited dilution method. Real-time q-RT-PCR, Western Blot and ICC were performed to investigate SPARC mRNA and protein expressions in high invasive subclones and low invasive subclones. Then lentivirus vector with SPARC shRNA was constructed and infected the highly invasive subclones. Real-time q-RT-PCR, Western Blot and ICC were also performed to investigate the changes of SPARC expression after viral infection. In functional assays, effects of SPARC knockdown on the biological behaviors of cervical cancer cells were investigated. The mechanisms of SPARC in cervical cancer proliferation, apoptosis and invasion were also researched. Results SPARC was over-expressed in the highly invasive subclones compared with the low invasive subclones. Knockdown of SPARC significantly suppressed cervical cancer cell proliferation, and induced cell cycle arrest at the G1/G0 phase through the p53/p21 pathway, also caused cell apoptosis accompanied by the decreased ratio of Bcl-2/Bax, and inhibited cell invasion and metastasis accompanied by down-regulated MMP2 and MMP9 expressions and up-regulated E-cadherin expression. Conclusion SPARC is related to the invasive phenotype of cervical cancer cells. Knockdown of SPARC significantly suppresses cervical cancer cell proliferation, induces cell apoptosis and inhibits cell invasion and metastasis. SPARC as a promoter improves cervical cancer cell growth and metastasis.

  13. Crystal morphology of sucrose influenced by rotation axes parallel to growth planes

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Three different types of growth forms of sucrose (P21) were found by calculating with the Fourier transform method of crystal morphology. The observed central distances of the (100) and (001) faces are smaller than those calculated. It will be shown that the two-fold screw axis, which runs parallel to these faces, influences the rate of growth. The effectiveness of these symmetry elements is relative to the rotation angle around the face normal.

  14. Transforming growth factor-β in the pathogenesis of breast cancer metastasis and fibrosis

    NARCIS (Netherlands)

    Petersen, Maj

    2010-01-01

    Since the discovery and cloning of TGF-β tremendous scientific effort has led to a so- phisticated understanding of the multifunctional actions of this pleiotropic growth factor. TGF-β regulates a myriad of processes in normal tissues and in disease pathogenesis. In cancer, TGF-β often suppress earl

  15. Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth

    NARCIS (Netherlands)

    Iida, J.; Dorchak, J.; Clancy, R.; Slavik, J.; Ellsworth, R.; Katagiri, Y.; Pugacheva, E.N.; Kuppevelt, T.H. van; Mural, R.J.; Cutler, M.L.; Shriver, C.D.

    2015-01-01

    There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the

  16. Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients

    NARCIS (Netherlands)

    Raber-Durlacher, J.E.; von Bültzingslöwen, I.; Logan, R.M.; Bowen, J.; Al-Azri, A.R.; Everaus, H.; Gerber, E.; Gomez, J.G.; Pettersson, B.G.; Soga, Y.; Spijkervet, F.K.L.; Tissing, W.J.E.; Epstein, J.B.; Elad, S.; Lalla, R.V.

    2013-01-01

    Purpose The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy. Methods A systematic review was conducted by the Mu

  17. Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing-Ping; Lin, Kai-Han; Liu, Chun-Yen; Yu, Ya-Chu; Wu, Pei-Tsun [Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (China); Chiu, Chien-Chih [Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Su, Chun-Li [Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan (China); Chen, Kwun-Min [Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan (China); Fang, Kang, E-mail: kangfang@ntnu.edu.tw [Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (China)

    2013-11-15

    In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53 expression attenuated drug sensitivity. The in vivo experiments demonstrated that teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential therapeutic agent by restraining cell growth through apoptotic death at low concentrations, teroxirone provides a feasible perspective in reversing tumorigenic phenotype of human lung cancer cells. - Highlights: • Teroxirone repressed tumor cell growth in nude mice of human lung cancer cells. • The apoptotic cell death reverted by caspase-3 inhibitor is related to p53 status. • Teroxirone provides a good candidate for lung cancer treatment.

  18. Enhanced mitochondrial glutamine anaplerosis suppresses pancreatic cancer growth through autophagy inhibition

    Science.gov (United States)

    Jeong, Seung Min; Hwang, Sunsook; Park, Kyungsoo; Yang, Seungyeon; Seong, Rho Hyun

    2016-01-01

    Cancer cells use precursors derived from tricarboxylic acid (TCA) cycle to support their unlimited growth. However, continuous export of TCA cycle intermediates results in the defect of mitochondrial integrity. Mitochondria glutamine metabolism plays an essential role for the maintenance of mitochondrial functions and its biosynthetic roles by refilling the mitochondrial carbon pool. Here we report that human pancreatic ductal adenocarcinoma (PDAC) cells have a distinct dependence on mitochondrial glutamine metabolism. Whereas glutamine flux into mitochondria contributes to proliferation of most cancer cells, enhanced glutamine anaplerosis results in a pronounced suppression of PDAC growth. A cell membrane permeable α-ketoglutarate analog or overexpression of glutamate dehydrogenase lead to decreased proliferation and increased apoptotic cell death in PDAC cells but not other cancer cells. We found that enhanced glutamine anaplerosis inhibits autophagy, required for tumorigenic growth of PDAC, by activating mammalian TORC1. Together, our results reveal that glutamine anaplerosis is a crucial regulator of growth and survival of PDAC cells, which may provide novel therapeutic approaches to treat these cancers. PMID:27477484

  19. Methylselenol, a selenium metabolite, inhibits colon cancer cell growth in vitro and in vivo

    Science.gov (United States)

    Methylselenol is hypothesized to be a critical selenium (Se) metabolite for anticancer activity. Submicromolar methylselenol exposure inhibited cell growth and led to an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, and an induction of apoptosis in cancerous colon HCT11...

  20. Hepatocyte growth factor/cMET pathway activation enhances cancer hallmarks in adrenocortical carcinoma

    Science.gov (United States)

    Phan, Liem M.; Fuentes-Mattei, Enrique; Wu, Weixin; Velazquez-Torres, Guermarie; Sircar, Kanishka; Wood, Christopher G.; Hai, Tao; Jimenez, Camilo; Cote, Gilbert J.; Ozsari, Levent; Hofmann, Marie-Claude; Zheng, Siyuan; Verhaak, Roeland; Pagliaro, Lance; Cortez, Maria Angelica; Lee, Mong-Hong; Yeung, Sai-Ching J.; Habra, Mouhammed Amir

    2015-01-01

    Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in ACC has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of ACC. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human ACC samples was positively associated with cancer-related biological processes including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of ACC cells with exogenous HCG resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA-mediated knockdown or pharmacological inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in ACC growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer. PMID:26282167

  1. Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2014-01-01

    BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus...

  2. Gene expression signature in organized and growth arrested mammaryacini predicts good outcome in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, Marcia V.; Martin, Katherine J.; Kenny, Paraic A.; Xhaja, Kris; Bosch, Irene; Yaswen, Paul; Bissell, Mina J.

    2006-02-08

    To understand how non-malignant human mammary epithelial cells (HMEC) transit from a disorganized proliferating to an organized growth arrested state, and to relate this process to the changes that occur in breast cancer, we studied gene expression changes in non-malignant HMEC grown in three-dimensional cultures, and in a previously published panel of microarray data for 295 breast cancer samples. We hypothesized that the gene expression pattern of organized and growth arrested mammary acini would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in two HMEC cell lines, 184 (finite life span) and HMT3522 S1 (immortal non-malignant), on successive days post-seeding in a laminin-rich extracellular matrix assay. Both HMECs underwent growth arrest in G0/G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines. We show that genes that are significantly lower in the organized, growth arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.

  3. Growth Factor Receptor-Directed Therapy in Human Breast Cancer

    Science.gov (United States)

    1997-12-01

    ligands which bind to EGFR, including EGF, TGF- 4 a a a, amphiregulin, and cripto - 1, and by the capability of EGFR to transactivate other type-I tyrosine...amplification in breast cancer was recently reported by Watson et al. (69). In this analysis, encompassing over 5,000 breast tumors, the amplification rate was...activation of c-myc oncogene expression. Oncogene 7: 1587-1594. 58. Shiu, R., Watson , P. and Dubik, D. (1993) C-myc oncogene expression in estrogen

  4. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells.

    Science.gov (United States)

    Prasain, Jeevan K; Rajbhandari, Rajani; Keeton, Adam B; Piazza, Gary A; Barnes, Stephen

    2016-09-14

    In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 μM. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 μM) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.

  5. A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth.

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    Lal-Nag, Madhu; McGee, Lauren; Guha, Rajarshi; Lengyel, Ernst; Kenny, Hilary A; Ferrer, Marc

    2017-01-01

    The tumor microenvironment plays an important role in the processes of tumor growth, metastasis, and drug resistance. We have used a multilayered 3D primary cell culture model that reproduces the human ovarian cancer metastatic microenvironment to study the effect of the microenvironment on the pharmacological responses of different classes of drugs on cancer cell proliferation. A collection of oncology drugs was screened to identify compounds that inhibited the proliferation of ovarian cancer cells growing as monolayers or forming spheroids, on plastic and on a 3D microenvironment culture model of the omentum metastatic site, and also cells already in preformed spheroids. Target-based analysis of the pharmacological responses revealed that several classes of targets were more efficacious in cancer cells growing in the absence of the metastatic microenvironment, and other target classes were less efficacious in cancer cells in preformed spheres compared to forming spheroid cultures. These findings show that both the cellular context of the tumor microenvironment and cell adhesion mode have an essential role in cancer cell drug resistance. Therefore, it is important to perform screens for new drugs using model systems that more faithfully recapitulate the tissue composition at the site of tumor growth and metastasis.

  6. Expression of the Bcl-2 protein BAD promotes prostate cancer growth.

    Directory of Open Access Journals (Sweden)

    Adrienne J Smith

    Full Text Available BAD, a pro-apoptotic protein of the Bcl-2 family, has recently been identified as an integrator of several anti-apoptotic signaling pathways in prostate cancer cells. Thus, activation of EGFR, GPCRs or PI3K pathway leads to BAD phosphorylation and inhibition of apoptosis. Increased levels of BAD in prostate carcinomas have also been reported. It appears contradictory that instead of limiting expression of pro-apoptotic protein, prostate cancer cells choose to increase BAD levels while keeping it under tight phosphorylation control. Analysis of the effect of BAD on prostate cancer xenografts has shown that increased BAD expression enhances tumor growth, while knockdown of BAD expression by shRNA inhibits tumor growth. Tissue culture experiments demonstrated that increased BAD expression stimulates proliferation of prostate cancer cells. These results suggest that increased expression of BAD provides a proliferative advantage to prostate tumors, while BAD dephosphorylation increases sensitivity of prostate cancer cells to apoptosis. Combination of proliferative and apoptotic properties prompts prostate cancer cells to be "addicted" to increased levels of phosphorylated BAD. Thus, kinases that phosphorylate BAD are plausible therapeutic targets; while monitoring BAD phosphorylation could be used to predict tumor response to treatments.

  7. miR-134 inhibits non-small cell lung cancer growth by targeting the epidermal growth factor receptor.

    Science.gov (United States)

    Qin, Qin; Wei, Furong; Zhang, Jianbo; Wang, Xingwu; Li, Baosheng

    2016-10-01

    The epidermal growth factor receptor (EGFR) is frequently activated in a wide range of solid tumours and represents an important therapeutic target. MicroRNAs (miRNAs) have recently been recognized as a rational and potential modality for anti-EGFR therapies. However, more EGFR-targeting miRNAs need to be explored. In this study, we identified a novel EGFR-targeting miRNA, miRNA-134 (miR-134), in non-small-cell lung cancer (NSCLC) cell lines. Luciferase assays confirmed that EGFR is a direct target of miR-134. In addition, the overexpression of miR-134 inhibited EGFR-related signaling and suppressed NSCLC cells proliferation by inducing cell cycle arrest and/or apoptosis, suggesting that miR-134 functions as a tumour suppressor in NSCLC. Further mechanistic investigation including RNAi and rescue experiments suggested that the down-regulation of EGFR by miR-134 partially contributes to the antiproliferative role of miR-134. Last, in vivo experiments demonstrated that miR-134 suppressed tumour growth of A549 xenograft in nude mice. Taken together, our findings suggest that miR-134 inhibits non-small cell lung cancer growth by targeting the EGFR.

  8. A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Kawa, Seiji [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan); Matsushita, Hirohisa; Ohbayashi, Hirokazu [Department of Research and Development, Nichirei Biosciences Inc., Tokyo 104-8402 (Japan); Semba, Kentaro [Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan)

    2009-07-03

    Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Accumulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC{sub 50} values comparable to trastuzumab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuzumab.

  9. Asymmetric cancer-cell filopodium growth induced by electric-fields in a microfluidic culture chip.

    Science.gov (United States)

    Wang, Chun-Chieh; Kao, Yu-Chiu; Chi, Pei-Yin; Huang, Ching-Wen; Lin, Jiunn-Yuan; Chou, Chia-Fu; Cheng, Ji-Yen; Lee, Chau-Hwang

    2011-02-21

    We combine a micro-fluidic electric-field cell-culture (MEC) chip with structured-illumination nano-profilometry (SINAP) to quantitatively study the variations of cancer cell filopodia under external direct-current electric field (dcEF) stimulations. Because the lateral resolution of SINAP is better than 150 nm in bright-field image modality, filopodia with diameters smaller than 200 nm can be observed clearly without fluorescent labeling. In the MEC chip, a homogeneous EF is generated inside the culture area that simulates the endogenous EF environment. With this MEC chip-SINAP system, we directly observe and quantify the biased growth of filopodia of lung cancer cells toward the cathode. The epidermal growth factor receptors around the cell edges are also redistributed to the cathodal side. These results suggest that cancer-cell filopodia respond to the changes in EFs in the microenvironment.

  10. Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth.

    Science.gov (United States)

    Waaler, Jo; Machon, Ondrej; von Kries, Jens Peter; Wilson, Steven Ray; Lundenes, Elsa; Wedlich, Doris; Gradl, Dietmar; Paulsen, Jan Erik; Machonova, Olga; Dembinski, Jennifer L; Dinh, Huyen; Krauss, Stefan

    2011-01-01

    Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at the level of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a gene expression profile analysis. In human colorectal cancer (CRC) cells, the new compounds JW67 and JW74 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably, AXIN2 protein levels were strongly increased after compound exposure. Long-term treatment with JW74 inhibited the growth of tumor cells in both a mouse xenograft model of CRC and in Apc(Min) mice (multiple intestinal neoplasia, Min). Our findings rationalize further preclinical and clinical evaluation of these new compounds as novel modalities for cancer treatment.

  11. Growth inhibiting effects of terazosin on androgen-independent prostate cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    许克新; 王向红; 凌明达; 王云川

    2003-01-01

    Objective To study the effects of an α1-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.Methods Two androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21WAF1 and p27KIP1.Results This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27KIP1.Conclusion This study provides evidence that the α1-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

  12. Activin is a potent growth suppressor of epithelial ovarian cancer cells.

    Science.gov (United States)

    Ramachandran, Anassuya; Marshall, Elaine S; Love, Donald R; Baguley, Bruce C; Shelling, Andrew N

    2009-11-28

    Although activin is a major cytokine produced by the ovary, its role in epithelial ovarian cancer is poorly defined. Here, we demonstrate a novel role for activin as a growth inhibitor of some (8/16) epithelial ovarian cancer cell lines. Unresponsive cell lines displayed transcriptional downregulation of the activin receptors ACTRIIA and ACTRIB, suggesting resistance to activin signalling. In response to activin, growth inhibited cell lines demonstrated activation of the canonical SMAD2/3/4, transcriptional induction of the CDK inhibitor p15INK4B, suppression of C-MYC levels and a G1 phase cell cycle arrest. Thus, activin is a potent inhibitor of proliferation of some epithelial ovarian cancer cell lines and its role in the pathogenesis of this disease needs to be re-evaluated.

  13. Thiazolidinediones enhance vascular endothelial growth factor expression and induce cell growth inhibition in non-small-cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Yoshizaki Yumiko

    2010-03-01

    Full Text Available Abstract Background It is known that thiazolidinediones are involved in regulating the expression of various genes, including the vascular endothelial growth factor (VEGF gene via peroxisome proliferator-activated receptor γ (PPARγ; VEGF is a prognostic biomarker for non-small-cell lung cancer (NSCLC. Methods In this study, we investigated the effects of troglitazone and ciglitazone on the mRNA expression of VEGF and its receptors in human NSCLC cell lines, RERF-LC-AI, SK-MES-1, PC-14, and A549. These mRNA expressions were evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR analysis. We also studied the effect of Je-11, a VEGF inhibitor, on the growth of these cells. Results In NSCLC cells, thiazolidinediones increased the mRNA expression of VEGF and neuropilin-1, but not that of other receptors such as fms-like tyrosine kinase and kinase insert domain receptor-1. Furthermore, the PPARγ antagonist GW9662 completely reversed this thiazolidinedione-induced increase in VEGF expression. Furthermore, the addition of VEGF inhibitors into the culture medium resulted in the reversal of thiazolidinedione-induced growth inhibition. Conclusions Our results indicated that thiazolidinediones enhance VEGF and neuropilin-1 expression and induce the inhibition of cell growth. We propose the existence of a pathway for arresting cell growth that involves the interaction of thiazolidinedione-induced VEGF and neuropilin-1 in NSCLC.

  14. Correlation of Serum Insulin-like Growth Factor 1 with Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Mohsen Ayati

    2012-10-01

    Full Text Available Background: Insulin-like growth factor-1 can act in both an autocrine and paracrine manner to promote normal growth and malignant cellular proliferation. The importance of this factor as a major regulatory peptide has been established for cells, in vitro and in vivo. However, the role of serum insulin-like growth factor-1 levels in the etiology of benign prostatic hyperplasia and prostate cancer has not received sufficient attention. The aim of this study was to determine the relationship between benign prostatic hyperplasia, prostate cancer, and serum insulin-like growth factor-1 levels.Methods: We collected blood samples from 68 individuals with prostate cancer (cases and 68 individuals with benign prostatic hyperplasia (controls who were patients at Imam Khomeini Hospital in Tehran, Iran. Those with benign prostatic hyperplasia had normal prostatic specific antigen levels 0.05. Mean serum insulin-like growth factor-1 levels were 219 ng/ml for the case group and 133 ng/ml for the control group, which was significant (P=0.0009. We did not observe any correlation between age and insulin-like growth factor-1 in the case group (P=0.83, r= -0.47, however there was a significant correlation in the control group (P=0.007, r=0.549. Although correlation between prostate volume and serum insulin-like growth factor-1 levels was not statistically significant in the case group (P=0.38, r=0.213, therewas a positive correlation observed in the control group (P<0.008, r=0.537.Conclusion: Our findings suggest that insulin-like growth factor-1 may have an etiologic role in prostate cancer. This interpretation is strengthened by the significant difference observed between serum insulin-like growth factor-1 levels in benign prostatic hyperplasia and prostate cancer patients. These results also offer additional opportunities for evaluating patients who have abnormal digital rectal exams or prostate specific antigen levels, yet their biopsies are normal. Under

  15. Exosomes in Tumor Microenvironment Influence Cancer Progression and Metastasis

    OpenAIRE

    2013-01-01

    Exosomes are small membrane vesicles of endocytic origin with a size of 50 – 100 nm. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donar cell to recipient cells. Many different cell types including immune cells, mesenchymal cells and cancer cells release exosomes. There is emerging evidence that cancer-derived exosomes contribute to the recruitment and reprogramming of constituents associated with tumor environment. Here, we discuss different mechani...

  16. Platelet Activating Factor: A Growth Factor for Breast Cancer

    Science.gov (United States)

    2006-09-01

    families are obtained only from the diet. The omega 3 family is enriched in fish and grains and the omega 6 family is enriched in the meats and oils... omega 3 and omega 6 fatty acids influences the synthesis of PAF. This idea came from the fact that these fatty acids must be removed from the precursor

  17. Glyphosate induces human breast cancer cells growth via estrogen receptors.

    Science.gov (United States)

    Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

  18. Socioeconomic position and mortality among patients with prostate cancer - influence of mediating factors

    DEFF Research Database (Denmark)

    Larsen, Signe Benzon; Brasso, Klaus; Christensen, Jane;

    2017-01-01

    (interquartile range 6.4-11.2 years). Patients with low socioeconomic position were more often overweight or obese at baseline. Low socioeconomic position was associated with increased prostate cancer-specific and all-cause death. The increased mortality could largely be explained by tumor aggressiveness......INTRODUCTION: Men with low socioeconomic position experience higher mortality after a prostate cancer diagnosis compared to men with a higher socioeconomic position, however, the specific mediators of this association are unclear. We therefore evaluated the influence of potential mediators...... on the association between socioeconomic position, and prostate cancer-specific and all-cause death in prostate cancer patients. MATERIALS AND METHODS: We conducted a cohort study of prostate cancer patients in the Danish Diet, Cancer and Health study. All patients completed questionnaires and anthropometric...

  19. Disulfiram Is a DNA Demethylating Agent and Inhibits Prostate Cancer Cell Growth

    Science.gov (United States)

    Lin, Jianqing; Haffner, Michael C.; Zhang, Yonggang; Lee, Byron H.; Brennen, W. Nathaniel; Britton, Justin; Kachhap, Sushant K.; Shim, Joong Sup; Liu, Jun O.; Nelson, William G.; Yegnasubramanian, Srinivasan; Carducci, Michael A.

    2011-01-01

    BACKGROUND The clinical success of the nucleoside analogs 5-aza-cytidine (5-azaC) and 5-aza-2′deoxycytidine (5-aza-dC) as DNA methyltransferase (DNMT) inhibitors has spurred interest in the development of non-nucleoside inhibitors with improved pharmacologic and safety profiles. Because DNMT catalysis features attack of cytosine bases by an enzyme thiol group, we tested whether disulfiram (DSF), a thiol-reactive compound with known clinical safety, demonstrated DNMT inhibitory activity. METHODS Inhibition of DNMT1 activity by DSF was assessed using methyltransferase activity assays with recombinant DNMT1. Next, prostate cancer cell lines were exposed to DSF and assessed for: i) reduction of global 5-methyl cytosine (5meC) content using liquid chromatography/tandem mass spectrometry (LC-MS/MS); ii) gene-specific promoter demethylation by methylation-specific PCR (MSP); and iii) gene-reactivation by real-time RT-PCR. DSF was also tested for growth inhibition using prostate cancer cell lines propagated in vitro in cell culture and in vivo as xenografts in nude mice. RESULTS Disulfiram showed a dose-dependent inhibition of DNMT1 activity on a hemimethylated DNA substrate. In prostate cancer cells in culture, DSF exposure led to reduction of global genomic 5meC content, increase in unmethylated APC and RARB gene promoters, and associated re-expression of these genes, but did not significantly alter prostate-specific antigen (PSA) expression. DSF significantly inhibited growth and clonogenic survival of prostate cancer cell lines in culture and showed a trend for reduced growth of prostate cancer xenografts. CONCLUSIONS Disulfiram is a non-nucleoside DNMT1 inhibitor that can reduce global 5meC content, reactivate epigenetically silenced genes, and significantly inhibit growth in prostate cancer cell lines. PMID:20809552

  20. Influence of organic wastes and seasonal environmental factors on growth and reproduction of Eisenia fetida.

    Science.gov (United States)

    Biradar, Pulikeshi M; Amoji, Sharabanna D

    2003-01-01

    Epigeic earthworms (E. fetida) were cultured on variety of organic wastes amended with cattle manure to determine the influence of diets and the seasonal environmental factors on growth and reproduction. The results showed that growth and reproductive strategies of E. fetida varied with different diets and seasons. Growth and reproduction of worms in all wastes were significantly more in winter and monsoon than in summer season. Hence winter and monsoon seasons could be considered congenial for vermiculture. During all seasons, worm activities were more in cattle manure followed by amended Bengal gram grain husk and Mixed Organic waste by E. fetida. Parthenin containing diet had deleterious effects on cocoon production.

  1. Macrophage inhibitory cytokine-1 (MIC-1/GDF15 gene deletion promotes cancer growth in TRAMP prostate cancer prone mice.

    Directory of Open Access Journals (Sweden)

    Yasmin Husaini

    Full Text Available The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15, is overexpressed by most cancers, including prostate cancer (PCa. Whilst its circulating levels are linked to cancer outcome, the role MIC-1/GDF15 plays in cancer development and progression is incompletely understood. To investigate its effect on PCa development and spread, we have used TRAMP prostate cancer prone mice bearing a germline deletion of MIC-1/GDF15 (TRAMPMIC-/-. On average TRAMPMIC-/- mice died about 5 weeks earlier and had larger prostatic tumors compared with TRAMP mice that were wild type for MIC-1/GDF15 (TRAMPMIC+/+. Additionally, at the time of death or ethical end point, even when adjusted for lifespan, there were no significant differences in the number of mice with metastases between the TRAMPMIC+/+ and TRAMPMIC-/- groups. However, consistent with our previous data, more than twice as many TRAMP mice overexpressing MIC-1/GDF15 (TRAMPfmsmic-1 had metastases than TRAMPMIC+/+ mice (p<0.0001. We conclude that germ line gene deletion of MIC-1/GDF15 leads to increased local tumor growth resulting in decreased survival consistent with an overall protective role for MIC-1/GDF15 in early primary tumor development. However, in advancing disease, as we have previously noted, MIC-1/GDF15 overexpression may promote local invasion and metastatic spread.

  2. Overexpression of GalNAc-transferase GalNAc-T3 promotes pancreatic cancer cell growth.

    Science.gov (United States)

    Taniuchi, K; Cerny, R L; Tanouchi, A; Kohno, K; Kotani, N; Honke, K; Saibara, T; Hollingsworth, M A

    2011-12-01

    O-linked glycans of secreted and membrane-bound proteins have an important role in the pathogenesis of pancreatic cancer by modulating immune responses, inflammation and tumorigenesis. A critical aspect of O-glycosylation, the position at which proteins are glycosylated with N-acetyl-galactosamine on serine and threonine residues, is regulated by the substrate specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferases (GalNAc-Ts). Thus, GalNAc-Ts regulate the first committed step in O-glycosylated protein biosynthesis, determine sites of O-glycosylation on proteins and are important for understanding normal and carcinoma-associated O-glycosylation. We have found that one of these enzymes, GalNAc-T3, is overexpressed in human pancreatic cancer tissues and suppression of GalNAc-T3 significantly attenuates the growth of pancreatic cancer cells in vitro and in vivo. In addition, suppression of GalNAc-T3 induces apoptosis of pancreatic cancer cells. Our results indicate that GalNAc-T3 is likely involved in pancreatic carcinogenesis. Modification of cellular glycosylation occurs in nearly all types of cancer as a result of alterations in the expression levels of glycosyltransferases. We report guanine the nucleotide-binding protein, α-transducing activity polypeptide-1 (GNAT1) as a possible substrate protein of GalNAc-T3. GalNAc-T3 is associated with O-glycosylation of GNAT1 and affects the subcellular distribution of GNAT1. Knocking down endogenous GNAT1 significantly suppresses the growth/survival of PDAC cells. Our results imply that GalNAc-T3 contributes to the function of O-glycosylated proteins and thereby affects the growth and survival of pancreatic cancer cells. Thus, substrate proteins of GalNAc-T3 should serve as important therapeutic targets for pancreatic cancers.

  3. Influences of the environment on the endocrine and paracrine fish growth hormone-insulin-like growth factor-I system.

    Science.gov (United States)

    Reinecke, M

    2010-04-01

    Insulin-like growth factor-I (IGF-I) is a key component of the complex system that regulates differentiation, development, growth and reproduction of fishes. The IGF-I gene is mainly expressed in the liver that represents the principal source of endocrine IGF-I but also in numerous other organs where the hormone most probably acts in an autocrine-paracrine manner. The primary stimulus for synthesis and release of IGF-I is growth hormone (GH) from the anterior pituitary. Thus, in analogy to mammals, it is usual to speak of a fish 'GH-IGF-I axis'. The GH-IGF-I system is affected by changes in the environment and probably represents a target of endocrine disrupting compounds (EDC) that impair many physiological processes in fishes. Thus, the review deals with the influences of changes in different environmental factors, such as food availability, temperature, photoperiod, season, salinity and EDCs, on GH gene expression in pituitary, IGF-I gene expression in liver and extrahepatic sites and the physiological effects resulting from the evoked alterations in endocrine and local IGF-I. Environmental influences certainly interact with each other but for convenience of the reader they will be dealt with in separate sections. Current trends in GH-IGF-I research are analysed and future focuses are suggested at the end of the sections.

  4. Growth inhibition and apoptosis induction of Sulindac on Human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yun-Lin Wu; Bo Sun; Xue-Jun Zhang; Sheng-Nian Wang; Heng-Yi He; Min-Min Qiao; Jie Zhong; Jia-Yu Xu

    2001-01-01

    AIM: To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC)cells. METHODS: The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG2and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX(2) and Bcl-2 were detected by Westem dot blotting. RESULTS: Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG2 and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG2 cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24hours incubation with sulindac at 2mmol. L-1 and 4mmol.L-1, the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG2 cells but not in MKN28 cells. CONCLUSION: Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater then that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.

  5. Effects of Selenium Yeast on Oxidative Stress, Growth Inhibition, and Apoptosis in Human Breast Cancer Cells.

    Science.gov (United States)

    Guo, Chih-Hung; Hsia, Simon; Shih, Min-Yi; Hsieh, Fang-Chin; Chen, Pei-Chung

    2015-01-01

    Recent evidence suggests that selenium (Se) yeast may exhibit potential anti-cancer properties; whereas the precise mechanisms remain unknown. The present study was aimed at evaluating the effects of Se yeast on oxidative stress, growth inhibition, and apoptosis in human breast cancer cells. Treatments of ER-positive MCF-7 and triple-negative MDA-MB-231 cells with Se yeast (100, 750, and 1500 ng Se/mL), methylseleninic acid (MSA, 1500 ng Se/mL), or methylselenocysteine (MSC, 1500 ng Se/mL) at a time course experiment (at 24, 48, 72, and 96 h) were analyzed. Se yeast inhibited the growth of these cancer cells in a dose- and time-dependent manner. Compared with the same level of MSA, cancer cells exposure to Se yeast exhibited a lower growth-inhibitory response. The latter has also lower superoxide production and reduced antioxidant enzyme activities. Furthermore, MSA (1500 ng Se/mL)-exposed non-tumorigenic human mammary epithelial cells (HMEC) have a significant growth inhibitory effect, but not Se yeast and MSC. Compared with MSA, Se yeast resulted in a greater increase in the early apoptosis in MCF-7 cells as well as a lower proportion of early and late apoptosis in MDA-MB-231 cells. In addition, nuclear morphological changes and loss of mitochondrial membrane potential were observed. In conclusion, a dose of 100 to 1500 ng Se/mL of Se yeast can increase oxidative stress, and stimulate growth inhibitory effects and apoptosis induction in breast cancer cell lines, but does not affect non-tumorigenic cells.

  6. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    Science.gov (United States)

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate.

  7. Influence of the gravity on interface shape during crystal growth of LICAF

    Institute of Scientific and Technical Information of China (English)

    刘永才; 陈万春

    2000-01-01

    A Galerkin finite element method, together with the boundary conformal mapping tech-nique, is used to investigate the change of melt/crystal interface under low gravity during the growth of LICAF system. Results have shown that strong convection can cause a deeply concave interface to-ward the crystal, and significantly increase radial thermal gradients nearthe interface. The flow intensi-ty and the change of the gravity have a linear relationship under low gravity ( g0 = 10 -2-10-6). At small Ma number, the maximum acceleration for keeping a planar growth interface is gmax = 1 x 10-3g under our given conditions. in addition, the growth velocity may have some influence on the growth interface shape even at vg gravity level, indicating that the growth velocity cannot be too fast even when convection is very weak.

  8. CD73-Generated Adenosine: Orchestrating the Tumor-Stroma Interplay to Promote Cancer Growth

    Directory of Open Access Journals (Sweden)

    Bertrand Allard

    2012-01-01

    Full Text Available Despite the coming of age of cancer immunotherapy, clinical benefits are still modest. An important barrier to successful cancer immunotherapy is that tumors employ a number of mechanisms to facilitate immune escape, including the production of anti-inflammatory cytokines, the recruitment of regulatory immune subsets, and the production of immunosuppressive metabolites. Significant therapeutic opportunity exists in targeting these immunosuppressive pathways. One such immunosuppressive pathway is the production of extracellular adenosine by CD73, an ectonucleotidase overexpressed in various types of cancer. We hereafter review the biology of CD73 and its role in cancer progression and metastasis. We describe the role of extracellular adenosine in promoting tumor growth through paracrine and autocrine action on tumor cells, endothelial cells, and immune cells.

  9. Epidermal growth factor receptor inhibitors in colorectal cancer treatment: What's new?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide. The treatment of patients with metastatic colon cancer comprises different regimens of chemotherapeutic compounds (fluoropyrimidines, irinotecan and oxaliplatin) and new targeted therapies. Interestingly, most recent trials that attempt to expose patients to all five-drug classes (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab) achieve an overall survival well over 2 years. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit for colorectal cancer mainly cetuximab, panitumumab, erlotinib and gefitinib. We will also describe briefly the molecular steps that lie beneath them and the different clinical or molecular mechanisms that are reported for resistance and response.

  10. Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

    Directory of Open Access Journals (Sweden)

    Yao Jorge L

    2008-04-01

    Full Text Available Abstract Background Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods Flat panel detector-based cone beam computed tomography (FPDCT was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT. Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1 protein expression. Results Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071 and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.. Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion

  11. 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...... antimetabolites using two cell lines with different phenotypic origins, and found that it is effective in inhibiting the growth of these cell lines. Using immunohistochemistry, we also showed high or moderate expression levels of proteins targeted by the validated antimetabolite. Identified anti-growth factors...

  12. Thiazolidinediones enhance vascular endothelial growth factor expression and induce cell growth inhibition in non-small-cell lung cancer cells

    OpenAIRE

    Yoshizaki Yumiko; Kumei Shima; Tanno Sachie; Motomura Wataru; Yoshizaki Takayuki; Tanno Satoshi; Okumura Toshikatsu

    2010-01-01

    Abstract Background It is known that thiazolidinediones are involved in regulating the expression of various genes, including the vascular endothelial growth factor (VEGF) gene via peroxisome proliferator-activated receptor γ (PPARγ); VEGF is a prognostic biomarker for non-small-cell lung cancer (NSCLC). Methods In this study, we investigated the effects of troglitazone and ciglitazone on the mRNA expression of VEGF and its receptors in human NSCLC cell lines, RERF-LC-AI, SK-MES-1, PC-14, and...

  13. Knockdown of RAGE inhibits growth and invasion of gastric cancer cells

    Directory of Open Access Journals (Sweden)

    X.C. Xu

    2013-11-01

    Full Text Available The receptor for advanced glycation endproducts (RAGE is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of RAGE in gastric cancer is still elusive. In this study, we investigated the expression and molecular mechanisms of RAGE in gastric cancer cells. Forty cases of gastric cancer and corresponding adjacent non-cancerous tissues (ANCT were collected, and the expression of RAGE was assessed using immunohistochemistry (IHC in biopsy samples. Furthermore, RAGE signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE used to transfect into human gastric cancer SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA and matrix metallopeptidase-2 (MMP-2 was detected by Real-time PCR and Western blot assays. Cell proliferative activities and invasive capability were respectively determined by MTT and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. As a consequence, RAGE was found highly expressed in cancer tissues compared with the ANCT (70.0% vs 45.0%, P=0.039, and correlated with lymph node metastases (P=0.026. Knockdown of RAGE reduced cell proliferation and invasion of gastric cancer with decreased expression of AKT, PCNA and MMP-2, and induced cell apoptosis and cycle arrest. Altogether, upregulation of RAGE expression is associated with lymph node metastases of gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of gastric cancer cells through AKT pathway, suggesting that RAGE may represent a potential therapeutic target for this aggressive malignancy.

  14. Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

    OpenAIRE

    Alberto, María R.; Manca de Nadra,María C.; Arena, Mario E.

    2012-01-01

    The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arg...

  15. Angiostatin inhibits pancreatic cancer cell proliferation and growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    Ding-Zhong Yang; Jing He; Ji-Cheng Zhang; Zhuo-Ren Wang

    2005-01-01

    AIM: To observe the biologic behavior of pancreatic cancer cells in vitro and in vivo, and to explore the potential value of angiostatin gene therapy for pancreatic cancer.METHODS: The recombinant vector pcDNA3.1(+)-angiostatin was transfected into human pancreatic cancer cells PC-3 with Lipofectamine 2000, and paralleled with the vector and mock control. Angiostatin transcription and protein expression were determined by immunofluorescence and Western blot. The stable cell line was selected by G418. The supernatant was collected to treat endothelial cells. Cell proliferation and growth in vitro were observed under microscope. Cell growth curves were plotted.The troms-fected or untroms-fected cells overexpressing angiostatin vector were implanted subcutaneously into nude mice. The size of tumors was measured, and microvessel density count (MVD) in tumor tissues was assessed by immunohistochemistry with primary anti-CD34antibody.RESULTS: After transfected into PC-3 with Lipofectamine 2000 and selected by G418, macroscopic resistant cell clones were formed in the experimental group transfected with pcDNA 3.1(+)-angiostatin and vector control. But untreated cells died in the mock control. Angiostatin protein expression was detected in the experimental group by immunofluorescence and Western-blot. Cell proliferation and growth in vitro in the three groups were observed respectively under microscope. After treatment with supernatant, significant differences were observed in endothelial cell (ECV-304) growth in vitro. The cell proliferation and growth were inhibited. In nude mice model, markedly inhibited tumorigenesis and slowed tumor expansion were observed in the experimental group as compared to controls, which was parallel to the decreased microvessel density in and around tumor tissue.CONCLUSION: Angiostatin does not directly inhibit human pancreatic cancer cell proliferation and growth in vitro,but it inhibits endothelial cell growthin vitro. It exerts the anti

  16. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    Science.gov (United States)

    Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

    2015-01-01

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

  17. PUTATIVE ROLE OF ADIPOSE TISSUE IN GROWTH AND METABOLISM OF COLON CANCER CELLS

    Directory of Open Access Journals (Sweden)

    Betty eSchwartz

    2014-06-01

    Full Text Available Newly emerging data highlight obesity as an important risk factor for developing certain types of cancer, including colorectal cancer. Although evidence supports a link between the two, the mechanisms responsible for this relationship have not yet been fully elucidated. Hypertrophied and dysfunctional adipose tissue of the obese state is characterized by low-grade inflammation. Adipokines and cytokines secreted from adipocytes, together with the abundant availability of lipids from adipocytes in the tumor microenvironment, promote adhesion, migration, and invasion of tumor cells and support tumor progression and uncontrolled growth. One of the predisposed targets of the deleterious effects exerted by secretions from adipose tissue in obesity are the activities associated with the cellular mitochondria. Mitochondrial oxidative metabolism plays a key role in meeting cells' energetic demands by oxidative phosphorylation (OxPhos. Here we discuss: (a the dynamic relationship between glycolysis, the tricarboxylic acid (TCA cycle, and OxPhos; (b the evidence for impaired OxPhos (i.e. mitochondrial dysfunction in colon cancer; (c the mechanisms by which mitochondrial dysfunction can predispose to cancer. We propose that impaired OxPhos increases susceptibility to colon cancer since OxPhos is sensitive to a large number of factors that are intrinsic to the host (e.g. inflammation.Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes should reveal new therapeutic possibilities.

  18. Involvement of Ghrelin-Growth Hormone Secretagogue Receptor System in Pathoclinical Profiles of Digestive System Cancer

    Institute of Scientific and Technical Information of China (English)

    Zhigang WANG; Weigang WANG; Wencai QIU; Youben FAN; Jun ZHAO; Yu WANG; Qi ZHENG

    2007-01-01

    Ghrelin receptor has been shown to be expressed along the human gastrointestinal tract.Recent studies showed that ghrelin and a synthetic ghrelin receptor agonist improved weight gain and lean body mass retention in a rat model of cancer cachexia by acting on ghrelin receptor, that is, growth hormone secretagogue receptor (GHS-R). This study aims to explore the expression and the distribution of ghrelin receptor in human gastrointestinal tract cancers and to investigate the possible involvement of the ghrelin-GHS-R system in human digestive cancers. Surgical human digestive cancer specimens were obtained from various portions of the gastrointestinal tract from different patients. The expression of ghrelin receptor in these tissues was detected by tissue microarray technique. Our results showed that ghrelin receptor was expressed in cancers throughout the gastrointestinal tract, mainly in the cytoplasm of mucosal layer cells.Its expression level possibly correlated with organ type, histological grade, tumor-nodes-metastases stage,and nutrition status (weight loss) of the patients. For the first time, we identified the distribution of ghrelin receptor in digestive system cancers. Our results implied that the ghrelin-GHS-R system might be involved in the pathoclinical profiles of digestive cancers.

  19. Downregulation of Akt1 Inhibits Anchorage-Independent Cell Growth and Induces Apoptosis in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xuesong Liu

    2001-01-01

    Full Text Available The serine/threonine kinases, Akti/PKBα, Akt2/PKBβ, and Akt3/PKBγ, play a critical role in preventing cancer cells from undergoing apoptosis. However, the function of individual Akt isoforms in the tumorigenicity of cancer cells is still not well defined. In the current study, we used an AM antisense oligonucleotide (AS to specifically downregulate Akti protein in both cancer and normal cells. Our data indicate that AM AS treatment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment also induces apoptosis in these cancer cells as demonstrated by FRCS analysis and a caspase activity assay. Conversely, Akti AS treatment has little effect on the cell growth and survival of normal human cells including normal human fibroblast (NHF, fibroblast from muscle (FBM, and mammary gland epithelial 184135 cells. In addition, AM AS specifically sensitizes cancer cells to typical chemotherapeutic agents. Thus, Akti is indispensable for maintaining the tumorigenicity of cancer cells. Inhibition of AM may provide a powerful sensitization agent for chemotherapy specifically in cancer cells.

  20. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

    2014-05-09

    Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.

  1. cAMP/CREB-regulated LINC00473 marks LKB1-inactivated lung cancer and mediates tumor growth.

    Science.gov (United States)

    Chen, Zirong; Li, Jian-Liang; Lin, Shuibin; Cao, Chunxia; Gimbrone, Nicholas T; Yang, Rongqiang; Fu, Dongtao A; Carper, Miranda B; Haura, Eric B; Schabath, Matthew B; Lu, Jianrong; Amelio, Antonio L; Cress, W Douglas; Kaye, Frederic J; Wu, Lizi

    2016-06-01

    The LKB1 tumor suppressor gene is frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Loss of LKB1 promotes cancer progression and influences therapeutic responses in preclinical studies; however, specific targeted therapies for lung cancer with LKB1 inactivation are currently unavailable. Here, we have identified a long noncoding RNA (lncRNA) signature that is associated with the loss of LKB1 function. We discovered that LINC00473 is consistently the most highly induced gene in LKB1-inactivated human primary NSCLC samples and derived cell lines. Elevated LINC00473 expression correlated with poor prognosis, and sustained LINC00473 expression was required for the growth and survival of LKB1-inactivated NSCLC cells. Mechanistically, LINC00473 was induced by LKB1 inactivation and subsequent cyclic AMP-responsive element-binding protein (CREB)/CREB-regulated transcription coactivator (CRTC) activation. We determined that LINC00473 is a nuclear lncRNA and interacts with NONO, a component of the cAMP signaling pathway, thereby facilitating CRTC/CREB-mediated transcription. Collectively, our study demonstrates that LINC00473 expression potentially serves as a robust biomarker for tumor LKB1 functional status that can be integrated into clinical trials for patient selection and treatment evaluation, and implicates LINC00473 as a therapeutic target for LKB1-inactivated NSCLC.

  2. Influence of growth hormone on growth and onset of puberty ofRahmani ewe lamb

    Institute of Scientific and Technical Information of China (English)

    K H El-Shahat; N F Khaled; F I El-Far

    2014-01-01

    Objective:To study the effect of somatotropin administration on growth and puberty attainment of Rahmani ewes -lamb.Methods:TwelveRahmani ewes–lamb of6-7 months of age and average body weight(24.75±0.16) kg were randomly allotted into two equal groups.The first group served as control and the second group was somatotropin-treated.The ewe-lambs were weighed at the start and at the end of the experiment.In addition, the body condition score, withers height and heart girth were determined at the end of the study.Blood samples were collected weekly till the end of experiment(Twelve weeks).Sera samples were assayed for progesterone, insulin-like growth factor-1(IGF-1) glucose, total cholesterol, high density lipoprotein and urea.Results:It indicated that the somatotropin-treated group attained puberty2.5 weeks(18 days) earlier than control one.Somatotropin-treatedRahmani ewe lambs had higher body weight, and body condition score than those of the control one.A similar tendency was observed in average daily gain, withers height and heart girth.Somatotropin administration had a beneficial effect on blood born metabolites as indicated by increased serum glucose, total lipids, cholesterol,IGF-1 and decreased urea ofRahmani ewes- lamb as compared to control one.Conclusion:Somatotropin administration enhanced puberty inRahmani ewe lambs.This is due to increased provision of trophic signals(represented by increasedSerumIGF-1 secretions) and/or blood-borne metabolites(glucose, cholesterol and lipid).

  3. Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome

    NARCIS (Netherlands)

    De Smedt, Ann; Brouns, Raf; Uyttenboogaart, Maarten; De Raedt, Sylvie; Moens, Maarten; Wilczak, Nadine; Luijckx, Gert-Jan; De Keyser, Jacques

    2011-01-01

    Background and Purpose-Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. Methods-Concentrations of IGF-I and IGF binding protein 3 were measured

  4. Automatic Stand Modeling of Casting Rate Influence on Solid Phase Growth of Round Ingot inside Crystallizer

    Directory of Open Access Journals (Sweden)

    A. N. Chichko

    2006-01-01

    Full Text Available The method of calculation and results of computer dynamics modeling of solid ingot skin in a crystallizer are presented in the paper. The paper shows influence of ingot drawing rate on dynamics of solid ingot skin growth in the continuous casting machine at steel grades used at Republic Unitary Enterprise «Belarussian Metallurgical Works» (BMZ.

  5. Growth of tropical legume cover crops as influenced by nitrogen fertilization and Rhizobia

    Science.gov (United States)

    Tropical legume cover crops are important components in cropping systems due to their role in improving soil quality. Information is limited on the influence of nitrogen (N) fertilization on growth of tropical legume cover crops grown on Oxisols. A greenhouse experiment was conducted to evaluate the...

  6. Influence of intrauterine growth restriction on renal function in the adult rat

    NARCIS (Netherlands)

    Schreuder, M. F.; Van Wijk, J. A. E.; Fodor, M.; Delemarre-van de Waal, H. A.

    2007-01-01

    Intrauterine growth restriction (IUGR) has been shown to influence renal development and lead to fewer nephrons. Data on long term renal function after IUGR are limited. We studied the effect on renal function of IUGR in aging rats. IUGR was induced using a model of bilateral uterine artery ligation

  7. Combined influence of growth and drying conditions on the activity of dried Lactobacillus plantarum

    NARCIS (Netherlands)

    Linders, L.J.M.; Kets, E.P.W.; Bont, J.A.M. de; Riet, K.V. van 't

    1998-01-01

    The production of active dried starter cultures can be influenced at several levels in the production process. In this paper the following process factors are discussed: osmotic stress during growth and cell density prior to drying. Contradicting results are reported in the literature on the influen

  8. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer.

    Science.gov (United States)

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

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells (SUM-149). Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E-cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase activity. These findings suggest that Reishi is an effective anti-IBC therapeutic.

  9. Experimental investigation of the influence of electric field on frost layer growth under natural convection condition

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The influence of direct current (DC) electric field on the thickness and mass of frost on a cold vertical plate was investigated. The photos of frost layer growth were taken with and without the presence of electric field, and results showed that the electric field has a strong influence on the frost thickness. The influences of cold plate temperature and ambient temperature on frost thickness and frost mass were also investigated under the natural convection condition with electric field. Experimental results demonstrated that the cold plate temperature has very strong effect on the frost layer thickness, but its influence on frost mass is minor; the influence of ambient temperature on the frost mass is more obvious than that on the frost thickness.

  10. Growth of cyanophage N-1 under the influence of heavy metal ions.

    Science.gov (United States)

    Sarma, T A; Kaur, Sukhrish P

    2005-01-01

    The growth of cyanophage N-1 in the cyanobacterium Nostoc muscorum under the influence of heavy metal ions, namely Co2+, Cr6+, Cu2+, Mn2+ and Ni2+ has been studied. One-step growth experiments revealed that heavy metal ions extended the latent period by 1-2 hrs with a concomitant decrease in the phage burst size. The latter was reduced in the order Cu2/Mn2+, Ni2+, Co2+ and Cr6+. The treatment of the phage-infected bacteria with heavy metal ions did not induce mutations affecting either the phage plaque morphology or burst size. The final phage titer after such a treatments was lowest with Co2+, Cu2+ and Cr6+. The inhibition of the phage growth under the influence of heavy metal ions is discussed in context with the interaction of cyanophage N-1 with the photosynthetic reactions in the host bacteria.

  11. BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion

    Directory of Open Access Journals (Sweden)

    Michalski Christoph W

    2007-12-01

    Full Text Available Abstract Background Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP, and pancreatic ductal adenocarcinoma (PDAC using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules. Results Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells. Conclusion BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.

  12. Influence of glucocorticoids and growth hormone on insulin sensitivity in humans.

    Science.gov (United States)

    Yuen, K C J; Chong, L E; Riddle, M C

    2013-06-01

    The seminal concept proposed by Sir Harold Himsworth more than 75 years ago that a large number of patients with diabetes were 'insulin insensitive', now termed insulin resistance, has now expanded to include several endocrine syndromes, namely those of glucocorticoid excess, and growth hormone excess and deficiency. Synthetic glucocorticoids are increasingly used to treat a wide variety of chronic diseases, whereas the beneficial effects of recombinant growth hormone replacement therapy in children and adults with growth hormone deficiency have now been well-recognized for over 25 years. However, clinical and experimental studies have established that increased circulating levels of glucocorticoids and growth hormone can also lead to worsening of insulin resistance, glucose intolerance, overt diabetes mellitus and cardiovascular disease. Improved understanding of the physiological 24-h rhythmicity of glucocorticoid and growth hormone secretion and its influence on the dawn phenomenon and the Staub-Trauggot effect has therefore led to renewed interest in studies on the mechanisms of insulin resistance induced by exogenous administration of glucocorticoids and growth hormone in humans. In this review, we describe the physiological events that result from the presence of resistance to insulin action at the level of skeletal muscle, adipose tissue, and liver, describe the known mechanisms of glucocorticoid- and growth hormone-mediated insulin resistance, and provide an update of the contributions of glucocorticoids and growth hormone to understanding the pathophysiology of insulin resistance and its effects on several endocrine syndromes.

  13. Regulation of prostaglandin metabolism by calcitriol attenuates growth stimulation in prostate cancer cells.

    Science.gov (United States)

    Moreno, Jacqueline; Krishnan, Aruna V; Swami, Srilatha; Nonn, Larisa; Peehl, Donna M; Feldman, David

    2005-09-01

    Calcitriol exhibits antiproliferative and pro-differentiation effects in prostate cancer. Our goal is to further define the mechanisms underlying these actions. We studied established human prostate cancer cell lines and primary prostatic epithelial cells and showed that calcitriol regulated the expression of genes involved in the metabolism of prostaglandins (PGs), known stimulators of prostate cell growth. Calcitriol significantly repressed the mRNA and protein expression of prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), the key PG synthesis enzyme. Calcitriol also up-regulated the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme initiating PG catabolism. This dual action was associated with decreased prostaglandin E2 secretion into the conditioned media of prostate cancer cells exposed to calcitriol. Calcitriol also repressed the mRNA expression of the PG receptors EP2 and FP, providing a potential additional mechanism of suppression of the biological activity of PGs. Calcitriol treatment attenuated PG-mediated functional responses, including the stimulation of prostate cancer cell growth. The combination of calcitriol with nonsteroidal anti-inflammatory drugs (NSAIDs) synergistically acted to achieve significant prostate cancer cell growth inhibition at approximately 2 to 10 times lower concentrations of the drugs than when used alone. In conclusion, the regulation of PG metabolism and biological actions constitutes a novel pathway of calcitriol action that may contribute to its antiproliferative effects in prostate cells. We propose that a combination of calcitriol and nonselective NSAIDs might be a useful chemopreventive and/or therapeutic strategy in men with prostate cancer, as it would allow the use of lower concentrations of both drugs, thereby reducing their toxic side effects.

  14. Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer.

    Science.gov (United States)

    Brown, Wells S; Tan, Li; Smith, Andrew; Gray, Nathanael S; Wendt, Michael K

    2016-09-01

    Therapeutic targeting of late-stage breast cancer is limited by an inadequate understanding of how tumor cell signaling evolves during metastatic progression and by the currently available small molecule inhibitors capable of targeting these processes. Herein, we demonstrate that both β3 integrin and fibroblast growth factor receptor-1 (FGFR1) are part of an epithelial-mesenchymal transition (EMT) program that is required to facilitate metastatic outgrowth in response to fibroblast growth factor-2 (FGF2). Mechanistically, β3 integrin physically disrupts an interaction between FGFR1 and E-cadherin, leading to a dramatic redistribution of FGFR1 subcellular localization, enhanced FGF2 signaling and increased three-dimensional (3D) outgrowth of metastatic breast cancer cells. This ability of β3 integrin to drive FGFR signaling requires the enzymatic activity of focal adhesion kinase (FAK). Consistent with these mechanistic data, we demonstrate that FGFR, β3 integrin, and FAK constitute a molecular signature capable of predicting decreased survival of patients with the basal-like subtype of breast cancer. Importantly, covalent targeting of a conserved cysteine in the P-loop of FGFR1-4 with our newly developed small molecule, FIIN-4, more effectively blocks 3D metastatic outgrowth as compared with currently available FGFR inhibitors. In vivo application of FIIN-4 potently inhibited the growth of metastatic, patient-derived breast cancer xenografts and murine-derived metastases growing within the pulmonary microenvironment. Overall, the current studies demonstrate that FGFR1 works in concert with other EMT effector molecules to drive aberrant downstream signaling, and that these events can be effectively targeted using our novel therapeutics for the treatment of the most aggressive forms of breast cancer. Mol Cancer Ther; 15(9); 2096-106. ©2016 AACR.

  15. Psychological well-being and Posttraumatic growth in caregivers of cancer patients

    Directory of Open Access Journals (Sweden)

    Claudia eCormio

    2014-11-01

    Full Text Available IntroductionAlthough research has shown that many cancer patients report positive life changes following cancer diagnosis, there are few data in the literature related to PTG in caregivers of cancer patients. However, the few studies available have shown that this kind of positive changes can also be experienced by family members. The aims of this study were to explore PTG in caregivers of cancer patients and to investigate correlations between the Posttraumatic growth, psychological status and QoL of caregivers and those of patients, taking into account also clinical and socio-demographic aspects.Methods We enrolled 60 patient/caregiver pairs in the Department of Medical Oncology of the National Research Center ‘Giovanni Paolo II’ in Bari. Both patients and caregivers were assessed using the following scales: Posttraumatic growth Inventory (PTGI; Hospital anxiety and depression scale; Short Form (36 Health Survey (SF-36; ECOG Performance Status. Clinical and socio-demographic data were collected. ResultsCaregivers showed significantly higher scores than patients in the dimension of personal strength. Furthermore, we found a significantly close association between anxiety and depression of caregivers with those of patients. Younger caregivers were better than older ones in terms of physical activity, vitality, mental health, and social activities. Although the degree of relationship with the patient has no significant effect on the dependent variables of the study, it was found that caregivers with a degree of kinship more distant to the patient have less physical pain than the closest relatives.ConclusionResults of the present study show that caregivers of cancer patients may experience post-traumatic growth as the result of their caregiver role. It would be interesting to investigate in future research which factor may mediate the presence of post-traumatic growth.

  16. Maximum Inhibition of Breast Cancer/Stem Cell Growth by Concomitant Blockage of Key Receptors

    Directory of Open Access Journals (Sweden)

    Mossa Gardaneh

    2012-01-01

    Full Text Available The blockage of cancer cell growth and division is the prime objective in clinical cancer therapy both at early stages and for inhibition of minimal residual disease and relapse. The failure of conventional therapies in treating breast cancer (BC has prompted dissection of signalling pathways involved in BC cell growth and characterisation of cellular receptors. Specific sets of membrane-bound receptors promote disarrayed self-renewal of BC stem cells and deregulated BC cell proliferation. Individual blockage of each receptor promotes only incomplete inhibition of BC cell growth and partial regression of metastasis. Such monotherapies are based on either chemotherapy or monoclonal antibodies. However, they do not provide long-lasting benefits and are further compromised by increasing resistance the cancer cells acquire against therapeutic agents, by their evasion of receptor blockage and by adoption of alternative growth routes that are induced by cross-talks between key receptors. On the other hand, dual targeting approaches, including receptor blockage combined with chemotherapy, produce prolonged overall survival but, nevertheless, complicate treatment by inducing side effects. Based on the complex nature of BC, combined targeted strategies that potentially confer maximum coverage for treatment cannot be effective without overcoming drug resistance initiated and further induced by inter-receptor communications. This implies that a comprehensive strategy based on concomitant inhibition of key receptors could provide an ultimate solution for effective treatment of aggressive types of BC. Such a strategy would likely be capable of targeting breast tumour cells and BC stem cells alike eventually forcing the cancer to regress.

  17. Fatty acid modulation of autoinducer (AI-2) influenced growth and macrophage invasion by Salmonella Typhimurium.

    Science.gov (United States)

    Widmer, Kenneth W; Jesudhasan, Palmy; Pillai, Suresh D

    2012-03-01

    Autoinducer-2 (AI-2) is a small molecule that is involved in bacterial cell-to-cell signaling whose precursor formation is mediated by luxS. A luxS mutant of Salmonella Typhimurium PJ002 (ΔluxS) was grown in glucose-containing M-9 minimal medium supplemented with varying concentrations (1×, 10×, and 100×) of long-chain fatty acids (linoleic acid, oleic acid, palmitic acid, and stearic acid) to study the influence of fatty acids on growth rate and macrophage invasion. Additionally, in vitro synthesized AI-2 was added to this medium to identify the influence of AI-2 on S. Typhimurium PJ002 (ΔluxS) growth rate and macrophage invasion. The growth rate constant (k) for each experimental treatment was determined based on OD₆₀₀ values recorded during 12 h of incubation. There was a significant (p=0.01) increase in the growth rate of S. Typhimurium PJ002 (ΔluxS) in the presence of AI-2 when compared to the phosphate-buffered saline (PBS) control. However, fatty acids either singly or in a mixture were unable to influence AI-2's effect on growth rate. The presence of AI-2 significantly (p=0.02) decreased the invasiveness of S. Typhimurium PJ002 (ΔluxS) towards the murine macrophage cell line, RAW 264.7. However, the fatty acid mixture was able to reverse this reduction and restore invasiveness to background levels. These results suggest that, while AI-2 may enhance the growth rate and reduce macrophage invasion by the luxS mutant S. Typhimurium PJ002 (ΔluxS), fatty acids may influence the virulence in S. Typhimurium (PJ002) by modulating AI-2 activity.

  18. Influence of water relations and growth rate on plant element uptake and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Greger, Maria [Stockholm Univ. (Sweden). Dept. of Botany

    2006-02-15

    Plant uptake of Ni, Sr, Mo, Cs, La, Th, Se, Cl and I was examined to determine how plant water relations and growth rate influence the uptake and distribution of these elements in the studied plants. The specific questions were how water uptake and growth rate influenced the uptake of various nuclides and how transpiration influenced translocation to the shoot. The knowledge gained will be used in future modelling of radionuclide leakage from nuclear waste deposits entering the ecosystem via plants. The plant studied was willow, Salix viminalis, a common plant in the areas suggested for waste disposal; since there can be clone variation, two different clones having different uptake properties for several other heavy metals were used. The plants were grown in nutrient solution and the experiments on 3-month-old plants were run for 3 days. Polyethylene glycol was added to the medium to decrease the water uptake rate, a fan was used to increase the transpiration rate, and different light intensities were used to produce different growth rates. Element concentration was analysed in roots and shoots. The results show that both the uptake and distribution of various elements are influenced in different ways and to various extents by water flow and plant growth rate, and that it is not possible from the chemical properties of these elements to know how they will react. However, in most cases increased growth rate diluted the concentration of the element in the tissue, reduced water uptake reduced the element uptake, while transpiration had no effect on the translocation of elements to the shoot. The clones did not differ in terms of either the uptake or translocation of the elements, except that I was not taken up and translocated to the shoot in one of the clones when the plant water flow or growth rate was too low. Not all of the elements were found in the plant in the same proportions as they had been added to the nutrient solution.

  19. The influence of competition and dimensionalspatial characteristics of trees on their radial growth in Old-Growth Slătioara forest, Romania

    Directory of Open Access Journals (Sweden)

    Mihai-Leonard Duduman

    2010-11-01

    Full Text Available The paper tries to identify how the radial growths of trees from old-growth forests areinfluenced by some forest structural elements, but also how the radial growths depend on the biometriccharacteristics of trees. The analysis was made for mixed natural stands of coniferous and beech fromSlătioara Natural Reserve. All selected natural stands have an uneven-aged structure. The main resultshave showed that tree diameter influences the radial growth especially in the case of shadow intolerantspecies (Norway spruce; when the preferences for light are decreasing, the correlation level betweenthe two mentioned characteristics is also decreasing (beech, silver fir. The influence of neighbouringcompetitors on the radial growths of trees from the three main species was determined. The first tencompetitor trees were identified and their competition on the reference trees was calculated according tothe Hegyi pattern. It was found that, in natural uneven-aged stands, radial growths are mostly influencedby the competition exerted by the first nine competitor neighbours for Norway spruce, the first twocompetitor neighbours for silver fir and the first seven in case of beech. The competing neighbours thatmostly influence the radial growth were analysed with respect to their azimuth against the referencetrees. It was observed that the radial growths of Norway spruce are mostly influenced by the competitorslocated in S and SE. For silver fir and beech the highest influence over the radial growths comes from thecompetitors located in NE and E.

  20. Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance.

    Science.gov (United States)

    Lupien, Mathieu; Meyer, Clifford A; Bailey, Shannon T; Eeckhoute, Jérôme; Cook, Jennifer; Westerling, Thomas; Zhang, Xiaoyang; Carroll, Jason S; Rhodes, Daniel R; Liu, X Shirley; Brown, Myles

    2010-10-01

    Estrogen receptor α (ERα) expression in breast cancer is predictive of response to endocrine therapy; however, resistance is common in ERα-positive tumors that overexpress the growth factor receptor ERBB2. Even in the absence of estrogen, ERα can be activated by growth factors, including the epidermal growth factor (EGF). EGF induces a transcriptional program distinct from estrogen; however, the mechanism of the stimulus-specific response is unknown. Here we show that the EGF-induced ERα genomic targets, its cistromes, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ERα cistrome specifically regulates genes found overexpressed in ERBB2-positive human breast cancers. This provides a potential molecular explanation for the endocrine therapy resistance seen in ERα-positive breast cancers that overexpress ERBB2. These results suggest a central role for ERα in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ERα, as opposed to blocking its estrogen responsiveness alone.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-09

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

  2. Epidermal Growth Factor Receptor Overexpression as a Target for Auger Electron Radiotherapy of Breast Cancer

    Science.gov (United States)

    2002-08-01

    radiotherapeutic agent for breast cancer. © 2001 Elsevier Science Inc . All rights reserved. Keywords: Breast cancer; Indium-111; Epidermal growth factor receptor... Science Inc . All rights reserved. PII: S0969-8051(01)00262-1 896 .1. Wang et al. / Nuclear Medicine and Biology 28 (2001) 895-902 A NW3 rn- NH, + NHC...raymond.reilly@utoronto.ca (R.M. Reilly). (cDTPAA) with an E-amino group on a lysine residue or the 0969-8051/01/$ - see front matter © 2001 Elsevier

  3. Insulin-like growth factor-I receptor in proliferation and motility of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Minoru; Tomizawa; Fuminobu; Shinozaki; Takao; Sugiyama; Shigenori; Yamamoto; Makoto; Sueishi; Takanobu; Yoshida

    2010-01-01

    AIM:To develop a molecular therapy for pancreatic cancer, the insulin-like growth factor-I (IGF-I) signaling pathway was analyzed.METHODS: Pancreatic cancer cell lines (MIA-Paca2, NOR-P1, PANC-1, PK-45H, PK-1, PK-59 and KP-4) were cultured in media with 10 mL/L fetal bovine serum. Western blotting analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Picropodophyllin (PPP), a specific inhibitor of IGF-IR, LY294002, a specific inhibitor of phosphatidylinositol3 kinase (PI3K), and PD980...

  4. Influence of obesity and bariatric surgery on gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Anna Carolina Batista Dantas; Marco Aurelio Santo; Roberto de Cleva; Rubens Antônio Aissar Sallum; Ivan Cecconello

    2016-01-01

    Esophageal and gastric cancer (GC) are related to obesity and bariatric surgery. Risk factors, such as gastroesophageal reflux and Helicobacter pylori, must be investigated and treated in obese population. After surgery, GC reports are anecdotal and treatment is not standardized. This review aims to discuss GC related to obesity before and after bariatric surgery.

  5. How fibrosis influences imaging and surgical decisions in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Mert eErkan

    2012-10-01

    Full Text Available Our understanding of pancreatic ductal adenocarcinoma is shifting away from a disease of malignant ductal cells-only, towards a complex system where tumor evolution is a result of interaction of cancer cells with their microenvironment. This change has led to intensification of research focusing on the fibrotic stroma of pancreatic ductal adenocarcinoma. Pancreatic stellate cells are the main fibroblastic cells of the pancreas which are responsible for producing the desmoplasia in chronic pancreatitis and pancreatic ductal adenocarcinoma. Clinically, the effect of desmoplasia is two-sided; on the negative side it is a hurdle in the diagnosis of pancreatic ductal adenocarcinoma because the fibrosis in cancer resembles that of chronic pancreatitis. It is also believed that pancreatic stellate cells and pancreatic fibrosis are partially responsible for the therapy resistance in pancreatic cancer. On the positive side, a fibrotic pancreas is safer to operate on compared to a fatty and soft pancreas which is prone for postoperative pancreatic fistula. In this review the impact of pancreatic fibrosis on diagnosis of pancreatic cancer and surgical decisions are discussed from a clinical point of view.

  6. Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Tilburt Jon C

    2011-05-01

    Full Text Available Abstract Background Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history. Methods We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk. Results Of 1028 titles identified, 53 articles met our criteria. Most (92% used an observational design and focused on women (70% with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups and few employed theory-driven analytic strategies to decipher interrelationships of factors. Conclusions Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although

  7. Ets-1 controls breast cancer cell balance between invasion and growth.

    Science.gov (United States)

    Furlan, Alessandro; Vercamer, Chantal; Bouali, Fatima; Damour, Isabelle; Chotteau-Lelievre, Anne; Wernert, Nicolas; Desbiens, Xavier; Pourtier, Albin

    2014-11-15

    Ets-1 overexpression in human breast cancers is associated with invasiveness and poor prognosis. By overexpressing Ets-1 or a dominant negative mutant in MMT breast cancer cells, we previously highlighted the key role of Ets-1 in coordinating multiple invasive features of these cells. Interestingly, we also noticed that Ets-1 decreased the density of breast cancer cells cultured in three-dimensional extracellular matrix gels. The 3D context was instrumental to this phenomenon, as such downregulation was not observed in cells grown on two-dimensional plastic or matrix-coated dishes. Ets-1 overexpression was deleterious to anchorage-independent growth of MMT cells in soft agar, a standard model for in vitro tumorigenicity. The relevance of this mechanism was confirmed in vivo, during primary tumor growth and in a metastatic assay of lung colonization. In these models, Ets-1 was associated with epithelial-to-mesenchymal transition features and modulated the ratio of Ki67-positive cells, while hardly affecting in vivo apoptotic cell death. Finally, siRNA-mediated knockdown of Ets-1 in human breast cancer cell lines also decreased colony growth, both in anchorage-independent assays and 3D extracellular matrix cultures. These in vitro and in vivo observations shed light on an unsuspected facet of Ets-1 in breast tumorigenesis. They show that while promoting malignancy through the acquisition of invasive features, Ets-1 also attenuates breast tumor cell growth and could therefore repress the growth of primary tumors and metastases. This work also demonstrates that 3D models may reveal mechanisms of tumor biology that are cryptic in standard 2D models.

  8. SL-01, an oral derivative of gemcitabine, inhibited human breast cancer growth through induction of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Qin, Yi-Zhuo; Wang, Rui-Qi [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China); Li, Wen-Bao, E-mail: wbli92128@yahoo.com [Sanlugen PharmaTech, Rm 506, No. 2766 Yingxiu Road, Jinan 250101 (China); Qu, Xian-Jun, E-mail: qxj@sdu.edu.cn [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China)

    2013-08-23

    Highlights: •SL-01 is an oral derivative of gemcitabine. •SL-01 possessed activity against human breast cancer growth via apoptotic induction. •SL-01’s activity was more potently than that of gemcitabine. •SL-01 inhibited cancer growth without toxicity to mice. -- Abstract: SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. Conclusion: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine.

  9. Human mitochondrial transcription factor A functions in both nuclei and mitochondria and regulates cancer cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Han, Bin [Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan); Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan); Department of Urology, Shengjing Hospital of China Medical University, Shenyang (China); Izumi, Hiroto; Yasuniwa, Yoshihiro; Akiyama, Masaki; Yamaguchi, Takahiro [Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan); Fujimoto, Naohiro; Matsumoto, Tetsuro [Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan); Wu, Bin [Department of Urology, Shengjing Hospital of China Medical University, Shenyang (China); Tanimoto, Akihide [Department of Pathology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima (Japan); Sasaguri, Yasuyuki [Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan); Kohno, Kimitoshi, E-mail: k-kohno@med.uoeh-u.ac.jp [Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu (Japan)

    2011-04-29

    Highlights: {yields} Mitochondrial transcription factor A (mtTFA) localizes in nuclei and binds tightly to the nuclear chromatin. {yields} mtTFA contains two putative nuclear localization signals (NLS) in the HMG-boxes. {yields} Overexpression of mtTFA enhances the growth of cancer cells, whereas downregulation of mtTFA inhibits their growth by regulating mtTFA target genes, such as baculoviral IAP repeat-containing 5 (BIRC5; also known as survivin). {yields} Knockdown of mtTFA expression induces p21-dependent G1 cell cycle arrest. -- Abstract: Mitochondrial transcription factor A (mtTFA) is one of the high mobility group protein family and is required for both transcription from and maintenance of mitochondrial genomes. However, the roles of mtTFA have not been extensively studied in cancer cells. Here, we firstly reported the nuclear localization of mtTFA. The proportion of nuclear-localized mtTFA varied among different cancer cells. Some mtTFA binds tightly to the nuclear chromatin. DNA microarray and chromatin immunoprecipitation assays showed that mtTFA can regulate the expression of nuclear genes. Overexpression of mtTFA enhanced the growth of cancer cell lines, whereas downregulation of mtTFA inhibited their growth by regulating mtTFA target genes, such as baculoviral IAP repeat-containing 5 (BIRC5; also known as survivin). Knockdown of mtTFA expression induced p21-dependent G1 cell cycle arrest. These results imply that mtTFA functions in both nuclei and mitochondria to promote cell growth.

  10. Tissue-scale, personalized modeling and simulation of prostate cancer growth

    Science.gov (United States)

    Lorenzo, Guillermo; Scott, Michael A.; Tew, Kevin; Hughes, Thomas J. R.; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

    2016-11-01

    Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion-reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

  11. A Possible Link Between the Pubertal Growth of Girls and Ovarian Cancer in Their Daughters

    Science.gov (United States)

    BARKER, DAVID J. P.; OSMOND, CLIVE; THORNBURG, KENT L.; KAJANTIE, EERO; ERIKSSON, JOHAN G.

    2017-01-01

    At puberty, the distance between the iliac crests of the female pelvis, measured by the intercristal and interspinous diameters, increases rapidly. This is mainly controlled by estrogens. We have followed up 6,370 women who were born in Helsinki during 1934–1944, and whose mothers’ pelvic bones were measured during routine antenatal care. We have previously reported that women whose mothers had larger intercristal diameters had higher rates of breast cancer. We postulated that large intercristal diameters are markers of high circulating concentrations of estrogen, which are established at puberty, persist through reproductive life and cause genetic instability in differentiating breast cells in female embryos. We now report on ovarian cancer in the same cohort. Our hypothesis was that the risk of this cancer would also be higher in women whose mothers had broader hips. We found that, when compared with all other women, the hazard ratio for ovarian cancer was 3.3 (95% CI 1.6–7.0, P = 0.004) in the daughters of mothers whose interspinous diameter was greater than 27 cm. Among mothers who had an early menarche, each measure of broad hips was associated with increased risk of ovarian cancer in their daughters. We postulate that ovarian cancer is initiated by exposure of the fetal ovary to maternal sex hormones. Concentrations of these hormones may be higher in mothers who had an early menarche. The maternal sex hormone profile that initiates ovarian cancer may be the product of poor nutrition and growth in early childhood followed by catch-up pre-pubertal growth. PMID:18461601

  12. DAC can restore expression of NALP1 to suppress tumor growth in colon cancer.

    Science.gov (United States)

    Chen, C; Wang, B; Sun, J; Na, H; Chen, Z; Zhu, Z; Yan, L; Ren, S; Zuo, Y

    2015-01-22

    Despite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.

  13. Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

    Science.gov (United States)

    Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

    2016-10-01

    This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

  14. Insulin-like growth factor 2 silencing restores taxol sensitivity in drug resistant ovarian cancer.

    Science.gov (United States)

    Brouwer-Visser, Jurriaan; Lee, Jiyeon; McCullagh, KellyAnne; Cossio, Maria J; Wang, Yanhua; Huang, Gloria S

    2014-01-01

    Drug resistance is an obstacle to the effective treatment of ovarian cancer. We and others have shown that the insulin-like growth factor (IGF) signaling pathway is a novel potential target to overcome drug resistance. The purpose of this study was to validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and to determine the efficacy of targeting IGF2 in vivo. An analysis of The Cancer Genome Atlas (TCGA) data in the serous ovarian cancer cohort showed that high IGF2 mRNA expression is significantly associated with shortened interval to disease progression and death, clinical indicators of drug resistance. In a genetically diverse panel of ovarian cancer cell lines, the IGF2 mRNA levels measured in cell lines resistant to various microtubule-stabilizing agents including Taxol were found to be significantly elevated compared to the drug sensitive cell lines. The effect of IGF2 knockdown on Taxol resistance was investigated in vitro and in vivo. Transient IGF2 knockdown significantly sensitized drug resistant cells to Taxol treatment. A Taxol-resistant ovarian cancer xenograft model, developed from HEY-T30 cells, exhibited extreme drug resistance, wherein the maximal tolerated dose of Taxol did not delay tumor growth in mice. Blocking the IGF1R (a transmembrane receptor that transmits signals from IGF1 and IGF2) using a monoclonal antibody did not alter the response to Taxol. However, stable IGF2 knockdown using short-hairpin RNA in HEY-T30 effectively restored Taxol sensitivity. These findings validate IGF2 as a potential therapeutic target in drug resistant ovarian cancer and show that directly targeting IGF2 may be a preferable strategy compared with targeting IGF1R alone.

  15. RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth.

    Science.gov (United States)

    Qin, Yu; Chen, Wangbing; Xiao, Yao; Yu, Wendan; Cai, Xin; Dai, Meng; Xu, Tingting; Huang, Wenlin; Guo, Wei; Deng, Wuguo; Wu, Taihua

    2015-09-29

    hTERT is the key component of telomerase and its overactivation contributes to maintaining telomere length and cell immortalization. Previously, we identified RFPL3 as a new transcription activator of hTERT in lung cancers. However, the exact mechanism of RFPL3 in mediating hTERT activation and its associated signal regulatory network remain unclear. In this study, we found that RFPL3 colocalized and interacted directly with CBP in the nucleus of lung cancer cells. Immunohistochemical analysis of tissue microarrays of lung cancers revealed the simultaneous overexpression of both RFPL3 and CBP predicted relatively poor prognosis. Furthermore, we confirmed their synergistic stimulation on hTERT expression and tumor cell growth. The binding of RFPL3 to hTERT promoter was reduced markedly when CBP was knocked down by its specific siRNA or suppressed by its inhibitor in lung cancer cells with stable overexpression of RFPL3. When one of the two proteins RFPL3 and CBP was upregulated or downregulated, whereas the another remains unchanged, hTERT expression and telomerase activity were activated or repressed accordingly. In the meantime, the growth of lung cancer cells was also promoted or attenuated accordingly. Furthermore, we also found that RFPL3 coordinated with CBP to upregulate hTERT through the CBP-induced acetylation of RFPL3 protein and their co-anchoring at hTERT promoter region. Collectively, our results reveal a new mechanism of hTERT regulation in lung cancer cells and suggest the RFPL3/CBP/hTERT signaling pathway may be a new targets for lung cancer treatment.

  16. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.

    Science.gov (United States)

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita

    2013-01-01

    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  17. Factors Influencing Body Image in Women with Breast Cancer: A Comprehensive Literature Review

    Science.gov (United States)

    Rezaei, Maedeh; Elyasi, Forouzan; Janbabai, Ghasem; Moosazadeh, Mahmood; Hamzehgardeshi, Zeinab

    2016-01-01

    Context Many psycho-socioeconomic and other types factors associated with cancer, the treatment process, and changes in patients’ physical appearance and sexual function influence the body image of women with breast cancer. The purpose of this study was to determine which factors influence the body image of women with breast cancer. Data Collection A narrative literature review was conducted. Electronic databases, including Google Scholar, SID, Magiran, IranDoc, Barekat, Web of Science, Science Direct, Cochrane Library, ProQuest, Scopus, and PubMed, including Medline, were searched to retrieve articles published from 1993 to 2016 using the keywords breast cancer, treatment, body image, and related factors. The quality of selected studies was appraised using a checklist adapted from Samadaee-Gelehkolaee (2016). Results Of 690 articles retrieved in the search, 190 articles were selected for full text appraisal. Finally, 44 articles were selected for data analysis. The results were classified under three headings: bio-psycho-socioeconomic factors, factors associated with the disease and treatment processes, and physical appearance and sexual function. Conclusions The findings of this review showed that many factors can influence the body image of women suffering from breast cancer. These factors were predictors of patients’ inter-personal and intra-personal relationships with their partners and others who influenced various other aspects of their lives, possibly leading to many life’s issues. These factors must be identified and considered to make the most appropriate decisions for patients. The strength of this study lies in the exploration of factors influencing the body image of women with breast cancer which earlier studies did not consider. Moreover, the authors believe that this research has addressed nearly all the factors that are real concerns in the body image of women with breast cancer. PMID:28184329

  18. ST13, a proliferation regulator, inhibits growth and migration of colorectal cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Rui BAI; Zhong SHI; Jia-wei ZHANG; Dan LI; Yong-liang ZHU; Shu ZHENG

    2012-01-01

    Background and objective:ST13,is the gene encoding the HSP70 interacting protein (HIP).Previous research has shown that ST13 mRNA and protein levels are down-regulated in colorectal cancer (CRC) tissues compared with adjacent normal tissues.This study aims at the role of ST13 in the proliferation and migration of CRC cells.Methods:The transcript level of ST13 in different CRC cell lines was evaluated by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).ST13-overexpressed and ST13-knockdown CRC cells were constructed respectively by lentiviral transduction,followed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay,plate colony formation,cell-cycle analysis,and migration assays to evaluate the influence of ST13 on proliferation and migration in vitro.Moreover,a mouse xenograft study was performed to test in vivo tumorigenicity of ST13-knockdown CRC cells.Results:Lentivirus-mediated overexpression of ST13 in CRC cells inhibited cell proliferation,colony formation,and cell migration in vitro.In contrast,down-regulation of ST13 by lentiviralbased short hairpin RNA (shRNA) interference in CRC cells significantly increased cell proliferation and cloning efficiency in vitro.In addition,down-regulation of ST13 expression significantly increased the tumorigenicity of CRC cells in vivo.Conclusions:ST13 gene is a proliferation regulator that inhibits tumor growth in CRC and may affect cell migration.

  19. Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhu; Bao-Ming Yu; Yu-Bao Ji; Ming-Hua Zheng; Dong-Hua Li

    2002-01-01

    AIM: To evaluate the effect of reactive oxygen species suchas hydrogen peroxide on the progression of human coloncancer.METHODS: Human colon carcinoma cell lines, LS174T andHCT8, were treated respectively with 10- 5,10- 7 or 10- 9 mol@L- 1 hydrogen peroxide for 24h, and co-cultured with humanendothelial cell line ECV-304. The migration of ECV-304induced by cancer cells was calculated and the expressionlevel of vascular endothelial growth factor in cancer cellswas determined by RT-PCR analysis and ELISA.Dactinomycin of 1.5mg@ L-1 which could block transcriptionof cancer cells was applied to observe the effects of H2O2 ontranscriptional activity and the relative half-life of VEGFmRNA. Finally, to evaluate the effect H2O2 on NF-κB activityin colon cancer cells, NF-κB in cytoplasm and nucleus of thecells were detected with FITC-tagged antibody and itspresence in the nucleus (Fn ) Vs cytoplasm ( Fc ) wasmonitored by measuring the green fluorescence integratedover the nucleus by laser scanning cytometry(LSC).RESULTS: Exogenouse hydrogen peroxide of lowconcentration increased the migration of endothelial cellsinduced by colon cancer cells. When cancer cells weretreated with 10-5 mol@ L-1 H2O2, the migration number ofendothelial cells induced by LS174T cells was 203 ± 70, andthe number induced by HCT8 cells was 145 ± 65. The twovalues were significantly higher than those treated with otherconcentrations of h2O2 ( P < 0.01 ). The expression ofvascular endothelial growth factor in cancer cells, whichcould be blocked by dactinomycin, were increased to acertain degree, while the relative half-life of VEGF mRNAwas not prolonged after treatment with hydrogen peroxide.The activity of NF-κB in colon cells rose after the cells wereexposed to hydrogen peroxide for 24h. The Fn values inHCT8 cells were 91 ± 13 (0 mol@ L- 1 h2O2) and 149 ± 40( 10-5mol@L-1 h2O2) ( P< 0.05), in LS174T cells were 127 ± 35(0mol@L-1 H2O2) and 192± 11(10-5 mol@L-1 h2O2) (P< 0.05).lt is similar

  20. Influence of Body Mass Index on Tumor Pathology and Survival in Uterine Cancer

    DEFF Research Database (Denmark)

    Kristensen, Anne Bjerrum; Hare-Bruun, Helle; Høgdall, Claus Kim;

    2016-01-01

    for uterine cancer or atypical endometrial hyperplasia (International Classification of Diseases-10 codes D070, DC549) 2005 to 2012 (n = 6003). MAIN OUTCOME MEASURES: Impact of BMI on type I and II endometrial cancer survival. MATERIALS AND METHODS: Danish Gynecological Cancer Database data on women with type......OBJECTIVE: To evaluate the influence of body mass index (BMI) on endometrial tumor pathology, stage and complication rate and to identify individual prognostic factors, such as BMI, in types I and II endometrial cancer. DESIGN: Register study included all Danish women who underwent surgery...... I and II endometrial cancer were retrieved. Kaplan-Meier plot was used to illustrate differences in survival in relation to BMI. Log-rank test was used to demonstrate difference between the curves. Cox regression hazard model was used to estimate hazard ratios (HR) of the effect of BMI on overall...

  1. TERT Polymorphism rs2853669 Influences on Lung Cancer Risk in the Korean Population.

    Science.gov (United States)

    Yoo, Seung Soo; Do, Sook Kyung; Choi, Jin Eun; Lee, Shin Yup; Lee, Jaehee; Cha, Seung Ick; Kim, Chang Ho; Park, Jae Yong

    2015-10-01

    Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.

  2. Forced Expression of ZNF143 Restrains Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Kimitoshi Kohno

    2011-10-01

    Full Text Available We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143 regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression in the cell cycle, we established two cells with forced expression of ZNF143 derived from PC3 prostate cancer cell lines. These cell lines overexpress genes associated with cell cycle and cell division, such as polo-like kinase 1 (PLK1, aurora kinase B (AURKB and some minichromosome maintenance complex components (MCM. However, the doubling time of cells with forced expression of ZNF143 was approximately twice as long as its control counterpart cell line. Analysis following serum starvation and re-seeding showed that PC3 cells were synchronized at G1 in the cell cycle. Also, ZNF143 expression fluctuated, and was at its lowest level in G2/M. However, PC3 cells with forced expression of ZNF143 synchronized at G2/M, and showed lack of cell cycle-dependent fluctuation of nuclear expression of MCM proteins. Furthermore, G2/M population of both cisplatin-resistant PCDP6 cells over-expressing ZNF143 (derived from PC3 cells and cells with forced expression of ZNF143 was significantly higher than that of each counterpart, and the doubling time of PCDP6 cells is about 2.5 times longer than that of PC3 cells. These data suggested that fluctuations in ZNF143 expression are required both for gene expression associated with cell cycle and for cell division.

  3. Forced Expression of ZNF143 Restrains Cancer Cell Growth

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Hiroto, E-mail: h-izumi@med.uoeh-u.ac.jp; Yasuniwa, Yoshihiro; Akiyama, Masaki; Yamaguchi, Takahiro; Kuma, Akihiro; Kitamura, Noriaki; Kohno, Kimitoshi [Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555 (Japan)

    2011-10-19

    We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143) regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression in the cell cycle, we established two cells with forced expression of ZNF143 derived from PC3 prostate cancer cell lines. These cell lines overexpress genes associated with cell cycle and cell division, such as polo-like kinase 1 (PLK1), aurora kinase B (AURKB) and some minichromosome maintenance complex components (MCM). However, the doubling time of cells with forced expression of ZNF143 was approximately twice as long as its control counterpart cell line. Analysis following serum starvation and re-seeding showed that PC3 cells were synchronized at G1 in the cell cycle. Also, ZNF143 expression fluctuated, and was at its lowest level in G2/M. However, PC3 cells with forced expression of ZNF143 synchronized at G2/M, and showed lack of cell cycle-dependent fluctuation of nuclear expression of MCM proteins. Furthermore, G2/M population of both cisplatin-resistant PCDP6 cells over-expressing ZNF143 (derived from PC3 cells) and cells with forced expression of ZNF143 was significantly higher than that of each counterpart, and the doubling time of PCDP6 cells is about 2.5 times longer than that of PC3 cells. These data suggested that fluctuations in ZNF143 expression are required both for gene expression associated with cell cycle and for cell division.

  4. Influence of Urbanization on Growth of Rural Residents’ Consumption in Western Ethnic Minority Areas of China

    Institute of Scientific and Technical Information of China (English)

    Xiaofang; ZOU

    2015-01-01

    To make clear the relation between urbanization and growth of rural resident consumption in western ethnic minority areas of China,this paper selected cross-sectional area of 12 provinces( cities) in western ethnic minority areas in 2005- 2013 and made an empirical analysis through building panel data of influence of urbanization on rural resident consumption. Results indicate that there is positive correlation between urbanization and rural resident consumption growth in western ethnic minority areas. Urbanization increases income level of rural residents,strengthens demonstration effect of urban residents on rural resident consumption,and accordingly promotes rural resident consumption growth in western ethnic minority areas. Therefore,it is required to accelerate urbanization development,expand channels of increasing farmers’ income,improve resident consumption environment,and bring into play promotion function of counties,to drive rural resident consumption growth in western ethnic minority areas.

  5. Annexin A1 influences in breast cancer: Controversies on contributions to tumour, host and immunoediting processes.

    Science.gov (United States)

    Tu, Yan; Johnstone, Cameron N; Stewart, Alastair G

    2017-02-14

    Annexin A1 is a multifunctional protein characterised by its actions in modulating the innate and adaptive immune response. Accumulating evidence of altered annexin A1 expression in many human tumours raises interest in its functional role in cancer biology. In breast cancer, altered annexin A1 expression levels suggest a potential influence on tumorigenic and metastatic processes. However, reports of conflicting results reveal a relationship that is much more complex than first conceptualised. In this review, we explore the diverse actions of annexin A1 on breast tumour cells and various host cell types, including stromal immune and structural cells, particularly in the context of cancer immunoediting.

  6. Preconceptions influence women’s perceptions of information on breast cancer screening

    DEFF Research Database (Denmark)

    Henriksen, Mikael Johannes Vuokko; Guassora, Ann Dorrit Kristiane; Brodersen, John

    2015-01-01

    Background: Screening for breast cancer has been subject to intense debate in recent decades regarding benefits and risks. Participation in breast cancer screening should be based on informed choice, and most countries approach this by sending information leaflets with invitations to attend...... in breast cancer screening. Second, we discuss how information and attitudes held prior to receiving the invitation influence the perception of the balance between the benefits and risks harms of screening. Methods: We used a qualitative design and interviewed six women who were soon to receive their first...

  7. Identification of microprocessor-dependent cancer cells allows screening for growth-sustaining micro-RNAs.

    Science.gov (United States)

    Peric, D; Chvalova, K; Rousselet, G

    2012-04-19

    Micro-RNAs are deregulated in cancer cells, and some are either tumor suppressive or oncogenic. In addition, a link has been established between decreased expression of micro-RNAs and transformation, and several proteins of the RNA interference pathway have been shown to be haploinsufficient tumor suppressors. Oncogenic micro-RNAs (oncomiRs) could represent new therapeutic targets, and their identification is therefore crucial. However, structural and functional redundancy between micro-RNAs hampers approaches relying on individual micro-RNA inhibition. We reasoned that in cancer cells that depend on oncomiRs, impairing the micro-RNA pathway could lead to growth perturbation rather than increased tumorigenesis. Identifying such cells could allow functional analyses of individual micro-RNAs by complementation of the phenotypes observed upon global micro-RNA inhibition. Therefore, we developed episomal vectors coding for small hairpin RNAs targeting either Drosha or DGCR8, the two components of the microprocessor, the nuclear micro-RNA maturation complex. We identified cancer cell lines in which both vectors induced colony growth arrest. We then screened for individual micro-RNAs complementing this growth arrest, and identified miR-19a, miR-19b, miR-20a and miR-27b as major growth-sustaining micro-RNAs. However, the effect of miR-19a and miR-19b was only transient. In addition, embryonic stem cell-derived micro-RNAs with miR-20a seeds were much less efficient than miR-20a in sustaining cancer cell growth, a finding that contrasted with results obtained in stem cells. Finally, we showed that the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10, a shared target of miR-19 and miR-20, was functionally involved in the growth arrest induced by microprocessor inhibition. We conclude that our approach allowed to identify microprocessor-dependent cancer cells, which could be used to screen for growth-sustaining micro-RNAs. This complementation screen

  8. Non-surgical factors influencing lymph node yield in colon cancer

    Institute of Scientific and Technical Information of China (English)

    Patrick Wood; Colin Peirce; Jurgen Mulsow

    2016-01-01

    There are numerous factors which can affect the lymph node(LN) yield in colon cancer specimens.The aim of this paper was to identify both modifiable and nonmodifiable factors that have been demonstrated toaffect colonic resection specimen LN yield and to summarise the pertinent literature on these topics.A literature review of Pub Med was performed to identify the potential factors which may influence the LN yield in colon cancer resection specimens.The terms used for the search were:LN,lymphadenectomy,LN yield,LN harvest,LN number,colon cancer and colorectal cancer.Both nonmodifiable and modifiable factors were identified.The review identified fifteen non-surgical factors:(13 nonmodifiable,2 modifiable) which may influence LN yield.LN yield is frequently reduced in older,obese patients and those with male sex and increased in patients with right sided,large,and poorly differentiated tumours.Patient ethnicity and lower socioeconomic class may negatively influence LN yield.Pre-operative tumour tattooing appears to increase LN yield.There are many factors that potentially influence the LN yield,although the strength of the association between the two varies greatly.Perfecting oncological resection and pathological analysis remain the cornerstones to achieving good quality and quantity LN yields in patients with colon cancer.

  9. Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks.

    Science.gov (United States)

    Wu, Xuping; Smavadati, Shirin; Nordfjäll, Katarina; Karlsson, Krister; Qvarnström, Fredrik; Simonsson, Martin; Bergqvist, Michael; Gryaznov, Sergei; Ekman, Simon; Paulsson-Karlsson, Ylva

    2012-12-01

    Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1 week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased γ-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer.

  10. Effects of combined octreotide and aspirin on the growth of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    唐承薇; 王春晖; 汤丽平

    2003-01-01

    Objective To investigate the effects of the combination of octreotide and aspirin on the growth of gastric cancer. Methods Proliferation of gastric cancer cell lines treated with octreotide or aspirin was determined by 3 H-thymidine incorporation. After xenografts of human gastric cancer were implanted orthotropically in the stomach of nude mice, they were administered octreotide plus aspirin for 8 weeks. The mRNA of somatostatin receptor in the tissues of gastric carcinoma was detected by reverse transcription polymerase chain reaction (RT-PCR). Cyclooxygenase-2 in gastric cancer tissues was measured by immuno~histochemistry. Results Both octreotide and aspirin significantly reduced the 3 H-thymidine incorporation of gastric cancer cells. Xenografts in situ were found in all stomachs of nude mice except for two in the combination group. Either size or weight of tumors treated by octreotide, aspirin or in combination was significantly reduced as compared with that of controls. The inhibition rate for tumor was 60.6% (octreotide), 39.3% (aspirin), and 85.6% (in combination) respectively. No severe side effects were observed in any treated groups. Somatostatin receptor-2 and -3 were expressed in the transplanted gastric adenocarcinomas. Aspirin could down-regulate the strong expression of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice.Conclusion A combination of octreotide and aspirin significantly inhibited proliferation of gastric cancer through mediation of somatosatin receptors and suppression of cyclooxygenase-2.

  11. New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis.

    Science.gov (United States)

    Hugo, Honor J; Saunders, C; Ramsay, R G; Thompson, E W

    2015-12-01

    The medicinal use of aspirin stretches back to ancient times, before it was manufactured in its pure form in the late 19th century. Its accepted mechanistic target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark discovery, the therapeutic application of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has increased dramatically. The most significant benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given the recognized role of CI in cancer development, the use of long-term NSAID treatment in the prevention of cancer is an enticing possibility. COX-2 is a key driver of CI, and here we review COX-2 expression as a predictor of survival in various cancer types, including breast. Obesity and post-partum involution are natural inflammatory states that are associated with increased breast cancer risk. We outline the COX-2 mediated mechanisms contributing to the growth of cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we examine the potential regulation of COX-2 by c-Myb, and the possible interplay between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha (HIF1α)/COX-2 in invasive pathways in breast cancer.

  12. THE EMERGING ROLE OF INSULIN AND INSULIN-LIKE GROWTH FACTOR SIGNALING IN CANCER STEM CELLS

    Directory of Open Access Journals (Sweden)

    Roberta eMalaguarnera

    2014-02-01

    Full Text Available Cancer cells frequently exploit the IGF signaling, a fundamental pathway mediating development, cell growth and survival. As a consequence, several components of the IGF signaling are deregulated in cancer and sustain cancer progression. However, specific targeting of IGF-IR in humans has resulted efficacious only in small subsets of cancers, making researches wondering whether IGF system targeting is still worth pursuing in the clinical setting. Although no definite answer is yet available, it has become increasingly clear that other components of the IGF signaling pathway, such as IR-A, may substitute for the lack of IGF-IR, and induce cancer resistance and/or clonal selection. Moreover, accumulating evidence now indicates that IGF signaling is a central player in the induction/maintenance of epithelial mesenchymal transition (EMT and cell stemness, two strictly related programs, which play a key role in metastatic spread and resistance to cancer treatments. Here we review the evidences indicating that IGF signaling enhances the expression of transcription factors implicated in the EMT program and has extensive crosstalk with specific pathways involved in cell pluripotency and stemness maintenance. In turn, EMT and cell stemness activate positive feed-back mechanisms causing upregulation of various IGF signaling components. These findings may have novel translational implications.

  13. TRPV6 alleles do not influence prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Flockerzi Veit

    2009-10-01

    Full Text Available Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6 is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Methods Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. Results We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Conclusion Our results show that the frequencies of trpv6

  14. Franchised fast food brands: An empirical study of factors influencing growth

    Directory of Open Access Journals (Sweden)

    Christopher A. Wingrove

    2017-01-01

    Full Text Available Orientation: Franchising is a popular and multifaceted business arrangement that captures a sizeable portion of the restaurant industry worldwide. Research purpose: The study empirically investigated the influence of various site location and branding factors on the growth of franchised fast food restaurant brands across the greater Gauteng region. Motivation of the study: Researching which factors influence the growth of franchised fast food restaurant brands is important for an emerging market context such as South Africa when considering the marked increase in the consumption of fast foods. Design: A sample of 140 customers was surveyed from 12 leading franchised fast food outlets. Primary data were collected for various items representing site location and brand factors. Regression analysis was used to test the hypotheses. Findings: The overall findings showed that convenience and central facilities of a retail location are positively and significantly associated with the growth of the franchise fast food outlet. Practical implications: The study findings have implications for practitioners who need to take into account which factors influence revenue growth, since targeted interventions may be required to implement sustainable strategies by franchisors. Contribution: The findings may serve as a catalyst for this growing and important activity in South Africa and other emerging markets.

  15. Study of factors influencing dose distribution of brachytherapy in cervical cancer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To study the factors which influence the dose distribution of brachytherapy in cervical cancer.Methods Ninety-five patients with cervical cancer Ⅱ-Ⅲb received fundamental radiation therapy including brachytherapy in our department from Aug.2004 to Nov.2005.The deviation of isodose curve of brachytherapy was based on A-B reference system,and the deviation of dose was defined by measuring in a practical standard body model.Results The factors influencing isodose offset significantly were parametrial...

  16. Regulation of MCF-7 breast cancer cell growth by beta-estradiol sulfation.

    Science.gov (United States)

    Falany, Josie L; Macrina, Nancy; Falany, Charles N

    2002-07-01

    Estrogen stimulation is an important factor in human breast cancer cell growth and development. Metabolism of beta-estradiol (E2), the major endogenous human estrogen, is important in regulating both the level and activity of the hormone in breast tissues. Conjugation of E2 with a sulfonate moiety is an inactivation process since the sulfate ester formed by this reaction can not bind and activate the estrogen receptor. In human tissues including the breast, estrogen sulfotransferase (EST, SULT1E1) is responsible for high affinity E2 sulfation activity. EST is expressed in human mammary epithelial (HME) cells but not in most cultured breast cancer cell lines, including estrogen responsive MCF-7 cells. Stable expression of EST in MCF-7 cells at levels similar to those detected in HME cells significantly inhibits cell growth at physiologically relevant E2 concentrations. The mechanism of cell growth inhibition involves the abrogation of responses observed in growth factor expression in MCF-7 cells following E2 stimulation. MCF-7 cells expressing EST activity did not show a decrease in estrogen receptor-alpha levels, nor a characteristic increase in progesterone receptor or decrease in transforming growth factor-beta expression upon exposure to 100 pM or 1 nM E2. The lack of response in these MCF-7 cells is apparently due to the rapid sulfation and inactivation of free E2 by EST. These results suggest that loss of EST expression in the transformation of normal breast tissues to breast cancer may be an important factor in increasing the growth responsiveness of preneoplastic or tumor cells to estrogen stimulation.

  17. Influence of competition and rainfall manipulation on the growth responses of savanna trees and grasses.

    Science.gov (United States)

    February, Edmund C; Higgins, Steven I; Bond, William J; Swemmer, Louise

    2013-05-01

    In this study, we explored how rainfall manipulation influenced competitive interactions between grasses and juvenile trees (small nonreproductive trees capable of resprouting) in savanna. To do this, we manipulated rainfall amount in the field using an incomplete factorial experiment that determined the effects of rainfall reduction, no manipulation, rainfall addition, and competition between grasses and trees on grass and tree growth. As response variables, we focused on several measures of tree growth and Disc Pasture Meter settling height as an estimate of grass aboveground biomass. We conducted the study over four years, at two sites in the Kruger National Park, South Africa. Our results show that rainfall manipulation did not have substantial effects on any of the measures of tree growth we considered. However, trees at plots where grasses had been removed grew on average 15 cm more in height and 1.3-1.7 times more in basal area per year than those in plots with grasses. Grass biomass was not influenced by the presence of trees but was significantly and positively influenced by rainfall addition. These findings were not fundamentally influenced by soil type or by prevailing precipitation, suggesting applicability of our results to a wide range of savannas. Our results suggest that, in savannas, increasing rainfall serves to increase the competitive pressure exerted by grasses on trees. The implication is that recruitment into the adult tree stage from the juvenile stage is most likely in drought years when there is little competition from grass for resources and grass fuel loads are low.

  18. Inhibition of PRL-2·CNNM3 Protein Complex Formation Decreases Breast Cancer Proliferation and Tumor Growth.

    Science.gov (United States)

    Kostantin, Elie; Hardy, Serge; Valinsky, William C; Kompatscher, Andreas; de Baaij, Jeroen H F; Zolotarov, Yevgen; Landry, Melissa; Uetani, Noriko; Martínez-Cruz, Luis Alfonso; Hoenderop, Joost G J; Shrier, Alvin; Tremblay, Michel L

    2016-05-13

    The oncogenic phosphatase of regenerating liver 2 (PRL-2) has been shown to regulate intracellular magnesium levels by forming a complex through an extended amino acid loop present in the Bateman module of the CNNM3 magnesium transporter. Here we identified highly conserved residues located on this amino acid loop critical for the binding with PRL-2. A single point mutation (D426A) of one of those critical amino acids was found to completely disrupt PRL-2·human Cyclin M 3 (CNNM3) complex formation. Whole-cell voltage clamping revealed that expression of CNNM3 influenced the surface current, whereas overexpression of the binding mutant had no effect, indicating that the binding of PRL-2 to CNNM3 is important for the activity of the complex. Interestingly, overexpression of the CNNM3 D426A-binding mutant in cancer cells decreased their ability to proliferate under magnesium-deprived situations and under anchorage-independent growth conditions, demonstrating a PRL-2·CNNM3 complex-dependent oncogenic advantage in a more stringent environment. We further confirmed the importance of this complex in vivo using an orthotopic xenograft breast cancer model. Finally, because molecular modeling showed that the Asp-426 side chain in CNNM3 buries into the catalytic cavity of PRL-2, we showed that a PRL inhibitor could abrogate complex formation, resulting in a decrease in proliferation of human breast cancer cells. In summary, we provide evidence that this fundamental regulatory aspect of PRL-2 in cancer cells could potentially lead to broadly applicable and innovative therapeutic avenues.

  19. Differential expression of growth factor receptors and membrane-bound tumor markers for imaging in male and female breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeroen F Vermeulen

    Full Text Available INTRODUCTION: Male breast cancer accounts for 0.5-1% of all breast cancers and is generally diagnosed at higher stage than female breast cancers and therefore might benefit from earlier detection and targeted therapy. Except for HER2 and EGFR, little is known about expression of growth factor receptors in male breast cancer. We therefore investigated expression profiles of growth factor receptors and membrane-bound tumor markers in male breast cancer and gynecomastia, in comparison with female breast cancer. METHODS: Tissue microarrays containing 133 male breast cancer and 32 gynecomastia cases were stained by immunohistochemistry for a panel of membrane-bound targets and compared with data on 266 female breast cancers. RESULTS: Growth factor receptors were variably expressed in 4.5% (MET up to 38.5% (IGF1-R of male breast cancers. Compared to female breast cancer, IGF1-R and carbonic anhydrase 12 (CAXII were more frequently and CD44v6, MET and FGFR2 less frequently expressed in male breast cancer. Expression of EGFR, HER2, CAIX, and GLUT1 was not significantly different between male and female breast cancer. Further, 48.1% of male breast cancers expressed at least one and 18.0% expressed multiple growth factor receptors. Since individual membrane receptors are expressed in only half of male breast cancers, a panel of membrane markers will be required for molecular imaging strategies to reach sensitivity. A potential panel of markers for molecular imaging, consisting of EGFR, IGF1-R, FGFR2, CD44v6, CAXII, GLUT1, and CD44v6 was positive in 77% of male breast cancers, comparable to female breast cancers. CONCLUSIONS: Expression patterns of growth factor receptors and hypoxia membrane proteins in male breast cancer are different from female breast cancer. For molecular imaging strategies, a putative panel consisting of markers for EGFR, IGF1-R, FGFR2, GLUT1, CAXII, CD44v6 was positive in 77% of cases and might be considered for development of

  20. Factors Influencing Chemotherapy Goal Perception in Newly Diagnosed Cancer Patients.

    Science.gov (United States)

    Gumusay, Ozge; Cetin, Bulent; Benekli, Mustafa; Gurcan, Gamze; Ilhan, Mustafa N; Bostankolu, Basak; Ozet, Ahmet; Uner, Aytug; Coskun, Ugur; Buyukberber, Suleyman

    2016-06-01

    Cancer patients who start receiving chemotherapy have difficulty in understanding the state of their disease, the prognosis, and the purpose of treatment. We used a survey to evaluate the extent of perception of chemotherapy goal among cancer patients. Two hundred sixteen cancer patients who received chemotherapy for the first time participated in the study. The presence of depression and anxiety was assessed using the "Hospital Anxiety and Depression Scale" (HAD). The consistency between the patients' perception of the chemotherapy goal and the physician's perception was described as "right," and the inconsistency was described as "wrong." Among the patients who participated in the survey, 53.2 % (n = 115) were receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative treatment for metastatic disease. The rate of right and wrong perception of the chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the rate of confused patients was 18.9 % (n = 41). The level of education was shown to be the only parameter involved in accurate perception of the treatment purpose (hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219-0.903). In this study, there was a 51.9 % consistency between the physician's perception and that of the patient regarding the purpose of treatment. We demonstrated that the level of education was the unique factor in accurate perception of chemotherapy goal among cancer patients.

  1. Long noncoding RNA MALAT1-regulated microRNA 506 modulates ovarian cancer growth by targeting iASPP

    Directory of Open Access Journals (Sweden)

    Lei R

    2016-12-01

    Full Text Available Ruilin Lei,1,2,* Min Xue,2,* Lan Zhang,1 ZhongQiu Lin1 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 2Department of Obstetrics and Gynecology, Third Xiangya Hospital, Central South University, Changsha, China *These authors contributed equally to this work Abstract: MALAT1, an important cancer-associated long noncoding RNA (lncRNA, contributes to the development and progression of several cancers. Disordered expression of MALAT1 has been observed in several cancers, including cervical cancer, breast cancer, and ovarian cancer. However, the exact effects and molecular mechanisms of MALAT1 in ovarian cancer progression are still unknown. Here, we investigated the role of MALAT1 in human ovarian cancer cell lines and clinical tumor samples, in order to determine the function of this molecule. In our research, lncRNA-MALAT1 was specifically upregulated in ovarian cancer cell lines and promoted ovarian cancer-cell growth through targeting microRNA (miR-506. Knockdown of MALAT1 inhibited the proliferation and DNA synthesis of human ovarian cancer cell in vitro. In addition, miR-506-dependent iASPP regulation was required in MALAT1-induced ovarian cancer-cell growth. These findings indicated that MALAT1 might suppress tumor growth via miR-506-dependent iASPP regulation. Taken together, our data indicated that MALAT1 might be an oncogenic lncRNA that promotes proliferation of ovarian cancer and could be regarded as a therapeutic target in human ovarian cancer. Keywords: lncRNA, MALAT1, miR-506, ovarian cancer, iASPP

  2. Spatial Modelling of Urban Growth and Urban Influence: Approach of Regional Development in Developing Economy (India

    Directory of Open Access Journals (Sweden)

    Md. Julfikar ALI

    2012-12-01

    Full Text Available Urbanization and regional development are closely associated. Allocation of higher and lower order facilities and specialization of business influence urban growth which diffuses its benefits to the surrounding countryside. Subsequently, socio-economic development of the region comes into being. The continuous increase of urban size can not be sustained rather declining growth will certainly set in long run. Optimum level of its growth depends on the capacity of an urban centre to provide required facilities to the people in fair manner. Hierarchical growth of urban centres in association with location of civic amenities induces regional development in hierarchical dimension which is the common problem in developing economy. Subsequently, few of the urban centres are having large number of facilities while others are lacking corresponding to their population size. Formulation of pragmatic planning model is the rescue of wiping out such problems. It is an attempt to analyze the hierarchical growth of urban centres associated with their functional potentiality and diffusion of urban developmental impulses to the surrounding rural part. Further, it proposes a model for developing economy like India to solve the problem of regional variations of development. Besides, it examines the adequacy and inadequacy of facilities in the urban centres and puts forward planning recommendations, so that a balanced regional development would be achieved by not leaving any rural part out of the zone of functional influence of urban centre.

  3. Influence of arterial geometry on a model for growth rate of atheromas

    Energy Technology Data Exchange (ETDEWEB)

    Gessaghi, Valeria C [Facultad de Ingenieria, Universidad Nacional de La Pampa, General Pico, La Pampa (Argentina); Raschi, Marcelo A [Facultad de Ingenieria y Ciencias Exactas y Centro de Estudios Avanzados, Universidad Argentina de la Empresa, Ciudad Autonoma de Buenos Aires (Argentina); Larreteguy, Axel E [Facultad de Ingenieria y Ciencias Exactas y Centro de Estudios Avanzados, Universidad Argentina de la Empresa, Ciudad Autonoma de Buenos Aires (Argentina); Perazzo, Carlos A [Facultad de Ingenieria y Ciencias Exactas y Naturales, Universidad de Favaloro, Ciudad Autonoma de Buenos Aires, Argentina y CONICET (Argentina)

    2007-11-15

    Atherosclerosis is a disease that affects medium and large size arteries and it can partially or totally obstruct blood flow through them. The lack of blood supply to the heart or the brain can cause an infarct or a stroke with fatal consequences or permanent effects. This disease involves the proliferation of cells and the accumulation of fat, cholesterol, cell debris, calcium and other substances in the artery wall. Such accumulation results in the formation of atherosclerotic plaques called atheromas, which may cause the obstruction of the blood flow. Cardiovascular diseases, among which atherosclerosis is the most frequent, are the first cause of death in developed countries. The published works in the subject suggest that hemodynamic forces on arterial walls have influence on the localization, initial development and growth rate of atheromas. This paper presents a model for this growth rate, and explores the influence of the bifurcation angle on the blood flow patterns and on the predictions of the model in a simplified carotid artery. The choice of the carotid bifurcation as the subject for this study obeys the fact that atheromas in this artery are often responsible for strokes. Our model predicts a larger initial growth rate in the external walls of the bifurcation and smaller growth area and lower growth rates as the bifurcation angle is increased. The reason for this seems to be the appearance of helical flow patterns as the angle is increased.

  4. Gastrointestinal cancers: influence of gut microbiota, probiotics and prebiotics.

    Science.gov (United States)

    Serban, Daniela Elena

    2014-04-10

    Cancers of the gastrointestinal (GI) tract continue to represent a major health problem, despite progress in therapy. Gut microbiota is a key element related to the genesis of GI cancers, countless papers addressing this burning issue across the world. We provide an updated knowledge of the involvement of gut microbiota in GI tumorigenesis, including its underlying mechanisms. We present also a comprehensive review of the evidence from animal and clinical studies using probiotics and/or prebiotics in the prevention and/or therapy of GI tumours, of GI cancer therapy-related toxicity and of post-operative complications. We summarize the anticarcinogenic mechanisms of these biotherapeutics from in vitro, animal and clinical interventions. More research is required to reveal the interactions of microflora with genetic, epigenetic and immunologic factors, diet and age, before any firm conclusion be drawn. Well-designed, randomized, double blind, placebo-controlled human studies using probiotics and/or prebiotics, with adequate follow-up are necessary in order to formulate directions for prevention and therapy.

  5. Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

    Directory of Open Access Journals (Sweden)

    Hsieh Fu-Chuan

    2008-10-01

    Full Text Available Abstract Background Constitutive activation of signal transducer and activator of transcription 3 (Stat3 signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results We found that elevated Stat3 phosphorylation in 19 of 100 (19% bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC. The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin and a cell cycle regulating gene (cyclin D1 was associated with the cell growth inhibition and apoptosis. Conclusion These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

  6. Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils

    Directory of Open Access Journals (Sweden)

    Ming Yuan

    2016-01-01

    Full Text Available Neutrophils have a traditional role in inflammatory process and act as the first line of defense against infections. Although their contribution to tumorigenesis and progression is still controversial, accumulating evidence recently has demonstrated that tumor-associated neutrophils (TANs play a key role in multiple aspects of cancer biology. Here, we detected that chemokine CXCL1 was dramatically elevated in serum from 3LL tumor-bearing mice. In vitro, 3LL cells constitutively expressed and secreted higher level of CXCL1. Furthermore, knocking down CXCL1 expression in 3LL cells significantly hindered tumor growth by inhibiting recruitment of neutrophils from peripheral blood into tumor tissues. Additionally, tumor-infiltrated neutrophils expressed higher levels of MPO and Fas/FasL, which may be involved in TAN-mediated inhibition of CD4+ and CD8+ T cells. These results demonstrate that tumor-derived CXCL1 contributes to TANs infiltration in lung cancer which promotes tumor growth.

  7. Twenty-third annual Pezcoller Symposium: engineering influences in cancer research.

    NARCIS (Netherlands)

    Friedl, P.H.; Hubbell, J.; Livingston, D.; Mihich, E.

    2012-01-01

    The cross-disciplinary focus of the meeting highlighted recent progress in physical and genetic analysis and engineering of cancer disease models. As the central theme, mechanical forces affecting cell signaling, growth, differentiation, and metastasis were discussed with emphasis on the tumor micro

  8. Expression and functional role of orphan receptor GPR158 in prostate cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Nitin Patel

    Full Text Available Prostate cancer (PCa is the second-leading cause of cancer-related mortality, after lung cancer, in men from developed countries. In its early stages, primary tumor growth is dependent on androgens, thus generally can be controlled by androgen deprivation therapy (ADT. Eventually however, the disease progresses to castration-resistant prostate cancer (CRPC, a lethal form in need of more effective treatments. G-protein coupled receptors (GPCRs comprise a large clan of cell surface proteins that have been implicated as therapeutic targets in PCa growth and progression. The findings reported here provide intriguing evidence of a role for the newly characterized glutamate family member GPR158 in PCa growth and progression. We found that GPR158 promotes PCa cell proliferation independent of androgen receptor (AR functionality and that this requires its localization in the nucleus of the cell. This suggests that GPR158 acts by mechanisms different from other GPCRs. GPR158 expression is stimulated by androgens and GPR158 stimulates AR expression, implying a potential to sensitize tumors to low androgen conditions during ADT via a positive feedback loop. Further, we found GPR158 expression correlates with a neuroendocrine (NE differentiation phenotype and promotes anchorage-independent colony formation implying a role for GPR158 in therapeutic progression and tumor formation. GPR158 expression was increased at the invading front of prostate tumors that formed in the genetically defined conditional Pten knockout mouse model, and co-localized with elevated AR expression in the cell nucleus. Kaplan-Meier analysis on a dataset from the Memorial Sloan Kettering cancer genome portal showed that increased GPR158 expression in tumors is associated with lower disease-free survival. Our findings strongly suggest that pharmaceuticals targeting GPR158 activities could represent a novel and innovative approach to the prevention and management of CRPC.

  9. In vitro growth inhibitory effects of cytochalasins and derivatives in cancer cells.

    Science.gov (United States)

    Van Goietsenoven, Gwendoline; Mathieu, Véronique; Andolfi, Anna; Cimmino, Alessio; Lefranc, Florence; Kiss, Robert; Evidente, Antonio

    2011-05-01

    The in vitro anticancer activity of eight natural cytochalasins and three hemisynthetic derivatives of cytochalasin B on six cancer cell lines was evaluated. The IC (50) in vitro growth inhibitory concentrations, as determined by an MTT colorimetric assay, ranged between 3 and 90 µM and did not relate to the intrinsic sensitivity of the cancer cell lines to proapoptotic stimuli. Structure activity relationship (SAR) analyses revealed that the presence of an unmodified hydroxyl group at C-7 of the perhydroisoinsolyl-1-one residue as well as the functionalities and the conformational freedom of the macrocycle are all important features for cytochalasin-mediated anticancer activities in vitro. Computer-assisted phase-contrast microscopy revealed two groups of cytochalasins, i.e., cytotoxic versus cytostatic ones. Our data open new possibilities for tuning cytochalasin targets and developing nontoxic, cytostatic cytochalasins to combat cancers associated with poor prognoses, such as those that display intrinsic resistance to proapoptotic stimuli.

  10. Compartment-specific activation of PPARγ governs breast cancer tumor growth, via metabolic reprogramming and symbiosis.

    Science.gov (United States)

    Avena, Paola; Anselmo, Wanda; Whitaker-Menezes, Diana; Wang, Chenguang; Pestell, Richard G; Lamb, Rebecca S; Hulit, James; Casaburi, Ivan; Andò, Sebastiano; Martinez-Outschoorn, Ubaldo E; Lisanti, Michael P; Sotgia, Federica

    2013-05-01

    The role of PPARγ in cancer therapy is controversial, with studies showing either pro-tumorigenic or antineoplastic effects. This debate is very clinically relevant, because PPARγ agonists are used as antidiabetic drugs. Here, we evaluated if the effects of PPARγ on tumorigenesis are determined by the cell type in which PPARγ is activated. Second, we examined if the metabolic changes induced by PPARγ, such as glycolysis and autophagy, play any role in the tumorigenic process. To this end, PPARγ was overexpressed in breast cancer cells or in stromal cells. PPARγ-overexpressing cells were examined with respect to (1) their tumorigenic potential, using xenograft models, and (2) regarding their metabolic features. In xenograft models, we show that when PPARγ is activated in cancer cells, tumor growth is inhibited by 40%. However, when PPARγ is activated in stromal cells, the growth of co-injected breast cancer cells is enhanced by 60%. Thus, the effect(s) of PPARγ on tumorigenesis are dependent on the cell compartment in which PPARγ is activated. Mechanistically, stromal cells with activated PPARγ display metabolic features of cancer-associated fibroblasts, with increased autophagy, glycolysis and senescence. Indeed, fibroblasts overexpressing PPARγ show increased expression of autophagic markers, increased numbers of acidic autophagic vacuoles, increased production of L-lactate, cell hypertrophy and mitochondrial dysfunction. In addition, PPARγ fibroblasts show increased expression of CDKs (p16/p21) and β-galactosidase, which are markers of cell cycle arrest and senescence. Finally, PPARγ induces the activation of the two major transcription factors that promote autophagy and glycolysis, i.e., HIF-1α and NFκB, in stromal cells. Thus, PPARγ activation in stromal cells results in the formation of a catabolic pro-inflammatory microenvironment that metabolically supports cancer growth. Interestingly, the tumor inhibition observed when PPARγ is

  11. Targeting the insulin-like growth factor network in cancer therapy.

    Science.gov (United States)

    Heidegger, Isabel; Pircher, Andreas; Klocker, Helmut; Massoner, Petra

    2011-04-15

    During the last decades, changes in the insulin-like growth factor (IGF) signaling have been related to the pathogenesis of cancer. Therefore, IGFs became highly attractive therapeutic cancer targets. Several drugs including monoclonal antibodies (mAB), small molecule tyrosine kinase inhibitors (RTKIs), anti-sense oligonucleotids (ASOs) and IGF-binding proteins (IGFBPs) targeting the IGF axis were developed. With over 60 ongoing clinical trials, the IGF1 receptor (IGF1R) is currently one of the most studied molecular targets in the field of oncology. In this review, we provide an overview on the IGF axis, its signaling pathways and its significance in neoplasia. We critically review the preclinical and clinical studies investigating the role of IGF1R as a cancer target and discuss preliminary results and possible limitations.

  12. [Effects of green tea on growth inhibition and immune regulation of Lewis lung cancer in mice].

    Science.gov (United States)

    Zhu, M; Gong, Y; Ge, G

    1997-11-01

    C57/BL6J mice were inoculated with Lewis lung cancer cells as an experimental model to study the effects of green tea on cancer prevention, inhibition of tumor growth and immune regulation in mice with tumor. Results showed that weight of thymus in C57/BL6J mice and its index declined, proportion of positive CD4 subgroup of T lymphocyte and ratio of CD4+, to CD8+ reduced, baseline chemilumi-nescence decreased in peripheral white blood cells, yeast zymosan stimulated chemiluminescence increased, and number of immunoglobulin M formation cells decreased. It indicated that green tea had obvious inhibition in Lewis lung cancer and protective effects, to various extent, on adverse changes of above indices.

  13. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth

    Science.gov (United States)

    Kim, Sung Eun; Zhang, Li; Ma, Kai; Riegman, Michelle; Chen, Feng; Ingold, Irina; Conrad, Marcus; Turker, Melik Ziya; Gao, Minghui; Jiang, Xuejun; Monette, Sebastien; Pauliah, Mohan; Gonen, Mithat; Zanzonico, Pat; Quinn, Thomas; Wiesner, Ulrich; Bradbury, Michelle S.; Overholtzer, Michael

    2016-11-01

    The design of cancer-targeting particles with precisely tuned physicochemical properties may enhance the delivery of therapeutics and access to pharmacological targets. However, a molecular-level understanding of the interactions driving the fate of nanomedicine in biological systems remains elusive. Here, we show that ultrasmall (<10 nm in diameter) poly(ethylene glycol)-coated silica nanoparticles, functionalized with melanoma-targeting peptides, can induce a form of programmed cell death known as ferroptosis in starved cancer cells and cancer-bearing mice. Tumour xenografts in mice intravenously injected with nanoparticles using a high-dose multiple injection scheme exhibit reduced growth or regression, in a manner that is reversed by the pharmacological inhibitor of ferroptosis, liproxstatin-1. These data demonstrate that ferroptosis can be targeted by ultrasmall silica nanoparticles and may have therapeutic potential.

  14. Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy

    Directory of Open Access Journals (Sweden)

    Ewelina Hoffman

    2013-08-01

    Full Text Available Arsenic trioxide (As2O3 has recently been identified as an effective drug in different types of cancer therapy. It is a useful pharmacological agent in acute promyelocytic leukemia (APL treatment, especially the form that is resistant to conventional chemotherapy with all-trans retinoic acid (ATRA. What is more, laboratory data suggest that As2O3 is also active when it comes to several solid tumor cell lines. However, the mechanism of action is not fully understood. As2O3 in high doses triggers apoptosis, while in lower concentrations it induces partial differentiation. The As2O3 mechanism of action involves effects on mitochondrial transmembrane potential which lead to apoptosis. It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins. This publication presents the current knowledge about the influence of arsenic trioxide in cancer cells.

  15. Influence of probiotics on the growth and digestive enzyme activity of white Pacific shrimp ( Litopenaeus vannamei)

    Science.gov (United States)

    Gómez, R. Geovanny D.; Shen, M. A.

    2008-05-01

    The influence of Bacillus probiotics on the digestive enzyme activity and the growth of Litopenaeus vannamei were determined in this study. The shrimp was treated with five percentages (1.5, 3.0, 4.5, 6.0 and 7.5) of probiotics ( Bacillus spp.) supplemented to the feed and cultured for 45d. The growth measured as the weight gain at the end of culturing was significantly ( Pprobiotic-treated shrimps than that of the control (without receiving probiotics). Activities of protease and amylase, two digestive enzymes of the midgut gland and the intestine were significantly ( Pprobiotic-treated shrimp than in the control.

  16. Influence of protein hydrolysis on the growth kinetics of β-lg fibrils.

    Science.gov (United States)

    Kroes-Nijboer, Ardy; Venema, Paul; Bouman, Jacob; van der Linden, Erik

    2011-05-17

    Recently it was found that protein hydrolysis is an important step in the formation of β-lactoglobulin fibrils at pH 2 and elevated temperatures. The objective of the present study was to further investigate the influence of hydrolysis on the kinetics of fibril formation. Both the hydrolysis of β-lactoglobulin and the growth of the fibrils were followed as a function of time and temperature, using SDS polyacrylamide gel electrophoresis and a Thioflavin T fluorescence assay. As an essential extension to existing models, the quantification of the effect of the hydrolysis on the fibrillar growth was established by a simple polymerization model including a hydrolysis step.

  17. Amplification of fibroblast growth factor receptor-1 in breast cancer and the effects of brivanib alaninate.

    Science.gov (United States)

    Shiang, Christine Y; Qi, Yuan; Wang, Bailiang; Lazar, Vladimir; Wang, Jing; Fraser Symmans, W; Hortobagyi, Gabriel N; Andre, Fabrice; Pusztai, Lajos

    2010-10-01

    Fibroblast growth factor receptor-1 (FGFR-1) is amplified in 10% of human breast cancers. The goal of this study was to test the correlation between FGFR-1 amplification and expression and sensitivity to brivanib, an FGFR-1 small molecule inhibitor, in breast cancer cell lines in vitro. Using CGH array and gene expression profiling, FGFR-1 DNA copy number, mRNA, and protein expression were measured in 21 cell lines and correlated with growth inhibition by brivanib. We examined FGFR-1 autophosphorylation and kinase activity, as well as phosphorylation of downstream signaling molecules in response to bFGF and brivanib exposure. CAMA, MDA-MB-361, and HCC38 cells had FGFR-1 amplification and protein overexpression. Brivanib GI(50) values were significantly lower in the gene amplified (15.17 μM, n = 3) compared to normal copy number (69.09 μM, n = 11) or FGFR-1 deleted (76.14 μM, n = 7) cells (P = 0.0107). Among nonamplified cells, there was no correlation between FGFR-1 mRNA or protein expression levels and brivanib sensitivity. Two of three FGFR-1 amplified cells were sensitive to bFGF-induced growth stimulation, which was blocked by brivanib. In cells with amplified FGFR-1, brivanib decreased receptor autophosphorylation, inhibited bFGF-induced tyrosine kinase activity, and reduced phosphorylation of ERK and AKT. Breast cancer cell lines with FGFR-1 gene amplification and protein overexpression are more sensitive to growth inhibition by brivanib than nonamplified cells. These findings suggest that FGFR-1 amplification or protein overexpression in breast cancers may be an indicator for brivanib treatment, where it may have direct anti-proliferative effects in addition to its' anti-angiogenic effects.

  18. Optimal Therapeutic Strategy for Non-small Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor

    Directory of Open Access Journals (Sweden)

    Zhong SHI

    2015-02-01

    Full Text Available Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in non-small cell lung cancer (NSCLC patients, it is still controversial about how to combine EGFR-TKI with chemotherapy and other targeted drugs. We have made a summary on the current therapeutic models of EGFR-TKI combined with chemotherapy/bevacizumab in this review and aimed to find the optimal therapeutic strategy for NSCLC patients with EGFR mutation.

  19. Rationale for targeting fibroblast growth factor receptor signaling in breast cancer

    OpenAIRE

    André, Fabrice; Cortés, Javier

    2015-01-01

    Fibroblast growth factor receptor (FGFR) signaling is involved in multiple biological processes, including cell proliferation, survival, differentiation, migration, and apoptosis during embryonic development and adult tissue homeostasis. Given its role in the activation of critical signaling pathways, aberrant FGFR signaling has been implicated in multiple cancer types. A comprehensive search of PubMed and congress abstracts was conducted to identify reports on FGFR pathway components in brea...

  20. Damaged DNA binding protein 2 plays a role in breast cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Zilal Kattan

    Full Text Available The Damaged DNA binding protein 2 (DDB2, is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER-positive (MCF-7 and T47D, but not in ER-negative breast cancer (MDA-MB231 and SKBR3 or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold higher in ER-positive than in ER-negative tumor samples (P = 0.0208 from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase. These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer.

  1. Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate.

    Science.gov (United States)

    Warin, Renaud; Xiao, Dong; Arlotti, Julie A; Bommareddy, Ajay; Singh, Shivendra V

    2010-05-01

    Benzyl isothiocyanate (BITC), a constituent of cruciferous vegetables such as garden cress, inhibits growth of human breast cancer cell lines in culture. The present study was undertaken to determine in vivo efficacy of BITC against MDA-MB-231 human breast cancer xenografts. The BITC administration retarded growth of MDA-MB-231 cells subcutaneously implanted in female nude mice without causing weight loss or any other side effects. The BITC-mediated suppression of MDA-MB-231 xenograft growth correlated with reduced cell proliferation as revealed by immunohistochemical analysis for Ki-67 expression. Analysis of the vasculature in the tumors from BITC-treated mice indicated smaller vessel area compared with control tumors based on immunohistochemistry for angiogenesis marker CD31. The BITC-mediated inhibition of angiogenesis in vivo correlated with downregulation of vascular endothelial growth factor (VEGF) receptor 2 protein levels in the tumor. Consistent with these results, BITC treatment suppressed VEGF secretion and VEGF receptor 2 protein levels in cultured MDA-MB-231 cells. Moreover, the BITC-treated MDA-MB-231 cells exhibited reduced capacity for migration compared with vehicle-treated control cells. In contrast to cellular data, BITC administration failed to elicit apoptotic response as judged by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. In conclusion, the present study demonstrates in vivo anti-cancer efficacy of BITC against MDA-MB-231 xenografts in association with reduced cell proliferation and suppression of neovascularization. These preclinical observations merit clinical investigation to determine efficacy of BITC against human breast cancers.

  2. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells.

    Science.gov (United States)

    Einbond, Linda Saxe; Wen-Cai, Ye; He, Kan; Wu, Hsan-au; Cruz, Erica; Roller, Marc; Kronenberg, Fredi

    2008-06-01

    The purpose of this report is to explore the growth inhibitory effect of extracts and compounds from black cohosh and related Cimicifuga species on human breast cancer cells and to determine the nature of the active components. Black cohosh fractions enriched for triterpene glycosides and purified components from black cohosh and related Asian species were tested for growth inhibition of the ER(-) Her2 overexpressing human breast cancer cell line MDA-MB-453. Growth inhibitory activity was assayed using the Coulter Counter, MTT and colony formation assays. Results suggested that the growth inhibitory activity of black cohosh extracts appears to be related to their triterpene glycoside composition. The most potent Cimicifuga component tested was 25-acetyl-7,8-didehydrocimigenol 3-O-beta-d-xylopyranoside, which has an acetyl group at position C-25. It had an IC(50) of 3.2microg/ml (5microM) compared to 7.2microg/ml (12.1microM) for the parent compound 7,8-didehydrocimigenol 3-O-beta-d-xylopyranoside. Thus, the acetyl group at position C-25 enhances growth inhibitory activity. The purified triterpene glycoside actein (beta-d-xylopyranoside), with an IC(50) equal to 5.7microg/ml (8.4microM), exhibited activity comparable to cimigenol 3-O-beta-d-xyloside. MCF7 (ER(+)Her2 low) cells transfected for Her2 are more sensitive than the parental MCF7 cells to the growth inhibitory effects of actein from black cohosh, indicating that Her2 plays a role in the action of actein. The effect of actein on Her2 overexpressing MDA-MB-453 and MCF7 (ER(+)Her2 low) human breast cancer cells was examined by fluorescent microscopy. Treatment with actein altered the distribution of actin filaments and induced apoptosis in these cells. These findings, coupled with our previous evidence that treatment with the triterpene glycoside actein induced a stress response and apoptosis in human breast cancer cells, suggest that compounds from Cimicifuga species may be useful in the prevention and

  3. STC1 expression is associated with tumor growth and metastasis in breast cancer.

    Science.gov (United States)

    Chang, Andy C-M; Doherty, Judy; Huschtscha, Lily I; Redvers, Richard; Restall, Christina; Reddel, Roger R; Anderson, Robin L

    2015-01-01

    Stanniocalcin-1 (STC1) is a secreted glycoprotein implicated in several pathologies including retinal degeneration, cerebral ischemia, angiogenesis and inflammation. Aberrant STC1 expression has been reported in breast cancer but the significance of this is not clear. High levels of STC1 expression were found in the aggressive 4T1 murine mammary tumor cells and in the MDA-MB-231 human breast cancer line. To investigate its significance, stable clones with STC1 down-regulation using shRNA were generated in both tumor models. The consequences of STC1 down-regulation on cell proliferation, chemotactic invasion, tumor growth and metastasis were assessed. Down-regulation of STC1 in the 4T1 murine mammary tumor cells had a major impact on mammary tumor growth. This observation was replicated in a second tumor model with the MDA-MB-231 human breast cancer line, with a significant reduction in primary tumor formation and a major inhibition of metastasis as well. Interestingly, in both models, proliferation in vitro was not affected. Subsequent microarray gene expression profiling identified 30 genes to be significantly altered by STC1 down-regulation, the majority of which are associated with known hallmarks of carcinogenesis. Furthermore, bioinformatic analysis of breast cancer datasets revealed that high expression of STC1 is associated with poor survival. This is the first study to show definitively that STC1 plays an oncogenic role in breast cancer, and indicates that STC1 could be a potential therapeutic target for treatment of breast cancer patients.

  4. Growth Factor Receptors and Apoptosis Regulators: Signaling Pathways, Prognosis, Chemosensitivity and Treatment Outcomes of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Siddik Sarkar

    2009-01-01

    Full Text Available Biomarkers of breast cancer are necessary for prognosis and prediction to chemotherapy. Prognostic biomarkers provide information regarding outcome irrespective of therapy, while predictive biomarkers provide information regarding response to therapy. Candidate prognostic biomarkers for breast cancers are growth factor receptors, steroid receptors, Ki-67, cyclins, urokinase plasminogen activator, p53, p21, pro- and anti-apoptotic factors, BRCA1 and BRCA2. But currently, the predictive markers are Estrogen and Progesterone receptors responding to endocrine therapy, and HER-2 responding to herceptin. But there are numerous breast cancer cases, where tamoxifen is ineffective even after estrogen receptor positivity. This lead to search of new prognostic and predictive markers and the number of potential markers is constantly increasing due to proteomics and genomics studies. However, most biomarkers individually have poor sensitivity or specificity, or other clinical value. It can be resolved by studying various biomarkers simultaneously, which will help in better prognosis and increasing sensitivity for chemotherapeutic agents. This review is focusing on growth factor receptors, apoptosis markers, signaling cascades, and their correlation with other associated biomarkers in breast cancers. As our knowledge regarding molecular biomarkers for breast cancer increases, prognostic indices will be developed that combine the predictive power of individual molecular biomarkers with specific clinical and pathologic factors. Rigorous comparison of these existing as well as emerging markers with current treatment selection is likely to see an escalation in an era of personalized medicines to ensure the breast cancer patients receive optimal treatment. This will also solve the treatment modalities and complications related to chemotherapeutic regimens.

  5. Transfection of promyelocytic leukemia in retrovirus vector inhibits growth of human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    Lei LI; Da-lin HE

    2005-01-01

    Aim: To construct a recombinant retrovirus vector carrying human promyelocytic leukemia (PML) cDNA and identify its expression and biology role in bladder cancer UM-UC-2 cells for future gene therapy. Methods: PML full-length cDNA was inserted into the EcoR I and BamHI site of pLXSN vector containing the long terminal repeat (LTR) promoter. The vector was identified by restriction enzyme digestion and then transfected into PA317 packaging cell line by calcium phosphate coprecipitation. PML cDNA was detected by polymerase chain reaction (PCR) and the protein was identified by laser confocal microscopy and Western blot in bladder cancer cells, respectively. The morphology was observed by inverted phase contrast microscope, and MTT assay determined growth curve of the bladder cancer cells. Results: Restriction enzyme digestion proved that a 2.1kb PML cDNA was inserted into the pLXSN vector. PCR assay demonstrated that 304 bp fragments were found in UM-UC-2/pLPMLSN transfects. Laser confocal microscopy showed speck dots fluorescence in the UM-UC-2/pLPMLSN nucleus.A 90 kD specific brand was found by Western blot. MTT assay demonstrated the UM-UC-2/pLPMLSN bladder cancer growth inhibition. Conclusion: The retrovirus pLPMLSN vector was successfully constructed and could generate high effective expression of human PML in bladder cancer cell UM-UC-2, suggesting that PML recombinant retrovirus have potential utility in the gene therapy for bladder cancer.

  6. Retinoic acid inhibits endometrial cancer cell growth via multiple genomic mechanisms.

    Science.gov (United States)

    Cheng, You-Hong; Utsunomiya, Hiroki; Pavone, Mary Ellen; Yin, Ping; Bulun, Serdar E

    2011-04-01

    Previous studies have indicated that retinoic acid (RA) may be therapeutic for endometrial cancer. However, the downstream target genes and pathways triggered by ligand-activated RA receptor α (RARα) in endometrial cancer cells are largely unknown. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and immunoblotting assays were used to assess the roles of RA and the RA agonist (AM580) in the growth of endometrial cancer cells. Illumina-based microarray expression profiling of endometrial Ishikawa cells incubated with and without AM580 for 1, 3, and 6 h was performed. We found that both RA and AM580 markedly inhibited endometrial cancer cell proliferation, while knockdown of RARα could block AM580 inhibition. Knockdown of RARα significantly increased proliferating cell nuclear antigen and BCL2 protein levels. Incubation of Ishikawa cells with or without AM580 followed by microarray expression profiling showed that 12 768 genes out of 47 296 gene probes were differentially expressed with significant P values. We found that 90 genes were the most regulated genes with the most significant P value (PAM580 highly regulated these genes, whereas chromatin immunoprecipitation-PCR assay demonstrated that ligand-activated RARα interacted with the promoter of these genes in intact endometrial cancer cells. AM580 also significantly altered 18 pathways including those related to cell growth, differentiation, and apoptosis. In conclusion, AM580 treatment of Ishikawa cells causes the differential expression of a number of RARα target genes and activation of signaling pathways. These pathways could, therefore, mediate the carcinogenesis of human endometrial cancer.

  7. Silencing of ghrelin receptor expression inhibits endometrial cancer cell growth in vitro and in vivo.

    Science.gov (United States)

    Fung, Jenny N T; Jeffery, Penny L; Lee, John D; Seim, Inge; Roche, Deborah; Obermair, Andreas; Chopin, Lisa K; Chen, Chen

    2013-07-15

    Ghrelin is a 28-amino acid peptide hormone produced predominantly in the stomach but also in a range of normal cell types and tumors, where it has endocrine, paracrine, and autocrine roles. Previously, we have demonstrated that ghrelin has proliferative and antiapoptotic effects in endometrial cancer cell lines, suggesting a potential role in promoting tumor growth. In the present study, we investigated the effect of ghrelin receptor, GHSR, and gene silencing in vitro and in vivo and characterized ghrelin and GHSR1a protein expression in human endometrial tumors. GHSR gene silencing was achieved in the Ishikawa and KLE endometrial cancer cell lines, using a lentiviral short-hairpin RNA targeting GHSR. The effects of GHSR1a knockdown were further analyzed in vivo using the Ishikawa cell line in a NOD/SCID xenograft model. Cell proliferation was reduced in cultured GHSR1a knockdown Ishikawa and KLE cells compared with scrambled controls in the absence of exogenously applied ghrelin and in response to exogenous ghrelin (1,000 nM). The tumor volumes were reduced significantly in GHSR1a knockdown Ishikawa mouse xenograft tumors compared with scrambled control tumours. Using immunohistochemistry, we demonstrated that ghrelin and GHSR1a are expressed in benign and cancerous glands in human endometrial tissue specimens, although there was no correlation between the intensity of staining and cancer grade. These data indicate that downregulation of GHSR expression significantly inhibits endometrial cancer cell line and mouse xenograft tumour growth. This is the first preclinical evidence that downregulation of GHSR may be therapeutic in endometrial cancer.

  8. Treatment of pancreatic cancer with epidermal growth factor receptor-targeted therapy

    Directory of Open Access Journals (Sweden)

    Bryan A Faller

    2009-09-01

    Full Text Available Bryan A Faller, Barbara BurtnessDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USAAbstract: Pancreatic adenocarcinoma is a common malignancy that remains refractory to available therapies. Gemcitabine has long been the standard, first-line agent in advanced disease. The epidermal growth factor receptor (EGFR is a commonly expressed target in pancreatic cancer that is involved in tumor proliferation, metastasis, and induction of angiogenesis. The addition of the EGFR inhibitor erlotinib to gemcitabine has recently been demonstrated to provide a small, yet statistically significant, survival benefit in advanced disease. This has prompted further research into the applications of EGFR-targeted therapy in pancreatic cancer, albeit with disappointing results. Resistance to these therapies seems highly prevalent and has been implicated in their limited efficacy. The development of rash is associated with treatment efficacy and suggests that predictive factors may one day be identified to guide appropriate patient selection for these agents. Preclinical research has shown promise that resistance to EGFR-targeted therapies can be overcome through a variety of approaches. Application of this research in clinical trials may ultimately yield an unquestioned role for EGFR-targeted therapy in the management of this disease.Keywords: cetuximab, drug resistance, epidermal growth factor receptor, erlotinib, gemcitabine, pancreatic cancer

  9. Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases.

    Science.gov (United States)

    Nangia-Makker, Pratima; Raz, Tirza; Tait, Larry; Shekhar, Malathy P V; Li, Hong; Balan, Vitaly; Makker, Hemanckur; Fridman, Rafael; Maddipati, Krishnarao; Raz, Avraham

    2013-05-01

    Ocimum genus (a.k.a holy basil or tulsi) is a dietary herb used for its multiple beneficial pharmacologic properties including anti-cancer activity. Here we show that crude extract of Ocimum gratissimum (OG) and its hydrophobic and hydrophilic fractions (HB and HL) differentially inhibit breast cancer cell chemotaxis and chemoinvasion in vitro and retard tumor growth and temporal progression of MCF10ADCIS.com xenografts, a model of human breast comedo-ductal carcinoma in situ (comedo-DCIS). OG-induced inhibition of tumor growth was associated with decreases in basement membrane disintegration, angiogenesis and MMP-2 and MMP-9 activities as confirmed by in situ gelatin zymography and cleavage of galectin-3. There was also decrease in MMP-2 and MMP-9 activities in the conditioned media of OG-treated MCF10AT1 and MCF10AT1-EIII8 premalignant human breast cancer cells as compared with control. The MMP-2 and MMP-9 inhibitory activities of OG were verified in vitro using gelatin, a synthetic fluorogenic peptide and recombinant galectin-3 as MMP substrates. Mice fed on OG-supplemented drinking water showed no adverse effects compared with control. These data suggest that OG is non-toxic and that the anti-cancer therapeutic activity of OG may in part be contributed by its MMP inhibitory activity.

  10. Influence of Climate on the Growth of Hybrid Poplar in Michigan

    Directory of Open Access Journals (Sweden)

    Sophan Chhin

    2010-11-01

    Full Text Available This study examined the influence of climate on cumulative and interannual growth patterns of 18 full-sib families of hybrid poplars (Populus × smithii Boivin derived from different geographical locations (state counties of natural stands of aspen parents (trembling aspen (Populus tremuloides Michx. and bigtooth aspen (Populus grandidentata Michx.. The hybrids were subsequently planted in 1982 in southern mid-Michigan at Michigan State University (MSU Sandhill Research Area. Cumulative measures of hybrid poplar productivity (diameter, height, basal area, and stem volume in 2009 (28 years since plantation establishment were related via correlation analysis to geographical distances and climatic variables (temperature and precipitation between parental county locations and between parental locations and the plantation site. Tree-ring analysis methods (dendrochronology were also used to quantify the influence of climate (i.e., mean temperature and total precipitation at monthly and 3-month seasonal scales on interannual basal area growth rates of hybrid poplars. Analyses of cumulative measures of growth indicated a maternal effect: full-sib families had higher productivity if they had a maternal parent originating from a state county that was close to or had higher temperature (annual and summer and summer precipitation than corresponding parameters of the planting site. Principal component analysis indicated that 17 of the 18 full-sib families shared a large amount of common growth variation. Dendrochronological analyses of interannual growth-climate relationships indicated that growth was mainly affected by the degree of late summer to fall moisture stress in both the current and previous growth season, and the degree of winter harshness.

  11. Influence of intrauterine and extrauterine growth on neurodevelopmental outcome of monozygotic twins

    Directory of Open Access Journals (Sweden)

    R.K. Reolon

    2008-08-01

    Full Text Available There have been indications that intrauterine and early extrauterine growth can influence childhood mental and motor function. The objective of the present study was to evaluate the influence of intrauterine growth restriction and early extrauterine head growth on the neurodevelopmental outcome of monozygotic twins. Thirty-six monozygous twin pairs were evaluated at the corrected age of 12 to 42 months. Intrauterine growth restriction was quantified using the fetal growth ratio. The effects of birth weight ratio, head circumference at birth and current head circumference on mental and motor outcomes were estimated using mixed-effect linear regression models. Separate estimates of the between (interpair and within (intrapair effects of each measure on development were thus obtained. Neurodevelopment was assessed with the Bayley Scales of Infant Development, 2nd edition, by a psychologist blind to the exposure. A standardized neurological examination was performed by a neuropediatrician who was unaware of the exposures under investigation. After adjustment, birth weight ratio and head circumference at birth were not associated with motor or mental outcomes. Current head circumference was associated with mental but not with motor outcomes. Only the intrapair twin effect was significant. An increase of 1 cm in current head circumference of one twin compared with the other was associated with 3.2 points higher in Mental Developmental Index (95%CI = 1.06-5.32; P < 0.03. Thus, no effect of intrauterine growth was found on cognition and only postnatal head growth was associated with cognition. This effect was not shared by the co-twin.

  12. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shih-Chieh [Department of Internal Medicine, National Yang-Ming University Hospital, Yilan 260, Taiwan (China); Chang, Cheng-Yu [Department of Chest Medicine, Far Eastern Memorial Hospital, Taipei 220, Taiwan (China); Shih, Jin-Yuan, E-mail: jyshih@ntu.edu.tw [Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)

    2011-06-10

    Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) cases comprise approximately 85% of the lung cancer cases. Before the era of target therapy, platinum-based doublet chemotherapy only led to a median survival of 8–9 months and a one-year survival of 30%–40% in patients with advanced NSCLC. In July 2002, gefitinib, a small-molecule epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), was approved for the treatment of patients with advanced NSCLC in Japan. After the widespread use of gefitinib in the treatment of NSCLC, there have been many new studies regarding the association between the clinical anticancer efficacy of gefitinib and the somatic EGFR mutation status in patients with NSCLC. This article summarizes the role of EGFR mutations in lung cancer and the use of EGFR antagonists in the treatment of lung cancer and its associated adverse effects.

  13. Chemokines and chemokine receptors as promoters of prostate cancer growth and progression.

    Science.gov (United States)

    Salazar, Nicole; Castellan, Miguel; Shirodkar, Samir S; Lokeshwar, Bal L

    2013-01-01

    Prostate cancer (CaP) is estimated to be first in incidence among cancers, with more than 240,000 new cases in 2012 in the United States. Chemokines and their receptors provide survival, proliferation, and invasion characteristics to CaP cells in both primary sites of cancer and metastatic locations. The emerging data demonstrate that many chemokines and their receptors are involved in the multistep process of CaP, leading to metastasis, and, further, that these factors act cooperatively to enhance other mechanisms of tumor cell survival, growth, and metastasis. Changes of chemokine receptor cohorts may be necessary to activate tumor-promoting signals. Chemokine receptors can activate downstream effectors, such as mitogen-activated protein kinases, by complex mechanisms of ligand-dependent activation of cryptic growth factors; guanosine triphosphate-binding, protein-coupled activation of survival kinases; or transactivation of other receptors such as ErbB family members. We describe vanguard research in which more than the classic view of chemokine receptor biology was clarified. Control of chemokines and inhibition of their receptor activation may add critical tools to reduce tumor growth, especially in chemo-hormonal refractory CaP that is both currently incurable and the most aggressive form of the disease, accounting for most of the more than 28,000 annual deaths.

  14. Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells.

    Science.gov (United States)

    Payton-Stewart, Florastina; Tilghman, Syreeta L; Williams, LaKeisha G; Winfield, Leyte L

    2014-08-08

    Estrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily. They regulate the transcription of estrogen-responsive genes and mediate numerous estrogen related diseases (i.e., fertility, osteoporosis, cancer, etc.). As such, ERs are potentially useful targets for developing therapies and diagnostic tools for hormonally responsive human breast cancers. In this work, two benzimidazole-based sulfonamides originally designed to reduce proliferation in prostate cancer, have been evaluated for their ability to modulate growth in estrogen dependent and independent cell lines (MCF-7 and MDA-MB 231) using cell viability assays. The molecules reduced growth in MCF-7 cells, but differed in their impact on the growth of MDA-MB 231 cells. Although both molecules reduced estrogen response element (ERE) transcriptional activity in a dose dependent manner, the contrasting activity in the MDA-MB-231 cells seems to suggest that the molecules may act through alternate ER-mediated pathways. Further, the methyl analog showed modest selectivity for the ERβ receptor in an ER gene expression array panel, while the naphthyl analog did not significantly alter gene expression. The molecules were docked in the ligand binding domains of the ERα-antagonist and ERβ-agonist crystal structures to evaluate the potential of the molecules to interact with the receptors. The computational analysis complimented the results obtained in the assay of transcriptional activity and gene expression suggesting that the molecules upregulate ERβ activity while down regulating that of ERα.

  15. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    Science.gov (United States)

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2015-02-01

    Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro. However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

  16. SOX7 is involved in aspirin-mediated growth inhibition of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Shu-Yan Huang; Jing-Xin Feng; Yan-Yan Gao; Li Zhao; Jun Lu; Bai-Qu Huang; Yu Zhang

    2011-01-01

    AIM: To confirm the role of sex-determining region Y-box 7 (Sox7) in aspirin-mediated growth inhibition of COX-independent human colorectal cancer cells.METHODS: The cell survival percentage was examined by MTT (Moto-nuclear cell direc cytotoxicity) assay.SOX7 expression was assessed by using reverse transcription-polymerase chain reaction and Western blotting. SB203580 was used to inhibit the p38MAPK signal pathway. SOX7 promoter activity was detected by Luciferase reporter assay.RESULTS: SOX7 was upregulated by aspirin and was involved in aspirin-mediated growth inhibition of SW480 human colorectal cancer cells. The p38MAPK pathway played a role in aspirin-induced SOX7 expression, during which the AP1 transcription factors c-Jun and c-Fos upregulated SOX7 promoter activities.RESULTS: SOX7 is upregulated by aspirin and is involved in aspirin-mediated growth inhibition of human colorectal cancer SW480 cells.

  17. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction.

    Science.gov (United States)

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2015-05-10

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.

  18. Product formation from thiophene by a mixed bacterial culture. Influence of benzene as growth substrate

    DEFF Research Database (Denmark)

    Rivas, Isabelle Marie; Mosbæk, Hans; Arvin, Erik

    2003-01-01

    The influence of benzene as a growth substrate on the cometabolic conversion of thiophene was investigated in batch systems with microorganisms originating from an creosote contaminated site. Benzene was shown to stimulate the conversion of thiophene with a first-order rate, during the initial...... phase of transformation. The microorganisms were able to transform thiophene in the absence of benzene at a zero-order rate. Thiophene was converted to five oxidation products, regardless of the presence of benzene. Benzene had no influence on the distribution of these oxidation products. The main...

  19. BAYESIAN LOCAL INFLUENCE ASSESSMENTS IN A GROWTH CURVE MODEL WITH GENERAL COVARIANCE STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The objective of this paper is to present a Bayesian approach based on Kullback Leibler divergence for assessing local influence in a growth curve model with general covariance structure.Under certain prior distribution assumption,the Kullback-Leibler divergence is used to measure the influence of some minor perturbation on the posterior distribution of unknown parameter.This leads to the diagnostic statistic for detecting which response is locally influential.As an application,the common covariance-weighted perturbation scheme is thoroughly considered.

  20. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression

    DEFF Research Database (Denmark)

    Pouladi, Mahmoud A; Xie, Yuanyun; Skotte, Niels Henning;

    2010-01-01

    Levels of full-length huntingtin (FL htt) influence organ and body weight, independent of polyglutamine length. The growth hormone-insulin like growth factor-1 (GH-IGF-1) axis is well established as a regulator of organ growth and body weight. In this study, we investigate the involvement of the ...

  1. Geographic Patterns and Stand Variables Influencing Growth and Vigor of Populus tremuloides in the Sierra Nevada (USA)

    OpenAIRE

    2012-01-01

    Awareness of geographic patterns and stand variables that influence tree growth will help forest managers plan appropriate management and monitoring strategies. We quantified influences of stand location, species composition, stand density, and tree size on aspen tree growth and vigor around the Lake Tahoe Basin in the Sierra Nevada Mountains of California and Nevada, USA. Radial growth data were taken from increment cores. Aspen trees on the south and west sides of the lake grew 20–25% faste...

  2. Modeling invasive breast cancer: growth factors propel progression of HER2-positive premalignant lesions.

    Science.gov (United States)

    Pradeep, C-R; Zeisel, A; Köstler, W J; Lauriola, M; Jacob-Hirsch, J; Haibe-Kains, B; Amariglio, N; Ben-Chetrit, N; Emde, A; Solomonov, I; Neufeld, G; Piccart, M; Sagi, I; Sotiriou, C; Rechavi, G; Domany, E; Desmedt, C; Yarden, Y

    2012-08-01

    The HER2/neu oncogene encodes a receptor-like tyrosine kinase whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. However, the mechanisms underlying aggressiveness of HER2 (human epidermal growth factor receptor 2)-overexpressing tumors remain incompletely understood. Because it assists epidermal growth factor (EGF) and neuregulin receptors, we overexpressed HER2 in MCF10A mammary cells and applied growth factors. HER2-overexpressing cells grown in extracellular matrix formed filled spheroids, which protruded outgrowths upon growth factor stimulation. Our transcriptome analyses imply a two-hit model for invasive growth: HER2-induced proliferation and evasion from anoikis generate filled structures, which are morphologically and transcriptionally analogous to preinvasive patients' lesions. In the second hit, EGF escalates signaling and transcriptional responses leading to invasive growth. Consistent with clinical relevance, a gene expression signature based on the HER2/EGF-activated transcriptional program can predict poorer prognosis of a subgroup of HER2-overexpressing patients. In conclusion, the integration of a three-dimensional cellular model and clinical data attributes progression of HER2-overexpressing lesions to EGF-like growth factors acting in the context of the tumor's microenvironment.

  3. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  4. Highly sensitive quantitative imaging for monitoring single cancer cell growth kinetics and drug response.

    Directory of Open Access Journals (Sweden)

    Mustafa Mir

    Full Text Available The detection and treatment of cancer has advanced significantly in the past several decades, with important improvements in our understanding of the fundamental molecular and genetic basis of the disease. Despite these advancements, drug-screening methodologies have remained essentially unchanged since the introduction of the in vitro human cell line screen in 1990. Although the existing methods provide information on the overall effects of compounds on cell viability, they are restricted by bulk measurements, large sample sizes, and lack capability to measure proliferation kinetics at the individual cell level. To truly understand the nature of cancer cell proliferation and to develop personalized adjuvant therapies, there is a need for new methodologies that provide quantitative information to monitor the effect of drugs on cell growth as well as morphological and phenotypic changes at the single cell level. Here we show that a quantitative phase imaging modality known as spatial light interference microscopy (SLIM addresses these needs and provides additional advantages over existing proliferation assays. We demonstrate these capabilities through measurements on the effects of the hormone estradiol and the antiestrogen ICI182,780 (Faslodex on the growth of MCF-7 breast cancer cells. Along with providing information on changes in the overall growth, SLIM provides additional biologically relevant information. For example, we find that exposure to estradiol results in rapidly growing cells with lower dry mass than the control population. Subsequently blocking the estrogen receptor with ICI results in slower growing cells, with lower dry masses than the control. This ability to measure changes in growth kinetics in response to environmental conditions provides new insight on growth regulation mechanisms. Our results establish the capabilities of SLIM as an advanced drug screening technology that provides information on changes in proliferation

  5. Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Payton-Stewart, Florastina [Department of Chemistry, College of Arts and Sciences, Xavier University of Louisiana, New Orleans, LA (United States); Tilghman, Syreeta L. [Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA (United States); Williams, LaKeisha G. [Division of Clinical and Administrative Sciences, College of Pharmacy Xavier University of Louisiana, New Orleans, LA (United States); Winfield, Leyte L., E-mail: lwinfield@spelman.edu [Department of Chemistry, Spelman College, Atlanta, GA (United States)

    2014-08-08

    Highlights: • The methyl-substituted benzimidazole was more effective at inhibiting growth in MDA-MB 231 cells. • The naphthyl-substituted benzimidazole was more effective at inhibiting growth in MCF-7 cells than ICI. • The benzimidazole molecules demonstrated a dose-dependent reduction in ERE transcriptional activity. • The benzimidazole molecules had binding mode in ERα and ERβ comparable to that of the co-crystallized ligand. - Abstract: Estrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily. They regulate the transcription of estrogen-responsive genes and mediate numerous estrogen related diseases (i.e., fertility, osteoporosis, cancer, etc.). As such, ERs are potentially useful targets for developing therapies and diagnostic tools for hormonally responsive human breast cancers. In this work, two benzimidazole-based sulfonamides originally designed to reduce proliferation in prostate cancer, have been evaluated for their ability to modulate growth in estrogen dependent and independent cell lines (MCF-7 and MDA-MB 231) using cell viability assays. The molecules reduced growth in MCF-7 cells, but differed in their impact on the growth of MDA-MB 231 cells. Although both molecules reduced estrogen response element (ERE) transcriptional activity in a dose dependent manner, the contrasting activity in the MDA-MB-231 cells seems to suggest that the molecules may act through alternate ER-mediated pathways. Further, the methyl analog showed modest selectivity for the ERβ receptor in an ER gene expression array panel, while the naphthyl analog did not significantly alter gene expression. The molecules were docked in the ligand binding domains of the ERα-antagonist and ERβ-agonist crystal structures to evaluate the potential of the molecules to interact with the receptors. The computational analysis complimented the results obtained in the assay of transcriptional activity and gene expression suggesting that the molecules

  6. Mediastinal staging for lung cancer: the influence of biopsy volume

    DEFF Research Database (Denmark)

    Nelson, Elof; Pape, Christian; Jørgensen, Ole Dan;

    2010-01-01

    biopsy volume has any influence on the result of conventional cervical mediastinoscopy. In this study, we investigated the influence of biopsy volume and the number of lymph node stations biopsied during mediastinoscopy on the probability of demonstrating N2-disease in patients with NSCLC. METHODS: We...... retrospectively. Demographics and the number of lymph node stations biopsied were recorded, and the volume of biopsies from each lymph node station was calculated. RESULTS: Multivariate logistic regression analysis demonstrated that larger biopsy volume was significantly associated with increased probability...... of demonstrating N2-disease (pBiopsy volume from lymph...

  7. Uptake of caprolactam and its influence on growth and oxygen production of Desmodesmus quadricauda algae.

    Science.gov (United States)

    Kalinová, Jana Pexová; Tříska, Jan; Vrchotová, Naděžda; Novák, Jan

    2016-06-01

    The consumption of polyamides produced from caprolactam is increasing continuously, and for that reason the danger of environmental contamination by this lactam is also rising. This study's aim was to evaluate the influence of caprolactam on the growth and oxygen production of the green alga Desmodesmus quadricauda and on caprolactam uptake by this alga. The presence of caprolactam in water was observed to cause the algae significantly to increase its oxygen production. Caprolactam concentration of 5,000 mg/L stopped algae growth after 6 days and influenced coenobia structure (seen as disappearance of pyrenoids, deformation of cells) but did not decrease the number of cells in the coenobia. Caprolactam uptake is probably passive but relatively rapid. Maximum concentration in the algae was reached after 18-24 h.

  8. Modeling cancer immunotherapy: Assessing the effects of lymphocytes on cancer cell growth and motility

    Science.gov (United States)

    Ramos, R. A.; Zapata, Jair; Condat, C. A.; Deisboeck, Thomas S.

    2013-05-01

    A mesoscopic model is used to describe the effects of lymphocyte activity on a growing tumor. The model yields novel insights into the tumor-immune system interaction. In particular, we found that the presence of a putative chemotactic messenger that helps guide the lymphocytes towards the tumor is not critical to elicit the anti-tumor effects of the immune system, while lymphocytes that block tumor cell migration contribute to limit cancer expansion and thus have a more significant therapeutic impact.

  9. Influence of Containment on the Growth of Silicon-Germanium (ICESAGE): A Materials Science Investigation

    Science.gov (United States)

    Volz, M. P.; Mazuruk, K.; Croll, A.

    2014-01-01

    A series of Ge Si crystal growth experiments are planned to be conducted in the Low 1-x x Gradient Furnace (LGF) onboard the International Space Station. The primary objective of the research is to determine the influence of containment on the processing-induced defects and impurity incorporation in germanium-silicon alloy crystals. A comparison will be made between crystals grown by the normal and "detached" Bridgman methods and the ground-based float zone technique. Crystals grown without being in contact with a container have superior quality to otherwise similar crystals grown in direct contact with a container, especially with respect to impurity incorporation, formation of dislocations, and residual stress in crystals. "Detached" or "dewetted" Bridgman growth is similar to regular Bridgman growth in that most of the melt is in contact with the crucible wall, but the crystal is separated from the wall by a small gap, typically of the order of 10-100 microns. Long duration reduced gravity is essential to test the proposed theory of detached growth. Detached growth requires the establishment of a meniscus between the crystal and the ampoule wall. The existence of this meniscus depends on the ratio of the strength of gravity to capillary forces. On Earth, this ratio is large and stable detached growth can only be obtained over limited conditions. Crystals grown detached on the ground exhibited superior structural quality as evidenced by measurements of etch pit density, synchrotron white beam X-ray topography and double axis X-ray diffraction.

  10. The Garlic Allelochemical Diallyl Disulfide Affects Tomato Root Growth by Influencing Cell Division, Phytohormone Balance and Expansin Gene Expression

    Science.gov (United States)

    Cheng, Fang; Cheng, Zhihui; Meng, Huanwen; Tang, Xiangwei

    2016-01-01

    Diallyl disulfide (DADS) is a volatile organosulfur compound derived from garlic (Allium sativum L.), and it is known as an allelochemical responsible for the strong allelopathic potential of garlic. The anticancer properties of DADS have been studied in experimental animals and various types of cancer cells, but to date, little is known about its mode of action as an allelochemical at the cytological level. The current research presents further studies on the effects of DADS on tomato (Solanum lycopersicum L.) seed germination, root growth, mitotic index, and cell size in root meristem, as well as the phytohormone levels and expression profile of auxin biosynthesis genes (FZYs), auxin transport genes (SlPINs), and expansin genes (EXPs) in tomato root. The results showed a biphasic, dose-dependent effect on tomato seed germination and root growth under different DADS concentrations. Lower concentrations (0.01–0.62 mM) of DADS significantly promoted root growth, whereas higher levels (6.20–20.67 mM) showed inhibitory effects. Cytological observations showed that the cell length of root meristem was increased and that the mitotic activity of meristematic cells in seedling root tips was enhanced at lower concentrations of DADS. In contrast, DADS at higher concentrations inhibited root growth by affecting both the length and division activity of meristematic cells. However, the cell width of the root meristem was not affected. Additionally, DADS increased the IAA and ZR contents of seedling roots in a dose-dependent manner. The influence on IAA content may be mediated by the up-regulation of FZYs and PINs. Further investigation into the underlying mechanism revealed that the expression levels of tomato EXPs were significantly affected by DADS. The expression levels of EXPB2 and beta-expansin precursor were increased after 3 d, and those of EXP1, EXPB3 and EXLB1 were increased after 5 d of DADS treatment (0.41 mM). This result suggests that tomato root growth may be

  11. The garlic allelochemical diallyl disulfide affects tomato root growth by influencing cell division, phytohormone balance and expansin gene expression

    Directory of Open Access Journals (Sweden)

    Fang Cheng

    2016-08-01

    Full Text Available Diallyl disulfide (DADS is a volatile organosulfur compound derived from garlic (Allium sativum L., and it is known as an allelochemical responsible for the strong allelopathic potential of garlic. The anticancer properties of DADS have been studied in experimental animals and various types of cancer cells, but to date, little is known about its mode of action as an allelochemical at the cytological level. The current research presents further studies on the effects of DADS on tomato (Solanum lycopersicum L. seed germination, root growth, mitotic index and cell size in root meristem, as well as the phytohormone levels and expression profile of auxin biosynthesis genes (FZYs, auxin transport genes (SlPINs and expansin genes (EXPs in tomato root. The results showed a biphasic, dose-dependent effect on tomato seed germination and root growth under different DADS concentrations. Lower concentrations (0.01-0.62 mM of DADS significantly promoted root growth, whereas higher levels (6.20-20.67 mM showed inhibitory effects. Cytological observations showed that the cell length of root meristem was increased and that the mitotic activity of meristematic cells in seedling root tips was enhanced at lower concentrations of DADS. In contrast, DADS at higher concentrations inhibited root growth by affecting both the length and division activity of meristematic cells. However, the cell width of the root meristem was not affected. Additionally, DADS increased the IAA and ZR contents of seedling roots in a dose-dependent manner. The influence on IAA content may be mediated by the up-regulation of FZYs and PINs. Further investigation into the underlying mechanism revealed that the expression levels of tomato EXPs were significantly affected by DADS. The expression levels of EXPB2 and beta-expansin precursor were increased after 3 d, and those of EXP1, EXPB3 and EXLB1 were increased after 5 d of DADS treatment (0.41 mM. This result suggests that tomato root growth

  12. Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk

    NARCIS (Netherlands)

    Voskuil, Dorien W.; Vrieling, Alina; Korse, Catharina M.; Beijnen, Jos H.; Bonfrer, Johannes M. G.; van Doorn, Jaap; Kaas, Reinie; Oldenburg, Hester S. A.; Russell, Nicola S.; Rutgers, Emiel J. T.; Verhoef, Senno; van Leeuwen, Flora E.; van't Veer, Laura J.; Rookus, Matti A.

    2008-01-01

    Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases se

  13. Influence of climate on radial growth of Pinus cembra within the alpine timberline ecotone.

    Science.gov (United States)

    Oberhuber, Walter

    2004-03-01

    Radial growth variability and response to interannual climate variation of Cembran pine (Pinus cembra L.) were studied in the timberline ecotone on Mt. Patscherkofel (2246 m a.s.l.). The study area, which is in the inner alpine dry region of the Central Austrian Alps, is characterized by a continental climate with minimum precipitation in winter (about 150 mm during December-February) and frequent occurrence of warm dry winds (Föhn) in early spring. The hypothesis that spatial and temporal variability of radial growth is caused by site-related differences in sensitivity to winter stress (i.e., desiccation) was examined by applying dendroclimatological techniques. Ordination methods applied to tree ring time series revealed that spatial variability in radial growth is influenced by the local site factors elevation and slope aspect. Growth-climate relationships were explored using Pearson product-moment correlation coefficients and multiple regression analysis. Radial growth at the timberline was positively correlated with temperature in July and was also strongly correlated with mild temperatures in the previous autumn and high precipitation in winter (January-March). At the tree line, temperatures in the previous autumn and precipitation in late winter (March) also controlled radial growth, whereas July temperature was not significantly correlated with ring width. Because previous autumn temperature and winter precipitation were the main growth-determining factors at the timberline and the tree line, and both of these climate variables are known to influence susceptibility of trees to winter stress, the results support the working hypothesis. Analysis of climatic conditions in extreme growth years confirmed the high sensitivity of tree ring growth to precipitation in late winter (March) at the tree line plots. Furthermore, extent of growth reduction and release varied spatially and temporarily, with south- and west-facing stands showing a higher sensitivity to

  14. Influence of body temperature on bacterial growth rates in experimental pneumococcal meningitis in rabbits.

    OpenAIRE

    Small, P M; Täuber, M G; Hackbarth, C J; Sande, M A

    1986-01-01

    We examined the role of fever as a host defense in experimental pneumococcal meningitis in rabbits. Twelve hours after intracisternal inoculation of an encapsulated type 3 Streptococcus pneumoniae strain, body temperature was manipulated by using two different anesthetic drugs: pentobarbital, which did not affect temperature, and urethane, which mitigated the febrile response to infection. Growth rates of pneumococci in cerebrospinal fluid were dramatically influenced by modification of the f...

  15. Influence of Factor Input on Forestry Economic Growth of Jilin Province

    Institute of Scientific and Technical Information of China (English)

    Yufen XU; Miao WANG

    2016-01-01

    Forestry is a fundamental industry of national economy. In social development of human beings,forestry plays an essential role in expanding employment,realizing rural prosperity and safeguarding ecological safety. This paper firstly introduced current development situations of forestry in Jilin Province. Then,it analyzed influence of factor input on forestry economic growth of Jilin Province by linear regression analysis method. Finally,it came up with pertinent recommendations.

  16. Antifreeze protein modulates cell survival during cryopreservation: mediation through influence on ice crystal growth.

    OpenAIRE

    Carpenter, J F; Hansen, T N

    1992-01-01

    Antifreeze proteins (AFPs) are extremely efficient at inhibiting ice recrystallization in frozen solutions. Knight and Duman [Knight, C. A. & Duman, J. G. (1986) Cryobiology 23, 256-263] have proposed that this may be an important function of the proteins in freeze-tolerant organisms. We have tested this proposal in vitro by characterizing the influence of AFP on the recovery of cryopreserved cells, which often can survive cooling and yet subsequently be damaged by ice crystal growth during w...

  17. Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling.

    Science.gov (United States)

    Nehybova, Tereza; Smarda, Jan; Daniel, Lukas; Brezovsky, Jan; Benes, Petr

    2015-08-01

    Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.

  18. Alterations of expression and regulation of transforming growth factor beta in human cancer prostate cell lines.

    Science.gov (United States)

    Blanchère, M; Saunier, E; Mestayer, C; Broshuis, M; Mowszowicz, I

    2002-11-01

    TGF beta can promote and/or suppress prostate tumor growth through multiple and opposing actions. Alterations of its expression, secretion, regulation or of the sensitivity of target cells can lead to a favorable environment for tumor development. To gain a better insight in TGF beta function during cancer progression, we have used different cultured human prostate cells: preneoplastic PNT2 cells, the androgen-dependent LNCaP and the androgen-independent PC3 and DU145 prostate cancer cell lines. We have studied by specific ELISA assays in conditioned media (CM), the secretion of TGF beta 1 and TGF beta 2 in basal conditions and after hormonal treatment (DHT or E2) and the expression of TGF beta 1 mRNA by Northern blot. We have also compared the effect of fibroblast CM on TGF beta secretion by the different cell types. Compared to PNT2 cells, cancer cell lines secrete lower levels of active TGF beta which are not increased in the presence of fibroblast CM. LNCaP cells respond to androgen or estrogen treatment by a 10-fold increase of active TGF beta secretion while PC3 and DU145 are unresponsive. In conclusion, prostate cancer cell lines have lost part of their ability to secrete and activate TGF beta, and to regulate this secretion through stromal-epithelial interactions. Androgen-sensitive cancer cells may compensate this loss by hormonal regulation.

  19. Immunohistochemical Evaluation of Insulin-like Growth Factor I Receptor Status in Cervical Cancer Specimens

    Directory of Open Access Journals (Sweden)

    Nakamura,Keiichiro

    2008-08-01

    Full Text Available The insulin-like growth factor I receptor (IGF-IR is exceptionally overexpressed in many cervicalcancer-derived cell lines. It is postulated that a decrease of p53 protein levels due to human papillomavirus (HPV infection may contribute to the up-regulation of IGF-IR expression in cervical cancer cells because transcription of IGF-IR is strictly down-regulated by p53. To evaluate this fact in clinical cervical cancer specimens, we checked the expression levels and activated status of IGF-IR by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens obtained by conization or hysterectomy were stained with anti-IGF-IR and with an antibody recognizing phosphorylated tyrosine at its c-terminus. The expression levels of IGF-IR were significantly high in cervical intraepithelial neoplasia (CIN III and invasive cancer specimens. Phosphorylation of IGF-IR was promoted in all CIN and invasive cancer specimens, and its intensity was related to the promotion of lesions. Interestingly, IGF-IR overexpression was missing in the basal layer of CIN I and II lesions, whereas it was evenly distributed in CIN III and invasive cancer lesions. This IGF-IR overexpression pattern may be utilized in the diagnosis of HPV infection status in CIN lesions.

  20. CARP-1 / CCAR1: A biphasic regulator of cancer cell growth and apoptosis

    Science.gov (United States)

    Muthu, Magesh; Cheriyan, Vino T.; Rishi, Arun K.

    2015-01-01

    Targeted cancer therapy using small molecule inhibitors (SMIs) has been useful in targeting the tumor cells while sparing the normal cells. Despite clinical success of many targeted therapies, their off-target effects and development of resistance are emerging as significant and challenging problems. Thus, there is an urgent need to identify targets to devise new means to treat cancers and their drug-resistant phenotypes. CARP-1/CCAR1 (Cell division cycle and apoptosis regulator 1), a peri-nuclear phospho-protein, plays a dynamic role in regulating cell growth and apoptosis by serving as a co-activator of steroid/thyroid nuclear receptors, β-catenin, Anaphase Promoting Complex/Cyclosome (APC/C) E3 ligase, and tumor suppressor p53. CARP-1/CCAR1 also regulates chemotherapy-dependent apoptosis. CARP-1/CCAR1 functional mimetics (CFMs) are a novel SMIs of CARP-1/CCAR1 interaction with APC/C. CFMs promote apoptosis in a manner independent of p53. CFMs are potent inhibitors of a variety of cancer cells including the drug (Adriamycin or Tamoxifen)-resistant breast cancer cells but not the immortalized breast epithelial cells, while a nano-lipid formulation of the lead compound CFM-4 improves its bioavailability and efficacy in vivo when administered orally. This review focuses on the background and pleiotropic roles of CARP-1/CCAR1 as well as its apoptosis signaling mechanisms in response to chemotherapy in cancer cells. PMID:25894788

  1. Linoleic acid suppresses colorectal cancer cell growth by inducing oxidant stress and mitochondrial dysfunction

    Directory of Open Access Journals (Sweden)

    Shen Shengrong

    2010-09-01

    Full Text Available Abstract Some polyunsaturated fatty acids (PUFAs, if not all, have been shown to have tumoricidal action, but their exact mechanism(s of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA inhibited tumor cell growth at high concentrations (above 300 μM; while low concentrations (100-200 μM promoted proliferation. Analysis of cell mitochondrial membrane potential, reactive oxygen species (ROS formation, malondialdehyde (MDA accumulation and superoxide dismutase (SOD activity suggested that anti-cancer action of LA is due to enhanced ROS generation and decreased cell anti-oxidant capacity that resulted in mitochondrial damage. Of the three cell lines tested, semi-differentiated colorectal cancer cells RKO were most sensitive to the cytotoxic action of LA, followed by undifferentiated colorectal cancer cell line (LOVO while the normal human umbilical vein endothelial cells (HUVEC were the most resistant (the degree of sensitivity to LA is as follows: RKO > LOVO > HUVEC. LA induced cell death was primed by mitochondrial apoptotic pathway. Pre-incubation of cancer cells with 100 μM LA for 24 hr enhanced sensitivity of differentiated and semi-differentiated cells to the subsequent exposure to LA. The relative resistance of LOVO cells to the cytotoxic action of LA is due to a reduction in the activation of caspase-3. Thus, LA induced cancer cell apoptosis by enhancing cellular oxidant status and inducing mitochondrial dysfunction.

  2. The insulin-like growth factor (IGF) axis as an anticancer target in prostate cancer.

    Science.gov (United States)

    Heidegger, Isabel; Massoner, Petra; Sampson, Natalie; Klocker, Helmut

    2015-10-28

    Prostate cancer (PCa) is the most common cancer and the second leading cause of cancer death in males. In recent years, several new targeting agents have been introduced for the treatment of advanced stages of the disease. However, development of resistance limits the efficacy of new drugs and there is a further need to develop additional novel treatment approaches. One of the most investigated targets in cancer research is the insulin-like growth factor (IGF) axis, whose receptors are overexpressed in several cancer entities including PCa. In preclinical studies in PCa, targeting of the IGF axis receptors showed promising anti-tumor effects. Currently available data on clinical studies do not meet the expectations for this new treatment approach. In this review we provide a summary of preclinical and clinical studies on the IGF axis in PCa including treatment with monoclonal antibodies and tyrosine kinase inhibitors. Moreover, we summarize preliminary results from ongoing studies and discuss limitations and side effects of the substances used. We also address the role of the IGF axis in the biomarkers setting including IGF-binding proteins and genetic variants.

  3. Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers

    Directory of Open Access Journals (Sweden)

    Nathan Simon

    2016-05-01

    Full Text Available Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling has been of high importance, and multiple examples have been approved for human use. However, many of the current small molecule or antibody-based therapeutics are of limited effectiveness due to the inevitable development of resistance and toxicity to normal tissues. Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the decades, many bacterial- or plant-based immunotoxins have been developed with the goal of targeting the broad range of cancers reliant upon EGFR overexpression. Many examples demonstrate excellent anti-cancer properties in preclinical development, and several EGFR-targeted immunotoxins have progressed to human trials. This review summarizes much of the past and current work in the development of immunotoxins for targeting EGFR-driven cancers.

  4. Detecting the epidermal growth factor receptors status in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    MENG Xue; YU Jin-ming

    2011-01-01

    Non-small cell lung cancer is one of the leading causes of all cancer deaths,but despite years of research,it is still difficult to predict the response and clinical outcome of the disease.In recent years,new treatment strategies targeting the epidermal growth factor receptors (EGFR) have been developed.EGFR is one of the most frequently over expressed proteins in various cancers,including lung cancer,and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments.Therefore,EGFR has become an attractive target for various treatment strategies.However,it is important to note that not all patients with lung cancer are suitable for targeted treatment,and that patients should be selected for this treatment.Several studies have proven that the status of the EGFR can be both an indicator of suitability for treatment with,and predict the likelihood of response to EGFR targeted therapy.There are many standard techniques to be used for the detection of EGFR.This overview summarizes the ongoing and future investigations to determine the status of the EGFR.

  5. MicroRNA-29a Promotes Pancreatic Cancer Growth by Inhibiting Tristetraprolin

    Directory of Open Access Journals (Sweden)

    Xian-Jun Sun

    2015-09-01

    Full Text Available Background/Aims: The microRNA (miR 29 family has been studied extensively for its involvement in several diseases, and aberrant expression of its members is associated with tumorigenesis and cancer progression. Here, we examined the role of miR-29a in pancreatic cancer and the involvement of tristetraprolin (TTP. Methods: We monitored miR-29a and TTP expression in pancreatic cancer by qRT-PCR and western blotting. The effect of miR-29a on pancreatic cancer was determined through MTT assay and migration assay. The results were validated in the tumorigenesis model. Results: We found that miR-29a was up regulated in pancreatic tumor tissues and cell lines and positively correlated with metastasis. Ectopic expression of miR-29a increased the expression of pro-inflammatory factors and epithelial-mesenchymal transition (EMT markers, through down regulating TTP. TTP was down regulated in tumor tissues, and its ectopic expression decreased cell viability and migration in vitro, inhibited tumor growth and the EMT phenotype in vivo, and reversed the effect of miR-29a on tumor cell proliferation and invasion in vitro and in vivo. Conclusion: Our results suggest that miR-29a acts as an oncogene by down regulating TTP and provide the basis for further studies exploring the potential of miR-29a and TTP as biomarkers and targets for the treatment of pancreatic cancer.

  6. Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts.

    Science.gov (United States)

    Lipner, Matthew B; Marayati, Raoud; Deng, Yangmei; Wang, Xianxi; Raftery, Laura; O'Neil, Bert H; Yeh, Jen Jen

    2016-01-01

    There is currently tremendous interest in developing anti-cancer therapeutics targeting cell signaling pathways important for both cancer cell metabolism and growth. Several epidemiological studies have shown that diabetic patients taking metformin have a decreased incidence of pancreatic cancer. This has prompted efforts to evaluate metformin, a drug with negligible toxicity, as a therapeutic modality in pancreatic cancer. Preclinical studies in cell line xenografts and one study in patient-derived xenograft (PDX) models were promising, while recently published clinical trials showed no benefit to adding metformin to combination therapy regimens for locally advanced and metastatic pancreatic cancer. PDX models in which patient tumors are directly engrafted into immunocompromised mice have been shown to be excellent preclinical models for biomarker discovery and therapeutic development. We evaluated the response of four PDX tumor lines to metformin treatment and found that all four of our PDX lines were resistant to metformin. We found that the mechanisms of resistance may occur through lack of sustained activation of adenosine monophosphate-activated protein kinase (AMPK) or downstream reactivation of the mammalian target of rapamycin (mTOR). Moreover, combined treatment with metformin and mTOR inhibitors failed to improve responses in cell lines, which further indicates that metformin alone or in combination with mTOR inhibitors will be ineffective in patients, and that resistance to metformin may occur through multiple pathways. Further studies are required to better understand these mechanisms of resistance and inform potential combination therapies with metformin and existing or novel therapeutics.

  7. Information Booklets about Cancer: Factors Influencing Patient Satisfaction and Utilisation.

    Science.gov (United States)

    Butow, Phyllis; Brindle, Elizabeth; McConnell, David; Boakes, Robert; Tattersall, Martin

    1998-01-01

    Explored factors influencing patient satisfaction with and utilization of information booklets. Patients (N=36) rated five booklets, and strongly preferred one with a grade-eight reading level. The relationship of preference and recall was investigated. No difference between those who seek or avoid information was found. Additional findings are…

  8. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis

    Directory of Open Access Journals (Sweden)

    Li Q

    2013-07-01

    Full Text Available Qingli Li,1,2 Mark J Lambrechts,1 Qiuyang Zhang,1 Sen Liu,1 Dongxia Ge,1 Rutie Yin,2 Mingrong Xi,2 Zongbing You1 1Departments of Structural and Cellular Biology and Orthopaedic Surgery, Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane Center for Stem Cell Research and Regenerative Medicine, and Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA; 2Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA, are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy. Keywords: serine hydroxymethyltransferase, prostate cancer, apoptosis

  9. Epidermal growth factor receptor regulates β-catenin location, stability, and transcriptional activity in oral cancer

    Directory of Open Access Journals (Sweden)

    Hung Hsing-Wen

    2010-03-01

    Full Text Available Abstract Background Many cancerous cells accumulate β-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR signaling in the accumulation of β-catenin in the nuclei of oral cancer cells. Results We used two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM1 cells and one with elevated EGFR expression (SAS cells, and measured downstream effects, such as phosphorylation of β-catenin and GSK-3β, association of β-catenin with E-cadherin, and target gene regulation. We also studied the expression of EGFR, β-catenin, and cyclin D1 in 112 samples of oral cancer by immunostaining. Activation of EGFR signaling increased the amount of β-catenin in the nucleus and decreased the amount in the membranes. EGF treatment increased phosphorylation of β-catenin (tyrosine and GSK-3β(Ser-(9, resulting in a loss of β-catenin association with E-cadherin. TOP-FLASH and FOP-FLASH reporter assays demonstrated that the EGFR signal regulates β-catenin transcriptional activity and mediates cyclin D1 expression. Chromatin immunoprecipitation experiments indicated that the EGFR signal affects chromatin architecture at the regulatory element of cyclin D1, and that the CBP, HDAC1, and Suv39h1 histone/chromatin remodeling complex is involved in this process. Immunostaining showed a significant association between EGFR expression and aberrant accumulation of β-catenin in oral cancer. Conclusions EGFR signaling regulates β-catenin localization and stability, target gene expression, and tumor progression in oral cancer. Moreover, our data suggest that aberrant accumulation of β-catenin under EGFR activation is a malignancy marker of oral cancer.

  10. Study of factors influencing dose distribution of brachytherapy in cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Liu Zi; Gao Ying; Luo Wei; Wang Guoqing; Wang Ruihua; Zheng Wei; Liu Rui

    2008-01-01

    Objective To study the factors which influence the dose distribution of brachytherapy in cervical cancer. Methods Ninety-five patients with cervical cancer Ⅱ - Ⅲ b received fundamental radiation therapy including brachytherapy in our department from Aug. 2004 to Nov. 2005. The deviation of isodose curve of brachytherapy was based on A-B reference system, and the deviation of dose was defined by measuring in a practical standard body model. Results The factors influencing isodose offset significantly were parametrial infiltrating degree, and anatomy factor of cervical cancer and operating skill. The degree of isodose offset could not be lowered with the increased frequency of brachytherapy. Conclusion Making simulation in cervical brachythecapy is necessary not only for the identification of the deviation of isodose curve but also for adjusting the dose distribution and revising the plan of radiotherapy.

  11. Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients

    NARCIS (Netherlands)

    Goossens, Maria E; Buntinx, Frank; Zeegers, Maurice P; Driessen, J H M; De Bruin, Marie L; de Vries, Frank

    2015-01-01

    OBJECTIVE: The aim of this study is to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new-user design (inception cohort). METHODS: We conducted a retrospective cohort study using data from the UK Clin

  12. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Wei [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Li, Ying; Zhao, Haixia; Xie, Xianfei; Zheng, Hao; Wang, Chenlong; Wang, Xue [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Guifang [Department of Pathology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Cai, Xiaojun [Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 (United States); Yang, Jing, E-mail: yangjingliu@yahoo.com.cn [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-10-01

    Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation. -- Highlights: ► CYP4Z1 overexpression promotes human breast cancer growth and angiogenesis. ► The pro-angiogenic effects of CYP4Z1 have

  13. Influence of growth conditions on the performance of InP nanowire solar cells.

    Science.gov (United States)

    Cavalli, Alessandro; Cui, Yingchao; Kölling, Sebastian; Verheijen, Marcel A; Plissard, Sebastien R; Wang, Jia; Koenraad, Paul M; Haverkort, Jos E M; Bakkers, Erik P A M

    2016-11-11

    Nanowire based solar cells have attracted great attention due to their potential for high efficiency and low device cost. Photovoltaic devices based on InP nanowires now have characteristics comparable to InP bulk solar cells. A detailed and direct correlation of the influence of growth conditions on performance is necessary to improve efficiency further. We explored the effects of the growth temperature, and of the addition of HCl during growth, on the efficiency of nanowire array based solar cell devices. By increasing HCl, the saturation dark current was reduced, and thereby the nanowire solar cell efficiency was enhanced from less than 1% to 7.6% under AM 1.5 illumination at 1 sun. At the same time, we observed that the solar cell efficiency decreased by increasing the tri-methyl-indium content, strongly suggesting that these effects are carbon related.

  14. Influence of growth conditions on the performance of InP nanowire solar cells

    Science.gov (United States)

    Cavalli, Alessandro; Cui, Yingchao; Kölling, Sebastian; Verheijen, Marcel A.; Plissard, Sebastien R.; Wang, Jia; Koenraad, Paul M.; Haverkort, Jos E. M.; Bakkers, Erik P. A. M.

    2016-11-01

    Nanowire based solar cells have attracted great attention due to their potential for high efficiency and low device cost. Photovoltaic devices based on InP nanowires now have characteristics comparable to InP bulk solar cells. A detailed and direct correlation of the influence of growth conditions on performance is necessary to improve efficiency further. We explored the effects of the growth temperature, and of the addition of HCl during growth, on the efficiency of nanowire array based solar cell devices. By increasing HCl, the saturation dark current was reduced, and thereby the nanowire solar cell efficiency was enhanced from less than 1% to 7.6% under AM 1.5 illumination at 1 sun. At the same time, we observed that the solar cell efficiency decreased by increasing the tri-methyl-indium content, strongly suggesting that these effects are carbon related.

  15. Influences of Natural Colloid in Seawater on the Growth of a Microalga

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Colloid concentrates were obtained by employing a cross-flow filtration system to ultrafiltrate seawater(which was pre-filtrated by 0.45 μm acetate cellulose membrane) sucessively with three membranes.The retentions (colloid concentrates) and control sample(in which colloid was removed)were then inoculated with a microalga and cultivated in vitro.After continuously monitoring cell content during cultivation,it was found that colloid had an obvious beneficial effect on the growth of microalga.Although colloids with different sizes influenced microalga's growth in different extent and ways,a brief conclusion could be draw from experiments that colloid might be a potential nutrition source for microalga's growth.

  16. The influence of Plant Growth Promoting Rhizobacteria (PGPR on the reduction of abiotic stresses in crops

    Directory of Open Access Journals (Sweden)

    Omid Alizadeh

    2011-12-01

    Full Text Available Plants are always subjected to biotic and abiotic stresses in the environment which haveinfluences on the growth and development of the plants. Beneficial free-living soil bacteria are usuallyreferred as Plant-Growth Promoting Rhizobacteria or PGPR. Different plant growth-promotingRhizosphere bacteria, including associative bacteria such as: Azospirillum, Bacillus, Pseudomonas andEnterobacter group have been used for their beneficial influences on plants. Typically, PGPRs areassociated with plants root and augment plant productivity and immunity; however, recent worksshowed that PGPRs not have just induced the systemic tolerance to abiotic stress such as salt anddrought, but also they have increased the nutrient uptake from soils, and as a result the hazardousaccumulation of nitrates and phosphates in the agricultural soils can be reduced by usage of them.

  17. Isolated Isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk

    NARCIS (Netherlands)

    Vrieling, A.; Rookus, M.A.; Kampman, E.; Bonfrer, J.M.G.; Korse, C.M.; Doorn, van J.; Lampe, J.W.; Cats, A.; Witteman, B.J.M.; Leeuwen, van F.E.; van't Veer, L.J.; Voskuil, D.W.

    2007-01-01

    Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conduc

  18. Anthocyanin Induces Apoptosis of DU-145 Cells In Vitro and Inhibits Xenograft Growth of Prostate Cancer

    Science.gov (United States)

    Ha, U-Syn; Bae, Woong Jin; Kim, Su Jin; Yoon, Byung Il; Hong, Sung Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Hwang, Sung Yeoun; Wang, Zhiping

    2015-01-01

    Purpose To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). Materials and Methods The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2×106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. Results Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. Conclusion This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model. PMID:25510742

  19. Piperine inhibits the growth and motility of triple-negative breast cancer cells.

    Science.gov (United States)

    Greenshields, Anna L; Doucette, Carolyn D; Sutton, Kimberly M; Madera, Laurence; Annan, Henry; Yaffe, Paul B; Knickle, Allison F; Dong, Zhongmin; Hoskin, David W

    2015-02-01

    Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated the effect of piperine on the growth and motility of triple-negative breast cancer (TNBC) cells. Piperine inhibited the in vitro growth of TNBC cells, as well as hormone-dependent breast cancer cells, without affecting normal mammary epithelial cell growth. Exposure to piperine decreased the percentage of TNBC cells in the G2 phase of the cell cycle. In addition, G1- and G2-associated protein expression was decreased and p21(Waf1/Cip1) expression was increased in piperine-treated TNBC cells. Piperine also inhibited survival-promoting Akt activation in TNBC cells and caused caspase-dependent apoptosis via the mitochondrial pathway. Interestingly, combined treatment with piperine and γ radiation was more cytotoxic for TNBC cells than γ radiation alone. The in vitro migration of piperine-treated TNBC cells was impaired and expression of matrix metalloproteinase-2 and -9 mRNA was decreased, suggesting an antimetastatic effect by piperine. Finally, intratumoral administration of piperine inhibited the growth of TNBC xenografts in immune-deficient mice. Taken together, these findings suggest that piperine may be useful in the treatment of TNBC.

  20. Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer

    Science.gov (United States)

    Sobani, Zain A; Sawant, Ashwin; Jafri, Mikram; Correa, Amit Keith; Sahin, Ibrahim Halil

    2016-01-01

    Epidermal growth factor receptor (EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer (CRC). Evidence from clinical trials indicates that cetuximab and panitumumab (anti-EGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS (KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade. PMID:27777877

  1. Soil factors exhibit greater influence than bacterial inoculation on alfalfa growth and nitrogen fixation.

    Science.gov (United States)

    Neumann, Ute; Kosier, Bob; Jahnke, Joachim; Priefer, Ursula B; Al-Halbouni, Djamila

    2011-09-01

    In order to study the effects of soil factors and bacterial inoculation on alfalfa (Medicago sativa), plants were inoculated with Ensifer meliloti L33 and Azospirillum brasilense Sp7 in pot experiments using two different soils separately as well as in a mixture. One soil was contaminated with chemical waste products; the other was an arable soil. Soil factors, including the availability of macro- and micronutrients as well as carbon and nitrogen contents, were found to exhibit a much greater influence on the growth of alfalfa than any of the inoculations. In contaminated soil, the shoot and root growth of alfalfa was decreased and nodules were diminished and ineffective. Bacterial inoculations did not significantly improve this hostile growth environment. However, in a mixture (44% arable, 22% contaminated soil, 34% vermiculite), growth conditions for alfalfa were improved so that shoot dry weight and nodule numbers increased up to 100- and 20-fold, respectively, compared with the contaminated soil. For the strain L33, its persistence in the rhizosphere was correlated to the presence of its host plant, but its dynamics were influenced by competition with indigenous rhizobia. The strain Sp7, once provided with a suitable soil, was not dependent on the plant's rhizosphere, but it enhanced the performance of L33 and native rhizobia.

  2. STUDY OF THE INFLUENCE OF OZONE ON THE GROWTH PROCESSES OF MAIZE SEEDS

    Directory of Open Access Journals (Sweden)

    Shevchenko A. A.

    2015-01-01

    Full Text Available Increasing the yield of crops is a global challenge substantiated by the scientists from all over the world. To achieve this goal, there are various ways, one of which is the ozonation of seeds before sowing. This method inhibits harmful microflora, which could be formed on the seed during the period of storage, and excites the chemical processes within the seed that can accelerate the process of growth. But despite the positive effect of ozone-air mixture of seeds and a variety of conducting research there is still no reliable data on the technological parameters of ozone effects on seed crops (e.g., corn. In this regard, we have conducted experimental studies to determine the effective parameters of the ozonation of corn seeds, such as the concentration of ozone in the ozone-air mixture, exposure time and binning after treatment. The influence of these parameters was assessed by changes in growth performance of seed, such as germination, germination and growth of strength. Just at the end of the pilot study we carried out a statistical analysis of the data, which allowed us to estimate the degree of influence of each independent parameter (ozone concentration, exposure time, binning after treatment for each dependent parameter (germination energy, germination, growth force. The data obtained is presented in the article

  3. Influence of near null magnetic field on in vitro growth of potato and wild Solanum species.

    Science.gov (United States)

    Rakosy-Tican, Lenuta; Aurori, C M; Morariu, V V

    2005-10-01

    The influence of near null magnetic field on in vitro growth of different cultures of potato and related Solanum species was investigated for various exposure times and dates. Potato (Solanum tuberosum L. cv. Désirée) in vitro cultures of shoot tips or nodal segments were used. Three different exposure periods revealed either stimulation or inhibition of root, stem, or leaf in vitro growth after 14 or 28 days of exposure. In one experiment the significant stimulation of leaf growth was also demonstrated at biochemical level, the quantity of chlorophyll a and b and carotenoids increasing more than two-fold. For the wild species Solanum chacoense, S. microdontum, and S. verrucosum, standardized in vitro cultures of nodal stem segments were used. Root and stem growth was either stimulated or slightly inhibited after 9 days exposure to near null magnetic field. Callus cultures obtained from potato dihaploid line 120/19 were maintained in near null magnetic field in 2 different months. For these experiments as well as for Solanum verrucosum, callus cultures recorded either slight inhibition or no effect on fresh weight. For all experiments significant growth variation was brought about only when geomagnetic activity (AP index) showed variations at the beginning of in vitro growth and when the explant had at least one meristematic tissue. Moreover longer maintenance in near null magnetic field, 28 days as compared to 14 days or the controls, can also make a difference in plant growth in response to geomagnetic field variations when static component was reduced to zero value. These results of in vitro plant growth stimulation by variable component of geomagnetic field also sustain the so-called seasonal "window" effect.

  4. The influence of travel time on breast cancer characteristics, receipt of primary therapy, and surveillance mammography.

    Science.gov (United States)

    Onega, Tracy; Cook, Andrea; Kirlin, Beth; Shi, Xun; Alford-Teaster, Jennifer; Tuzzio, Leah; Buist, Diana S M

    2011-08-01

    Travel time has been shown to influence some aspects of cancer characteristics at diagnosis and care for women with breast cancer, but important gaps remain in our understanding of its impact. We examined the influence of travel time to the nearest radiology facility on breast cancer characteristics, treatment, and surveillance for women with early-stage invasive breast cancer. We included 1,012 women with invasive breast cancer (stages I and II) who had access to care within an integrated health care delivery system in western Washington State. The travel times to the nearest radiology facility were calculated for all the U.S. Census blocks within the study area and assigned to women based on residence at diagnosis. We collected cancer characteristics, primary and adjuvant therapies, and surveillance mammography for at least 2.5 years post diagnosis and used multivariable analyses to test the associations of travel time. The majority of women (68.6%) lived within 20 min of the nearest radiology facility, had stage I disease (72.7%), received breast conserving therapy (68.7%), and had annual surveillance mammography the first 2 years after treatment (73.7%). The travel time was not significantly associated with the stage or surveillance mammography after adjusting for covariates. Primary therapy was significantly related to travel time, with greater travel time (>30 min vs. ≤ 10 min) associated with a higher likelihood of mastectomy compared to breast conserving surgery (RR = 1.53; 95% CI, 1.16-2.01). The travel time was not associated with the stage at diagnosis or surveillance mammography receipt. The travel time does seem to influence the type of primary therapy among women with breast cancer, suggesting that women may prefer low frequency services, such as mastectomy, if geographic access to a radiology facility is limited.

  5. Prenatal influences on size, velocity and tempo of infant growth: findings from three contemporary cohorts.

    Directory of Open Access Journals (Sweden)

    Costanza Pizzi

    Full Text Available BACKGROUND: Studying prenatal influences of early life growth is relevant to life-course epidemiology as some of its features have been linked to the onset of later diseases. METHODS: We studied the association between prenatal maternal characteristics (height, age, parity, education, pre-pregnancy body mass index (BMI, smoking, gestational diabetes and hypertension and offspring weight trajectories in infancy using SuperImposition by Translation And Rotation (SITAR models, which parameterize growth in terms of three biologically interpretable parameters: size, velocity and tempo. We used data from three contemporary cohorts based in Portugal (GXXI, n=738, Italy (NINFEA, n=2,925, and Chile (GOCS, n=959. RESULTS: Estimates were generally consistent across the cohorts for maternal height, age, parity and pre-pregnancy overweight/obesity. Some exposures only affected one growth parameter (e.g. maternal height (per cm: 0.4% increase in size (95% confidence interval (CI:0.3; 0.5, others were either found to affect size and velocity (e.g. pre-pregnancy underweight vs normal weight: smaller size (-4.9%, 95% CI:-6.5; -3.3, greater velocity (5.9%, 95% CI:1.9;10.0, or to additionally influence tempo (e.g. pre-pregnancy overweight/obesity vs normal weight: increased size (7.9%, 95% CI:4.9;10.8, delayed tempo (0.26 months, 95% CI:0.11;0.41, decreased velocity (-4.9%, 95% CI: -10.8;0.9. CONCLUSIONS: By disentangling the growth parameters of size, velocity and tempo, we found that prenatal maternal characteristics, especially maternal smoking, pre-pregnancy overweight and underweight, parity and gestational hypertension, are associated with different aspects of infant weight growth. These results may offer insights into the mechanisms governing infant growth.

  6. [Exploration of the Factors Influencing Multi-Drug Cancer Chemotherapy in the Elderly - A Retrospective Study].

    Science.gov (United States)

    Ogata, Kentaro; Tamura, Kazuo; Kiyomi, Fumiaki; Takamatsu, Yasushi; Kamimura, Hidetoshi

    2016-12-01

    Multi-drug administration is problematic in elderly patients, and the situation is further complicated in those with cancer, owing to a high possibility of side effects and augmentation due to interactions between concomitant or previous drugs the patients are receiving and the anti-cancer drugs administered. Analysis of the factors that influence the likelihood of cancer chemotherapy multi-drug administration in the elderly showed that age alone was a fundamental risk factor for multi-drug administration, comorbidities, and drug interactions. In addition, the risks of drug interaction with chemotherapy were approximately 5.8 fold for drugs administered to treat hypertension, and approximately 10.3 fold for cardiovascular agents. Because of increased cancer morbidity, it is important to reduce the risks associated with the treatment.

  7. Aurora kinase inhibitors attached to iron oxide nanoparticles enhances inhibition of the growth of liver cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiquan [Southeast University, State Key Laboratory of Bioelectronics and Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering (China); Xie, Li [Southeast University, Zhongda Hospital, School of Medicine (China); Zheng, Ming; Yao, Juan [Jiangsu Chai Tai Tianqing Pharmaceutical Co. Ltd. (China); Song, Lina [Southeast University, State Key Laboratory of Bioelectronics and Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering (China); Chang, Weiwei [Jiangsu Chai Tai Tianqing Pharmaceutical Co. Ltd. (China); Zhang, Yu; Ji, Min, E-mail: minji888@hotmail.com; Gu, Ning, E-mail: guning@seu.edu.cn [Southeast University, State Key Laboratory of Bioelectronics and Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering (China); Zhan, Xi, E-mail: zhan01@gmail.com [University of Maryland School of Medicine, The Center of Vascular and Inflammatory Diseases, The Department of Pathology (United States)

    2015-06-15

    We have developed a novel Aurora kinase inhibitor (AKI) AM-005, an analogue of pan-AKI AT-9283. To improve the intracellular efficacy of AM-005 and AT-9283, we utilized magnetite nanoparticles (NPs) to deliver AM-005 and AT-9283 into human SMMC-7721 and HepG2 liver cancer cells. The drug-loaded NPs were prepared through quasi-emulsion solvent diffusion of magnetite NPs with AM-005 or AT-9283. The encapsulated drugs were readily released from NPs, preferentially at low pHs. Upon exposure, cancer cells effectively internalized drug-loaded NPs into lysosome-like vesicles, which triggered a series of cellular changes, including the formation of enlarged cytoplasm, the significant increase of membrane permeability, and the generation of reactive oxygen species (ROS). The increased ROS synthesis sustained over 72 h, whereas that in the cells treated with free-form drugs declined rapidly after 48 h. However, chemical sequestration of the iron core of NPs had a minor influence on the generation of intracellular ROS. On the other hand, uncoupling of AM-005 uptake with NP internalization into cells failed to induce ROS synthesis. Overall, our approach achieved two-fold increase in suppressing the viability of tumor cells in vitro and the growth of tumors in vivo. We conclude that magnetite NPs can be used as pH responsive nanocarriers that are able to improve the efficacy of AKIs.

  8. 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

    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...... 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...... regulation. There was no indication of differences in cell proliferative characteristics between the different NCAM-transfected and the control transfected cells as determined by flow cytometric DNA analysis, suggesting an increased cell loss as the reason for decreased in vivo growth rate of the NCAM...

  9. Study of wavy laminar growth of human urinary bladder cancer cell line in vitro

    Institute of Scientific and Technical Information of China (English)

    DENG Guo-hong; CONG Yan-guang; LIU Jun-kang; XU Qi-wang; YUAN Ze-tao

    2001-01-01

    To observe the ordered growth behavior of human urinary bladder cancer cell line (BIU) under culture in vitro. Methods: The suspension of BIU cells was spread locally in a culture container. When the cells grew along the wall to form a cellular colony, macroscopic and microscopic observations complemented with measurements of the parameters including expanding diameter, expanding rate, cell shape, average cell density, average cell size, dehydrogenase activity and sensitivity to pH were conducted dynamically. Results: During cell culture, obvious laminar characteristics appeared in localized growing BIU cell colonies and there was difference between the cells of different zones in shape, size, density, dehydrogenase activity and sensitivity to pH. Conclusion: Space closing and bio-dissipation result in self-organization of BIU cells with ordered growth behavior. The present experiment offers a simple, controllable model for the study of wavy growth of human cells.

  10. Influence of place card health education on the post-traumatic growth in laryngeal cancer patients after the operation%台签式健康教育对喉癌术后患者创伤后成长的影响

    Institute of Scientific and Technical Information of China (English)

    邢蕾; 钱聪

    2014-01-01

    Objective To explore the effect of place card health education on the post-traumatic growth in laryngeal cancer patients after the operation .Methods Ninety-two laryngeal cancer patients from January 2012 to December 2013 were chosen and divided into the control group and the observation group , each with 46 cases.The control group received the routine health education , and the observation group received the place card health education on the basis of the routine health education .The patients were surveyed by Posttraumatic Growth Inventory ( PTGI ) , Jalowies coping scale , General Self-Efficacy Scale ( GSES ) before and after the health education.Results The total score of PTGI was (76.38 ±14.75) in the observation group, and was better than (52.18 ±12.02) in the control group, and the difference was statistically significant ( t=5.986, P<0.05).The score of GSES was (50.92 ±12.78) in the observation group, and was higher than (35.98 ± 6.72) in the control group, and the difference was statistically significant ( t =5.785, P <0.05 ).The differences were found in the all dimension of Jalowies coping scale before and after the health education ( P<0.05).The score of PTGI of laryngeal cancer patients after the operation was positively correlated with looking for support, optimism, face, and emotional catharsis included by Jalowies coping scale ( r =0.402,0.412, 0.325,0.336, respectively;P<0.05), and was negatively correlated with escape , fate, palliative, self-relying included by Jalowies coping scale (r=-0.352,-0.372,-0.363,-0.341, respectively;P<0.05).The score of PTGI was positively correlated with self-efficacy(r=0.396,P<0.05).Conclusions Place card health education can make the patients to raise positive response to the disease and learn to regulate negative emotions so as to improve their self-efficacy and promote their post-traumatic growth.%目的:探讨台签式健康教育对喉癌术后患者创伤后成长的影响。方法选取2012年1月-2013

  11. Influence of dissolved hydrogen on the fatigue crack growth behaviour of AISI 4140 steel

    Science.gov (United States)

    Ramasagara Nagarajan, Varun

    Many metallic structural components come into contact with hydrogen during manufacturing processes or forming operations such as hot stamping of auto body frames and while in service. This interaction of metallic parts with hydrogen can occur due to various reasons such as water molecule dissociation during plating operations, interaction with atmospheric hydrogen due to the moisture present in air during stamping operations or due to prevailing conditions in service (e.g.: acidic or marine environments). Hydrogen, being much smaller in size compared to other metallic elements such as Iron in steels, can enter the material and become dissolved in the matrix. It can lodge itself in interstitials locations of the metal atoms, at vacancies or dislocations in the metallic matrix or at grain boundaries or inclusions (impurities) in the alloy. This dissolved hydrogen can affect the functional life of these structural components leading to catastrophic failures in mission critical applications resulting in loss of lives and structural component. Therefore, it is very important to understand the influence of the dissolved hydrogen on the failure of these structural materials