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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. Monitoring noise-resonant effects in cancer growth influenced by spontaneous fluctuations and periodic treatment

    CERN Document Server

    Fiasconaro, Alessandro; Spagnolo, Bernardo; Gudowska-Nowak, Ewa

    2007-01-01

    In the paper we investigate a mathematical model describing the growth of tumor in the presence of immune response of a host organism. The dynamics of tumour and immune cells is based on the generic Michaelis-Menten kinetics describing interaction and competition between the tumour and the immune system. The appropriate phenomenological equation modeling cell-mediated immune surveillance against cancer is of the predator-prey form and within a given choice of parameters exhibits bistability. Under the influence of spontaneous weak fluctuations, the model may be analyzed in terms of a stochastic differential equation bearing the form of an overdamped Langevin-like dynamics in the external quasi-potential represented by a double well. We analyze properties of the system within the range of parameters for which the potential wells are of the same depth and when the additional perturbation describing a periodic treatment is insufficient to overcome the barrier height and to cause cancer extinction. In this case t...

  3. The influence of myeloid-derived suppressor cells on angiogenesis and tumor growth after cancer surgery.

    Science.gov (United States)

    Wang, Jun; Su, Xiaosan; Yang, Liu; Qiao, Fei; Fang, Yu; Yu, Lu; Yang, Qian; Wang, Yiyin; Yin, Yanfeng; Chen, Rui; Hong, Zhipeng

    2016-06-01

    While myeloid-derived suppressor cells (MDSCs) have been reported to participate in the promotion of angiogenesis and tumor growth, little is known about their presence and function during perioperative period. Here, we demonstrated that human MDSCs expressing CD11b(+) , CD33(+) and HLA-DR(-) significantly increased in lung cancer patients after thoracotomy. CD11b(+) CD33(+) HLA-DR(-) MDSCs isolated 24 hr after surgery from lung cancer patients were more efficient in promoting angiogenesis and tumor growth than MDSCs isolated before surgical operation in allograft tumor model. In addition, CD11b(+) CD33(+) HLA-DR(-) MDSCs produced high levels of MMP-9. Using an experimental lung metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and Gr-1(+) CD11b(+) MDSCs at postoperative period were enhanced in proportion to the degree of surgical manipulation. We also examined that syngeneic bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of Gr-1(+) CD11b(+) MDSCs and further prevented lung metastasis formation in the mice undergoing laparotomy. Taken together, our results suggest that postoperatively induced MDSCs were qualified with potent proangiogenic and tumor-promotive ability and this cell population should be considered as a target for preventing postoperative tumor metastasis. PMID:26756887

  4. Thyroid Growth and Cancer.

    Science.gov (United States)

    Williams, Dillwyn

    2015-09-01

    It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term 'cancer' to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID:26558233

  5. Influences of noise correlation and time delay on stochastic resonance induced by multiplicative signal in a cancer growth system

    International Nuclear Information System (INIS)

    This paper investigates the stochastic resonance (SR) phenomenon induced by the multiplicative periodic signal in a cancer growth system with the cross-correlated noises and time delay. To describe the periodic change of the birth rate due to the periodic treatment, a multiplicative periodic signal is added to the system. Under the condition of small delay time, the analytical expression of the signal-to-noise ratio RSNR is derived in the adiabatic limit. By numerical calculation, the effects of the cross-correlation strength λ and the delay time τ on RSNR are respectively discussed. The existence of a peak in the curves of RSNR as a function of the noise intensities indicates the occurrence of the SR phenomenon. It is found that λ and τ play opposite role on the SR phenomenon, i.e., the SR is suppressed by increasing λ whereas it is enhanced with the increase of τ, which is different from the case where the periodic signal is additive. (general)

  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. Macroscopic dynamics of cancer growth

    Science.gov (United States)

    Menchón, S. A.; Condat, C. A.

    2007-04-01

    Macroscopic modeling is used to describe various aspects of cancer growth. A recently proposed “dysnamical exponent” hypothesis is critically examined in the context of the angiogenic development. It is also shown that the emergence of necroses facilitates the growth of avascular tumors; the model yields an excellent fit to available experimental data, allowing for the determination of growth parameters. Finally, the global effects of an applied antitumoral immunotherapy are investigated. It is shown that, in the long run, the application of a therapeutical course leads to bigger tumors by weakening the intraspecific competition between surviving viable cancer cells. The strength of this model lies in its simplicity and in the amount of information that can be gleaned using only very general ideas.

  8. Influence of TP53 and CDH1 genes in hepatocellular cancer spheroid formation and culture: a model system to understand cancer cell growth mechanics

    OpenAIRE

    Pomo, Joseph M.; Taylor, Robert M; Gullapalli, Rama R

    2016-01-01

    Background Spheroid based culture methods are gaining prominence to elucidate the role of the microenvironment in liver carcinogenesis. Additionally, the phenomenon of epithelial-mesenchymal transition also plays an important role in determining the metastatic potential of liver cancer. Tumor spheroids are thus important models to understand the basic biology of liver cancer. Methods We cultured, characterized and examined the formation of compact 3-D micro-tumor spheroids in five hepatocellu...

  9. Microgravity alters cancer growth and progression.

    Science.gov (United States)

    Jhala, Dhwani V; Kale, Raosaheb K; Singh, Rana P

    2014-01-01

    Study of the process of cancer initiation, growth and progression in altered gravity is of utmost importance considering the health status of researchers visiting in space and future scope of space tourism. Microgravity affects various cells in the body differently; however, the mechanisms of such effects are not understood completely. Therefore, it is imperative to explore various physiological and biochemical processes, particularly those which can influence the process of carcinogenesis. If the changes in physiological or biochemical processes do not revert back to normalcy even after returning from the space to earth, it may lead to various aberrations and morphological changes during the life span. Such changes could lead to pathological conditions including cancer. For example, microgravity is observed to suppress the activity of immune cells, which itself increases the risk of cancer development. It is little known how the microgravity affects cellular and molecular events that determine physiological and biological responses. There is also a possibility of changes in epigenetic signatures during microgravity exposure which remains unexplored. Herein, we have reviewed the effect of microgravity on relevant molecular and biological processes, and how it could influence the course of cancer development. In this regard, we have also highlighted the areas of research that require more attention to bridge the gap of understanding for such biological processes. PMID:24720362

  10. The relapses of cancerous growths of anal canal

    International Nuclear Information System (INIS)

    In this chapter of book authors give information about general comprehensions of the relapses of anal canal cancerous growths, the classification of the relapses of anal canal cancerous growths, frequency of the relapses of anal canal cancerous growths, the diagnostics of the relapses of anal canal cancerous growths and prophylaxis and treatment of relapses

  11. The Influence of Education on Economic Growth

    Directory of Open Access Journals (Sweden)

    ŞTEFAN CRISTIAN CIUCU

    2014-05-01

    Full Text Available In transition countries affected by uncertainty, the educational system usually suffers from lack of funds from the government and it is affected by various reforms. It is important to see how education influences economic growth and how this growth can be improved by investing in education. In this article, after a literature and econometric models review, the influence of primary, secondary and tertiary education over the GDP growth will be analyzed for Bulgaria, Czech Republic and the Netherlands, using regressions models, with the aid of computer software tool EViews. The models will be tested in order to obtain a good and reliable model.

  12. Ormeloxifene efficiently inhibits ovarian cancer growth

    Science.gov (United States)

    Maher, Diane M.; Khan, Sheema; Nordquist, Jordan; Ebeling, Mara C.; Bauer, Nichole A.; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C.; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer. PMID:25306892

  13. Epidermal Growth Factor Receptor in Pancreatic Cancer

    International Nuclear Information System (INIS)

    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

  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. Pumpkin Fruit Influence on Calves’ Growth

    OpenAIRE

    A. SHIMKUS; A. SHIMKIENE; G. STANYTE

    2014-01-01

    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, dige...

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

    Science.gov (United States)

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

    2011-11-01

    Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes. PMID:22043817

  17. Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis

    Directory of Open Access Journals (Sweden)

    Rajesha Rupaimoole

    2015-12-01

    Full Text Available Long noncoding RNAs (lncRNAs significantly influence the development and regulation of genome expression in cells. Here, we demonstrate the role of lncRNA ceruloplasmin (NRCP in cancer metabolism and elucidate functional effects leading to increased tumor progression. NRCP was highly upregulated in ovarian tumors, and knockdown of NRCP resulted in significantly increased apoptosis, decreased cell proliferation, and decreased glycolysis compared with control cancer cells. In an orthotopic mouse model of ovarian cancer, siNRCP delivered via a liposomal carrier significantly reduced tumor growth compared with control treatment. We identified NRCP as an intermediate binding partner between STAT1 and RNA polymerase II, leading to increased expression of downstream target genes such as glucose-6-phosphate isomerase. Collectively, we report a previously unrecognized role of the lncRNA NRCP in modulating cancer metabolism. As demonstrated, DOPC nanoparticle-incorporated siRNA-mediated silencing of this lncRNA in vivo provides therapeutic avenue toward modulating lncRNAs in cancer.

  18. Nicotinic acetylcholine receptors mediate lung cancer growth

    Directory of Open Access Journals (Sweden)

    PaulDGardner

    2013-09-01

    Full Text Available Ion channels modulate ion flux across cell membranes, activate signal transduction pathways, and influence cellular transport – vital biological functions that are inexorably linked to cellular processes that go awry during carcinogenesis. Indeed, deregulation of ion channel function has been implicated in cancer-related phenomena such as unrestrained cell proliferation and apoptotic evasion. As the prototype for ligand-gated ion channels, nicotinic acetylcholine receptors (nAChRs have been extensively studied in the context of neuronal cells but accumulating evidence also indicate a role for nAChRs in carcinogenesis. Recently, variants in the nAChR genes CHRNA3, CHRNA5, and CHRNB4 have been implicated in nicotine dependence and lung cancer susceptibility. Here, we silenced the expression of these three genes to investigate their function in lung cancer. We show that these genes are necessary for the viability of small cell lung carcinomas (SCLC, the most aggressive type of lung cancer. Furthermore, we show that nicotine promotes SCLC cell viability whereas an α3β4-selective antagonist, α-conotoxin AuIB, inhibits it. Our findings posit a mechanism whereby signaling via α3/α5/β4-containing nAChRs promotes lung carcinogenesis.

  19. 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...

  20. Epidermal growth factor receptor targeted molecularly therapies of cancers

    International Nuclear Information System (INIS)

    Epidermal growth factor receptor (EGFR) has been known to be a significant factor in the development and growth of many types of cancers. It is now accepted that the EGFR signal transduction net work plays an important role in multiple tumorigenic processes, contributing to cancer cell proliferation, angiogenesis, and metastasis, as well as protection from apoptosis. Recently, EGFR monoclonal antibodies (McAb) and epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors have been validated as new treatment approach for those EGFR-positive cancers and have shown activity aginst advanced, chemofractory cancers in clinical trials. This article focuses on three EGFR targeted molecularly therapies of cancers. (authors)

  1. Intergenerational influences on child growth and undernutrition.

    Science.gov (United States)

    Martorell, Reynaldo; Zongrone, Amanda

    2012-07-01

    coverage of programmes that can be implemented and modest impact should be expected instead. The Lancet series on Maternal and Child Undernutrition estimated that implementation to scale of proven interventions in high burden countries would reduce stunting by one-third; this is perhaps a realistic upper bound for impact for high quality programmes, unless accompanied by sweeping improvements in social services and marked reductions in poverty. Finally, because so much can be achieved in a single generation, intergenerational influences are unlikely to be an important explanation for lack of programme impact aimed at the window of the first 1000 days. Failure to prevent linear growth failure in developing countries has serious consequences for short- and long-term health as well as for the formation of human capital. The nutrition transition has created a double burden by adding obesity and related chronic diseases to the public health agenda of countries still struggling with the 'old' problems of maternal and child undernutrition. The challenge ahead is to increase efforts to prevent linear growth failure while keeping child overweight at bay. PMID:22742617

  2. Influences of androgen on the growth of human prostate cancer PC-3M model in nude mice and the changes of the androgen receptor levels and protein kinase C activity

    International Nuclear Information System (INIS)

    Nude mice bearing transplanted human prostate cancer cell line PC-3M were treated with male sex hormone. Results demonstrated that low dose of testosterone propionate (TP) (50 mg/kg wt.) stimulated the tumor growth, and the androgen receptor (AR) levels and protein kinase C (PKC) activity were elevated in the tumor tissue. On the contrary higher dose of TP (400 mg/kg wt.) inhibited the tumor growth, and the AR level and PKC activity in tumor tissue were reduced significantly. These results showed that TP has a biphasic effect on the growth of human prostate cancer PC-3M cell line. The mechanism of the biphasic effect and its relationship between AR and PKC levels are also discussed

  3. 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. |

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Polymorphisms in the Insulin-Like Growth Factor Axis Are Associated with Gastrointestinal Cancer

    OpenAIRE

    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 receptor (IGFR-I) were associated with several stages of cancer. Here, the prevalence of the single nucleotide polymorphisms (SNPs) rs6214 in the IGF type I (IGF-I) gene and rs6898743 in the growth hormo...

  6. Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Michael Reiter; Igor Tsaur; Georg Bartsch; Axel Haferkamp; 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 regu...

  7. Expressions of Generativity and Posttraumatic Growth in Adult Cancer Survivors

    Science.gov (United States)

    Bellizzi, Keith M.

    2004-01-01

    Much of the psycho-oncology research that has been conducted to date has focused on understanding the negative psychological and psychosocial sequelae of cancer. However, a growing body of evidence suggests that many cancer survivors report psychological growth following a diagnosis of cancer. Further, there are few studies that examine the…

  8. Physicians’ influence on breast cancer patient compliance

    Science.gov (United States)

    Kostev, Karel; Waehlert, Lilia; Jockwig, Achim; Jockwig, Barbara; Hadji, Peyman

    2014-01-01

    In recent years there have been major advances in the treatment of breast cancer. However, taking the prescribed medication for a sufficient period of time is crucial to the success of any therapy. Thus far, no database-based studies have been published in German-speaking countries empirically examining the influence of the physician on the compliance of patients. The aim of this study is to investigate, quantify, and critically discuss the effect treating physicians have on the compliance of their breast cancer patients. Patients with a confirmed breast cancer diagnosis who started therapy (tamoxifen or aromatase inhibitors) between January 2001 and December 2011 were selected from the representative IMS Disease Analyzer database and analyzed with regard to their compliance. Practices were grouped into two categories concerning the compliance of all treated patients. A regression model showed that a breast cancer patient who is treated in a practice with a trend toward poor compliance has a nearly 60% higher risk for treatment discontinuation than would be the case in a practice with good compliance. It shows how important it is to motivate physicians to strive toward good compliance rates. PMID:24454275

  9. 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

  10. Proepithelin is an autocrine growth factor for bladder cancer

    OpenAIRE

    Lovat, Francesca; Bitto, Alessandro; Xu, Shi-Qiong; Fassan, Matteo; Goldoni, Silvia; Metalli, David; Wubah, Vera; McCue, Peter; Serrero, Ginette; Gomella, Leonard G.; Baffa, Raffaele; Iozzo, Renato V.; Morrione, Andrea

    2009-01-01

    The growth factor proepithelin functions as an important regulator of proliferation and motility. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian and renal cancer, as well as glioblastomas. Using recombinant proepithelin on 5637 transitional cell carcinoma-derived cells, we have shown previously that proepithelin plays a critical role in bladder cancer by promoting motility of bladder cancer cells. In this study, we used the ONCO...

  11. Adversarial Growth in Telephone Counsellors: Psychological and Environmental Influences

    Science.gov (United States)

    O'Sullivan, Julian; Whelan, Thomas A.

    2011-01-01

    The aims of this study were to investigate the level of adversarial growth among telephone counsellors, and to examine the influence of psychological and environmental factors on growth. In particular, the effect of compassion fatigue, empathy, environmental support and calls per shift on posttraumatic growth was assessed. Sixty-four telephone…

  12. Temperature influence on phytoplankton community growth rates

    Science.gov (United States)

    Sherman, Elliot; Moore, J. Keith; Primeau, Francois; Tanouye, David

    2016-04-01

    A large database of field estimates of phytoplankton community growth rates in natural populations was compiled and analyzed to determine the apparent temperature effect on phytoplankton community growth rate. We conducted an ordinary least squares regression to optimize the parameters in two commonly used growth-temperature relations (Arrhenius and Q10 models). Both equations fit the observational data equally with the optimized parameter values. The optimum apparent Q10 value was 1.47 ± 0.08 (95% confidence interval, CI). Microzooplankton grazing rates closely matched the temperature trends for phytoplankton growth. This likely reflects a dynamic adjustment of biomass and grazing rates by the microzooplankton to match their available food source, illustrating tight coupling of phytoplankton growth and microzooplankton grazing rates. The field-measured temperature effect and growth rates were compared with estimates from the satellite Carbon-based Productivity Model (CbPM) and three Earth System Models (ESMs), with model output extracted at the same month and sampling locations as the observations. The optimized, apparent Q10 value calculated for the CbPM was 1.51, with overestimation of growth rates. The apparent Q10 value in the Community Earth System Model (V1.0) was 1.65, with modest underestimation of growth rates. The GFDL-ESM2M and GFDL-ESM2G models produced apparent Q10 values of 1.52 and 1.39, respectively. Models with an apparent Q10 that is significantly greater than ~1.5 will overestimate the phytoplankton community growth response to the ongoing climate warming and will have spatial biases in estimated growth rates for the current era.

  13. Factors influencing the prognosis in bladder cancer

    International Nuclear Information System (INIS)

    In the categories T1, T2 and T3NxM0 bladder cancer, with a diameter not exceeding 5 cm, the treatment in the Rotterdam Radio-Therapy Institute consists of interstitial irradiation with needles containing radioactive material. The results of treatment and the role of additional external irradiation are discussed. Category T3NxM0 tumors with a diameter exceeding 5 cm are treated by external irradiation followed by cystectomy; the results are presented here. Factors influencing prognosis appeared to be the degree of differentiation, number of transurethral resections (TURs) prior to definitive treatment, intravenous pyelography (IVP), vascular invasion, T category after preoperative irradiation, and postsurgical histopathologically-assessed T category (pT)

  14. 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.

  15. Influence of substrate morphology on Pb growth

    International Nuclear Information System (INIS)

    The crystallographic structure and morphology of Pb layers in their early stage of growth on Si(3 3 5) surface are studied with Reflection High Electron Energy Diffraction (RHEED) and specific resistivity techniques. The vicinal Si(3 3 5), with different surface morphology controlled by the amount of predeposited Au, was used as a substrate. Changes in the substrate morphology, from disordered step distribution through a perfectly ordered Si(3 3 5) to a hill-and-valley structure consisting of wide (1 1 1) terraces and high Miller index facets, cause switching between one- and two-dimensional growth of the Pb structures

  16. The classification and staging of cancerous growths of the anal canal

    International Nuclear Information System (INIS)

    In this chapter authors give information about frequency of cancerous growths of the anal canal, general analysis of observations the classification and staging of cancerous growths of the anal canal, clinical-anatomy classification of cancerous growths of the anal canal and staging of cancerous growths of anal canal

  17. FH535 inhibited metastasis and growth of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Wu MY

    2015-07-01

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

  18. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2013-01-01

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

  20. 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.

  1. Relation of erythrocyte and iron indices to oral cancer growth

    International Nuclear Information System (INIS)

    Background and purpose: Anaemia is known to influence prognosis of head and neck cancer patients, but how anaemia and tumour growth influences each other is not clear. The present study investigates the relation of erythrocyte and iron indices of oral cancer patients to primary tumour size (Tsize), invasiveness and lymph node involvement. Materials and methods: The haemoglobin (Hb), erythrocyte count (RBC), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), Serum iron (SFe), transferrin iron-binding capacity (TIBC) and transferrin saturation (%Fe) were evaluated in 217 untreated patients with epidermoid cancer of the bucco-gingivo-palatine area. The association of erythrocyte and iron indices with sex, tumour size groups, invasion of adjacent structures and lymph node involvement, as well as the relation of SFe to Hb were analyzed. Results: Most of the patients were anaemic in terms of Hb (63%), RBC (43%) and PCV (48.4%) but almost all had normal or higher MCH (97.3%) and MCV (93.3%) though MCHC was less than normal in 70.7%. Normal or higher SFe was seen in nearly 70% and TIBC in 45% of patients. Hb, RBC and PCV were significantly lower in women, but there was no difference between men and women in the case of MCV, MCH and MCHC. Primary tumour size showed negative association with Hb, RBC and PCV but positive association with MCH (4 cm: 31. 7 pg; P=0.04) and MCHC (4 cm: 32.1; P=0.006). MCV, SFe, TIBC and %Fe did not show any relation to primary tumour size. None of the indices had any relation to invasion of adjacent structures or lymph node involvement. MCH, MCHC and MCV were not different in men and women but women had significantly lower Hb, RBC and PCV. The SFe showed poor correlation with Hb. Conclusions: The negative association of Hb, RBC and PCV with tumour size is most likely due to chronic RBC destruction, probably tumour induced, with the products of haemolysis

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

    Science.gov (United States)

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

    2013-08-01

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

  3. The multifaceted mechanism of Leptin signaling within tumor microenvironment in driving breast cancer growth and progression.

    Directory of Open Access Journals (Sweden)

    Sebastiano eAndò

    2014-11-01

    Full Text Available Adipokines represent likely candidates to mediate the increased breast cancer risk and the enhanced progression associated with obesity. Other contributors to obesity-related cancer progression are insulin/IGF-1 pathways and hormones. Among these, the adipokine leptin is the most intensively studied in both metabolism in general and in cancer due to the fact that leptin levels increase in proportion of fat mass. Leptin is primarily synthesized from adipocytes, but it is also produced by other cells including fibroblasts. In this latter case, it has been well demonstrated how cancer-associated fibroblasts express leptin receptor and secrete leptin which sustains a short autocrine loop and is able to target tumor epithelial cells enhancing breast cancer cell motility and invasiveness. In addition, it has been reported that leptin may induce breast cancer to undergo a transition from epithelial to spindle-like mesenchymal morphology, activating the signaling pathways devoted to the EMT. Thus, it emerges how leptin may play a crucial role in mediating malignant cell and tumor microenvironment interactions. Here, we present an overview of the role of leptin in breast cancer, covering the following topics: 1 leptin as an amplifier of estrogen signaling in tumor epithelial cells contributing to the promotion of carcinogenesis; 2 leptin as a crucial player in mediating tumor-stroma interaction and influencing EMT-linked mechanisms, that may sustain breast cancer growth and progression; 3 leptin and leptin receptor targeting as novel therapeutic strategies for breast cancer treatment.

  4. 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.

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

    International Nuclear Information System (INIS)

    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

  6. 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.

  7. 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.

  8. Factors Influencing Selection of Treatment for Colorectal Cancer Patients

    OpenAIRE

    Cavalli-Björkman, Nina

    2012-01-01

    In Sweden and elsewhere there is evidence of poorer cancer survival for patients of low socioeconomic status (SES), and in some settings differences in treatment by SES have been shown. The aim of this thesis was to explore factors which influence cancer treatment decisions, such as knowledge reaped from clinical trials, patient-related factors, and physician-related factors. In a register study of colorectal cancer, all stages, patients were stratified for SES-factors. Differences were seen ...

  9. 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......-malignant human lung tissue bank. RESULTS: miR-34c, miR-145, and miR-142-5p were repressed in transgenic lung cancers. Findings were confirmed by real-time and semiquantitative reverse transcription-PCR as well as in situ hybridization assays. Similar miRNA profiles occurred in human normal versus malignant lung...

  10. 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.

  11. 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 the NCAM-transfected cells. The fact that NCAM expression influences growth regulation attributes a pivotal role to this cell adhesion molecule during ontogenesis and tumor development....

  12. 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. PMID:25136960

  13. 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.

  14. Cancer-related trauma, stigma and growth: the 'lived' experience of head and neck cancer.

    Science.gov (United States)

    Threader, J; McCormack, L

    2016-01-01

    Head and neck cancer is associated with multiple layers of distress including stigma. Stigma attraction or devalued social identity is twofold: (1) it is a cancer associated with lifestyle risk factors and (2) treatment often results in confronting facial disfigurement. Subjective interpretations from nine head and neck cancer patients were analysed using Interpretative Phenomenological Analysis. An overarching superordinate theme--Distress, Stigma and Psychological Growth--encompassed four subordinate themes. Two themes captured the expressed trauma and terror as a result of diagnosis and treatment, and two the redefining of self despite stigma through meaning making. Distress was interpreted as a catalyst for awakening new life interpretations and combined with social support to facilitate two distinct pathways of growth: (1) psychological growth without support; (2) psychological and relational growth with support. Previously unfelt empathetic understanding and altruism for others with cancer emerged from the impact of stigma on 'self'. Acceptance allowed a new sense of identity that recognised cancer-related traumatic distress as integral to growth for these participants. The present study offers a unique insight into cancer-related trauma and stigma and the potential to redefine a more accepting, empathic and altruistic 'self' for psychological growth. Implications are discussed. PMID:25899673

  15. 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.

  16. STAMP alters the growth of transformed and ovarian cancer cells

    International Nuclear Information System (INIS)

    Steroid receptors play major roles in the development, differentiation, and homeostasis of normal and malignant tissue. STAMP is a novel coregulator that not only enhances the ability of p160 coactivator family members TIF2 and SRC-1 to increase gene induction by many of the classical steroid receptors but also modulates the potency (or EC50) of agonists and the partial agonist activity of antisteroids. These modulatory activities of STAMP are not limited to gene induction but are also observed for receptor-mediated gene repression. However, a physiological role for STAMP remains unclear. The growth rate of HEK293 cells stably transfected with STAMP plasmid and overexpressing STAMP protein is found to be decreased. We therefore asked whether different STAMP levels might also contribute to the abnormal growth rates of cancer cells. Panels of different stage human cancers were screened for altered levels of STAMP mRNA. Those cancers with the greatest apparent changes in STAMP mRNA were pursued in cultured cancer cell lines. Higher levels of STAMP are shown to have the physiologically relevant function of reducing the growth of HEK293 cells but, unexpectedly, in a steroid-independent manner. STAMP expression was examined in eight human cancer panels. More extensive studies of ovarian cancers suggested the presence of higher levels of STAMP mRNA. Lowering STAMP mRNA levels with siRNAs alters the proliferation of several ovarian cancer tissue culture lines in a cell line-specific manner. This cell line-specific effect of STAMP is not unique and is also seen for the conventional effects of STAMP on glucocorticoid receptor-regulated gene transactivation. This study indicates that a physiological function of STAMP in several settings is to modify cell growth rates in a manner that can be independent of steroid hormones. Studies with eleven tissue culture cell lines of ovarian cancer revealed a cell line-dependent effect of reduced STAMP mRNA on cell growth rates. This cell

  17. Alterations of the genes involved in the PI3K and estrogen-receptor pathways influence outcome in human epidermal growth factor receptor 2-positive and hormone receptor-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Chemotherapy with trastuzumab is widely used for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but a significant number of patients with the tumor fail to respond, or relapse. The mechanisms of recurrence and biomarkers that indicate the response to the chemotherapy and outcome are not fully investigated. Genomic alterations were analyzed using single-nucleotide polymorphism arrays in 46 HER2 immunohistochemistry (IHC) 3+ or 2+/fluorescent in situ hybridization (FISH)+ breast cancers that were treated with neoadjuvant chemotherapy with paclitaxel, cyclophosphamid, epirubicin, fluorouracil, and trastuzumab. Patients were classified into two groups based on presence or absence of alterations of 65 cancer-associated genes, and the two groups were further classified into four groups based on genomic HER2 copy numbers or hormone receptor status (HR+/−). Pathological complete response (pCR) and relapse-free survival (RFS) rates were compared between any two of the groups. The pCR rate was 54% in 37 patients, and the RFS rate at 3 years was 72% (95% CI, 0.55-0.89) in 42 patients. The analysis disclosed 8 tumors with nonamplified HER2 and 38 tumors with HER2 amplification, indicating the presence of discordance in tumors diagnosed using current HER2 testing. The 8 patients showed more difficulty in achieving pCR (P=0.019), more frequent relapse (P=0.018), and more frequent alterations of genes in the PI3K pathway (P=0.009) than the patients with HER2 amplification. The alterations of the PI3K and estrogen receptor (ER) pathway genes generally indicated worse RFS rates. The prognostic significance of the alterations was shown in patients with a HR+ tumor, but not in patients with a HR- tumor when divided. Alterations of the PI3K and ER pathway genes found in patients with a HR+ tumor with poor outcome suggested that crosstalk between the two pathways may be involved in resistance to the current chemotherapy with trastuzumab. We

  18. Posttraumatic growth in parents of childhood cancer survivors

    Czech Academy of Sciences Publication Activity Database

    Slezáčková, Alena

    Oslo: NPA, 2009. s. 327-327. [European Congress of Psychology /11./. 08.07-11.07.2009, Oslo] R&D Projects: GA ČR GA406/07/1384 Institutional research plan: CEZ:AV0Z70250504 Keywords : posttraumatic growth * parents * childhood cancer survivors Subject RIV: AN - Psychology

  19. Epidermal growth factor receptor in primary human lung cancer

    International Nuclear Information System (INIS)

    Cell membranes were prepared from 12 human lung cancers for the study of the expression of epidermal growth factor receptors (EGFR). EGFR concentration was estimated by ligand binding studies using 125I-radiolabeled EGF. The dissociation constants of the high affinity sites were identical, 1.48 nmol and 1.1 nmol in cancer and normal lung tissues, the EGFR contents were higher in lung cancer tissues (range: 2.25 to 19.39 pmol·g-1 membrane protein) than that in normal tissues from the same patients (range: 0.72 to 7.43 pmol·g-1 membrane protein). These results suggest that EGF and its receptor may play a role in the regulatory mechanisms in the control of lung cellular growth and tumor promotion

  20. Small Is Beautiful: Insulin-Like Growth Factors and Their Role in Growth, Development, and Cancer

    Science.gov (United States)

    Maki, Robert G.

    2010-01-01

    Insulin-like growth factors were discovered more than 50 years ago as mediators of growth hormone that effect growth and differentiation of bone and skeletal muscle. Interest of the role of insulin-like growth factors in cancer reached a peak in the 1990s, and then waned until the availability in the past 5 years of monoclonal antibodies and small molecules that block the insulin-like growth factor 1 receptor. In this article, we review the history of insulin-like growth factors and their role in growth, development, organism survival, and in cancer, both epithelial cancers and sarcomas. Recent developments regarding phase I to II clinical trials of such agents are discussed, as well as potential studies to consider in the future, given the lack of efficacy of one such monoclonal antibody in combination with cytotoxic chemotherapy in a first-line study in metastatic non–small-cell lung adenocarcinoma. Greater success with these agents clinically is expected when combining the agents with inhibitors of other cell signaling pathways in which cross-resistance has been observed. PMID:20975071

  1. Influence of forced convection on unidirectional growth of crystals

    International Nuclear Information System (INIS)

    Influence of forced convection on the growth rate of KDP crystal grown by unidirectional method has been investigated. The results were compared with the crystal grown under free convection conditions. To the best of our knowledge the effect of forced convection on unidirectional growth has been reported for the first time. An apparatus was designed and developed for growth of crystals by cooling under forced convection conditions. The growth rate achieved under forced convection was double to that under free convection conditions. Transmittance in the visible region for the crystals grown under the two types of convection regimes was ∼90%. Birefringence and Mach-Zehnder interferometry shows good refractive index homogeneity of the grown crystals.

  2. Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model

    OpenAIRE

    Hung, Ming-Szu; Xu, Zhidong; Chen, Yu; Smith, Emmanuel; Mao, Jian-Hua; Hsieh, David; Lin, Yu-Ching; Yang, Cheng-Ta; Jablons, David M.; You, Liang

    2013-01-01

    Casein kinase II (CK2) inhibitors suppress cancer cell growth. In this study, we examined the inhibitory effects of a novel CK2 inhibitor, hematein, on tumor growth in a murine xenograft model. We found that in lung cancer cells, hematein inhibited cancer cell growth, Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increased apoptosis. In a murine xenograft model of lung cancer, hematein inhibited tumor growth without significant toxicity to the mice tested. Molecular docking showed t...

  3. Influence of growth retardant on growth and development of Euphorbia pulcherrima Willd. ex Klotzsch

    OpenAIRE

    Anna Pobudkiewicz

    2014-01-01

    This study was undertaken to evaluate the influence of single foliar flurprimidol treatment on morphology and transpiration of ‘Roman’ and ‘Freedom Red’ poinsettias. The growth retardant flurprimidol (Topflor 015 SL) was applied once as a foliar spray at concentrations of 5, 10 or 15 mg × dm-3 when lateral shoots were about 5 cm in length. Single foliar flurprimidol treatment was sufficient to inhibit stem elongation of both poinsettia cultivars. The degree of growth inhibition depended on cu...

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

    Science.gov (United States)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels; Løkkegaard, Ellen; Kjær, Susanne Krüger

    2016-05-01

    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 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 (0.83, 0.72-0.96 and 0.89, 0.80-1.00), compared to never users. Transdermal estrogen-only therapy implied more protection than oral administration, while no significant influence was found of regimen, progestin type, nor of tibolone. The benefit of HT was stronger for long-term hormone users; and hormone users were at lower risk of advanced stage of colorectal cancer, which seems supportive for a causal association between hormone therapy and colorectal cancer. PMID:26758900

  5. Role of nucleostemin in growth regulation of gastric cancer,liver cancer and other malignancies

    Institute of Scientific and Technical Information of China (English)

    Si-Jin Liu; Zi-Wei Cai; Ya-Jun Liu; Mei-Yu Dong; Li-Qiu Sun; Guo-Fa Hu; Ying-Yun Wei; Wei-De Lao

    2004-01-01

    AIM: To examine the role of nucleostemin in the growth regulation of gastric cancer, liver cancer and other cancers.METHODS: RT-PCR was used to clone the fragment ofnucleostemin cDNA from HEK 293 cells. Eighteen kinds of malignant tumor tissues including gastric adenocarcinoma and liver cancer tissues, 3 kinds of benign tumor tissues, 3kinds of benign hyperplastic tissues and normal tissues were employed to examine nucleostemin gene expression by RT-PCR, Slot blot, Northern blot andin situ hybridization.RESULTS: We successfully cloned a 570 bp fragment of nucleostemin-cDNA from HEK-293 cells. All detected malignant tumor tissues, benign tumor tissues, and benign hyperplastic tissues had high levels of nucleostemin expression. Nucleostemin was also expressed in human placenta tissue at a high level. In terminally differentiated normal human adult kidney and mammary gland tissues,no nucleostemin expression could be detected.CONCLUSION: Nucleostemin can help regulate the proliferation of both cancer cells and stem cells. It might play an important role in the growth regulation of gastric cancer, liver cancer and other cancers.

  6. Influence of nutrition and various substrates on spruce seedling growth

    Directory of Open Access Journals (Sweden)

    Đukić Matilda

    2004-01-01

    Full Text Available The results of the influence of main macronutrients (N, P, and K on growth and development of spruce (Picea abies L. Karst one-year old seedlings are presented. They were grown in containers, in nursery conditions, on four different substrates. There is a good influence on biogenous element contents, height, root collar diameter, needle length and mass, root mass as well as physiological vitality of spruce seedlings. It was observed that the effect of nutrition depends also on the type of substrate.

  7. Triterpenes in cancer: significance and their influence.

    Science.gov (United States)

    Gill, Balraj Singh; Kumar, Sanjeev; Navgeet

    2016-09-01

    Natural products are enriched with numerous compounds with a broad spectrum of therapeutics indication suggesting the role of functional moieties as a core pharmacophore. This review highlights the role of triterpene in targeting signaling pathways in cancer. Advancement in cellular, biochemical, experimental, and computational approaches provides new insights into various pathways in cancer. In signaling network, triterpenes primarily target membrane receptors which control and modulates expression level of the biological responses. Triterpenes are immunomodulatory targeting nuclear factor kappa B, toll-like receptors, signal transducer and activator of transcription 3, and PI3K/Akt/mTOR. Triterpenes isolated from plants and fungus mainly focus on the process of apoptosis while other signaling areas in the cancer are still shrouded. Some of the triterpenes have already passed the clinical trial, whereas many more have been proven to yield effective results. This review would help the researchers to study the role of triterpenes in cancer, thus, helping them to discover and design efficacious therapeutics agents. PMID:27344437

  8. Analysis of Pancreatic Cancer Microenvironment: Role of Macrophage Infiltrates and Growth Factors Expression

    Directory of Open Access Journals (Sweden)

    Katarzyna Gardian, Sława Janczewska, Waldemar L. Olszewski, Marek Durlik

    2012-01-01

    Full Text Available Background: Research over the last twenty years has yielded much insight into pancreatic cancer biology, but it has neither improved diagnostics methods nor the way of treatment. The question remains as to what the critical deciding factor is in making pancreatic cancer such an aggressive disease.Methods: Pancreatic tumor tissue came from 36 patients. To assess lymphatic vessels color lymphangiography and immunohistochemistry were used. Activity of matrix metalloproteinases was studied with gel and in situ zymography. Expression of growth factors and infiltrating immune cells were investigated using immunohistochemistry.Results: Our study revealed that the structures that correspond to lymphatic vessels were not observed in tumor center but only at the edge of the tumor. All studied growth factors were present in tumor tissue. We found that the difference in expression between G2 and G3 stage was statistically relevant in cases of c-Met receptor. Inflammatory cells were present around neoplastic glands and also strongly around nerves infiltrated by cancer cells. The number of infiltrating macrophages in tumor tissue was significantly higher in group with metastases to lymph nodes.Conclusion: We showed two factors that influence pancreatic cancer progression and invasion: c-Met receptors and macrophages infiltrating tumor tissue. Based on our analysis, this indicates that epithelial-mesenchymal transition might be crucial in the progression of pancreatic cancer.

  9. 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.

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

    DEFF Research Database (Denmark)

    Morch, Lina Steinrud; Lidegaard, Ojvind; Keiding, Niels;

    2016-01-01

    .83, 0.72-0.96 and 0.89, 0.80-1.00), compared to never users. Transdermal estrogen-only therapy implied more protection than oral administration, while no significant influence was found of regimen, progestin type, nor of tibolone. The benefit of HT was stronger for long-term hormone users; and hormone......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...

  11. Posttraumatic growth in parents of childhood cancer patients

    Czech Academy of Sciences Publication Activity Database

    Slezáčková, Alena; Blatný, Marek; Jelínek, Martin; Vlčková, I.; Kepák, T.

    Copenhagen: Danish School of Education, Aarhus University, 2010. s. 148-148. [5th European Conference on Positive Psychology. 23.06.2010-26.06.2010, Copenhagen] R&D Projects: GA ČR GA406/09/1255 Institutional research plan: CEZ:AV0Z70250504 Keywords : posttraumatic growth * childhood cancer * positive psychology Subject RIV: AN - Psychology http://www.ecpp2010.dk/media/ECPP_-_Book_of_Abstracts_-_24_06_2010.pdf

  12. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes

    OpenAIRE

    Geetanjali Kharmate; Elham Hosseini-Beheshti; Josselin Caradec; Mei Yieng Chin; Tomlinson Guns, Emma S.

    2016-01-01

    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 ...

  13. 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. PMID:26489631

  14. 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.

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

    OpenAIRE

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

    2015-01-01

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

  16. The effects of radiotherapy on the hormone receptor concentration and tumor growth in xenotransplanted human breast cancer

    International Nuclear Information System (INIS)

    The influence of radiotherapy on tumor growth and hormone receptor concentration (estrogen-, progesteronreceptor) in xenotransplanted human breast cancer is observed. Tumor growth significantly is delayed under therapy during the first 35 days after radiation. Renewed growth follows after that time. After the first days of treatment the ER and PR concentration decreases considerably and finally reaches 40% respectively 30% of the pretreatment level for a period of approximately 35 days after the end of radiotherapy. In general radiation therapy seems to affect the PR stronger than the ER. After this period ER and PR levels increase again with the regrowing tumor. The results point out that radiotherapy reduces the concentration of ER and PR in human breast cancer. Therefore the assay of steroid receptors in human breast cancer after radiation therapy is useful in predicting hormone dependency and prognosis only when receptor concentrations are positive. (orig.)

  17. [Influences and psychological structures in breast cancer].

    Science.gov (United States)

    Bucher, R; Rodovalho, J C; Ferreira, T C

    1986-12-01

    A sample of 16 patients with malignant breast tumors were examined by means of an interview, a questionnaire, and the Szondi Test together with a comparison group of 56 patients with benign breast tumors. The patients were divided into two age groups, those below and above 40 years of age. In this way studies done in other countries to investigate the personality structure of cancer patients were replicated. Emphasis was given to the following issues: self-destructive and/or masochistic tendencies, attitudes of depressive resignation, and conflicts with respect to femininity and motherhood. The results showed several significant differences by which benign tumor patients can be better characterized. These patients presented symptoms, experiences and structures of the neurotic type. The cancer patients presented structures closer to the psychosomatic type, with rigid negation of conflicts (in relation to sex, identification, violence and aggression), and with an unreal insertion in the world. Their somatizations are not conversive; they are interpreted as effects of the destructive and violent tendencies which, without release for the lack of adequate contacts with objects, are directed toward themselves. However, this cannot properly be called a masochistic structure because the destructive tendencies do not have a sexual origin, rather they are part of a vehement negation of others and of life itself, in the sense of a primary death drive. It is impossible to tell, however, to what point these characteristics are already the effects of the breast problems, or whether they have more causal relevance as certain previous personal experiences indicate. PMID:3591399

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Jennie Ong

    Full Text Available 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 receptor (IGFR-I were associated with several stages of cancer. Here, the prevalence of the single nucleotide polymorphisms (SNPs rs6214 in the IGF type I (IGF-I gene and rs6898743 in the growth hormone receptor (GHR gene in patients with GI cancer and controls was studied. MATERIALS & METHODS: In this Dutch case-control study, DNA isolated from blood of 1,457 GI cancer patients; 438 patients with head and neck cancer (HNC, 475 with esophageal cancer (EC and 544 with colorectal cancer (CRC and 1,457 matched controls, was used to determine the rs6214 and rs6898743 genotypes by polymerase chain reaction. The association between these SNPs and GI cancer, HNC, esophageal adenocarcinoma (EAC, esophageal squamous-cell carcinoma (ESCC and proximal or distal CRC was studied. Odds ratios (ORs with 95% confidence interval (95% CI were calculated via unconditional logistic regression. RESULTS: Overall for GI cancer, the ORs for SNPs rs6214 and rs6898743 were approximately 1.0 (p-value>0.05, using the most common genotypes GG as reference. An OR of 1.54 (95% CI, 1.05-2.27 was found for EC for genotype AA of rs6214. The ORs for EAC were 1.45 (95% CI, 1.04-2.01 and 1.71 (95% CI, 1.10-2.68, for genotypes GA and AA, respectively. Genotype GC of rs6898743 showed an OR of 0.47 (95% CI, 0.26-0.86 for ESCC. CONCLUSION: The A allele of SNP rs6214 in the IGF-I gene was associated with EAC, and with HNC in women. The GC genotype of rs6898743 in the GHR gene was negatively associated with ESCC.

  1. Influence of semi-volatile species on particle hygroscopic growth

    Science.gov (United States)

    Villani, Paolo; Sellegri, Karine; Monier, Marie; Laj, Paolo

    2013-11-01

    In this study, we use a Tandem Differential Mobility Analyser (TDMA) system combining particle volatilization and humidification conditioning (VH-TDMA) to test the effect of the gentle volatilization of a small fraction of the atmospheric particles on the particle hygroscopic growth in several environments (urban to remote). We first give an overview of the Hygroscopic Growth Factors (HGF) in these various environments, showing that in most of them, aerosol particles are externally mixed. We then show that the particle hygroscopicity can either be increased or decreased after thermal conditioning of the particle at moderate temperatures (50-110 °C). The hygroscopic growth factor changes induced by volatilization indicate that some volatile compounds, although present at low concentrations, can significantly influence the hygroscopic growth of particles in a way that can most of time be theoretically explained if simplified assumptions are used. However, simplified assumptions occasionally fail over several hours to explain hygroscopic changes, kinetic/surface effects observed at remote environments are suspected to be important.

  2. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Makiko; Kataoka, Hiroaki, E-mail: mejina@med.miyazaki-u.ac.jp [Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2014-09-29

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.

  3. Epidermal growth factor receptor inhibition in lung cancer: status 2012.

    Science.gov (United States)

    Hirsch, Fred R; Jänne, Pasi A; Eberhardt, Wilfried E; Cappuzzo, Federico; Thatcher, Nick; Pirker, Robert; Choy, Hak; Kim, Edward S; Paz-Ares, Luis; Gandara, David R; Wu, Yi-Long; Ahn, Myung-Ju; Mitsudomi, Tetsuya; Shepherd, Frances A; Mok, Tony S

    2013-03-01

    Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing. PMID:23370315

  4. CSR1 suppresses tumor growth and metastasis of prostate cancer.

    Science.gov (United States)

    Yu, Guoying; Tseng, George C; Yu, Yan Ping; Gavel, Tim; Nelson, Joel; Wells, Alan; Michalopoulos, George; Kokkinakis, Demetrius; Luo, Jian-Hua

    2006-02-01

    Prostate cancer is frequent among men over 45 years of age, but it generally only becomes lethal with metastasis. In this study, we identified a gene called cellular stress response 1 (CSR1) that was frequently down-regulated and methylated in prostate cancer samples. Survival analysis indicated that methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1 protein expression, was associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in prostate cancer cell lines DU145 and PC3 resulted in a two- to threefold decrease in colony formation and a 10-fold reduction in anchorage-independent growth. PC3 cells stably expressing CSR1 had an average threefold decrease in their ability to invade in vitro. Expression of CSR1 in PC3 cell xenografts produced a dramatic reduction (>8-fold) in tumor size, rate of invasion (0 versus 31%), and mortality (13 versus 100%). The present findings suggest that CSR1 is a potent tumor sup-pressor gene. PMID:16436673

  5. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    International Nuclear Information System (INIS)

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases

  6. Meloxicam inhibits the growth of colorectal cancer cells.

    Science.gov (United States)

    Goldman, A P; Williams, C S; Sheng, H; Lamps, L W; Williams, V P; Pairet, M; Morrow, J D; DuBois, R N

    1998-12-01

    Cyclooxygenase-2 has been reported to play an important role in colorectal carcinogenesis. The effects of meloxicam (a COX-2 inhibitor) on the growth of two colon cancer cell lines that express COX-2 (HCA-7 and Moser-S) and a COX-2 negative cell line (HCT-116) were evaluated. The growth rate of these cells was measured following treatment with meloxicam. HCA-7 and Moser-S colony size were significantly reduced following treatment with meloxicam; however, there was no significant change in HCT-116 colony size with treatment. In vivo studies were performed to evaluate the effect of meloxicam on the growth of HCA-7 cells when xenografted into nude mice. We observed a 51% reduction in tumor size after 4 weeks of treatment. Analysis of COX-1 and COX-2 protein levels in HCA-7 tumor lysates revealed a slight decrease in COX-2 expression levels in tumors taken from mice treated with meloxicam and no detectable COX-1 expression. Here we report that meloxicam significantly inhibited HCA-7 colony and tumor growth but had no effect on the growth of the COX-2 negative HCT-116 cells. PMID:9886578

  7. HMGCR is up-regulated in gastric cancer and promotes the growth and migration of the cancer cells.

    Science.gov (United States)

    Chushi, Li; Wei, Wu; Kangkang, Xie; Yongzeng, Feng; Ning, Xie; Xiaolei, Chen

    2016-08-01

    Alteration of metabolic profile is one of the hallmarks of cancer cells. Statin, the inhibitors for synthesis of cholesterol, has shown anti-cancer effects on the gastric cancer cells. However, the functions of its target, HMGCR, in the progression of gastric cancer remain unknown. In the present study, we investigated the expression profile and the biological functions of HMGCR in gastric cancer. It was found that the expression of HMGCR was increased in gastric cancer tissues. Over-expression of HMGCR promoted the growth and migration of gastric cancer cells, while knocking down the expression of HMGCR inhibited the growth, migration and tumorigenesis of gastric cancer cells. In the further molecular mechanism study, HMGCR was shown to activate Hedgehog/Gli1 signaling and promoted the expression of Gli1 target genes. Taken together, this study demonstrated the tumor-promoting effects of HMGCR in gastric cancer and suggested HMGCR as a promising therapeutic target. PMID:27085483

  8. Oncogenic herpesvirus HHV-8 promotes androgen-independent prostate cancer growth.

    Science.gov (United States)

    Mygatt, Justin G; Singhal, Adit; Sukumar, Gauthaman; Dalgard, Clifton L; Kaleeba, Johnan A R

    2013-09-15

    Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)-mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer. PMID:24005834

  9. СOLORECTAL CANCER AND INCULIN-LIKE GROWTH FACTORS

    Directory of Open Access Journals (Sweden)

    A. A. Nikolayev

    2015-02-01

    Full Text Available Insulin-like growth factors (IGF 1 and 2 and IGF binding proteins (IGFBP 1 and 3 levels were measured by ELISA techniques in blood serum of 74 primary colorectal cancer (СRC patients and 30 control practically healthy persons. Significant increase of IGF-1 level and decrease of IGFBP-3 level were demonstrated in patients’ serum as compared to control group. Sensitivity of IGF-1 as a prospective diagnostic СRС marker comprised 80 % with 75 % specificity using 140 ng/ml as cut-off level. Significant negative association was found be-tween both patients and donors’ age and serum IGF-1 levels, but in CRC patients it was much weaker than in control group. No associations were found between serum IGF 1 and 2 levels and main criteria of colorectal cancer progression.

  10. 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...... ovarian cancer and 321 women with borderline epithelial ovarian tumors was carried out to test the association between tag single-nucleotide polymorphisms (tSNPs) (n=58) in this pathway and risk of ovarian cancer. We found no association between variation in IGF1, IGFBP1 or IGFBP3 and risk of invasive...... disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at P<0.05 and followed-up one of the associated SNPs. We conducted genotyping in 3216 additional non-Hispanic white cases and 5382 additional controls and were able to independently replicate our initial...

  11. Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence.

    Science.gov (United States)

    Ruder, Elizabeth H; Dorgan, Joanne F; Kranz, Sibylle; Kris-Etherton, Penny M; Hartman, Terryl J

    2008-08-01

    The perinatal period, childhood, and adolescence are important intervals for breast cancer risk development. Endogenous estrogen exposure is thought to be highest in utero, and exposure to estrogens throughout life plays an important role in increasing breast cancer risk. Some evidence suggests that breast tissue is not fully differentiated until after the first full-term pregnancy; thus, breast tissue might be more susceptible to carcinogenic influences during early life and adolescence. Birth characteristics of the daughter, including gestational age, birth weight, and birth length are associated with maternal hormone levels during the index pregnancy, and birth size has been related to daughter's timing of puberty and adult breast cancer incidence. Furthermore, early life and adolescence are critical times for maturation of the hypothalamic pituitary ovarian axis, which regulates production of ovarian hormones including estrogen and progesterone. Childhood height, growth, diet, and body mass index (BMI) have also been associated with breast cancer risk later in life. Of the examined characteristics, we conclude that the available evidence is suggestive of a positive relationship of breast cancer risk with birth weight, birth length, and adolescent height, and an inverse relationship with gestational age and childhood BMI, although several inconsistencies exist in the literature. The best evidence for a relationship of adolescent diet and adult breast cancer risk is indirect, and the relationship of diet, weight status, and weight gain in childhood deserves further attention. The interaction of birth characteristics with established risk factors over the life course, such as age at menarche, in addition to gene-environment interactions, require more research. Further study is also needed to clarify the biologic mechanisms influencing the observed associations. PMID:18757260

  12. Reduced expression of epidermal growth factor receptor related protein in gastric cancer

    OpenAIRE

    Moon, W. S.; Tarnawski, A S; Chai, J.; Yang, J. T.; Majumdar, A.P.N.

    2005-01-01

    Objectives: The recently cloned epidermal growth factor receptor related protein (ERRP) has been proposed to be a negative regulator of the epidermal growth factor receptor (EGFR). Because of the causal involvement of EGFR and its ligands in gastric cancer growth, we investigated expression of ERRP and cell proliferation in human gastric cancer.

  13. Influence of crystallographic orientation on growth behavior of spherical voids

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-ming; LIU Wen-hui; TANG Jian-guo; YE Ling-ying

    2008-01-01

    The influence of crystallographic orientation on the void growth in FCC crystals was numerically simulated with 3D crystal plasticity finite element by using a 3D unit cell including a spherical void, and the rate-dependent crystal plasticity theory was implemented as a user material subroutine. The results of the simulations show that crystallographic orientation has significant influence on the growth behavior of the void. Different active slip systems of the regions around the void cause the discontinuity in lattice rotation around the void, and the corner-like region is formed. In the case of the void located at grain boundary, large heterogeneous deformation occurs between the two grains, and the equivalent plastic deformation along grain boundary near the void in the case of θ=45°(θ is the angle between grain boundary direction and X-axis) is larger than the others. Large difference of orientation factor of the two grains leads to large equivalent plastic deformation along grain boundary, and the unit cell is more likely to fail by intergranular fracture.

  14. 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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Price, Karina J. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6008 (Australia); Tsykin, Anna [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Giles, Keith M. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Sladic, Rosemary T. [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); Epis, Michael R. [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Ganss, Ruth [Laboratory for Cancer Medicine Angiogenesis Unit, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); Goodall, Gregory J. [Centre for Cancer Biology, SA Pathology, Adelaide, SA 5000 (Australia); School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005 (Australia); Department of Medicine, University of Adelaide, Adelaide, SA 5005 (Australia); Leedman, Peter J., E-mail: peter.leedman@waimr.uwa.edu.au [Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and University of Western Australia Centre for Medical Research, Perth, WA 6000 (Australia); School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6008 (Australia)

    2012-10-19

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

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

    International Nuclear Information System (INIS)

    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

  19. Influence of semi-volatile species on particle hygroscopic growth

    Directory of Open Access Journals (Sweden)

    P. Villani

    2009-01-01

    Full Text Available The hygroscopic properties of aerosol particles are often related to their content of soluble material, on the basis of the Kohler theory. Recent studies, however, seem to indicate that the role of aerosol particle semi-volatile fraction properties has been underestimated. In this study, we use a novel method based on a Tandem Differential Mobility Analyser (TDMA system combining particle volatilization and humidification conditioning (VH-TDMA to test the effect of the gentle volatilization of a small fraction of the atmospheric particles on the particle hygroscopic growth in several environments (urban to remote. Results show that the particle hygroscopic properties can either be enhanced or decreased after thermal conditioning of the particle at moderate temperatures (50 to 110°C. The hygroscopic growth factor changes induced by volatilization indicate that some volatile compounds, although present at low concentrations, drastically influence the hygroscopic growth of particles in the way that can not be predicted by the Kohler theory at equilibrium.

  20. 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.

  1. The influence of metformin in the etiology of selected cancers

    OpenAIRE

    Pawałowska, Monika; Markowska, Anna

    2012-01-01

    Obesity, hypertension and glucose tolerance disorders have become a growing concern in recent years. It is estimated that over 220 million people suffer from diabetes. It is a condition conducive to cardiovascular diseases, nephropathy, retinopathy and neuropathy but also to the development of many types of cancer. Insulin resistance and hyperinsulinemia lead to increased concentration of insulin-like growth factors, activation of IGF-R receptors, activation of PI3K and Ras-Raf pathways and r...

  2. 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.

  3. Growth, yield and seed production of okra as influenced by different growth regulators

    International Nuclear Information System (INIS)

    Plant growth regulators (PGRs) affect various aspects of plant physiology, mainly vegetative and reproductive traits including yield and seed production. Therefore, different concentrations (0, 50, 100 and 200 ppm) of gibberellic acid (GA3) and naphthalene acetic acid (NAA), alone or in different combinations were sprayed on okra plants at 2-true leaf stage, to ascertain their impact on plant growth, pod production, seed yield and seed quality. All variables regarding vegetative and reproductive growth were significantly influenced by different concentrations of the growth regulators except number of days taken to flowering. Growth regulators were less effective when applied individually as compared to their combined use; however, performance of plants treated with individual PGR was better than the untreated plants. The number of leaves plant/sup -1/ and plant height was higher in plants when sprayed with GA/sub 3/ and NAA at the rate 200+100 ppm as well as with GA/sub 3/ and NAA at the rate 200+200 ppm. The number of pods plant/sup -1/, pod length, pod fresh and dry weight, seed yield and seed quality (in terms of germination percentage and 1000-seed weight) was maximum in plants receiving foliar spray of both GA3 and NAA at the rate 200+200 ppm. These results signify the role of GA/sub 3/ and NAA in okra pod production for fresh consumption as well as for seed yield. (author)

  4. Transforming growth factor-β and breast cancer: Transforming growth factor-β/SMAD signaling defects and cancer

    International Nuclear Information System (INIS)

    Transforming growth factor-β (TGF-β) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-β are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative responses are mediated by a signaling system that includes two types of cell surface receptors and intracellular signal transducers, the SMAD proteins. Different molecular mechanisms can lead to loss of antiproliferative TGF-β responses in tumor cells, including mutations in components of the signaling system and inhibition of the SMAD signaling pathway by aberrant activities of various regulatory molecules. Some of these mechanisms will be discussed, with emphasis on their potential involvement in breast tumorigenesis

  5. Applied electric field enhances DRG neurite growth: influence of stimulation media, surface coating and growth supplements

    Science.gov (United States)

    Wood, Matthew D.; Willits, Rebecca Kuntz

    2009-08-01

    Electrical therapies have been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. This enhanced neural growth existed even after the electric field (EF) or stimulation was removed, but the factors that may influence the enhanced growth, such as stimulation media or surface coating, have not been fully investigated. This study characterized neurite outgrowth and branching under various conditions: EF magnitude and application time, ECM surface coating, medium during EF application and growth supplements. A uniform, low-magnitude EF (24 or 44 V m-1) was applied to dissociated chick embryo dorsal root ganglia seeded on collagen or laminin-coated surfaces. During the growth period, cells were either exposed to NGF or N2, and during stimulation cells were exposed to either unsupplemented media (Ca2+) or PBS (no Ca2+). Parallel controls for each experiment included cells exposed to the chamber with no stimulation and cells remaining outside the chamber. After brief electrical stimulation (10 min), neurite length significantly increased 24 h after application for all conditions studied. Of particular interest, increased stimulation time (10-100 min) further enhanced neurite length on laminin but not on collagen surfaces. Neurite branching was not affected by stimulation on any surface, and no preferential growth of neurites was noted after stimulation. Overall, the results of this report suggest that short-duration electric stimulation is sufficient to enhance neurite length under a variety of conditions. While further data are needed to fully elucidate a mechanism for this increased growth, these data suggest that one focus of those investigations should be the interaction between the growth cone and the substrata.

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

    DEFF Research Database (Denmark)

    Boysen, T.; Friborg, J.; Andersen, Allan; Poulsen, G.N.; Wohlfahrt, J.; Melbye, M.

    2008-01-01

    The Inuit cancer pattern is characterized by high frequencies of Epstein-Barr Virus (EBV)-associated carcinomas of the nasopharynx and salivary glands. The reasons are unknown, but genetic and environmental factors are believed to be involved. Using data from the well-defined Inuit population in...... [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...... 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...

  7. 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.

  8. Posttraumatic growth following cancer: links to quality of life.

    Science.gov (United States)

    Tomich, Patricia L; Helgeson, Vicki S

    2012-10-01

    This study examined the linkage of posttraumatic growth (PTG) to quality of life (QOL) among individuals newly diagnosed with cancer. Individuals (26 men, 36 women) reported PTG 3 months postdiagnosis (T1) and 3 months later (T2). Cross-sectional analyses revealed a linear association between PTG and QOL-more PTG was related to worse mental health at T1 (β = -.28). PTG, however, revealed a quadratic relationship with depressive symptoms at T1 and physical health at T2: Individuals with high or low levels of PTG had fewer depressive symptoms and better QOL than those with moderate levels. Longitudinal analyses revealed a linear association between PTG and QOL; more PTG at T1 predicted better physical health at T2. There were no longitudinal curvilinear associations. Although the linear links of PTG to QOL were contradictory within this study, both of the curvilinear relations, although not robust, confirm previous research. Further analyses differentiated low, medium, and high PTG groups in terms of perceiving cancer as stressful, intrusive thoughts, and coping strategies. Overall, relations of PTG to adjustment may be more complex and dynamic than previously assumed. Clinicians should consider the notion that more growth may sometimes, but not always, be better. PMID:23073975

  9. Influence of various growth parameters on fungal growth and volatile metabolite production by indoor molds.

    Science.gov (United States)

    Polizzi, Viviana; Adams, An; De Saeger, Sarah; Van Peteghem, Carlos; Moretti, Antonio; De Kimpe, Norbert

    2012-01-01

    A Penicillium polonicum, an Aspergillus ustus and a Periconia britannica strain were isolated from water-damaged environments and the production of microbial volatile organic compounds (MVOCs) was investigated by means of headspace solid-phase microextraction followed by GC-MS analysis. The most important MVOCs produced were 2-methylisoborneol, geosmin and daucane-type sesquiterpenes for P. polonicum, 1-octen-3-ol, 3-octanone, germacrene D, δ-cadinene and other sesquiterpenes for A. ustus and the volatile mycotoxin precursor aristolochene together with valencene, α-selinene and β-selinene for P. britannica. Different growth conditions (substrate, temperature, relative humidity) were selected, resembling indoor parameters, to investigate their influence on fungal metabolism in relation with the sick building syndrome and the results were compared with two other fungal strains previously analyzed under the same conditions. In general, the range of MVOCs and the emitted quantities were larger on malt extract agar than on wallpaper and plasterboard, but, overall, the main MVOC profile was conserved also on the two building materials tested. The influence of temperature and relative humidity on growth and metabolism is different for different fungal species, and two main patterns of behavior could be distinguished. Results show that, even at suboptimal conditions for growth, production of fungal volatiles can be significant. PMID:22169393

  10. 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.

  11. 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. PMID:27041240

  12. Influence of growth retardant on growth and development of Euphorbia pulcherrima Willd. ex Klotzsch

    Directory of Open Access Journals (Sweden)

    Anna Pobudkiewicz

    2014-09-01

    Full Text Available This study was undertaken to evaluate the influence of single foliar flurprimidol treatment on morphology and transpiration of ‘Roman’ and ‘Freedom Red’ poinsettias. The growth retardant flurprimidol (Topflor 015 SL was applied once as a foliar spray at concentrations of 5, 10 or 15 mg × dm-3 when lateral shoots were about 5 cm in length. Single foliar flurprimidol treatment was sufficient to inhibit stem elongation of both poinsettia cultivars. The degree of growth inhibition depended on cultivar and growth retardant concentration. As compared to the control, the shoots of flurprimidol treated ‘Roman’ and ‘Freedom Red’ plants were up to 44% and 37% shorter, respectively. The desirable plant heights for ‘Roman’ and ‘Freedom Red’ poinsettias were obtained with flurprimidol at concentrations of 5 and 10 mg × dm-3, respectively. The shoots of flurprimidol sprayed poinsettia were also more rigid and aligned relative to each other and thus the bracts on the plant were placed on the same level. The diameters of growth retardant treated poinsettias were up to 13% narrower. The leaf areas, petiole lengths, fresh and dry weights of ‘Roman’ and ‘Freedom Red’ poinsettias treated with flurprimidol were substantially smaller as compared to the control. The bract diameters of both poinsettia cultivars were only slightly affected by growth retardant application. Plants exposed to flurprimidol had also intensified green leaf pigmentation. There was almost no abscission of the oldest leaves in the low portions of growth retardant treated plants, compared to those of the control ones. Flurprimidol had no effect on transpiration rate per unit leaf area and stomatal conductance in both poinsettia cultivars. No phytotoxicity was observed in flurprimidol treated plants. Chemical name used: α-(1-methylethyl-α-[4-(trifluromethoxyphenyl]-5-pyrimidinemethanol (flurprimidol.

  13. 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.

  14. Influence of Rhizobacterial Inoculation on Growth of the Sweetpotato Cultivar

    Directory of Open Access Journals (Sweden)

    Y. Farzana

    2005-01-01

    Full Text Available Sweetpotato (Ipomoea batatas L. is the most important of local tuber crops in Malaysia. It is usually planted on marginal soils such as peat and sandy soils. Malaysian’s are consumed a lot of sweetpotatoes and its production requires high fertilizer input, which can lead to increased production cost and environment problems. The use of biofertilizer and bioenhancer such as N2 (nitrogen fixing bacteria and beneficial microorganism can reduce chemical fertilizer applications and consequently lower production cost. The pot experiment was conducted to determine the influence of rhizobacterial isolates on the response of sweetpotato plant growth. A total of five rhizobacterial isolates capable of producing indole-3-acetic acid (IAA were used. Four of the isolates were collected from sweetpotato rhizosphere and one isolate was imported. Cuttings of sweetpotato cultivars melaka and oren were planted in plastic pots containing alluvium soil. Cultures of the rhizobacterial isolates were inoculated at planting time, two and four weeks after planting. Plants were harvested 60 days after planting. The results showed that, three of isolates significantly increased the plant growth and the N, P, K, Ca and Mg uptake of sweetpotato cultivar.

  15. Cyclooxygenase-2 level and culture conditions influence NS398-induced apoptosis and caspase activation in lung cancer cells.

    Science.gov (United States)

    Chang, H C; Weng, C F

    2001-01-01

    Cyclooxygenases (COXs) catalyze the synthesis of prostaglandins (PGs) from arachidonic acid. Overexpression of COX-2 is frequently found in human cancers and is suggested to play an important role in tumorigenesis. Recent studies indicated that COX-2 inhibitors exert potent anti-cancer effects on a number of cancers. Interestingly, some COX-2 inhibitors potently induce apoptosis, while other COX-2 inhibitors primarily induce growth inhibition. Therefore, there is a variability in the effects that different COX-2 inhibitors have on cancer cells. In this study, we demonstrated that induction of apoptosis of high COX-2-expressing A549 lung cancer cells by a specific COX-2 inhibitor NS398 was observed in cells cultured under serum-free condition. However, this drug induced G1 growth arrest rather than apoptosis in A549 cells maintained in 10% serum medium. Conversely, low COX-2-expressing H226 lung cancer cells were resistant to NS398-induced apoptosis under both serum-free and serum-containing conditions. Moreover, our results showed that NS398-induced apoptosis is associated with activation of caspase-3, a cysteine protease that plays a crucial role in the execution phase of apoptosis. These results suggest that the cytotoxic effect of COX-2 inhibitors on cancer cells may be influenced by extracellular environments and the anti-cancer action of these inhibitors in vivo needs careful evaluation. Additionally, a correlation between the level of COX-2 expression and the extent of apoptosis induced by COX-2 inhibitors was found. PMID:11605058

  16. 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.

  17. Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3.

    Science.gov (United States)

    Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Shiva

    2011-06-01

    The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 -202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ(2)=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ(2)=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17-0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29-0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577 ng/ml, 3929 ng/ml and 3349 ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH. PMID:21536469

  18. Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy

    International Nuclear Information System (INIS)

    Purpose: To quantify the dose-time fractionation factors in preoperative radiation therapy for microscopic pelvic deposits of rectal cancer. This provides a biologic basis for understanding and improving the results of adjuvant therapies for this disease. Methods: The reduction in incidence of pelvic relapses as a function of radiation dose and overall treatment time was determined from the literature. The displacement of dose-response curves to higher doses reflects the growth during radiation treatment of subclinical pelvic deposits which are beyond the future surgical margins. Results: Dose-response curves are steep if the effect of overall duration of radiation therapy is accounted for. The time-related displacement of these steep dose-response curves is consistent with a median doubling time for malignant clonogenic cells of about 4 or 5 days, much faster than the growth rate of the average primary tumor at diagnosis. This rapid growth is evident within the first few days of irradiation, implying that the natural growth rate of these microscopic deposits if fast, and/or that an acceleration of growth follows initiation of radiation injury with a very short lag time. Conclusion: Subclinical pelvic deposits of rectal cancer grow rapidly during preoperative radiation therapy with an adverse influence on the rate of pelvic tumor control from protracting the duration of adjuvant treatment. Low doses only offer clinically relevant reduction in risk of pelvic relapses if the overall radiation treatment time is short. For a given overall treatment duration there is a relatively steep dose-response curve, predicting that significant improvements in tumor control are possible

  19. Influence of music on the growth of koi carp, Cyprinus carpio (Pisces: Cyprindae)

    OpenAIRE

    Vasantha, L.; Jeyakumar, A.; Pitchai, M.A.

    2003-01-01

    An experiment was carried out to investigate the influence of music on the growth of Koi Carp (Cyprinus carpio) by subjecting the fish to music. Weekly growth in weight was recorded and used to calculate the growth rate and specific growth rate. The difference in growth between the control and experiment groups of fishes was statistically tested for significance. It was observed that the growth of fish subjected to music was significantly higher.

  20. The Influence of Phorbol Ester on the Effect of Tamoxifen in Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To investigate the correlation between the activity of kinases in the growth factor signal transduction pathway and the development of resistance of breast cancer to tamoxifen, reporter gene regulated by the regulating fragment of CCD1 was transfected into the MCF-7 cells, and the influence of tamoxifen on the reporter gene expression was examined under different conditions of TPA treatment. Our results showed that the reporter gene expression was inhibited by tamoxifen and promoted by TPA. Furthermore, tamoxifen exerts an agonist effect on the reporter gene expression when the cells was treated by TPA previously for 12 h. It is concluded that TPA could induce estrogen-like effect of tamoxifen on estrogen receptor positive breast cancer cells and it may be one of the mechanisms responsible for the development of tamoxifen resistance.

  1. Carbohydrate-degrading bacteria closely associated with Tetraselmis indica: Influence on algal growth

    Digital Repository Service at National Institute of Oceanography (India)

    Arora, M.; Anil, A.C.; Delany, J.; Rajarajan, N.; Emami, K.; Mesbahi, E.

    to promote growth of the algae. These experiments revealed that microbes associated with the alga differentially influence algal growth dynamics. Bacterial presence on the cast-off cell wall products of the alga suggested the likely utilisation of algal cell...

  2. Assessing the influence of long-term urban growth scenarios on urban climate

    OpenAIRE

    Aguejdad, Rahim; Hidalgo, Julia; Doukari, Omar; Masson, Valéry; Houet, Thomas

    2012-01-01

    The objective of this paper is to assess the influence of future urban The objective of this paper is to assess the influence of future urban growth scenarios on future urban climate in Toulouse metropolitan area (France). Specifically, we aim to test the hypothesis that urban growth based on sprawling patterns has a significant influence on the Urban Heat Island (UHI) phenomena than compact patterns. Urban growth simulations, which are based on three contrasting scenarios built by 2100 with ...

  3. Growth dynamics of cancer cell colonies and their comparison with noncancerous cells

    Science.gov (United States)

    Huergo, M. A. C.; Pasquale, M. A.; González, P. H.; Bolzán, A. E.; Arvia, A. J.

    2012-01-01

    The two-dimensional (2D) growth dynamics of HeLa (cervix cancer) cell colonies was studied following both their growth front and the pattern morphology evolutions utilizing large population colonies exhibiting linearly and radially spreading fronts. In both cases, the colony profile fractal dimension was df=1.20±0.05 and the growth fronts displaced at the constant velocity 0.90±0.05 μm min-1. Colonies showed changes in both cell morphology and average size. As time increased, the formation of large cells at the colony front was observed. Accordingly, the heterogeneity of the colony increased and local driving forces that set in began to influence the dynamics of the colony front. The dynamic scaling analysis of rough colony fronts resulted in a roughness exponent α = 0.50±0.05, a growth exponent β = 0.32±0.04, and a dynamic exponent z=1.5±0.2. The validity of this set of scaling exponents extended from a lower cutoff lc≈60 μm upward, and the exponents agreed with those predicted by the standard Kardar-Parisi-Zhang continuous equation. HeLa data were compared with those previously reported for Vero cell colonies. The value of df and the Kardar-Parisi-Zhang-type 2D front growth dynamics were similar for colonies of both cell lines. This indicates that the cell colony growth dynamics is independent of the genetic background and the tumorigenic nature of the cells. However, one can distinguish some differences between both cell lines during the growth of colonies that may result from specific cooperative effects and the nature of each biosystem.

  4. Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients

    OpenAIRE

    Bacchi, Carlos E.; Heloísa Ciol; Queiroga, Eduardo M.; Benine, Lucimara C.; Silva, Luciana H.; Ojopi, Elida B.

    2012-01-01

    OBJECTIVE: Epidermal growth factor receptor is involved in the pathogenesis of non-small cell lung cancer and has recently emerged as an important target for molecular therapeutics. The KRAS oncogene also plays an important role in the development of lung cancer. The aim of this study was to evaluate the frequency of epidermal growth factor receptor and KRAS mutations in a population of Brazilian patients with non-small cell lung cancer. METHODS: A total of 207 specimens from Brazilian patien...

  5. Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress

    OpenAIRE

    Ketola, K; Hilvo, M; Hyötyläinen, T.; Vuoristo, A; Ruskeepää, A-L; Orešič, M; Kallioniemi, O; Iljin, K

    2012-01-01

    Background: We have shown that a sodium ionophore monensin inhibits prostate cancer cell growth. A structurally related compound to monensin, salinomycin, was recently identified as a putative cancer stem cell inhibitor. Methods: The growth inhibitory potential of salinomycin was studied in a panel of prostate cells. To get insights into the mechanism of action, a variety of assays such as gene expression and steroid profiling were performed in salinomycin-exposed prostate cancer cells. Resul...

  6. [Late endocrine and growth sequelae after cancer treatment in children].

    Science.gov (United States)

    Birkebaek, N H; Helgestad, J E

    1994-08-01

    Growth and endocrinological disturbances are possible late side-effects of cancer treatment in childhood. These side-effects can be treated, thus their discovery is important. The side-effects particularly appear in the years following treatment with irradiation and/or alkylating chemotherapy. After irradiation of the brain or the neck the function of the thyroid and the parathyroid glands should be tested every third month the first year, and later on annually. Two years after the end of treatment, the patient should be examined for growth hormone deficiency. This examination should be carried out annually. One should be alert to symptoms of pubertas praecox the years prior to puberty. At the age when puberty is expected and thereafter one should look for signs of secondary hypogonadism. Primary hypogonadism may follow radiotherapy below the diaphragm and/or treatment with alkylating chemotherapeutics; further, reduced fertility in men and early menopause in women may follow these treatments. The bone structure of the face and the teeth may be damaged by radiation and chemotherapy, so therefore yearly examination by a dentist with specialty in this subject is recommended. Surgery in order to improve function may be a possibility. PMID:7832924

  7. 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...

  8. Inhibition of Human Breast Cancer Xenograft Growth by Cruciferous Vegetable Constituent Benzyl Isothiocyanate

    OpenAIRE

    Warin, Renaud; Xiao, Dong; Arlotti, Julie A.; Bommareddy, Ajay; Singh, Shivendra V

    2010-01-01

    Benzyl isothiocyanate (BITC), a constituent of cruciferous vegetables such as gardencress, 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 c...

  9. Psychological well-being and posttraumatic growth in caregivers of cancer patients

    OpenAIRE

    Cormio, Claudia; Romito, Francesca; Viscanti, Giovanna; Turaccio, Marina; LORUSSO, VITO; Mattioli, Vittorio

    2014-01-01

    Introduction: Although 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...

  10. Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data

    OpenAIRE

    Jorge, S.E.D.C.; S.S. Kobayashi; Costa, D B

    2014-01-01

    Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGF...

  11. CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo

    OpenAIRE

    Lv, Zhi-Dong; Kong, Bin; Liu, Xiang-Ping; Dong, Qian; Niu, Hai-tao; Wang, Yong-Hua; Li, Fu-Nian; Wang, Hai-Bo

    2014-01-01

    Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the exp...

  12. Is Gompertzian or exponential kinetics a valid description of individual human cancer growth?

    Science.gov (United States)

    Retsky, M W; Swartzendruber, D E; Wardwell, R H; Bame, P D

    1990-10-01

    It is generally accepted that human cancers grow in an exponential or Gompertzian manner. This assumption is based on analysis of the growth of transplantable animal tumors and on averages of tumor growth in human populations. A computer model of breast cancer in individual patients has raised some doubts about this assumption. The computer model predicts an irregular pattern of tumor growth that incorporates plateaus or dormant periods separated by Gompertzian growth spurts. Since growth patterns involving plateaus are not predicted by conventionally accepted exponential or Gompertzian kinetics, sufficient documentation of their existence may be regarded as some evidence that the computer model is correct. The literature has been surveyed to identify growth patterns specifically predicted by the model. The literature contains clinical evidence from individual patients of this growth pattern in primary breast, large intestine and rectum, and pulmonary cancers and metastatic pulmonary cancer. Much data, including the only breast data, are not consistent with exponential or Gompertzian kinetics but are explainable by irregular growth kinetics. Exponential growth is valid for some tumors and for short times, but there are many papers citing significant deviations from that growth. Exponential growth may accurately describe averages of human tumor growth and growth of multipassaged experimental tumors, but it is not valid for all individual tumors. PMID:2259298

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

    OpenAIRE

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

    2014-01-01

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

  14. Influence of deformation on dolomite rim growth kinetics

    Science.gov (United States)

    Helpa, Vanessa; Rybacki, Erik; Grafulha Morales, Luiz Fernando; Dresen, Georg

    2015-04-01

    Using a gas-deformation apparatus stacks of oriented calcite (CaCO3) and magnesite (MgCO3) single crystals were deformed at T = 750° C and P = 400 MPa to examine the influence of stress and strain on magnesio-calcite and dolomite (CaMg[CO3]2) growth kinetics. Triaxial compression and torsion tests performed at constant stresses between 7 and 38 MPa and test durations between 4 and 171 hours resulted in bulk strains of 0.03-0.2 and maximum shear strains of 0.8-5.6, respectively. The reaction rims consist of fine-grained (2-7 μm) dolomite with palisade-shaped grains growing into magnesite reactants and equiaxed granular dolomite grains next to calcite. In between dolomite and pure calcite, magnesio-calcite grains evolved with an average grain size of 20-40 μm. Grain boundaries tend to be straighter at high bulk strains and equilibrium angles at grain triple junctions are common within the magnesio-calcite layer. Transmission electron microscopy shows almost dislocation free palisades and increasing dislocation density within granular dolomite towards the magnesio-calcite boundary. Within magnesio-calcite grains, dislocations are concentrated at grain boundaries. Variation of time at fixed stress (˜17 MPa) yields a parabolic time dependence of dolomite rim width, indicating diffusion-controlled growth, similar to isostatic rim growth behavior. In contrast, the magnesio-calcite layer growth is enhanced compared to isostatic conditions. Triaxial compression at given time shows no significant change of dolomite rim thickness (11±2 μm) and width of magnesio-calcite layers (33±5 μm) with increasing stress. In torsion experiments, reaction layer thickness and grain size decrease from the center (low stress/strain) to the edge (high strain/stress) of samples. Chemical analysis shows nearly stoichiometric composition of dolomite palisades, but enhanced Ca content within granular grains, indicating local disequilibrium with magnesio-calcite, in particular for twisted

  15. Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model.

    Science.gov (United States)

    Hung, Ming-Szu; Xu, Zhidong; Chen, Yu; Smith, Emmanuel; Mao, Jian-Hua; Hsieh, David; Lin, Yu-Ching; Yang, Cheng-Ta; Jablons, David M; You, Liang

    2013-11-01

    Casein kinase II (CK2) inhibitors suppress cancer cell growth. In this study, we examined the inhibitory effects of a novel CK2 inhibitor, hematein, on tumor growth in a murine xenograft model. We found that in lung cancer cells, hematein inhibited cancer cell growth, Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increased apoptosis. In a murine xenograft model of lung cancer, hematein inhibited tumor growth without significant toxicity to the mice tested. Molecular docking showed that hematein binds to CK2α in durable binding sites. Collectively, our results suggest that hematein is an allosteric inhibitor of protein kinase CK2 and has antitumor activity to lung cancer. PMID:24008396

  16. Exploring Important Influences on the Healthfulness of Prostate Cancer Survivors’ Diets

    OpenAIRE

    Coa, Kisha I.; Smith, Katherine Clegg; Klassen, Ann C.; Thorpe, Roland J, Jr; Caulfield, Laura E

    2015-01-01

    A cancer diagnosis is often conceptualized as a teachable moment when individuals might be motivated to make lifestyle changes. Many prostate cancer survivors, however, do not adhere to dietary guidelines. In this article, we explore how cancer impacted prostate cancer survivors’ diets and identify important influences on diet. Twenty prostate cancer survivors completed three 24-hour dietary recalls and an in-depth dietary interview. We analyzed interviews using a constant comparison approach...

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

    International Nuclear Information System (INIS)

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

  18. 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...

  19. Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2011-05-01

    Full Text Available Abstract Background Earlier studies have reported the production of histamine in colorectal cancers (CRCs. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4 is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107 and adjacent normal tissues (ANTs. To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. Conclusion The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

  20. Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

    International Nuclear Information System (INIS)

    Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs

  1. Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model.

    Science.gov (United States)

    Yin, Tao; He, Sisi; Shen, Guobo; Ye, Tinghong; Guo, Fuchun; Wang, Yongsheng

    2015-09-01

    Neuropsychological factors have been shown to influence tumor progression and therapeutic response. The present study investigated the effect of the dopamine receptor antagonist thioridazine on murine breast cancer. The anti‑tumor efficacy of thioridazine was assessed using a murine breast cancer model. Cell apoptosis and proliferation were analyzed in vitro using flow cytometry (FCM) and the MTT assay, respectively. Western blot analysis was performed to assess Akt, phosphorylated (p)‑Akt, signal transducer and activator of transcription (STAT) 3, p‑STAT3 and p‑p65 in tumor cells following treatment with thioridazine. The Ki67 index and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)‑positive apoptotic cells were assessed in the tumor sections. Thioridazine was found to reduce tumor growth, inhibit tumor cell proliferation and induce apoptosis in a dose‑ and time‑dependent manner in vitro. Thioridazine was also found to markedly inhibit tumor proliferation and induce tumor cell apoptosis in vivo as shown by the lower Ki67 index and increase in TUNEL‑positive cells. In addition, thioridazine was observed to inhibit the activation of the canonical nuclear factor κ‑light‑chain‑enhancer of activated B cells pathway and exert anti‑tumor effects by remodeling the tumor stroma, as well as inhibit angiogenesis in the tumor microenvironment. In conclusion, thioridazine was found to significantly inhibit breast tumor growth and the potential for thioridazine to be used in cancer therapy may be re‑evaluated and investigated in clinical settings. PMID:26095429

  2. 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.

  3. LEF1 in androgen-independent prostate cancer: regulation of androgen receptor expression, prostate cancer growth and invasion

    OpenAIRE

    Li, Yirong; Wang, Longgui; Zhang, Miao; Melamed, Jonathan; Liu, Xiaomei; Reiter, Robert; Wei, Jianjun; Peng, Yi; Zou, Xuanyi; Pellicer, Angel; Garabedian, Michael J.; Ferrari, Anna; Lee, Peng

    2009-01-01

    A major obstacle in treating prostate cancer is the development of androgen-independent disease. In this study, we examined LEF1 expression in androgen-independent cancer as well as its regulation of androgen receptor (AR) expression, prostate cancer growth and invasion in androgen-independent prostate cancer cells. Affymetrix microarray analysis of LNCaP and LNCaP-AI (androgen-independent variant LNCaP) cells revealed 100-fold increases in LEF1 expression in LNCaP-AI cells. We showed that LE...

  4. 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.

  5. Impact of Transfusion on Cancer Growth and Outcome.

    Science.gov (United States)

    Goubran, Hadi A; Elemary, Mohamed; Radosevich, Miryana; Seghatchian, Jerard; El-Ekiaby, Magdy; Burnouf, Thierry

    2016-01-01

    For many years, transfusion of allogeneic red blood cells, platelet concentrates, and plasma units has been part of the standard therapeutic arsenal used along the surgical and nonsurgical treatment of patients with malignancies. Although the benefits of these blood products are not a matter of debate in specific pathological conditions associated with life-threatening low blood cell counts or bleeding, increasing clinical evidence is nevertheless suggesting that deliberate transfusion of these blood components may actually lead to negative clinical outcomes by affecting patient's immune defense, stimulating tumor growth, tethering, and dissemination. Rigorous preclinical and clinical studies are needed to dimension the clinical relevance, benefits, and risks of transfusion of blood components in cancer patients and understand the amplitude of problems. There is also a need to consider validating preparation methods of blood components for so far ignored biological markers, such as microparticles and biological response modifiers. Meanwhile, blood component transfusions should be regarded as a personalized medicine, taking into careful consideration the status and specificities of the patient, rather than as a routine hospital procedure. PMID:27006592

  6. Selective pattern of cancer cell accumulation and growth using UV modulating printing of hydrogels.

    Science.gov (United States)

    Yang, Wenguang; Yu, Haibo; Wei, Fanan; Li, Gongxin; Wang, Yuechao; Liu, Lianqing

    2015-12-01

    Fabrication of extracellular microenvironment for cancer cell growth in vitro is an indispensable technique to precisely control the cell spatial arrangement and proliferation for cell-behavior research. Current micropatterning methods usually require relatively complicated operations, which makes it difficult to investigate the effects of different cell growth patterns. This manuscript proposes a DMD-based projection technique to quickly pattern a poly(ethylene) glycol diacrylate (PEGDA)-based hydrogel on a common glass substrate. Using this method, we can effectively control the growth patterns of cells. Compared with these traditional methods which employ digital dynamic mask, polymerization of PEGDA solution can be used to create arbitrary shaped microstructures with high efficiency, flexibility and repeatability. The duration of UV exposure is less than 10 s through controlling the projected illumination pattern. The ability of patterned PEGDA-coated film to hinder cell adhesion makes it possible to control area over which cells attach. In our experiments, we take advantage of the blank area to pattern cells, which allows cells to grow in various pre-designed shapes and sizes. And the patterning cells have a high viability after culturing for several days. Interestingly, we found that the restricted space could stiffen and strengthen the cells. These results indicate that cells and extracellular microenvironment can influence each other. PMID:26458559

  7. Influence of Sediment Nutrients on Growth of Emergent Hygrophila

    OpenAIRE

    Hanlon, David L.; Dingler, Peter M.

    2000-01-01

    Hygrophila ( Hygrophila polysperma (Roxb.) T. Anderson) is a plants which forms serious aquatic weed problems. Both submerged and emergent growth forms occur. Nutritional studies with a controlled release fertilizer and sediments collected from hygrophila-infested areas were conducted with the emergent growth habit to provide insights into growth of this introduced plant. Plant dry weights for experimental 16- week culture periods with low average temperatures we...

  8. 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. PMID:18823376

  9. Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

    International Nuclear Information System (INIS)

    Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm3 vs. 1195 ± 84 mm3, p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis

  10. 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.

  11. 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.

  12. Influence of Family History of Cancer on Engagement in Protective Health Behaviors

    Science.gov (United States)

    Amuta, Ann O.; Barry, Adam E.

    2015-01-01

    Background: Approximately 1580 people die from cancer each day. Family history is highlighted as an especially important indicator of cancer risk. Purpose: To determine whether having a family member with cancer influences preventive behaviors (e.g., smoking, physical activity, and screenings). Methods: We conducted a secondary data analysis…

  13. Pediatric cancer epigenome and the influence of folate

    OpenAIRE

    Yiu, Teresa T; Li, Wei

    2015-01-01

    Despite improvement in clinical treatment of childhood cancer, it remains the leading cause of disease-related mortality in children with survivors often suffering from treatment-related toxicity and premature death. Because childhood cancer is vastly different from cancer in adults, a thorough understanding of the underlying molecular mechanisms specific to childhood cancer is essential. Although childhood cancer contains much fewer mutations, a subset of cancer subtypes has a higher frequen...

  14. Pneumonitis after radiotherapy of lung cancer - incidence and influencing factors

    International Nuclear Information System (INIS)

    Background: The most important side effect in radiotherapy of lung cancer is pneumonitis. The incidence of pneumotitis was evaluated in a retrospective study in the patient collective of the University of Heidelberg. Therapy related and therapy independent factors have been evaluated. Results: Regarding the treatment prior to irradiation patients with primary irradiation were affected in 26.5% (17% slight, 9.5% severe), with postoperative irradiation in 14% (9.3% slight, 4.7% severe), with radiochemotherapy of small cell lung cancer (SCLC) in 15.4% (12% slight, 3.4% severe) by this side effect. These differences were not significant (p=0.32). The median onset of pneumonitis was 31 days after end of irradiation (severe 23 days, slight 44 days, p=0.026). By a univariate analysis the total dose at the prescription point was the most important factor (30 to 50.5 Gy 11%, 52 to 59 Gy 15%, 60 to 74 Gy 26%, p=0.007). High single doses (2.5 Gy) were only applied within a study of radiochemotherapy with a randomised sequential and alternating schedule. So that the increased rate of pneumonitis (42%) is not clearly separable from other influencing variables. A correlation between the applied techniques and the irradiated volume (measured by planimetric methods) was not demonstrable. Regarding the independent factors a high age, female sex and a low FeV1 were unfavourable. However, age and sex corrected FeV1 was not predictive. (orig./AJ)

  15. 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.

  16. PGE2-induced colon cancer growth is mediated by mTORC1

    International Nuclear Information System (INIS)

    Highlights: • PGE2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E2 (PGE2) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE2 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 PGE2-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE2 EP4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE2 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 PGE2-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

  17. Exploring the relationship between posttraumatic growth, cognitive processing, psychological distress, and social constraints in a sample of breast cancer patients.

    Science.gov (United States)

    Koutrouli, Natalia; Anagnostopoulos, Fotios; Griva, Fay; Gourounti, Kleanthi; Kolokotroni, Filippa; Efstathiou, Vasia; Mellon, Robert; Papastylianou, Dona; Niakas, Dimitris; Potamianos, Gregory

    2016-01-01

    Posttraumatic growth (the perception of positive life changes after an encounter with a trauma) often occurs among breast cancer patients and can be influenced by certain demographic, medical, and psychosocial parameters. Social constraints on disclosure (the deprivation of the opportunity to express feelings and thoughts regarding the trauma) and the cognitive processing of the disease seem to be involved in the development of posttraumatic growth. Through the present study the authors aim to: investigate the levels of posttraumatic growth in a sample of 202 women with breast cancer in Greece, explore the relationships between posttraumatic growth and particular demographic, medical, and psychosocial variables according to a proposed model, and test the role of social constraints in the relationship between automatic and deliberate cognitive processing of the trauma. The results showed that posttraumatic growth was evident in the majority of the sample and was associated inversely with age at diagnosis (β = -0.174, p reflective rumination (β = 0.323, p = .001). Social constraints were found to moderate the relationship between intrusions and reflective rumination. Implications of the results and suggestions for future research and practice are outlined. PMID:26605785

  18. Differential Expression of Growth Factor Receptors and Membrane-Bound Tumor Markers for Imaging in Male and Female Breast Cancer

    OpenAIRE

    Vermeulen, Jeroen F.; Robert Kornegoor; Elsken van der Wall; Petra van der Groep; Paul J. van Diest

    2013-01-01

    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 femal...

  19. Analysis of UHRF1 expression in human ovarian cancer tissues and its regulation in cancer cell growth.

    Science.gov (United States)

    Yan, Feng; Wang, Xiaoming; Shao, Lijia; Ge, Mengyuan; Hu, Xiaoya

    2015-11-01

    Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), known as ICB90 or Np95, has been found to be overexpressed in numerous cancers. In this study, we evaluated the expression level of UHRF1 in ovarian cancer. UHRF1 levels in paired ovarian cancer tissues and adjacent normal tissues from 80 ovarian cancer patients were detected using relative quantitatively PCR and Western blot. Small interfering RNA (siRNA) was introduced in two human ovarian cancer cell lines (SKOV-3 and OVCAR-3) to downregulate the expression of UHRF1. The proliferation of siRNA-treated cells was examined using cell counting kit-8 (CCK-8) assay. The growth of these cells showed a remarkable decrease. Moreover, flow cytometric and Hoechst 33342 assays were used to detect the apoptosis. The diagnostic value of UHRF1 messenger RNA (mRNA) expression in ovarian cancer was estimated by receiver-operator characteristic (ROC) curve. The correlation between UHRF1 mRNA expression and clinicopathologic features of ovarian cancer patients was evaluated by χ (2) test. Our results demonstrated that both UHRF1 mRNA and protein were highly expressed in ovarian cancer tissues and significantly higher than that in adjacent normal tissues. Moreover, the inhibition of UHRF1 may lead to cells to undergo apoptosis. Thus, UHRF1 could act as a new oncogenic factor in ovarian cancer and be a potential molecular target for ovarian cancer gene therapy. PMID:26070868

  20. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction

    OpenAIRE

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2015-01-01

    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 ...

  1. 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....

  2. How do patient and hospital features influence outcomes in small-cell lung cancer in England?

    OpenAIRE

    Rich, A L; Tata, L J; Free, C M; Stanley, R. A.; Peake, M D; Baldwin, D. R.; Hubbard , R B

    2011-01-01

    Background: Our aim was to systematically determine how features of patients and hospitals influence access to chemotherapy and survival for people with small-cell lung cancer in England. Methods: We linked the National Lung Cancer Audit and Hospital Episode Statistics and used multiple logistic and Cox regression analyses to assess the influence of patient and hospital features on small-cell lung cancer outcomes. Results: There were 7845 patients with histologically proven small-cell lung ca...

  3. Influence of Liaison Psychiatric Approach on Quality of Life in Patients with Newly Diagnosed Breast Cancer

    OpenAIRE

    Anton, Sanda; Mrđenović, Slobodan; Gugić, Damir; Tomanović, Katarina

    2008-01-01

    Having breast cancer represents traumatic stress event that can influence development of psychiatric disorders during psychological adjustment. The aim of research was to investigate influence of liaison psychiatric approach on quality of life in patients with breast cancer. Sample consisted of 120 women with breast cancer treated on Department for Oncology in University Hospital Osijek. Patients were in liaison psychiatric treatment for two months. They were estimated on the firs...

  4. Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain.

    OpenAIRE

    Binder, Claudia; Chuang, Eugenia; Habla, Christina; Bleckmann, Annalen; Schulz, Matthias; Bathgate, Ross; Einspanier, Almuth

    2014-01-01

    Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as ...

  5. Prostate cancer specific integrin αvβ3 modulates bone metastatic growth and tissue remodeling

    OpenAIRE

    McCabe, NP; De, S.; Vasanji, A; Brainard, J; Byzova, TV

    2007-01-01

    The management of pain and morbidity owing to the spreading and growth of cancer within bone remains to be a paramount problem in clinical care. Cancer cells actively transform bone, however, the molecular requirements and mechanisms of this process remain unclear. This study shows that functional modulation of the αvβ3 integrin receptor in prostate cancer cells is required for progression within bone and determines tumor-induced bone tissue transformation. Using histology and quantitative mi...

  6. Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression

    OpenAIRE

    2015-01-01

    Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-β and ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, ...

  7. The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer

    OpenAIRE

    Sahin Aysegul; Hu Limei; Akkiprik Mustafa; Hao Xishan; Zhang Wei

    2009-01-01

    Abstract Background Insulin-like growth factor binding protein 5 (IGFBP5) has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly ...

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

    OpenAIRE

    Liu Jinsong; Wang Huamin; Shmulevich Ilya; Mircean Cristian; Lee Eun-Ju; Niemistö Antti; Kavanagh John J; Lee Je-Ho; Zhang Wei

    2005-01-01

    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 wit...

  9. Andrographolide, an Herbal Medicine, Inhibits Interleukin-6 Expression and Suppresses Prostate Cancer Cell Growth

    OpenAIRE

    Chun, Jae Yeon; Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Liu, Chengfei; Yang, Joy; Evans, Christopher P.; Zhou, Qinghua; Gao, Allen C.

    2010-01-01

    Elevated interleukin-6 (IL-6), a major mediator of the inflammatory response, has been implicated in androgen receptor (AR) activation, cellular growth and differentiation, plays important roles in the development and progression of prostate cancer, and is a potential target in cancer therapy. Through drug screening using human prostate cancer cells expressing IL-6 autocrine loop, we found that andrographolide, a diterpenoid lactone isolated from a traditional Chinese and Indian medicinal pla...

  10. Vascular endothelial growth factor in the circulation in cancer patients may not be a relevant biomarker

    OpenAIRE

    Tatjana M H Niers; Richel, Dick J.; Meijers, Joost C.M.; Schlingemann, Reinier O.

    2011-01-01

    BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. METHODOLOGY: We determined VEGF levels in PECT, a medi...

  11. The cancer growth suppressor gene mda-7 selectively induces apoptosis in human breast cancer cells and inhibits tumor growth in nude mice

    OpenAIRE

    Su, Zao-Zhong; Madireddi, Malavi T.; Lin, Jiao Jiao; Young, Charles S. H.; Kitada, Shinichi; Reed, John C.; Goldstein, Neil I.; Fisher, Paul B.

    1998-01-01

    A differentiation induction subtraction hybridization strategy is being used to identify and clone genes involved in growth control and terminal differentiation in human cancer cells. This scheme identified melanoma differentiation associated gene-7 (mda-7), whose expression is up-regulated as a consequence of terminal differentiation in human melanoma cells. Forced expression of mda-7 is growth inhibitory toward diverse human tumor cells. The present studies elucidate the mechanism by which ...

  12. Influence of interphase anisotropy on lamellar eutectic growth patterns

    OpenAIRE

    GHOSH, Supriyo; Plapp, Mathis

    2015-01-01

    It is well documented in many experiments that crystallographic effects play an important role in the generation of two-phase patterns during the solidification of eutectic alloys. In particular, in lamellar composites, large patches of perfectly aligned lamellae are frequently observed. Moreover, the growth direction of the lamellae often markedly differs from the direction of the temperature gradient (the lamellae are tilted with respect to the main growth direction). Both of these effects ...

  13. Inherited susceptibility to cancer and other factors influencing occurrence of cancer

    International Nuclear Information System (INIS)

    The types of defects and polymorphisms leading to hereditary susceptibility to cancer include proneness to increased DNA damage, recessive syndromes of faulty DNA repair and differentiation, as well as dominant mutations of cell cycle and control proliferation. The cancer susceptibility syndromes inherited in a dominant fashion are caused by mutations in tumor suppressor genes. These genes are recessive in relation to wild type alleles. In two syndromes of hereditary mutations in tumor suppressor genes (Rb and WT2), their expression 'in vivo' may be influenced by the sex of the transmitting parent, what points to modulation by imprinting. Genetic heterogeneity of the population in susceptibility to genotoxic agents is related to the individual variation in acceptable levels of exposure to agents and factors, such as products of incomplete combustion (PIC), UV ('xeroderma pigmentosum') and ionizing radiation ('ataxia telangiectasia'). DNA damage and adducts are considered to be indicative of genotoxic exposure and its effect as well as modulation of carcinogenic damage by genetic polymorphisms. Gene and protein polymorphisms are considered as markers of increased individual risk. Since environmental factors are considered to be able to control, the individual susceptibility to enhanced DNA damage and environmentally induced cancers could be counteracted by decreasing the levels of contamination or exposure. This explains the wide interest in markers of this individual sensitivity. Most of the postulated markers of sensitivity to PIV do not, however, prove to be generally applicable in that sense. Their prognostic value is limited either by low amplitude of the effect, or by their character specific either to the population or to the cancer type. The polymorphisms most relevant to cancers induced by PIC exposures may be those of inductibility of benzopyrene hydroxylase, and some other DNA polymorphisms concerning the CYP1A1 gene. (author). 24 refs, 1 fig., 3 tabs

  14. Caribbean coral growth influenced by anthropogenic aerosol emissions

    Science.gov (United States)

    Kwiatkowski, Lester; Cox, Peter M.; Economou, Theo; Halloran, Paul R.; Mumby, Peter J.; Booth, Ben B. B.; Carilli, Jessica; Guzman, Hector M.

    2013-05-01

    Coral growth rates are highly dependent on environmental variables such as sea surface temperature and solar irradiance. Multi-decadal variability in coral growth rates has been documented throughout the Caribbean over the past 150-200 years, and linked to variations in Atlantic sea surface temperatures. Multi-decadal variability in sea surface temperatures in the North Atlantic, in turn, has been linked to volcanic and anthropogenic aerosol forcing. Here, we examine the drivers of changes in coral growth rates in the western Caribbean between 1880 and 2000, using previously published coral growth chronologies from two sites in the region, and a numerical model. Changes in coral growth rates over this period coincided with variations in sea surface temperature and incoming short-wave radiation. Our model simulations show that variations in the concentration of anthropogenic aerosols caused variations in sea surface temperature and incoming radiation in the second half of the twentieth century. Before this, variations in volcanic aerosols may have played a more important role. With the exception of extreme mass bleaching events, we suggest that neither climate change from greenhouse-gas emissions nor ocean acidification is necessarily the driver of multi-decadal variations in growth rates at some Caribbean locations. Rather, the cause may be regional climate change due to volcanic and anthropogenic aerosol emissions.

  15. Influence of Butylated Hydroxyanisole on the Growth, Hyphal Morphology, and the Biosynthesis of Fumonisins in Fusarium proliferatum

    Science.gov (United States)

    Li, Taotao; Jian, Qijie; Chen, Feng; Wang, Yong; Gong, Liang; Duan, Xuewu; Yang, Bao; Jiang, Yueming

    2016-01-01

    Fusarium proliferatum as a common fungus pathogen in foods can produce toxic fumonisins, which can cause animal diseases and increase risks of human cancers. On contrary, butylated hydroxyanisole (BHA) as a synthetic antioxidant offers a clue for preventing growth of fungal species and inhibiting production of mycotoxins. Unfortunately, information of the inhibitory mechanism of BHA on Fusarium species is still limited. In this study, influence of BHA treatment on growth and inhibition of fumonisin production in relation to the expression of the fumonisin biosynthesis-related genes of the F. proliferatum ZYF was investigated, which revealed that BHA had a negative influence on growth and fumonisin production of F. proliferatum. To further elucidate the mechanism of BHA on the growth of F. proliferatum, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to examine the F. proliferatum hyphae. The BHA treatment induced the loss of cytoplasm and cellular constituents, as well as distortion of mycelia, but it did not directly degrade the fumonisin. Furthermore, the BHA treatment markedly inhibited the expressions of FUM1 (a polyketide synthase encoding gene) and FUM8 (an aminotransferase encoding gene) genes, which resulted in the depression of metabolic pathway of F. proliferatum. The transcriptional analyses of the FUM1 and FUM8 genes confirmed a correlation between the fumonisin production and its gene expression. This study provided some insights into mechanisms of production of fumonisin and feasible prevention to reduce fumonisin contamination in favor of human and animal health. PMID:27468276

  16. Influence of Butylated Hydroxyanisole on the Growth, Hyphal Morphology, and the Biosynthesis of Fumonisins in Fusarium proliferatum.

    Science.gov (United States)

    Li, Taotao; Jian, Qijie; Chen, Feng; Wang, Yong; Gong, Liang; Duan, Xuewu; Yang, Bao; Jiang, Yueming

    2016-01-01

    Fusarium proliferatum as a common fungus pathogen in foods can produce toxic fumonisins, which can cause animal diseases and increase risks of human cancers. On contrary, butylated hydroxyanisole (BHA) as a synthetic antioxidant offers a clue for preventing growth of fungal species and inhibiting production of mycotoxins. Unfortunately, information of the inhibitory mechanism of BHA on Fusarium species is still limited. In this study, influence of BHA treatment on growth and inhibition of fumonisin production in relation to the expression of the fumonisin biosynthesis-related genes of the F. proliferatum ZYF was investigated, which revealed that BHA had a negative influence on growth and fumonisin production of F. proliferatum. To further elucidate the mechanism of BHA on the growth of F. proliferatum, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to examine the F. proliferatum hyphae. The BHA treatment induced the loss of cytoplasm and cellular constituents, as well as distortion of mycelia, but it did not directly degrade the fumonisin. Furthermore, the BHA treatment markedly inhibited the expressions of FUM1 (a polyketide synthase encoding gene) and FUM8 (an aminotransferase encoding gene) genes, which resulted in the depression of metabolic pathway of F. proliferatum. The transcriptional analyses of the FUM1 and FUM8 genes confirmed a correlation between the fumonisin production and its gene expression. This study provided some insights into mechanisms of production of fumonisin and feasible prevention to reduce fumonisin contamination in favor of human and animal health. PMID:27468276

  17. Influence of nitrogen on the growth and the properties of InAs quantum dots

    International Nuclear Information System (INIS)

    This work investigates the influence of nitrogen incorporation on the growth and the optical properties of InAs quantum dots on GaAs(001) substrates. On the basis of systematic growth interruptions it was shown that the large quantum dots nucleate at dislocations, which are already formed during the growth of the wetting layer. After solving the growth problems, the influence of different combinations of matrix layers on the structural and optical properties of the quantum dots was investigated in the second part of this work. The strain and bandgap of these layers were varied systematically. (orig.)

  18. Coping with early stage breast cancer: examining the influence of personality traits and interpersonal closeness

    OpenAIRE

    Saita, Emanuela; Acquati, Chiara; Kayser, Karen

    2015-01-01

    The study examines the influence of personality traits and close relationships on the coping style of women with breast cancer. A sample of 72 Italian patients receiving treatment for early stage breast cancer was recruited. Participants completed questionnaires measuring personality traits (Interpersonal Adaptation Questionnaire), interpersonal closeness (Inclusion of the Other in the Self Scale), and adjustment to cancer (Mini-Mental Adjustment to Cancer Scale). We hypothesized that diverse...

  19. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPKThr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPKSer485 phosphorylation and impaired AMPKThr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPKThr172 activation and suppression of the insulin/IGF signalling pathways

  20. Nerve growth factor: role in growth, differentiation and controlling cancer cell development.

    Science.gov (United States)

    Aloe, Luigi; Rocco, Maria Luisa; Balzamino, Bijorn Omar; Micera, Alessandra

    2016-01-01

    Recent progress in the Nerve Growth Factor (NGF) research has shown that this factor acts not only outside its classical domain of the peripheral and central nervous system, but also on non-neuronal and cancer cells. This latter observation has led to divergent hypothesis about the role of NGF, its specific distribution pattern within the tissues and its implication in induction as well as progression of carcinogenesis. Moreover, other recent studies have shown that NGF has direct clinical relevance in certain human brain neuron degeneration and a number of human ocular disorders. These studies, by suggesting that NGF is involved in a plethora of physiological function in health and disease, warrant further investigation regarding the true role of NGF in carcinogenesis. Based on our long-lasting experience in the physiopathology of NGF, we aimed to review previous and recent in vivo and in vitro NGF studies on tumor cell induction, progression and arrest. Overall, these studies indicate that the only presence of NGF is unable to generate cell carcinogenesis, both in normal neuronal and non-neuronal cells/tissues. However, it cannot be excluded the possibility that the co-expression of NGF and pro-carcinogenic molecules might open to different consequence. Whether NGF plays a direct or an indirect role in cell proliferation during carcinogenesis remains to demonstrate. PMID:27439311

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

    International Nuclear Information System (INIS)

    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. 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. 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-independent prostate cancer cell lines. Survivin

  3. 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.

  4. 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...

  5. Regenerating gene family member 4 promotes growth and migration of gastric cancer through protein kinase B pathway

    OpenAIRE

    Huang, Jiamiao; Yang, Ya; Yang, Jian; LI, XIAN

    2014-01-01

    Regenerating gene family member 4 (REG4), a secreted protein, is overexpressed in several cancers, including gastric cancer. The present study was undertaken to determine the roles of REG4 in the growth of gastric cancer in the nude mice and in the proliferation and migration in human gastric cancer cell line and its downstream signaling pathway. Gastric cancer models were elicited by intraperitoneally injecting MKN45 human gastric cancer cells and the tumor size was measured every other day....

  6. 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.

  7. Growth curve analysis of placental and fetal growth influenced by adjacent fetal sex status under crowded uterine conditions in pigs

    Science.gov (United States)

    Intrauterine position and sex of adjacent fetuses in litter bearing species have been implicated in physiological and behavioral differences in males and females. Our objective was to establish growth curves for fetal and placental weight gain as influenced by sex status of flanking fetuses under cr...

  8. 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.; Saunders, R.; Trolliard, G.; Soulestin, B.; Duclere, J.R.; Mosnier, J.P.; Henry, M.O.

    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...

  9. 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.

  10. Influence of soil temperature on growth traits of European beech seedlings

    OpenAIRE

    Peter C Frederick; Štraus, Ines; Mrak, Tanja; Hylton, Becky; Heath, Julie; Ferlan, Mitja; Spalding, Marilyn; Železnik, Peter; Kraigher, Hojka

    2014-01-01

    European beech (Fagus sylvatica L.) is an economically and ecologically important forest tree species in Europe. Expected future temperature increases due to global climate change may significantly affect growth of beech trees and consequently influence carbon cycling in beech forests. We tested the hypothesis that soil temperature influences the growth of both belowground and aboveground parts of beech seedlings. One-year-old seedlings were transferred into rhizotrons and subjected ...

  11. The influence of growth retardants and cytokinins on flowering of ornamental plants

    OpenAIRE

    Anna Pobudkiewicz

    2012-01-01

    Growth retardants are applied in order to obtain short and well compact plants. They usually inhibit stem elongation, but also can influence the flowering of plants. The aim of cytokinin application is to obtain well branched plants without removing the apical meristem. Cytokinins usually increase the number of axillary shoots but also can influence flowering. Growth retardants and cytokinins can affect flower size, pedicel length, number of flowers, flower longevity, abortion of flower buds ...

  12. Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms

    DEFF Research Database (Denmark)

    Rohde, Mikkel; Daugaard, Mads; Jensen, Mette Hartvig;

    2005-01-01

    Whereas the stress-inducible heat-shock protein 70 (Hsp70) has gained plenty of attention as a putative target for tumor therapy, little is known about the role of other Hsp70 proteins in cancer. Here we present the first thorough analysis of the expression and function of the cytosolic Hsp70...... survival of tumorigenic as well as nontumorigenic cells depended on Hsc70. Cancer cells depleted for Hsp70 and Hsp70-2 displayed strikingly different morphologies (detached and round vs. flat senescent-like), cell cycle distributions (G2/M vs. G1 arrest) and gene expression profiles. Only Hsp70-2 depletion...... proteins in human cancer cells and identify Hsp70-2, a protein essential for spermatogenesis, as an important regulator of cancer cell growth. Targeted knock-down of the individual family members by RNA interference revealed that both Hsp70 and Hsp70-2 were required for cancer cell growth, whereas the...

  13. The role of vascular endothelial growth factor in the tissue specific in vivo growth of prostate cancer cells.

    Science.gov (United States)

    Krupski, T; Harding, M A; Herce, M E; Gulding, K M; Stoler, M H; Theodorescu, D

    2001-01-01

    Despite the fact that cancer cells can be found in many vascular beds, continued growth of the metastatic tumor focus exhibits a significant degree of 'organ tropism', with only certain organs exhibiting the ravages of metastatic disease. Since a limiting factor to the growth of metastases beyond 2 mm in diameter, may be a lack of angiogenesis, we sought to determine whether tumor overexpression of vascular endothelial growth factor (VEGF), a potent angiogenic factor related to prostate cancer metastasis, is causally related to organ specific tumor growth in a prostate cancer xenograft model. LnCaP-C4-2 is a subline of the human prostate cancer cell line LnCaP which unlike its parent, has a predilection for growth in bone, a common site for human prostate cancer metastasis. LnCaP-C4-2, is tumorigenic when injected intrafemorally in mice but requires co-injection of stromal components (Matrigel) to be tumorigenic in the subcutaneous site. Because of this site-specific tumorigenicity profile and relatively low VEGF mRNA and protein expression, this line was transfected with a full length cDNA encoding the 165 isoform of VEGF. Cells either overexpressing or not expressing the transfected gene were selected for study in vivo and in vitro. Overexpression of VEGF did not seem to affect in vitro cell growth. Such overexpression did affect tumorigenicity and in vivo tumor growth rates when cells were inoculated in the subcutaneus site. Interestingly, the dependency of subcutaneous tumorigenicity on Matrigel co-inoculation was still observed in cells overexpressing VEGF. In contrast to the impact that VEGF overexpression has on subcutaneous tumorigenicity, no such effect was observed when cells were inoculated in orthotopic/prostate (primary) or intrafemoral (metastatic) sites. In view of the importance of tumor-stromal interactions in growth of xenografts, we sought to determine if the host strain is important to the observed tumorigenicity effects of VEGF overexpression

  14. CSR1 Suppresses Tumor Growth and Metastasis of Prostate Cancer

    OpenAIRE

    Yu, Guoying; Tseng, George C.; Yu, Yan Ping; Gavel, Tim; Nelson, Joel; Wells, Alan; Michalopoulos, George; Kokkinakis, Demetrius; Luo, Jian-Hua

    2006-01-01

    Prostate cancer is frequent among men over 45 years of age, but it generally only becomes lethal with metastasis. In this study, we identified a gene called cellular stress response 1 (CSR1) that was frequently down-regulated and methylated in prostate cancer samples. Survival analysis indicated that methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1 protein expression, was associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in pr...

  15. Vitamin K2-derived compounds induce growth inhibition in radioresistant cancer cells.

    Science.gov (United States)

    Amalia, Helfi; Sasaki, Ryohei; Suzuki, Yoko; Demizu, Yusuke; Bito, Toshinori; Nishimura, Hideki; Okamoto, Yoshiaki; Yoshida, Kenji; Miyawaki, Daisuke; Kawabe, Tetsuya; Mizushina, Yoshiyuki; Sugimura, Kazuro

    2010-01-01

    A strategy to overcome radioresistance in cancer treatment has been expected. To evaluate the strategy, appropriate experimental models are needed. Radioresistant tumour models were originally established from human colon cancer cells, and we evaluated their molecular basis. Next, the growth inhibitory effects of newly synthesized vitamin K2 (VK2)-related compounds were tested. Here, we showed that these novel compounds have growth inhibitory effects not only on cancer cells of various origins, but also on radioresistant cells, through the generation of reactive oxygen species (ROS). Human colon, lung, and breast cancer cell lines were used for testing the growth inhibitory activities of several chemical compounds. Radioresistant tumour models were established by fractionated radiation exposure. Irradiated cells were selected by a single cell cloning method, and their sensitivity to ionizing radiation was evaluated by a colony-forming assay. The VK2 derivatives (named MQ-1, MQ-2, and MQ-3) were chemically synthesized. To evaluate the generation of ROS, flow cytometer analyses were performed. A radioresistant tumour model was established from the HCT116 human colon cancer cell line. The radioresistant cells from HCT116 also showed resistance to cisplatin. In the radioresistant cells, NF-κB was highly activated. MQ-1, MQ-2, and MQ-3 showed greater growth inhibitory activities than VK2 not only in various cancer cells but also in radioresistant cells through the generation of ROS. In conclusion, a radioresistant tumour model was originally established from colon cancer cell lines through NF-κB activation, and it could be a useful tool for evaluating anti-tumour agents. Newly synthesized VK2 derivatives (MQ-1, MQ-2 and MQ-3) seemed to be potential anti-tumour agents in various cancers and radioresistant cancers. The efficacy of those compounds was related to the generation of ROS. These findings together might pave the way for the treatment of radioresistant or

  16. Emodin Inhibits Breast Cancer Growth by Blocking the Tumor-Promoting Feedforward Loop between Cancer Cells and Macrophages.

    Science.gov (United States)

    Iwanowycz, Stephen; Wang, Junfeng; Hodge, Johnie; Wang, Yuzhen; Yu, Fang; Fan, Daping

    2016-08-01

    Macrophage infiltration correlates with severity in many types of cancer. Tumor cells recruit macrophages and educate them to adopt an M2-like phenotype through the secretion of chemokines and growth factors, such as MCP1 and CSF1. Macrophages in turn promote tumor growth through supporting angiogenesis, suppressing antitumor immunity, modulating extracellular matrix remodeling, and promoting tumor cell migration. Thus, tumor cells and macrophages interact to create a feedforward loop supporting tumor growth and metastasis. In this study, we tested the ability of emodin, a Chinese herb-derived compound, to inhibit breast cancer growth in mice and examined the underlying mechanisms. Emodin was used to treat mice bearing EO771 or 4T1 breast tumors. It was shown that emodin attenuated tumor growth by inhibiting macrophage infiltration and M2-like polarization, accompanied by increased T-cell activation and reduced angiogenesis in tumors. The tumor inhibitory effects of emodin were lost in tumor-bearing mice with macrophage depletion. Emodin inhibited IRF4, STAT6, and C/EBPβ signaling and increased inhibitory histone H3 lysine 27 tri-methylation (H3K27m3) on the promoters of M2-related genes in tumor-associated macrophages. In addition, emodin inhibited tumor cell secretion of MCP1 and CSF1, as well as expression of surface anchoring molecule Thy-1, thus suppressing macrophage migration toward and adhesion to tumor cells. These results suggest that emodin acts on both breast cancer cells and macrophages and effectively blocks the tumor-promoting feedforward loop between the two cell types, thereby inhibiting breast cancer growth and metastasis. Mol Cancer Ther; 15(8); 1931-42. ©2016 AACR. PMID:27196773

  17. THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN

    Science.gov (United States)

    THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN.Harland and Liburdy (1) reported that 1.2-uT, 60-Hz magnetic fields could significantly block the inhibitory action of pharmacological levels of tamoxifen (10-7 M) on the growth of MCF-7 human br...

  18. Polynuclear aromatic hydrocarbons (PAHs) differentially influence growth of various emergent wetland species.

    Science.gov (United States)

    Zhang, Zhenhua; Rengel, Zed; Meney, Kathy

    2010-10-15

    The growth of emergent wetland plants may be influenced by toxic organic pollutants, which would influence the extent of phytoremediation when used in constructed wetlands. A series of glasshouse experiments were conducted to investigate the influence of polynuclear aromatic hydrocarbons (PAHs) on the growth of various emergent wetland species. The response of species to PAHs varied significantly. A significant interaction (species x PAH treatment) was observed for relative growth rates (RGRs) of Baumea juncea, Baumea articulata, Schoenoplectus validus and Juncus subsecundus in hydroponics with naphthalene, and of B. juncea and J. subsecundus in soils freshly spiked with phenanthrene and pyrene. In hydroponics, biomass of B. articulata significantly increased in the treatments with relatively low addition of naphthalene, whereas that of S. validus significantly increased with all naphthalene additions. In both hydroponics and soils, the growth of B. juncea increased with the PAH (phenanthrene and pyrene) additions, whereas that of J. subsecundus decreased in the treatments with relatively high concentrations of PAHs. The removal of PAHs from soil was not affected significantly by J. subsecundus after 70 days of growth and B. juncea after 150 days of growth. The growth of J. subsecundus was slightly (but not significantly) influenced by the PAH residues in soil. The effect of PAHs on wetland plant growth could be species-specific regardless of PAH types and media. The response of species to PAHs needs to be taken into account when selecting species for wetlands constructed for phytoremediation. PMID:20633994

  19. Mead acid inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo.

    Science.gov (United States)

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Hamazaki, Kei; Emoto, Yuko; Yuri, Takashi; Yuki, Michiko; Shikata, Nobuaki; Kawashima, Hiroshi; Tsubura, Airo

    2014-10-01

    The effects of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of breast cancer cell growth and metastasis were examined in vitro and in vivo by using the KPL-1 human breast cancer cell line. MA suppressed KPL-1 cell growth in culture with an IC50 value of 214.2 µM (65.7 µg/ml) for 72 h, and MA significantly suppressed transplanted KPL-1 tumor growth (tumor volume and tumor weight: 872±103 mm3 and 1,000±116 mg vs. 376±66 mm3 and 517±84 mg) and regional (axillary) lymph node metastasis (67%, 10/15 vs. 10%, 1/10) in female athymic mice fed an MA-rich diet for 8 weeks. Tumor suppression was due to the suppression of cell proliferation. In ELISA, although vascular endothelial growth factor (VEGF) levels were unchanged, VEGF receptor (VEGFR)1 and VEGFR2 levels were significantly decreased after treatment with a 214.2-µM dose of MA for 72 h; E-cadherin levels were unchanged. As VEGF, VEGFR1 and VEGFR2 expression was co-localized in KPL-1 cells, the mechanism leading to cell growth suppression was VEGF signaling directly to KPL-1 cells by an autocrine process. In contrast, MA did not influence angiogenesis. The mechanisms of action were through VEGF signaling directly to cancer cells. PMID:25109488

  20. Factors Influencing Growth of Women owned Micro and Small Enterprises A Survey of Kitale Municipality

    OpenAIRE

    Ruth Niva Ongachi; Henry M. Bwisa

    2013-01-01

    This study was exploring on the growth status of micro and small enterprises owned by women in Kitale municipality, Trans-Nzoia County, Rift valley province in Kenya and the factors that influenced the growth. The dependent variable in the study was growth, while the independent variables were education, social, cultural, environmental condition, skills, technology and financial capacity. A total of 70 respondents were interviewed using an interview guide instrument carefully developed with s...

  1. Channels Through Which Income Inequality Influences Growth: Fiscal and Political Instability Approaches

    OpenAIRE

    Araceli Ortega Díaz

    2005-01-01

    The present work encloses an analysis related to the channels through which income inequality affects economic growth and another related to the sources of economic growth. In the first, we use two-stage estimation with fixed effects finding that the fiscal effects of inequality on growth may depend on the government expenditure covariate. Secondly, we constructed a political instability index using principal components analysis, and look at its influence on income inequality and economic gro...

  2. Influence of different ammonium, lactate and glutamine concentrations on CCO cell growth

    OpenAIRE

    Slivac, Igor; Blajić, Višnja; Radošević, Kristina; Kniewald, Zlatko; Gaurina Srček, Višnja

    2010-01-01

    In this study the effects of ammonium and lactate on a culture of channel catfish ovary (CCO) cells were examined. We also made investigation on the influence of glutamine, since our previous research revealed that this amino acid stimulated CCO cell growth more than glucose in a concentration-dependent manner. The effect of ammonium in cell culture included the considerable decrease in cell growth rate with eventual growth arrest as well as the retardation of glucose consumption. At ammonium...

  3. 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

  4. Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

    Science.gov (United States)

    Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

    2008-07-01

    Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells. PMID:18469090

  5. Climate indices strongly influence old-growth forest carbon exchange

    Science.gov (United States)

    Wharton, Sonia; Falk, Matthias

    2016-04-01

    We present a decade and a half (1998–2013) of carbon dioxide fluxes from an old-growth stand in the American Pacific Northwest to identify ecosystem-level responses to Pacific teleconnection patterns, including the El Niño/Southern Oscillation (ENSO). This study provides the longest, continuous record of old-growth eddy flux data to date from one of the longest running Fluxnet stations in the world. From 1998 to 2013, average annual net ecosystem exchange (F NEE) at Wind River AmeriFlux was ‑32 ± 84 g C m‑2 yr‑1 indicating that the late seral forest is on average a small net sink of atmospheric carbon. However, interannual variability is high (>300 g C m‑2 yr‑1) and shows that the stand switches from net carbon sink to source in response to climate drivers associated with ENSO. The old-growth forest is a much stronger sink during La Niña years (mean F NEE = ‑90 g C m‑2 yr‑1) than during El Niño when the stand turns carbon neutral or into a small net carbon source (mean F NEE = +17 g C m‑2 yr‑1). Forest inventory data dating back to the 1930s show a similar correlation with the lower frequency Pacific North American (PNA) and Pacific Decadal Oscillation (PDO) whereby higher aboveground net primary productivity (F ANPP) is associated with cool phases of both the PNA and PDO. These measurements add evidence that carbon exchange in old-growth stands may be more sensitive to climate variability across shorter time scales than once thought.

  6. The Influence of Employee Ownership on Intrapreneurship and Growth

    OpenAIRE

    Klaneček, Alojz; Antončièč, Boštjan

    2007-01-01

    Programmes of workers’ participation and profit-sharing may not be as powerful a motivation as ownership. Owners of the majority of shares might like to include managers, experts and routine workers among the shareholders. This study empirically examines the relationship between employee ownership, intrapreneurship, and firm growth. Results of the empirical analysis do not completely support the hypothesis of a positive association between employee ownership and intrapreneurship nor the hypot...

  7. Can supplementary dietary fibre suppress breast cancer growth?

    OpenAIRE

    Stoll, B. A.

    1996-01-01

    Case-control studies in diverse populations around the world have reported a lower risk of breast cancer in association with higher intake of dietary fibre and complex carbohydrates. Although this has not been confirmed in prospective studies in the USA, the observations have prompted the hypothesis that prolonged use of dietary fibre supplements might reduce breast cancer risk in high-incidence populations. Several possible mechanisms of action have been suggested, all involving a reduction ...

  8. Cadmium and nickel combined influence on growth and development of the maize germinant

    OpenAIRE

    T. A. Demura

    2006-01-01

    Extent of toxic influence of cadmium and nickel joint action on growth and development of the maize germinant and plants’ adaptation capabilities to negative influence of heavy metals was studied. Specific protective activity of the phytohormones Emistim C and Zeastimulin under conditions of the cadmium and nickel joint action was shown.

  9. Influence of planting date and weed interference on sweet corn growth and development

    Science.gov (United States)

    Crop planting date and canopy density influence interactions between weeds and sweet corn (Zea mays L.); however, little is known about sweet corn growth response to weed interference. Field studies were conducted in 2004 and 2005 near Urbana, Illinois to quantify the influence of planting date and ...

  10. Tyrosine kinase signalling in breast cancer: Epidermal growth factor receptor and c-Src interactions in breast cancer

    International Nuclear Information System (INIS)

    Both the non-receptor tyrosine kinase, c-Src, and members of the epidermal growth factor (EGF) receptor family are overexpressed in high percentages of human breast cancers. Because these molecules are plasma membrane-associated and involved in mitogenesis, it has been speculated that they function in concert with one another to promote breast cancer development and progression. Evidence to date supports a model wherein c-Src potentiates the survival, proliferation and tumorigenesis of EGF receptor family members, in part by associating with them. Phosphorylation of the EGF receptor by c-SRC is also critical for mitogenic signaling initiated by the EGF receptor itself, as well as by several G-protein coupled receptors (GPCRs), a cytokine receptor, and the estrogen receptor. Thus, c-Src appears to have pleiotropic effects on cancer cells by modulating the action of multiple growth-promoting receptors

  11. 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.

  12. Neuroendocrine Cancer-Specific Up-Regulating Mechanism of Insulin-Like Growth Factor Binding Protein-2 in Small Cell Lung Cancer

    OpenAIRE

    Yazawa, Takuya; Sato, Hanako; Shimoyamada, Hiroaki; Okudela, Koji; Woo, Tetsukan; Tajiri, Michihiko; Ogura, Takashi; Ogawa, Nobuo; Suzuki, Takehisa; Mitsui, Hideaki; Ishii, Jun; Miyata, Chie; Sakaeda, Masashi; Goto, Kazuya; Kashiwagi, Korehito

    2009-01-01

    Small cell lung cancer (SCLC) exhibits insulin-like growth factor-dependent growth. SCLC is the most aggressive among known in vivo lung cancers, whereas in vitro growth of SCLC is paradoxically slow as compared with that of non-SCLC (NSCLC). In this study, we demonstrate that SCLC cells overexpress insulin-like growth factor binding protein (IGFBP)-2 via NeuroD, a neuroendocrine cell-specific transcription factor. Chromatin immunoprecipitation, electrophoretic mobility shift, and IGFBP-2 pro...

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

    OpenAIRE

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

    2009-01-01

    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...

  14. 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.

  15. Participation in bowel cancer screening: a qualitative exploration of the factors influencing participation and uptake

    OpenAIRE

    Azodo, Ijeoma

    2013-01-01

    Bowel cancer is major global public health problem. In the United Kingdom, it is the third most common cancer in men and women and second major cause of cancer deaths. It has been suggested that the risk of bowel cancer deaths can be reduced by 16% through regular bowel screening. However, screening uptake remains low. This research explored factors influencing participation in the NHS bowel cancer screening programme, specifically ‘the faecal occult blood test (FOBt)’ in the North East, York...

  16. Exploring important influences on the healthfulness of prostate cancer survivors' diets.

    Science.gov (United States)

    Coa, Kisha I; Smith, Katherine C; Klassen, Ann C; Thorpe, Roland J; Caulfield, Laura E

    2015-06-01

    A cancer diagnosis is often conceptualized as a teachable moment when individuals might be motivated to make lifestyle changes. Many prostate cancer survivors, however, do not adhere to dietary guidelines. In this article, we explore how cancer affected prostate cancer survivors' diets and identify important influences on diet. Twenty prostate cancer survivors completed three 24-hour dietary recalls and an in-depth dietary interview. We analyzed interviews using a constant comparison approach, and dietary recall data quantitatively to assess quality and qualitatively to identify food choice patterns. Most men reported not making dietary changes following their cancer diagnosis but did express an interest in healthy eating, primarily to facilitate weight loss. Men portrayed barriers to healthy eating that often outweighed their motivation to eat healthy. Public health programs should consider alternative ways of framing healthy eating programs for prostate cancer survivors that might be more effective than a cancer-specific focus. PMID:25857653

  17. Growth Inhibitory and Apoptosis-inducing Effects of Xanthohumol, a Prenylated Chalcone Present in Hops, in Human Prostate Cancer Cells

    OpenAIRE

    DEEB, D.; Gao, X; Jiang, H.; Arbab, A.S.; Dulchavsky, S. A.; Gautam, S.C.

    2010-01-01

    Promotion of apoptosis in cancer cells could potentially lead to the regression and improved prognosis of hormone-refractory prostate cancer. Xanthohumol (XN), a prenylated chalcone-derived from hops, has shown strong antitumorigenic activity towards diverse types of cancer cells. In the present study, the growth-inhibitory and apoptosis-inducing activity of XN was tested in hormone-sensitive and hormone-refractory human prostate cancer cells lines. Cell growth/viability assay (MTS) demonstra...

  18. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

    Science.gov (United States)

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-01-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  19. Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad

    OpenAIRE

    Nickerson, Nicole K.; Mohammad, Khalid S.; Gilmore, Jennifer L.; Crismore, Erin; Bruzzaniti, Angela; Guise, Theresa A.; Foley, John

    2012-01-01

    Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and oste...

  20. Influence of Listeria innocua on the growth of Listeria monocytogenes

    OpenAIRE

    Carvalheira, Ana; Eusébio, Cátia; Silva, Joana; Gibbs, Paul; Teixeira, Paula

    2009-01-01

    The growth of Listeria monocytogenes and Listeria innocua strains was monitored during this study: (i) in TSB–YE media and (ii) in a food matrix (pasteurized milk) according to the ISO 11290-1 methodology. Different inocula concentrations and mixtures were tested. The response was shown to be strain dependent. In TSB–YE the inhibition of a L. monocytogenes strain was observed in just one of the three mixtures (L. monocytogenes_1340 with L. innocua_11288) showing a reduction of 1.3...

  1. Influence of polychlorinated biphenyls on the growth of chicken embryos

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Yasuhiko; Hatano, Akira [Chub Women`s College, Gifu-ken (Japan)

    1994-12-31

    Incubation of chicken embryos with either 0.01 or 0.03 ppm polychlorinated biphenyls (PCBs) for 12, 15, or 18 d resulted in a significant decrease in liver and body weight associated with enhanced mortality. Teratological examination revealed an increased frequency of malformations including hydrops, eventration, wry neck, and brevicollis. PCB exposure was also found to produce histologic damage to liver and cutaneous tissue. Our data demonstrate that exposure of chicks to PCBs during development results in a retardation of growth, an increased incidence of malformations, and histopathologic damage. 9 refs., 2 figs., 4 tabs.

  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. Silencing of LASP-1 influences zyxin localization, inhibits proliferation and reduces migration in breast cancer cells

    International Nuclear Information System (INIS)

    LIM and SH3 protein (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell migration. LASP-1 is an actin binding protein, which also interacts with the proline-rich domains of zyxin, a scaffolding protein required for cell movement and gene transcription. In the present work, we analyzed the effect of LASP-1 on different human breast cancer cell lines. Transfection with LASP-1-specific siRNA resulted in a reduced protein level of LASP-1 in BT-20 and MCF-7 cell lines. The siRNA-treated cells were arrested in G2/M phase of cell cycle, and proliferation of the tumor cells was suppressed by 30-50% corresponding to around 50% of the cells being transfected successfully as seen by immunofluorescence. In addition, tumor cells showed a 50% reduced migration after siRNA treatment, while overexpression of LASP-1 in non-tumor PTK-2 cells, which do not express endogenous LASP-1, resulted in a significant increase in cell motility. LASP-1 silencing is accompanied with a reduced binding of the of LASP-1 binding partner zyxin to focal contacts without changes in actin stress fiber organization as observed in immunofluorescence experiments. The data provide evidence for an essential role of LASP-1 in tumor cell growth and migration, possibly by influencing the localization of zyxin

  4. Radioresponsiveness of locally advanced breast cancer. Analysis of factors influencing the response to radiation therapy

    International Nuclear Information System (INIS)

    The radioresponsiveness of locally advanced breast cancer was studied in 239 patients treated with primary RT from 1977 to 1985. The response to RT was assessed on clinical and histological bases. For patients with no residual disease or heavily damaged residual disease in the breast and negative axillary lymph nodes after RT, the 5-year probability of local tumour control (LTC) was 90%. Response to RT was mainly affected by the T and N stages. Primary tumour size or RT dose had only a moderate influence on tumour response in this stage of the disease. The 5-year LTC was 37% for N3 and 43% for T4d conditions. Heavy tumour tissue damage was associated with microcapillary lesions, while the microvasculature around the florid tumour growth was in better condition. Microcapillaries have to be regarded as an important target in RT. The oxygen supply may worsen during fractionated RT as a result of vascular damage. Chronically hypoxic cells may be killed earlier than euoxic ones. Findings indicate that the radioresponsiveness of locally advanced breast cancer is more likely to be attributable to the biological nature of the disease than to chronically hypoxic cells present during RT. (author)

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

    International Nuclear Information System (INIS)

    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

  6. 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.

  7. Influences of environmental and chemical parameters on the spatial growth patterns of four riverine cyprinid fishes

    Directory of Open Access Journals (Sweden)

    Liu C.

    2015-01-01

    Full Text Available Understanding intraspecific variability in fish somatic growth rates is important as growth is a key life history trait that plays a fundamental role in many biological and ecological processes. Here, the influence of environmental and chemical parameters was tested on intraspecific variability in growth rates of the cyprinid fishes roach Rutilus rutilus, chub Squalius cephalus and dace Leuciscus leuciscus across 13 rivers in England, and also compared with those for barbel Barbus barbus from the same rivers. Outputs indicated that growth rate responses to the parameters were species-specific, with more significant effects generally detected on juvenile growth than lifetime growth. For R. rutilus and S. cephalus, latitude (as a surrogate of temperature was the most significant predictor of their growth rates, with growth rates decreasing as latitude increased. Contrary to prediction, aspects of degraded water quality accelerated the growth rates of these fishes, except in B. barbus, although concentrations of nitrogenous compounds were below toxicity thresholds. This emphasizes the ability of populations of these cyprinid fishes to tolerate some environmental disturbances and, in entirety, suggests that the intraspecific variability in the growth rates of these fishes is significantly influenced by abiotic parameters and their association with levels of anthropogenic disturbance.

  8. Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth

    OpenAIRE

    Wan, Xinhai; Li, Zhi-gang; Yingling, Jonathan M.; Yang, Jun; Starbuck, Michael W.; Ravoori, Murali K.; Kundra, Vikas; Vazquez, Elba; Navone, Nora M.

    2011-01-01

    Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice ...

  9. Direct Observation of Transient Surface Species during Ge Nanowire Growth and Their Influence on Growth Stability.

    Science.gov (United States)

    Sivaram, Saujan V; Shin, Naechul; Chou, Li-Wei; Filler, Michael A

    2015-08-12

    Surface adsorbates are well-established choreographers of material synthesis, but the presence and impact of these short-lived species on semiconductor nanowire growth are largely unknown. Here, we use infrared spectroscopy to directly observe surface adsorbates, hydrogen atoms and methyl groups, chemisorbed to the nanowire sidewall and show they are essential for the stable growth of Ge nanowires via the vapor-liquid-solid mechanism. We quantitatively determine the surface coverage of hydrogen atoms during nanowire growth by comparing ν(Ge-H) absorption bands from operando measurements (i.e., during growth) to those after saturating the nanowire sidewall with hydrogen atoms. This method provides sub-monolayer chemical information at relevant reaction conditions while accounting for the heterogeneity of sidewall surface sites and their evolution during elongation. Our findings demonstrate that changes to surface bonding are critical to understand Ge nanowire synthesis and provide new guidelines for rationally selecting catalysts, forming heterostructures, and controlling dopant profiles. PMID:26147949

  10. The influence of low intensity microwave on some bacterial growth

    International Nuclear Information System (INIS)

    The action for of low intensity microwaves (power density 10 mW/cm2, frequency of about 10.75 GHz) on growth dynamics was searched in two microbial cultures: Staphylococcus aureus ATCC-6538 (Gram positive bacteria) and Escherichia coli ATCC-10536 (Gram negative bacteria). It was evaluated the number of living cells/ml using a JASCO spectrophotometer for measurements carried out at 3, 6 , 9, 12, 24, 36, 48 and 72 hours in samples and controls. The results obtained revealed a stimulatory effect of microwaves on cell multiplication in both tested bacteria all over the experiment. Statistical computation showed different mathematical functions for experimental graphs approach. Logarithmic function was found to fit to E. coli growth (correlation coefficient equal to 0.978) while exponential function was found to approximate S. aureus dynamics (correlation coefficient equal to 0.758). A low thermal effect could be the main cause of such behaviour, as expected. However, a non-thermal effect could also be involved in the dynamics of these pathogen microorganisms. (authors)

  11. 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.

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

    International Nuclear Information System (INIS)

    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 E2 (PGE2) 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.

  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. 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

  15. BRD4 Inhibitor Inhibits Colorectal Cancer Growth and Metastasis

    Directory of Open Access Journals (Sweden)

    Yuan Hu

    2015-01-01

    Full Text Available Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT. This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal.

  16. Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth.

    OpenAIRE

    Adams, W J; Lawson, J. A.; Morris, D. L.

    1994-01-01

    The effect of histamine and cimetidine on the growth of four human colon cancer cell lines was studied. Histamine significantly stimulated the uptake of tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and 116% of controls for C170 and LIM2412, respectively. This effect was antagonised by cimetidine, but not diphenhydramine. Histamine also stimulated a dose dependent increase in cyclic adenosine monophosphate accumulation in C170 cells, antagonised by cimetidine. ...

  17. Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

    OpenAIRE

    Camirand, Anne; Zakikhani, Mahvash; Young, Fiona; Pollak, Michael

    2005-01-01

    Introduction Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemo...

  18. 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

  19. Hedgehog Signaling Regulates Bladder Cancer Growth And Tumorigenicity

    OpenAIRE

    Fei, Dennis Liang; Sanchez-Mejias, Avencia; Wang, Zhiqiang; Flaveny, Colin; Long, Jun; Singh, Samer; Rodriguez-Blanco, Jezabel; Tokhunts, Robert; Giambelli, Camilla; Briegel, Karoline J.; Schulz, Wolfgang A; Gandolfi, A. Jay; Karagas, Margaret; Zimmers, Teresa A.; Jorda, Merce

    2012-01-01

    The role of HEDGEHOG (HH) signaling in bladder cancer remains controversial. The gene encoding the HH receptor and negative regulator PATCHED1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1 functioning as a classic tumor suppressor gene, loss-of-function mutations in the remaining copy of PTCH1 are not commonly found. Here, we provide direct evidence for a critical role of HH signaling in bladder carcinogenesis. We...

  20. In vitro effects of recombinant human growth hormone on growth of human gastric cancer cell line BGC823 cells

    Institute of Scientific and Technical Information of China (English)

    Jia-Yong Chen; Dao-Ming Liang; Ping Gan; Yi Zhang; Jie Lin

    2004-01-01

    AIM: To study the effects of recombinant human growth hormone (rhGH) on growth of human gastric cancer cell line in vitro.METHODS: Experiment was divided into control group,rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cell inhibitory rate, cell cycle, cell proliferation index (PI) and DNA inhibitory rate of human gastric cancer line BGC823, at different concentrations of rhGH treatment were studied by cell culture, MTT assay and flow cytometry.RESULTS: The distinctly accelerated effects of rhGH on multiplication of BGC823 cell line were not found in vitro.There was no statistical significance between rhGH group and control group, or between rhGH+L-OHP group and LOHP group (P>0.05). The cell growth curve did not rise.Cell inhibitory rate and cells arrested in G0-G1 phase were obviously increased. Meanwhile, cells in S phase and PI were distinctly decreased and DNA inhibitory rate was obviously increased in rhGH+L-OHP group in comparison with control group and rhGH group, respectively (P<0.01).Cell inhibitory rate showed an increasing trend and PI showed a decreasing trend in rhGH+L-OHP group compared with L-OHP group.CONCLUSION: In vitro rhGH does not accelerate the multiplication of human gastric cancer cells. It may increase the therapeutic efficacy when it is used in combination with anticancer drugs.

  1. 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.

  2. Influence of family size and birth order on risk of cancer: a population-based study

    OpenAIRE

    Sundquist Jan; Thomsen Hauke; Weires Marianne; Bevier Melanie; Hemminki Kari

    2011-01-01

    Abstract Background Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. Methods We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeco...

  3. Angiogenin mediates androgen-stimulated growth of prostate cancer cells and correlates with castration resistance

    OpenAIRE

    Li, Shuping; Hu, Miaofen G.; Sun, Yeqing; YOSHIOKA, NORIE; IBARAGI, SOICHIRO; Sheng, Jinghao; Sun, Guangjie; Kishimoto, Koji; Hu, Guo-fu

    2013-01-01

    Androgen receptor (AR) is a critical effector of prostate cancer (PCa) development and progression. Androgen-dependent PCa rely on the function of AR for growth and progression. Many castration-resistant PCa continue to depend on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of PCa cells. During androgen-dependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the...

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

    OpenAIRE

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

    2014-01-01

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

  5. Influence of Obesity on Anastomotic Leakage After Anterior Rectal Resectionperformed Due to Cancer

    Directory of Open Access Journals (Sweden)

    Piecuch Jerzy

    2015-03-01

    Full Text Available Anterior resection for rectal cancer carries the risk of serious complications, especially fistulas at the site of anastomosis. Numerous factors have been shown to impact anastomotic leakage. The results of studies on the influence of obesity on the frequency of anastomotic leakage after rectal resection performed due to cancer have been contradictory.

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

    International Nuclear Information System (INIS)

    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

  7. 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.

  8. Socio-cultural influences on the help-seeking behavior of patients with cancer.

    OpenAIRE

    Corner, Jessica L; Brindle, Lucy A

    2010-01-01

    Abstract ABSTRACT This paper sets out to review the influence of social processes on the timing of diagnosis of cancer and to explore the potential for promoting earlier diagnosis by addressing social factors which influence symptom recognition and the diagnostic process. Social processes refer to the means by which culture and social organisation may impact on timely cancer diagnosis. The paper calls for concerted action around an important and developing research agenda that...

  9. Diet-induced Obesity and Insulin Resistance Spur Tumor Growth and Cancer Cachexia in Rats Bearing the Yoshida Sarcoma

    OpenAIRE

    Honors, Mary Ann; Kinzig, Kimberly P.

    2014-01-01

    Obesity and insulin resistance are associated with increased risk of cancer and cancer mortality. However, it is currently unknown whether they contribute to the development of cancer cachexia, a syndrome that contributes significantly to morbidity and mortality in individuals with cancer. The present experiment addresses the question of whether pre-existing obesity and insulin resistance alter tumor growth and cancer cachexia symptoms in Yoshida sarcoma bearing male rats. Obesity and insulin...

  10. The roles of support seeking and race/ethnicity in posttraumatic growth among breast cancer survivors

    OpenAIRE

    Kent, Erin E.; Alfano, Catherine M.; Smith, Ashley Wilder; Bernstein, Leslie; McTiernan, Anne; Baumgartner, Kathy B.; Ballard-Barbash, Rachel

    2013-01-01

    Posttraumatic growth (PTG) after cancer can minimize the emotional impact of disease and treatment; however, the facilitators of PTG, including support-seeking, are unclear. We examined the role of support-seeking on PTG among 604 breast cancer survivors ages 40–64 from the Health Eating, Activity, and Lifestyle (HEAL) Study. Multivariable linear regression was used to examine predictors of support-seeking (participation in support groups and confiding in healthcare providers) as well as the ...

  11. IGFBP3 promotes esophageal cancer growth by suppressing oxidative stress in hypoxic tumor microenvironment

    OpenAIRE

    Natsuizaka, Mitsuteru; Kinugasa, Hideaki; Kagawa, Shingo; Whelan, Kelly A.; NAGANUMA, Seiji; Subramanian, Harry; Chang, Sanders; Nakagawa, Kei J; Rustgi, Naryan L; Kita, Yoshiaki; Natsugoe, Shoji; Basu, Devraj; Gimotty, Phyllis A.; Klein-Szanto, Andres J.; Diehl, J. Alan

    2014-01-01

    Insulin-like growth factor binding protein 3 (IGFBP3), a hypoxia-inducible gene, regulates a variety of cellular processes including cell proliferation, senescence, apoptosis and epithelial-mesenchymal transition (EMT). IGFBP3 has been linked to the pathogenesis of cancers. Most previous studies focus upon proapoptotic tumor suppressor activities of IGFBP3. Nevertheless, IGFBP3 is overexpressed in certain cancers including esophageal squamous cell carcinoma (ESCC), one of the most aggressive ...

  12. 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.

  13. 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.

  14. 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.

  15. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis

    OpenAIRE

    XIAN, SHU-LIN; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2014-01-01

    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 wa...

  16. Insulin-like growth factors and risk of kidney cancer in men

    OpenAIRE

    Major, J M; Pollak, M N; Snyder, K; Virtamo, J; Albanes, D

    2010-01-01

    Background: Insulin-like growth factor-I (IGF-I) has been shown to increase kidney growth, glomerular filtration rate, and renal function. Methods: In the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study of 29 133 Finnish male smokers aged 50–69 years, serum concentrations of IGF were measured in samples collected in 1985–1988. A total of 100 men with kidney cancer diagnosed ⩾5 years after blood collection through 1997 were compared with a subcohort of 400 men; logis...

  17. 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.

  18. Influence of oxygen transfer on Pseudomonas putida effects on growth rate and biodesulfurization capacity.

    Science.gov (United States)

    Escobar, S; Rodriguez, A; Gomez, E; Alcon, A; Santos, V E; Garcia-Ochoa, Felix

    2016-04-01

    The growth rate and desulfurization capacity accumulated by the cells during the growth of Pseudomonas putida KTH2 under different oxygen transfer conditions in a stirred and sparged tank bioreactor have been studied. Hydrodynamic conditions were changed using different agitation conditions. During the culture, several magnitudes associated to growth, such as the specific growth rate, the dissolved oxygen concentration and the carbon source consumption have been measured. Experimental results indicate that cultures are influenced by the fluid dynamic conditions into the bioreactor. An increase in the stirrer speed from 400 to 700 rpm has a positive influence on the cell growth rate. Nevertheless, the increase of agitation from 700 to 2000 rpm hardly has any influence on the growth rate. The effect of fluid dynamics on the cells development of the biodesulfurization (BDS) capacity of the cells during growth is different. The activities of the intracellular enzymes involved in the 4S pathway change with dissolved oxygen concentration. The enzyme activities have been evaluated in cells at several growth time and different hydrodynamic conditions. An increase of the agitation from 100 to 300 rpm has a positive influence on the development of the overall BDS capacity of the cells during growth. This capacity shows a decrease for higher stirrer speeds and the activity of the enzymes monooxygenases DszC and DszA decreases dramatically. The highest value of the activity of DszB enzyme was obtained with cells cultured at 100 rpm, while this activity decreases when the stirrer speed was increased higher than this value. PMID:26762940

  19. Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice

    OpenAIRE

    Yan, Wei; Wang, Ting-Yu; Fan, Qi-ming; Du, Lin; Xu, Jia-ke; Zhai, Zan-jing; Li, Hao-wei; Tang, Ting-ting

    2014-01-01

    Aim: To investigate the effects of plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica, on human breast cancer cell growth and the cancer cell-induced osteolysis in the bone microenvironment of mice. Methods: Human breast cancer cell subline MDA-MB-231SA with the ability to spread and grow in the bone was tested. The cell proliferation was determined using the CCK-8 assay. Apoptosis was detected with Annexin V/PI double-labeled flow cytometry. Red fluorescent prote...

  20. 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.

  1. 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.

  2. Growth inhibition of high-intensity focused ultrasound on hepatic cancer in vivo

    Institute of Scientific and Technical Information of China (English)

    Xiu-Jie Wang; Shu-Lan Yuan; Yan-Rong Lu; Jie Zhang; Bo-Tao Liu; Wen-Fu Zeng; Yue-Ming He; Yu-Rui Fu

    2005-01-01

    AIM: To investigate the damaging effect of high-intensity focused ultrasound (HIFU) on cancer cells and the inhibitory effect on tumor growth.METHODS: Murine H22 hepatic cancer cells were treated with HIFU at the same intensity for different lengths of time and at different intensities for the same length of timein vitro, the dead cancer cells were determined by trypan blue staining. Two groups of cancer cells treated with HIFU at the lowest and highest intensity were inoculated into mice. Tumor masses were removed and weighed after 2 wk, tumor growth in each group was confirmed pathologically.RESULTS: The death rate of cancer cells treated with HIFU at 1 000 W/cm2 for 0.5, 1, 2, 4, 8, and 12 s was 3.11±1.21%, 13.37±2.56%, 38.84±3.68%, 47.22±5.76%,87.55±7.32%, and 94.33±8.11%, respectively. A positive relationship between the death rates of cancer ceils and the length of HIFU treatment time was found (r = 0.96,P<0.01). The death rate of cancer cells treated with HIFU at the intensity of 100, 200, 400, 600, 800, and 1 000 W/cm2 for 8 s was 26.31±3.26%, 31.00±3.87%, 41.97±5.86%,72.23±8.12%, 94.90±8.67%, and 99.30±9.18%,respectively. A positive relationship between the death rates of cancer cells and the intensities of HIFU treatment was confirmed (r = 0.98, P<0.01). The cancer cells treated with HIFU at 1 000 W/cm2 for 8 s were inoculated into mice ex vivo. The tumor inhibitory rate was 90.35%compared to the control (P<0.01). In the experimental group inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 0.5 s, the tumor inhibitory rate was 22.9% (P<0.01). By pathological examination, tumor growth was confirmed in 8 out of 14 mice (57.14%, 8/14)inoculated with the cancer cells treated with HIFU at 1 000 W/cm2 for 8 s, which was significantly lower than that in the control (100%, 15/15, P<0.05).CONCLUSION: HIFU is effective on killing or damage of H22 hepatic cancer cellsin vitro and on inhibiting tumor growth in mice ex vivo.

  3. 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.

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

    International Nuclear Information System (INIS)

    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

  5. Influence of mineral suspension on the phytoplankton growth

    Science.gov (United States)

    Schure, L. A.; Aponasenko, A. D.; Postnikova, P. V.; Filimonov, V. S.; Lopatin, V. N.

    2006-02-01

    Effect of organomineral suspension on development of plankton community which are included in microbial food web has been studied in the laboratory and in the field. In the course of the model experiment it was found that in samples with adding suspension the chlorophyll concentration (C chl) increase runs more intensively and the longer time period. Increase C chl in the control ran up to 67 days with the following going out to the stationary level at maximum value 220 mkg/l. In samples with adding 100 mg/l suspension the stationary level was not reached to the 80 days of the experiment and the maximum chlorophyll concentration made 520 mkg/l. In field studies it was ascertained that all the parameters related to production characteristics of bacterioplankton as well as to organic matter adsorbed on mineral suspension greatly influence the production characteristics of phytoplankton. The multiplicative model of dependence of a primary production from primary factors of environment: the content of chlorophyll, specific absorption coefficient of light by the dissolved organic matter, content of adsorbed organic matter, bacterial production and destruction, mean size of phytoplankton cells is offered. It would follow from this model that if bacterioplankton production increases twice (at remaining other parameters constant) then primary production will be 2.5 times larger in the Khanka Lake, 1.9 times in the Yenisei River and 1.4 times in Krasnoyarsk water storage.

  6. 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.

  7. Micronutrient influence in Nannochloropsis sp. growth and biochemical profile

    Directory of Open Access Journals (Sweden)

    Catarina Rosado Correia

    2014-06-01

    Full Text Available Microalgae are a heterogeneous group, which includes various and distinct taxa. However, few genera are actively used in aquaculture, due to the lack of specific requirements, like adequate size, shape and non-toxic. Nannochloropsis sp. is one of the main microalgae used in aquaculture, due to its nutritional profile and for being a fast-growing microalgae. Despite its characteristics, large-scale culture of Nannochloropsis sp. is in constant improvement, in order to accomplish the best productivity, combined with an adequate biochemical profile. In an attempt to achieve this, an experimental set-up was tested with microalgae grown in four different culture media: (1 NutriBloom [NB] (commercial medium used at Necton’s facilities, (2 NutriBloom without cobalt [NB w/Co], (3 Simplex [S] (no addition of iron or any micronutrient and (4 Sea Mineral Solution [SMS]. Nannochloropsis’s contents of protein, carbohydrates, total lipid and PUFA’s were controlled at logarithmic and stationary phases of growth, using classical techniques, as mentioned in Lowry (1951, Dubois (1956, Bligh and Dyer (1959 and Lepage & Roy (1986. Higher productivity, dry weight and number of cells were achieved when cultured in NB and NB w/Co. In the logarithmic phase, NB w/Co presented the higher protein content, SMS showed the higher percentage of lipid and polyunsaturated fatty acids (PUFAS. In the stationary phase, S medium showed higher lipid percentage; nevertheless, NB medium presented the higher content of protein and PUFAs. In both phases, NB medium had the higher sugar content. Differences between micronutrient concentrations explain the verified variations in the microalgae’s biochemical profile, particularly iron, copper, cobalt and molybdenium variations.

  8. Receptor-interacting protein-1 promotes the growth and invasion in gastric cancer.

    Science.gov (United States)

    Zhu, Guangwei; Ye, Jianxin; Huang, Yongjian; Zheng, Wei; Hua, Jin; Yang, Shugang; Zhuang, Jinfu; Wang, Jinzhou

    2016-06-01

    The receptor-interacting protein-1 (RIP-1) is an important molecular in inflammation signaling pathways, but the role of RIP-1 in gastric cancer is largely unknown. In this study, we tested the expression of RIP-1 in gastric cancer samples and analyzed the effects of expression of RIP-1 on the prognosis in gastric cancer patients. We analyzed the role of the RIP-1 in gastric cancer cells and addressed the functional role of RIP-1 using a xenograft mouse model. A lentivirus-based effective RIP-1 siRNA vector was infected into HGC and AGS cells. The effect of RIP-1 siRNA on HGC and AGS cells were investigated by cell proliferation assay and invasion assay. Furthermore, we examined the role of RIP-1-siRNA on HGC cells in the mice with subcutaneous xenograft tumor, and preliminarily analyzed the underlying mechanisms. The results indicated that the expression of RIP-1 in the gastric cancer tissues was significantly higher than the expression in the normal gastric tissues. Additionally, RIP-1 immunoreactivity was positive at the site of invasion, but little or no immunoreactivity was detected at the gastric cancer parts of interstitial substance. Gastric cancer patients with high expression of RIP-1 had a poor survival rate. RIP-1 expression in the gastric cancer cell lines were general. HGC-R-1-RNAi-LV inhibited HGC and AGS cell proliferation and invasion ability in vitro. RIP-NF-κB/AP-1-VEGF-C signaling pathways have a crucial role in the regulate the biological functions of HGC cells. HGC-R-1-RNAi-LV suppressed tumor growth in the HGC cell subcutaneous xenograft model. In conclusion, our data indicate that RIP-1 promote the growth and invasion of gastric cancer in vitro and in vivo, additionally providing evidence that targeting RIP-1 may be useful in the treatment of gastric cancer. PMID:27035122

  9. Epidermal growth factor receptor analyses in colorectal cancer

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...... 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. No...

  10. Dual roles of PARP-1 promote cancer growth and progression

    OpenAIRE

    Schiewer, Matthew J.; Goodwin, Jonathan F.; Han, Sumin; Brenner, J. Chad; Augello, Michael A.; Dean, Jeffry L.; Liu, Fengzhi; Planck, Jamie L.; Ravindranathan, Preethi; Chinnaiyan, Arul M.; McCue, Peter; Gomella, Leonard G.; Raj, Ganesh V; Dicker, Adam P.; Brody, Jonathan R

    2012-01-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme that modifies substrates by poly(ADP-ribose)-ylation. PARP-1 has well-described functions in DNA damage repair, and also functions as a context-specific regulator of transcription factors. Using multiple models, data demonstrate that PARP-1 elicits pro-tumorigenic effects in androgen receptor (AR)-positive prostate cancer (PCa) cells, both in the presence and absence of genotoxic insult. Mechanistically, PARP-1 is recruited ...

  11. Functional characterization of Trip10 in cancer cell growth and survival

    Directory of Open Access Journals (Sweden)

    Yan Pearlly S

    2011-02-01

    Full Text Available Abstract Background The Cdc42-interacting protein-4, Trip10 (also known as CIP4, is a multi-domain adaptor protein involved in diverse cellular processes, which functions in a tissue-specific and cell lineage-specific manner. We previously found that Trip10 is highly expressed in estrogen receptor-expressing (ER+ breast cancer cells. Estrogen receptor depletion reduced Trip10 expression by progressively increasing DNA methylation. We hypothesized that Trip10 functions as a tumor suppressor and may be involved in the malignancy of ER-negative (ER- breast cancer. To test this hypothesis and evaluate whether Trip10 is epigenetically regulated by DNA methylation in other cancers, we evaluated DNA methylation of Trip10 in liver cancer, brain tumor, ovarian cancer, and breast cancer. Methods We applied methylation-specific polymerase chain reaction and bisulfite sequencing to determine the DNA methylation of Trip10 in various cancer cell lines and tumor specimens. We also overexpressed Trip10 to observe its effect on colony formation and in vivo tumorigenesis. Results We found that Trip10 is hypermethylated in brain tumor and breast cancer, but hypomethylated in liver cancer. Overexpressed Trip10 was associated with endogenous Cdc42 and huntingtin in IMR-32 brain tumor cells and CP70 ovarian cancer cells. However, overexpression of Trip10 promoted colony formation in IMR-32 cells and tumorigenesis in mice inoculated with IMR-32 cells, whereas overexpressed Trip10 substantially suppressed colony formation in CP70 cells and tumorigenesis in mice inoculated with CP70 cells. Conclusions Trip10 regulates cancer cell growth and death in a cancer type-specific manner. Differential DNA methylation of Trip10 can either promote cell survival or cell death in a cell type-dependent manner.

  12. URG11 promotes gastric cancer growth and invasion by activation of β-catenin signalling pathway

    OpenAIRE

    Du, Rui; Xia, Lin; Sun, Shiren; Lian, Zhaorui; Zou, Xue; Gao, Juan; Xie, Huahong; Fan, Rui; Song, Jiugang; Li, Xiaohua; Liu, Jie; Fan, Daiming

    2008-01-01

    Abstract Upregulated gene 11 (URG11), a new gene upregulated by Heptatitis B Virus X protein (HBx), was previously shown to activate β-catenin and promote hepatocellular growth and tumourigenesis. Although the oncogenic role of URG11 in the development of hepatocellular carcinoma has been well documented, its relevance to other human malignancies and the underlying molecular mechanisms remain largely unknown. Here we reported a novel function of URG11 to promote gastric cancer growth and meta...

  13. Fatty acid control of growth of human cervical and endometrial cancer cells.

    OpenAIRE

    Gleeson, R P; Ayub, M.; Wright, J T; Wood, C B; Habib, N.A.; Soutter, W P; Sullivan, M. H.; White, J. O.

    1990-01-01

    Stearic acid and iodo-stearic and inhibited cell growth in a cervical cancer cell line (HOG-1) in a dose-related manner, with a half maximal effect at 50 microM stearic acid. Addition of oleic acid abrogated the effect of stearic acid. EGF-stimulated DNA synthesis and growth of HOG-1 cells was inhibited in the presence of stearic acid without any apparent effect on EGF receptor number or affinity.

  14. Red radiation and choline compounds influence growth and greening of wheat seedlings

    International Nuclear Information System (INIS)

    The effects of 2-chloroethyltrimethylammonium chloride (CCh), 2-ethyltrimethylammonium chloride (Ch), and acetylcholine chloride (ACh) at concentrations of 1 microM-5 mM and of red radiation (R) pulse on growth, greening, and formation of the photosynthetic apparatus in etiolated wheat seedlings (Triticum aestivum cv. Moskovskaya-35) were examined. A short-term application of cholines and R pulse simulated the first leaf growth and its appearance from coleoptile, and inhibited the coleoptile growth. CCh, Ch, and R were stimulators of greening and increased the photosynthetic activity, whereas Ach did not influence the process of greening. Joint effects of R with cholines on the growth and photomorphogenesis were greater than the individual ones, whereas far-red (FR) radiation decreased the influence of cholines

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

    Directory of Open Access Journals (Sweden)

    J. Buczek

    2015-05-01

    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.

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

    OpenAIRE

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

    2011-01-01

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

  17. URG11 promotes gastric cancer growth and invasion by activation of β-catenin signalling pathway

    Science.gov (United States)

    Du, Rui; Xia, Lin; Sun, Shiren; Lian, Zhaorui; Zou, Xue; Gao, Juan; Xie, Huahong; Fan, Rui; Song, Jiugang; Li, Xiaohua; Liu, Jie; Fan, Daiming

    2010-01-01

    Abstract Upregulated gene 11 (URG11), a new gene upregulated by Heptatitis B Virus X protein (HBx), was previously shown to activate β-catenin and promote hepatocellular growth and tumourigenesis. Although the oncogenic role of URG11 in the development of hepatocellular carcinoma has been well documented, its relevance to other human malignancies and the underlying molecular mechanisms remain largely unknown. Here we reported a novel function of URG11 to promote gastric cancer growth and metastasis. URG11 was found to be highly expressed in gastric cancer tissues compared with adjacent nontumourous ones by immunohistochemical staining and western blot. Knockdown of URG11 expression by small interfering RNA (siRNA) effectively attenuated the proliferation, anchorage-independent growth, invasiveness and metastatic potential of gastric cancer cells. URG11 inhibition led to decreased expression of β-catenin and its nuclear accumulation in gastric cancer cells and extensive costaining between URG11 and β-catenin was observed in gastric cancer tissues. Transient transfection assays with the β-catenin promoter showed that it was inhibited by URG11-specific small inhibitory RNA. Moreover, suppression of endogenous URG11 expression results in decreased activation of β-catenin/TCF and its downstream effector genes, cyclinD1 and membrane type 1 matrix metallopeptidase (MT1-MMP), which are known to be involved in cell proliferation and invasion, respectively. Taken together, our data suggest that URG11 contributes to gastric cancer growth and metastasis at least partially through activation of β-catenin signalling pathway. These findings also propose a promising target for gene therapy in gastric cancer. PMID:19413886

  18. 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.

  19. Metastases and Colon Cancer Tumor Growth Display Divergent Responses to Modulation of Canonical WNT Signaling.

    Directory of Open Access Journals (Sweden)

    Chandan Seth

    Full Text Available Human colon cancers commonly harbor loss of function mutations in APC, a repressor of the canonical WNT pathway, thus leading to hyperactive WNT-TCF signaling. Re-establishment of Apc function in mice, engineered to conditionally repress Apc through RNAi, resolve the intestinal tumors formed due to hyperactivated Wnt-Tcf signaling. These and other results have prompted the search for specific WNT pathway antagonists as therapeutics for clinically problematic human colon cancers and associated metastases, which remain largely incurable. This widely accepted view seems at odds with a number of findings using patient-derived material: Canonical TCF targets are repressed, instead of being hyperactivated, in advanced colon cancers, and repression of TCF function does not generally result in tumor regression in xenografts. The results of a number of genetic mouse studies have also suggested that canonical WNT-TCF signaling drives metastases, but direct in vivo tests are lacking, and, surprisingly, TCF repression can enhance directly seeded metastatic growth. Here we have addressed the abilities of enhanced and blocked WNT-TCF signaling to alter tumor growth and distant metastases using xenografts of advanced human colon cancers in mice. We find that endogenous WNT-TCF signaling is mostly anti-metastatic since downregulation of TCF function with dnTCF generally enhances metastatic spread. Consistently, elevating the level of WNT signaling, by increasing the levels of WNT ligands, is not generally pro-metastatic. Our present and previous data reveal a heterogeneous response to modulating WNT-TCF signaling in human cancer cells. Nevertheless, the findings that a fraction of colon cancers tested require WNT-TCF signaling for tumor growth but all respond to repressed signaling by increasing metastases beg for a reevaluation of the goal of blocking WNT-TCF signaling to universally treat colon cancers. Our data suggest that WNT-TCF blockade may be effective

  20. Generation of Organ-conditioned Media and Applications for Studying Organ-specific Influences on Breast Cancer Metastatic Behavior.

    Science.gov (United States)

    Piaseczny, Matthew M; Pio, Graciella M; Chu, Jenny E; Xia, Ying; Nguyen, Kim; Goodale, David; Allan, Alison

    2016-01-01

    Breast cancer preferentially metastasizes to the lymph node, bone, lung, brain and liver in breast cancer patients. Previous research efforts have focused on identifying factors inherent to breast cancer cells that are responsible for this observed metastatic pattern (termed organ tropism), however much less is known about factors present within specific organs that contribute to this process. This is in part because of a lack of in vitro model systems that accurately recapitulate the organ microenvironment. To address this, an ex vivo model system has been established that allows for the study of soluble factors present within different organ microenvironments. This model consists of generating conditioned media from organs (lymph node, bone, lung, and brain) isolated from normal athymic nude mice. The model system has been validated by demonstrating that different breast cancer cell lines display cell-line specific and organ-specific malignant behavior in response to organ-conditioned media that corresponds to their in vivo metastatic potential. This model system can be used to identify and evaluate specific organ-derived soluble factors that may play a role in the metastatic behavior of breast and other types of cancer cells, including influences on growth, migration, stem-like behavior, and gene expression, as well as the identification of potential new therapeutic targets for cancer. This is the first ex vivo model system that can be used to study organ-specific metastatic behavior in detail and evaluate the role of specific organ-derived soluble factors in driving the process of cancer metastasis. PMID:27341354

  1. Influence of Co and B12 on the growth and nitrogen fixation of Trichodesmium

    OpenAIRE

    Irene B. Rodriguez; Ho, Tung-Yuan

    2015-01-01

    We investigated the influence of varying cobalt (Co) and B12 concentrations to growth and nitrogen fixation of Trichodesmium, a major diazotroph in the tropical and subtropical oligotrophic ocean. Here we show that sufficient inorganic Co, 20 pmol L-1, sustains the growth of Trichodesmium either with or without an additional B12 supply. We also found that in these culture conditions, nitrogen levels fixed by Trichodesmium were higher in treatments with insufficient B12 than in treatments with...

  2. Epidermal growth factor receptor (EGFR) polymorphisms and breast cancer among Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities Study

    OpenAIRE

    Connor, Avonne E.; Baumgartner, Richard N.; Baumgartner, Kathy B.; Pinkston, Christina M; John, Esther M.; Torres-Mejía, Gabriela; Hines, Lisa M.; Giuliano, Anna R.; Wolff, Roger K.; Slattery, Martha L.

    2013-01-01

    The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases, functions in cellular processes essential to the development of cancer. Overexpression of EGFR in primary breast tumors has been linked with poor prognosis. We investigated the associations between 34 EGFR tagging SNPs and breast cancer risk and breast cancer-specific mortality in 4,703 Hispanic and 3,030 non-Hispanic white women from the Breast Cancer Health Disparities Study. We evaluated ...

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

    OpenAIRE

    J. Buczek; G. Kubik-Dorosz; E. Tatkowska

    2015-01-01

    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 lev...

  4. INFLUENCE OF HEAVY METAL IONS CONCENTRATION ON GERMINATION AND PLANT GROWTH

    OpenAIRE

    Andra Pop

    2010-01-01

    chemical stress, provided the mechanisms of metal influences and features of the species of organism. This study focuses on the influence of the amount of heavy metals in germination and plant growth.For this study used seeds of beans, maize and cucumbers from polluted and unpolluted soils of Maramues. We followed these seed germination and growth on media enriched with heavy metal ions as Fe, Cu, Zn, Pb.Germination experiments in the presence of metal were performed on seeds of Phaseolus vul...

  5. The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Ginsburg Erika

    2010-05-01

    Full Text Available Abstract Background Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM derived from premenopausal African-American (AA or Caucasian-American (CAU breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women. Methods The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry. Results Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER-, progesterone receptor (PR/PR- cells were significantly more aggressive when in contact with AA ECM, as were ER+/PR+ cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER+/PR+ cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1

  6. Disseminated Mycobacterium chelonae Infection in a Patient Receiving an Epidermal Growth Factor Receptor Inhibitor for Advanced Head and Neck Cancer

    OpenAIRE

    Bark, Charles M.; Traboulsi, Rana S.; Honda, Kord; Starnes, Autumn M.; Jacobs, Michael R.; Rodriguez, Benigno

    2012-01-01

    We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient with head and neck cancer on salvage chemotherapy, including the epidermal growth factor receptor inhibitor cetuximab. Mycobacterium chelonae should be considered in the differential diagnosis of cutaneous infections in cancer patients receiving epidermal growth factor receptor inhibitors.

  7. 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

  8. Dietary phenethyl isothiocyanate inhibition of androgen-responsive LNCaP prostate cancer cell tumor growth correlates with decreased angiogenesis

    Science.gov (United States)

    Phenethyl isothiocyanate (PEITC), found in certain cruciferous vegetables, has antitumor activity in several cancer models, including prostate cancer. In our xenograft model, dietary administration of PEITC (100-150 mg/kg/d) inhibited androgen-responsive LNCaP human prostate cancer cell tumor growth...

  9. 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.

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

    International Nuclear Information System (INIS)

    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

  11. Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Kai-Xing Ai; Lin-Yuan Lu; Xin-Yu Huang; Wei Chen; Hui-Zhen Zhang

    2008-01-01

    AIM:To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer.METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed.RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues(P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4- and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis(P = 0.001), S100A4- (P = 0.008) and VEGF-positive expression (P= 0.016) were significantly independent prognostic predictors (P<0.05).CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.

  12. 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.

  13. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  15. Exosomes in Tumor Microenvironment Influence Cancer Progression and Metastasis

    OpenAIRE

    Kahlert, Christoph; Kalluri, Raghu

    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. 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.

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

    NARCIS (Netherlands)

    Raber-Durlacher, Judith E.; von Bultzingslowen, Inger; Logan, Richard M.; Bowen, Joanne; Al-Azri, Abdul Rahman; Everaus, Hele; Gerber, Erich; Garcia Gomez, Jess; Pettersson, Bo G.; Soga, Yoshihiko; Spijkervet, Fred K. L.; Tissing, Wim J. E.; Epstein, Joel B.; Elad, Sharon; Lalla, Rajesh V.

    2013-01-01

    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. A systematic review was conducted by the Mucositis Study Gr

  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. 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 su...

  20. 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

  1. 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.

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

    International Nuclear Information System (INIS)

    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

  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. PMID:20537012

  4. 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.

  5. TOTAL FACTOR PRODUCTIVITY - INFLUENCE FACTOR OF THE ECONOMIC GROWTH POTENTIAL. PRACTICAL APPLICATION

    Directory of Open Access Journals (Sweden)

    Florina Popa

    2015-07-01

    Full Text Available Adequate to the new requirements of economy, the economic research has achieved progresses in addressing the issues regarding the growth and development, the economists drawing a number of theories and models, in order to find resorts that lead to sustainable growth. The paper refers to the means of assessment and forecast of the potential growth of an economy, by using a mathematical model, whose production function takes into consideration the role of three factors, being highlighted the role of the Total Factor Productivity, as an element of influence on growth with the other two factors. The study includes an application of the model use, for the analysis of the growth potential of the economy, at national level.

  6. Adenovirus-delivered wwox inhibited lung cancer growth in vivo in a mouse model.

    Science.gov (United States)

    Zhou, Y; Shou, F; Zhang, H; You, Q

    2016-01-01

    Lung cancer is the most prevalent and deadly malignancy worldwide. This study investigated the possibility of inhibiting lung cancer in vivo with adenovirus-delivered WW domain-containing oxidoreductase (wwox). The lung cancer model was established by inoculating A549 lung cancer cells into the pleural space of nude mice. The control or wwox adenovirus was injected into the pleural space 7 days after cell inoculation and 14 days after first injection. The tumor number and burdens were measured 2 weeks after second virus injection. The carcinoembryonic antigen (CEA) and alpha-feto protein (AFP) levels in pleural effusion were analyzed by enzyme-linked immunosorbent assay. Apoptosis, proliferation and angiogenesis of tumor cells were assessed by terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling assay, proliferating cell nuclear antigen (PCNA) and CD31 staining, respectively. Ectopic wwox significantly reduced both the number and size of lung tumors accompanied by substantially lower CEA and AFP levels in pleural effusion. The expression levels of Bcl2, Bcl-xL, vascular endothelial growth factor, PCNA-positive and CD31-positive cells in the tumors were significantly decreased, whereas levels of p21 and p73 and apoptotic cells markedly increased in mice receiving the wwox virus. These data demonstrated that wwox delivered by adenovirus was able to inhibit the growth of lung cancer in vivo, indicating the potential of using wwox as a gene therapy agent for lung cancer. PMID:26516139

  7. 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.

  8. BMP10 inhibited the growth and migration of gastric cancer cells.

    Science.gov (United States)

    Lei, Haiming; Wang, Jian; Lu, Peihua; Si, Xinghua; Han, Koulan; Ruan, Tingyan; Lu, Junjie

    2016-03-01

    Bone morphogenetic protein 10 (BMP10), a novel member of BMP family, has been identified as an important regulator for angiogenesis. Dysregulation of BMP has been observed in several cancer types. However, its roles in gastric cancer (GC) remain unknown. In this study, the expression of BMP10 was found to be down-regulated in GC samples. Forced expression of BMP10 in GC cells inhibited its growth and migration, while knocking down the expression of BMP10 in GC cells promoted cell growth, migration, and metastasis. BMP10 was shown to negatively regulated beta-catenin/TCF signaling by up-regulating Axin protein level. Taken together, the present study revealed the suppressive function of BMP10 in gastric cancer. PMID:26419594

  9. Insulin-Like Growth Factor System in Cancer: Novel Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Varsha P. Brahmkhatri

    2015-01-01

    Full Text Available Insulin-like growth factors (IGFs are essential for growth and survival that suppress apoptosis and promote cell cycle progression, angiogenesis, and metastatic activities in various cancers. The IGFs actions are mediated through the IGF-1 receptor that is involved in cell transformation induced by tumour. These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs. We describe here the role of the IGF system in cancer, proposing new strategies targeting this system. We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review discusses the emerging view that blocking IGF via IGFBP is a better option than blocking IGF receptors. This can lead to the development of novel cancer therapies.

  10. Models of Growth Heterogeneous Cancer Cells with Chains Markoviens and Estimation of Their Fractal Dimension

    Directory of Open Access Journals (Sweden)

    Labib Sadek Terrissa

    2011-09-01

    Full Text Available Although little work in biometrics uses fractal geometry, we will discuss here biometrics cancer tissue examined under a microscope or simulated. The main purpose of our work is the simulation of the heterogeneous growth of cancerous tumors and the analysis of the appearance of their textures. The problem is to quantify the irregularity of their edges, which help enormously oncologists to give diagnoses to evaluate the treatment issued to their patients. We propose new algorithms, which generates growth models with the ability to produce a border irregularity similar to that of cancerous tumors and value their fractal dimension. The established models have two types of parameters: Algorithms describing the structure, and Scalar to quantify aspects modeled

  11. Growth/differentiation factor-15: prostate cancer suppressor or promoter?

    Czech Academy of Sciences Publication Activity Database

    Vaňhara, P.; Hampl, A.; Kozubík, Alois; Souček, Karel

    2012-01-01

    Roč. 15, č. 4 (2012), s. 320-328. ISSN 1365-7852 R&D Projects: GA MZd NS9600; GA MZd NS9956 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : MACROPHAGE-INHIBITORY CYTOKINE-1 * GROWTH-DIFFERENTIATION FACTOR-15 * TGF-BETA SUPERFAMILY Subject RIV: BO - Biophysics Impact factor: 2.811, year: 2012

  12. IGFBP-2 - taking the lead in growth, metabolism and cancer.

    Science.gov (United States)

    Yau, Steven W; Azar, Walid J; Sabin, Matthew A; Werther, George A; Russo, Vincenzo C

    2015-06-01

    The activity of the Insulin-like Growth Factors (IGFs) ligands elicited via their receptors and transduced by various intracellular signal pathways is modulated by the IGF Binding Proteins (IGFBPs). Among all the IGFBPs, IGFBP-2 has been implicated in the regulation of IGF activity in most tissue and organs. Besides binding to IGFs in the circulation these IGF-regulatory activities of IGFBP-2 involve interactions with components of the extracellular matrix, cell surface proteoglycans and integrin receptors. In addition to these local peri-cellular activities, IGFBP-2 exerts other key functions within the nucleus, where IGFBP-2 directly or indirectly promotes transcriptional activation of specific genes. All of these IGFBP-2 activities, intrinsic or dependent on IGFs, contribute to its functional roles in growth/development, metabolism and malignancy as evidenced by studies in IGFBP-2 animal models and also by many in vitro studies. Finally, preclinical studies have demonstrated that IGFBP-2 administration can be beneficial in improving metabolic responses (inhibition of adipogenesis and enhanced insulin sensitivity), while blockade of IGFBP-2 appears to be an effective approach to inhibiting tumour growth and metastasis. PMID:25617050

  13. Protein disulfide isomerases in the endoplasmic reticulum promote anchorage-independent growth of breast cancer cells.

    Science.gov (United States)

    Wise, Randi; Duhachek-Muggy, Sara; Qi, Yue; Zolkiewski, Michal; Zolkiewska, Anna

    2016-06-01

    Metastatic breast cancer cells are exposed to stress of detachment from the extracellular matrix (ECM). Cultured breast cancer cells that survive this stress and are capable of anchorage-independent proliferation form mammospheres. The purpose of this study was to explore a link between mammosphere growth, ECM gene expression, and the protein quality control system in the endoplasmic reticulum (ER). We compared the mRNA and protein levels of ER folding factors in SUM159PT and MCF10DCIS.com breast cancer cells grown as mammospheres versus adherent conditions. Publicly available gene expression data for mammospheres formed by primary breast cancer cells and for circulating tumor cells (CTCs) were analyzed to assess the status of ECM/ER folding factor genes in clinically relevant samples. Knock-down of selected protein disulfide isomerase (PDI) family members was performed to examine their roles in SUM159PT mammosphere growth. We found that cells grown as mammospheres had elevated expression of ECM genes and ER folding quality control genes. CTC gene expression data for an index patient indicated that upregulation of ECM and ER folding factor genes occurred at the time of acquired therapy resistance and disease progression. Knock-down of PDI, ERp44, or ERp57, three members of the PDI family with elevated protein levels in mammospheres, in SUM159PT cells partially inhibited the mammosphere growth. Thus, breast cancer cell survival and growth under detachment conditions require enhanced assistance of the ER protein folding machinery. Targeting ER folding factors, in particular members of the PDI family, may improve the therapeutic outcomes in metastatic breast cancer. PMID:27161215

  14. Stress Influences on Anoikis

    OpenAIRE

    Sood, Anil K; Lutgendorf, Susan K.

    2011-01-01

    It long has been suspected that psychosocial factors affect cancer development and progression. Although the connections between stress and cancer causation are not strong, epidemiological and clinical studies have provided strong links between cancer progression and several stress-related factors including chronic stress, depression, and social isolation. Recent molecular and biological studies have identified specific signaling pathways that influence cancer growth and metastasis. In partic...

  15. Withaferin A inhibits in vivo growth of breast cancer cells accelerated by Notch2 knockdown.

    Science.gov (United States)

    Kim, Su-Hyeong; Hahm, Eun-Ryeong; Arlotti, Julie A; Samanta, Suman K; Moura, Michelle B; Thorne, Stephen H; Shuai, Yongli; Anderson, Carolyn J; White, Alexander G; Lokshin, Anna; Lee, Joomin; Singh, Shivendra V

    2016-05-01

    The present study offers novel insights into the molecular circuitry of accelerated in vivo tumor growth by Notch2 knockdown in triple-negative breast cancer (TNBC) cells. Therapeutic vulnerability of Notch2-altered growth to a small molecule (withaferin A, WA) is also demonstrated. MDA-MB-231 and SUM159 cells were used for the xenograft studies. A variety of technologies were deployed to elucidate the mechanisms underlying tumor growth augmentation by Notch2 knockdown and its reversal by WA, including Fluorescence Molecular Tomography for measurement of tumor angiogenesis in live mice, Seahorse Flux analyzer for ex vivo measurement of tumor metabolism, proteomics, and Luminex-based cytokine profiling. Stable knockdown of Notch2 resulted in accelerated in vivo tumor growth in both cells reflected by tumor volume and/or latency. For example, the wet tumor weight from mice bearing Notch2 knockdown MDA-MB-231 cells was about 7.1-fold higher compared with control (P medicinal plant. Molecular underpinnings for tumor growth intensification by Notch2 knockdown included compensatory increase in Notch1 activation, increased cellular proliferation and/or angiogenesis, and increased plasma or tumor levels of growth stimulatory cytokines. WA administration reversed many of these effects providing explanation for its remarkable anti-cancer efficacy. Notch2 functions as a tumor growth suppressor in TNBC and WA offers a novel therapeutic strategy for restoring this function. PMID:27097807

  16. 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.

  17. SL-01, an oral gemcitabine derivative, inhibited human cancer growth more potently than gemcitabine

    International Nuclear Information System (INIS)

    SL-01, an oral gemcitabine derivative, was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine ring of gemcitabine. Our goal in this study was to evaluate the efficacy of SL-01 on the growth of human cancers with gemcitabine as control. Experiments were performed on human non-small cell lung cancer NCI-H460 and colon cancer HCT-116 both in vitro and in vivo. In vitro assays, SL-01 significantly inhibited the growth of cancer cells as determined by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Further studies indicated that SL-01 induced the cancer cells to apoptosis showing chromatin condensation and externalization of phosphatidylserine. In in vivo studies, we evaluated the efficacy of SL-01 in nude mice bearing human cancer xenografts. SL-01 effectively delayed the growth of NCI-H460 and HCT-116 without significant loss of body weight. Molecular analysis indicated that the high efficacy of SL-01 was associated with its ability to induce apoptosis as evidenced by increase of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) in tumor tissues. SL-01 also increased Bax/Bcl-2 ratio in cancer cells. These biological activities of SL-01 were more potential than that of gemcitabine. Based on these in vitro and in vivo results, SL-01 is proposed as a potent oral anticancer agent that may supplant the use of gemcitabine in the clinic. -- Highlights: ► An oral gemcitabine derivative SL-01 was synthesized. ► The effects of SL-01 were evaluated and its efficacy was compared with gemcitabine. ► The biological activities of SL-01 were more potent than that of gemcitabine. ► SL-01 could replace gemcitabine for clinical use.

  18. SL-01, an oral gemcitabine derivative, inhibited human cancer growth more potently than gemcitabine

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Cuirong; Yue, Bin; Liu, Huiping; Sun, Cuicui [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China); Li, Wenbao, E-mail: wbli@sanlugen.com [Sanlugen PharmaTech, Rm. 506, No. 2766 Yingxiu Road, Jinan 250101 (China); Qu, Xianjun, E-mail: qxj@sdu.edu.cn [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China)

    2012-08-01

    SL-01, an oral gemcitabine derivative, was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine ring of gemcitabine. Our goal in this study was to evaluate the efficacy of SL-01 on the growth of human cancers with gemcitabine as control. Experiments were performed on human non-small cell lung cancer NCI-H460 and colon cancer HCT-116 both in vitro and in vivo. In vitro assays, SL-01 significantly inhibited the growth of cancer cells as determined by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Further studies indicated that SL-01 induced the cancer cells to apoptosis showing chromatin condensation and externalization of phosphatidylserine. In in vivo studies, we evaluated the efficacy of SL-01 in nude mice bearing human cancer xenografts. SL-01 effectively delayed the growth of NCI-H460 and HCT-116 without significant loss of body weight. Molecular analysis indicated that the high efficacy of SL-01 was associated with its ability to induce apoptosis as evidenced by increase of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) in tumor tissues. SL-01 also increased Bax/Bcl-2 ratio in cancer cells. These biological activities of SL-01 were more potential than that of gemcitabine. Based on these in vitro and in vivo results, SL-01 is proposed as a potent oral anticancer agent that may supplant the use of gemcitabine in the clinic. -- Highlights: ► An oral gemcitabine derivative SL-01 was synthesized. ► The effects of SL-01 were evaluated and its efficacy was compared with gemcitabine. ► The biological activities of SL-01 were more potent than that of gemcitabine. ► SL-01 could replace gemcitabine for clinical use.

  19. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells.

    Science.gov (United States)

    Zakikhani, Mahvash; Dowling, Ryan; Fantus, I George; Sonenberg, Nahum; Pollak, Michael

    2006-11-01

    Recent population studies provide clues that the use of metformin may be associated with reduced incidence and improved prognosis of certain cancers. This drug is widely used in the treatment of type 2 diabetes, where it is often referred to as an "insulin sensitizer" because it not only lowers blood glucose but also reduces the hyperinsulinemia associated with insulin resistance. As insulin and insulin-like growth factors stimulate proliferation of many normal and transformed cell types, agents that facilitate signaling through these receptors would be expected to enhance proliferation. We show here that metformin acts as a growth inhibitor rather than an insulin sensitizer for epithelial cells. Breast cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against AMP kinase. This shows that AMP kinase pathway activation by metformin, recently shown to be necessary for metformin inhibition of gluconeogenesis in hepatocytes, is also involved in metformin-induced growth inhibition of epithelial cells. The growth inhibition was associated with decreased mammalian target of rapamycin and S6 kinase activation and a general decrease in mRNA translation. These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for activators of AMP kinase in cancer prevention and treatment. PMID:17062558

  20. 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

  1. Effects of plasmid-mediated growth hormone-releasing hormone in severely debilitated dogs with cancer.

    Science.gov (United States)

    Draghia-Akli, Ruxandra; Hahn, Kevin A; King, Glen K; Cummings, Kathleen K; Carpenter, Robert H

    2002-12-01

    Cachexia is a common manifestation of late stage malignancy and is characterized by anemia, anorexia, muscle wasting, loss of adipose tissue, and fatigue. Although cachexia is disabling and can diminish the life expectancy of cancer patients, there are still no effective therapies for this condition. We have examined the feasibility of using a myogenic plasmid to express growth hormone-releasing hormone (GHRH) in severely debilitated companion dogs with naturally occurring tumors. At a median of 16 days after intramuscular delivery of the plasmid, serum concentrations of insulin-like growth factor I (IGF-I), a measure of GHRH activity, were increased in 12 of 16 dogs (P intramuscular injection of a GHRH-expressing plasmid is both safe and capable of stimulating the release of growth hormone and IGF-I in large animals. The observed anabolic responses to a single dose of this therapy might be beneficial in patients with cancer-associated anemia and cachexia. PMID:12498779

  2. Multikinase inhibitor regorafenib inhibits the growth and metastasis of colon cancer with abundant stroma.

    Science.gov (United States)

    Takigawa, Hidehiko; Kitadai, Yasuhiko; Shinagawa, Kei; Yuge, Ryo; Higashi, Yukihito; Tanaka, Shinji; Yasui, Wataru; Chayama, Kazuaki

    2016-05-01

    Interaction between tumor cells and stromal cells plays an important role in the growth and metastasis of colon cancer. We previously found that carcinoma-associated fibroblasts (CAFs) expressed platelet-derived growth factor receptor-β (PDGFR-β) and that PDGFR targeted therapy using imatinib or nilotinib inhibited stromal reaction. Bone marrow-derived mesenchymal stem cells (MSCs) migrate to tumor stroma and differentiate into CAFs. A novel oral multikinase inhibitor regorafenib inhibits receptor tyrosine kinases expressed on stromal cells (vascular endothelial growth factor receptor 1-3, TIE2, PDGFR-β, and fibroblast growth factors) and tumor cells (c-KIT, RET, and BRAF). These molecules are involved in tumor growth, angiogenesis, lymphangiogenesis, and stromal activation. Therefore, we examined whether regorafenib impaired the tumor-promoting effect of CAFs/MSCs. KM12SM human colon cancer cells alone or KM12SM cells with MSCs were transplanted into the cecal wall of nude mice. Co-implantation of KM12SM cells with MSCs into the cecal wall of nude mice produced tumors with abundant stromal component and promoted tumor growth and lymph node metastasis. Single treatment with regorafenib inhibited tumor growth and metastasis by inhibiting both tumor cells and stromal reaction. This tumor-inhibitory effect of regorafenib was more obvious in tumors developed by co-implanting KM12SM cells with MSCs. Our data suggested that targeting of the tumor microenvironment with regorafenib affected tumor cell-MSC interaction, which in turn inhibited the growth and metastasis of colon cancer. PMID:26865419

  3. Influence of growth stresses and material properties on distortion of sawn timber - numerical investigation

    DEFF Research Database (Denmark)

    Johansson, Marie; Ormarsson, Sigurdur

    2009-01-01

    The board distortion that occurs during the sawing and the drying process causes major problems in the utilisation of sawn timber. The distortion is highly influenced by parameters such as spiral grain angle, modulus of elasticity, shrinkage, growth stresses and sawing pattern. In this study a fi...

  4. Does hyoid bone resection according to Sistrunk influence normal craniofacial growth? A cephalometric study.

    NARCIS (Netherlands)

    Joss-Vassalli, I.M.; Joss, C.U.; Gebauer, U.

    2009-01-01

    PURPOSE: To retrospectively evaluate the influence of hyoid bone resection according to Sistrunk in early age due to a thyroglossal duct cyst on craniofacial growth. MATERIALS AND METHODS: We retrospectively examined 10 patients (2 females and 8 males) having had hyoid bone resection according to Si

  5. In-situ PXRD studies of ZnO nanoparticle growth: How do various salts influence the hydrothermal growth of ZnO?

    DEFF Research Database (Denmark)

    Bøjesen, Espen Drath

    whole powder pattern modeling. Among the parameters studied were the influence of temperature, type of base used and how different ionic salts influence the growth. Results include findings that suggest that sodium nitrate influences the aspect ratio of synthesized particles and that lithium nitrate...

  6. 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...... 85 antimetabolites that can inhibit growth of, or even kill, any of the cell lines, while at the same time not being toxic for 83 different healthy human cell types. 60 of these antimetabolites were found to inhibit growth in all cell lines. Finally, we experimentally validated one of the 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...

  7. 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).

  8. 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.

  9. 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.

  10. 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

  11. MUC4 potentiates invasion and metastasis of pancreatic cancer cells through stabilization of fibroblast growth factor receptor 1

    OpenAIRE

    Rachagani, Satyanarayana; Muzafar A Macha; Moorthy P Ponnusamy; Haridas, Dhanya; Kaur, Sukhwinder; Jain, Maneesh; Batra, Surinder K.

    2012-01-01

    MUC4 is a type-1 transmembrane mucin differentially expressed in multiple cancers and has previously been shown to potentiate progression and metastasis of pancreatic cancer. In this study, we investigated the molecular mechanisms associated with the MUC4-induced invasion and metastasis in pancreatic cancer. Stable silencing of MUC4 in multiple pancreatic cancer cells resulted in the downregulation of N-cadherin and its interacting partner fibroblast growth factor receptor 1 (FGFR1) through d...

  12. Influence of water stress on the percentage of active root and plant growth of soybean

    International Nuclear Information System (INIS)

    Two experiments have been carried out to obtain data on the influence of water stress on active root and plant growth. In the first experiment water stress treatment was conducted seven days before plants were harvested. In the second experiment water stress treatment was done, when the plants were 35 days old, with watering at 3, 6, 9 and 12 days intervals up to the time when the plants reached the age of 50 days. To determine the active root growth on 0-10 cm and 10-20 cm depths, 32P in the form of KH232PO4 carrier free solution was used. The data obtained show that water stress has a significant influence on active root and plant growth. (author)

  13. Dutasteride May Slow the Growth of Early-Stage Prostate Cancer | Division of Cancer Prevention

    Science.gov (United States)

    For men who are undergoing active surveillance for early-stage prostate cancer, the drug dutasteride (Avodart) could help control the disease and prevent the need for more aggressive treatments. |

  14. Factors influencing cosmetic results after conservation therapy for breast cancer

    International Nuclear Information System (INIS)

    Purpose: Host, tumor, and treatment-related factors influencing cosmetic outcome are analyzed for patients receiving breast conservation treatment. Methods and Materials: Four-hundred and fifty-eight patients with evaluable records for cosmesis evaluation, a subset of 701 patients treated for invasive breast cancer with conservation technique between 1969 and 1990, were prospectively analyzed. In 243 patients, cosmetic evaluation was not adequately recorded. Cosmesis evaluation was carried out from 3.7 months to 22.3 years, median of 4.4 years. By pathologic stage, tumors were 62% T1N0, 14% T1N1, 15% T2N0, and 9% T2N1. The majority of patients were treated with 4-6 MV photons. Cosmetic evaluation was rated by both patient and physician every 4-6 months. A logistic regression analysis was completed using a stepwise logistic regression. P-values of 0.05 or less were considered significant. Excellent cosmetic scores were used in all statistical analyses unless otherwise specified. Results: At most recent follow-up, 87% of patients and 81% of physicians scored their cosmetic outcome as excellent or good. Eighty-two percent of physician and patient evaluations agreed with excellent-good vs. fair-poor rating categories. Analysis demonstrated a lower proportion of excellent cosmetic scores when related to patient age > 60 years (p = 0.001), postmenopausal status (p = 0.02), black race (p = 0.0034), and T2 tumor size (p = 0.05). Surgical factors of importance were: volume of resection > 100 cm3 (p = 0.0001), scar orientation compliance with the National Surgical Adjuvant Breast Project (NSABP) guidelines (p = 0.0034), and > 20 cm2 skin resected (p = 0.0452). Extent of axillary surgery did not significantly affect breast cosmesis. Radiation factors affecting cosmesis included treatment volume (tangential breast fields only vs. three or more fields) (p = 0.034), whole breast dose in excess of 50 Gy (p = 0.0243), and total dose to tumor site > 65 Gy (p = 0.06), as well as

  15. Insulin-like growth factor binding protein 2 is a marker for antiestrogen resistant human breast cancer cell lines but is not a major growth regulator

    DEFF Research Database (Denmark)

    Juncker-Jensen, A; Lykkesfeldt, A E; Worm, J;

    2006-01-01

    Antiestrogens target the estrogen receptor and counteract the growth stimulatory action of estrogen on human breast cancer. However, acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. To mimic acquired resistance, we have used a mode...... resistant cell growth was observed. Thus, we were able to establish IGFBP-2 as a marker for antiestrogen resistant breast cancer cell lines, although IGFBP-2 was not a major contributor to the resistant cell growth.......Antiestrogens target the estrogen receptor and counteract the growth stimulatory action of estrogen on human breast cancer. However, acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. To mimic acquired resistance, we have used a model...... system with the antiestrogen sensitive human breast cancer cell line MCF-7 and several antiestrogen resistant cell lines derived from the parental MCF-7 cell line. This model system was used to study the expression and possible involvement in resistant cell growth of insulin-like growth factor binding...

  16. 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.

  17. 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.

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

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. Elevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cells.

    Science.gov (United States)

    Shimo, Arata; Nishidate, Toshihiko; Ohta, Tomohiko; Fukuda, Mamoru; Nakamura, Yusuke; Katagiri, Toyomasa

    2007-02-01

    To elucidate molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out a genome-wide expression profile analysis of 81 breast cancer cases by means of a combination of cDNA microarray and laser microbeam microdissection. Among the upregulated genes, we focused on the functional significance of protein regulator of cytokinesis 1 (PRC1) in the development of breast cancer. Western blot analysis using breast cancer cell lines revealed a significant increase in endogenous PRC1 levels in G(2)/M phase. Treatment of breast cancer cells with small interfering RNA against PRC1 effectively suppressed its expression and inhibited the growth of breast cancer cell lines T47D and HBC5. Furthermore, we found an interaction between PRC1 and kinesin family member 2C/mitotic centromere-associated kinesin (KIF2C/MCAK) by coimmunoprecipitation and immunoblotting using COS-7 cells, in which these molecules were introduced exogenously. These findings suggest the involvement of a PRC1-KIF2C/MCAK complex in breast tumorigenesis, and this complex should be a promising target for the development of novel treatments for breast cancer. PMID:17233835

  1. Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key molecules in inflammatory breast cancer.

    Science.gov (United States)

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

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against cancer cells. We report the effects of Reishi on viability, apoptosis, invasion, and its mechanism of action in IBC cells (SUM-149). Results show that Reishi selectively inhibits cancer cell viability although it does not affect the viability of noncancerous mammary epithelial cells. Apoptosis induction is consistent with decreased cell viability. Reishi inhibits cell invasion and disrupts the cell spheroids that are characteristic of the IBC invasive pathology. Reishi decreases the expression of genes involved in cancer cell survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP-9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E-cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase activity. These findings suggest that Reishi is an effective anti-IBC therapeutic. PMID:21888505

  2. 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.

  3. Influence of water relations and growth rate on plant element uptake and distribution

    International Nuclear Information System (INIS)

    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

  4. Inhibition of nuclear factor-kappa B differentially affects thyroid cancer cell growth, apoptosis, and invasion

    Directory of Open Access Journals (Sweden)

    Schweppe Rebecca E

    2010-05-01

    Full Text Available Abstract Background Nuclear factor-κB (NF-κB is constitutively activated in many cancers and plays a key role in promoting cell proliferation, survival, and invasion. Our understanding of NF-κB signaling in thyroid cancer, however, is limited. In this study, we have investigated the role of NF-κB signaling in thyroid cancer cell proliferation, invasion, and apoptosis using selective genetic inhibition of NF-κB in advanced thyroid cancer cell lines. Results Three pharmacologic inhibitors of NF-κB differentially inhibited growth in a panel of advanced thyroid cancer cell lines, suggesting that these NF-κB inhibitors may have off-target effects. We therefore used a selective genetic approach to inhibit NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα. These studies revealed decreased cell growth in only one of five thyroid cancer cell lines (8505C, which occurred through a block in the S-G2/M transition. Resistance to TNFα-induced apoptosis was observed in all cell lines, likely through an NF-κB-dependent mechanism. Inhibition of NF-κB by mIκBα sensitized a subset of cell lines to TNFα-induced apoptosis. Sensitive cell lines displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK pathway, defining a potential mechanism of response. Finally, NF-κB inhibition by mIκBα expression differentially reduced thyroid cancer cell invasion in these thyroid cancer cell lines. Sensitive cell lines demonstrated approximately a two-fold decrease in invasion, which was associated with differential expression of MMP-13. MMP-9 was reduced by mIκBα expression in all cell lines tested. Conclusions These data indicate that selective inhibition of NF-κB represents an attractive therapeutic target for the treatment of advanced thyroid. However, it is apparent that global regulation of thyroid cancer cell growth and invasion is not achieved by NF-κB signaling alone. Instead, our

  5. Treatment with kaempferol suppresses breast cancer cell growth caused by estrogen and triclosan in cellular and xenograft breast cancer models.

    Science.gov (United States)

    Kim, Seung-Hee; Hwang, Kyung-A; Choi, Kyung-Chul

    2016-02-01

    As a phytoestrogen, kaempferol (Kaem) is one of bioflavonoids, which are found in a variety of vegetables including broccoli, tea and tomato. In this study, the antiproliferative effects of Kaem in triclosn (TCS)-induced cell growth were examined in MCF-7 breast cancer cells. TCS promoted the cell viability of MCF-7 cells via estrogen receptor α (ERα) as did 17β-estradiol (E2), a positive control. On the other hand, Kaem significantly suppressed E2 or TCS-induced cell growth. To elucidate the molecular mechanisms of TCS and Kaem, alterations in the expressions of cell cycle, apoptosis and metastasis-related genes were identified using western blot assay. The treatment of the cells with TCS up-regulated the protein expressions of cyclin D1, cyclin E and cathepsin D, while down-regulated p21 and bax expressions. Kaem reversed TCS-induced gene expressions in an opposite manner. The phosphorylation of IRS-1, AKT, MEK1/2 and ERK was increased by TCS, indicating that TCS induced MCF-7 cell proliferation via nongenomic ER signaling pathway associated with IGF-1R. Kaem presented an antagonistic activity on this signaling by down-regulating the protein expression of pIRS-1, pAkt and pMEK1/2 promoted by E2 or TCS. In an in vivo xenografted mouse model, tumor growth was induced by treatment with E2 or TCS, which was identified in the measurement of tumor volume, hematoxylin and eosin staining, bromodeoxyuridine and immunohistochemistry assay. On the contrary, E2 or TCS-induced breast tumor growth was inhibited by co-treatment with Kaem, which is consistent with in vitro results. Taken together, these results revealed that Kaem has an anticancer effect against procancer activity of E2 or TCS, a xenoestrogen, in breast cancer and may be suggested as a prominent agent to neutralize breast cancer risk caused by TCS. PMID:26878784

  6. The influence of family ties on men's prostate cancer screening, biopsy, and treatment decisions.

    Science.gov (United States)

    Shaw, Eric K; Scott, John G; Ferrante, Jeanne M

    2013-11-01

    Extensive research has focused on understanding family dynamics of men with prostate cancer. However, little qualitative work has examined the role of family ties on men's prostate cancer decisions across the spectrum of screening, diagnosis, and treatment. Using data from a larger study, we qualitatively explored the influence of family ties on men's prostate cancer decisions. Semistructured interviews were conducted with men ages ≥50 (N = 64), and data were analyzed using a grounded theory approach and a series of immersion/crystallization cycles. Three major themes of spousal/family member influence were identified: (a) spousal/family member alliance marked by open communication and shared decision making, (b) men who actively opposed spouse/family member pressure and made final decisions themselves, and (c) men who yielded to spouse/family member pressure. Our findings provide insights into men's relational dynamics that are important to consider for the shared decision-making process across the prostate cancer spectrum. PMID:23459024

  7. Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells

    International Nuclear Information System (INIS)

    Puerariae radix (PR) is a popular natural herb and a traditional food in Asia, which has antithrombotic and anti-allergic properties and stimulates estrogenic activity. In the present study, we investigated the effects of the PR isoflavones puerarin, daidzein, and genistein on the growth of breast cancer cells. Our data revealed that after treatment with PR isoflavones, a dose-dependent inhibition of cell growth occurred in HS578T, MDA-MB-231, and MCF-7 cell lines. Results from cell cycle distribution and apoptosis assays revealed that PR isoflavones induced cell apoptosis through a caspase-3-dependent pathway and mediated cell cycle arrest in the G2/M phase. Furthermore, we observed that the serum metabolites of PR (daidzein sulfates/glucuronides) inhibited proliferation of the breast cancer cells at a 50% cell growth inhibition (GI50) concentration of 2.35 μM. These results indicate that the daidzein constituent of PR can be metabolized to daidzein sulfates or daidzein glucuronides that exhibit anticancer activities. The protein expression levels of the active forms of caspase-9 and Bax in breast cancer cells were significantly increased by treatment with PR metabolites. These metabolites also increased the protein expression levels of p53 and p21. We therefore suggest that PR may act as a chemopreventive and/or chemotherapeutic agent against breast cancer by reducing cell viability and inducing apoptosis.

  8. Involvement of Fatty Acid Binding Protein 5 and PPARβ/δ in Prostate Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Elwin Morgan

    2010-01-01

    Full Text Available Fatty acid binding protein 5 (FABP5 delivers ligands from the cytosol directly to the nuclear receptor PPARβ/δ and thus facilitates the ligation and enhances the transcriptional activity of the receptor. We show here that expression levels of both FABP5 and PPARβ/δ are correlated with the tumorigenic potential of prostate cancer cell lines. We show further that FABP5 comprises a direct target gene for PPARβ/δ and thus the binding protein and its cognate receptor are engaged in a positive feedback loop. The observations demonstrate that, similarly to effects observed in mammary carcinomas, activation of the FABP5/PPARβ/δ pathway induces PPARβ/δ target genes involved in cell survival and growth and enhances cell proliferation and anchorage-independent growth in prostate cancer cells. Furthermore, the data show that downregulation of either FABP5 or PPARβ/δ inhibits the growth of the highly malignant prostate cancer PC3M cells. These studies suggest that the FABP5/PPARβ/δ pathway may play a general role in facilitating tumor progression and that inhibition of the pathway may comprise a novel strategy in treatment of cancer.

  9. Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp transcription factors.

    Directory of Open Access Journals (Sweden)

    Satya Pathi

    Full Text Available Acetylsalicylic acid (aspirin is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFκB. Moreover, we also showed by RNA interference that β-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

  10. Mediastinal staging for lung cancer: the influence of biopsy volume

    DEFF Research Database (Denmark)

    Nelson, Elof; Pape, Christian; Jørgensen, Ole Dan;

    2010-01-01

    OBJECTIVE: Mediastinal staging is of paramount importance prior to surgery for non-small-cell lung cancer (NSCLC) to identify patients with N2-disease. Mediastinoscopy remains the gold standard, and sampling from at least three lymph node stations is generally recommended. It is unknown whether...

  11. Factors influencing outcome of I-125 prostate cancer brachytherapy

    NARCIS (Netherlands)

    Hinnen, K.A.

    2011-01-01

    Brachytherapy is becoming an increasingly popular prostate cancer treatment, probably due to the specific advantages of the procedure, such as the minimal invasiveness and the lower chance of impotence and incontinence. Nonetheless, because of the long follow-up that is required to obtain prostate c

  12. Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain.

    Science.gov (United States)

    Binder, Claudia; Chuang, Eugenia; Habla, Christina; Bleckmann, Annalen; Schulz, Matthias; Bathgate, Ross; Einspanier, Almuth

    2014-01-01

    Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as elevated expression of the respective receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also associated with enhanced infiltration by tumour-associated macrophages which are known to promote tumour progression. Additionally, we show in an ex vivo model of metastatic brain colonization that porcine relaxin as well as human brain-specific relaxin-3 promotes invasion into the brain tissue and enhance interaction of breast cancer cells with the resident brain macrophages, the microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly enhance invasion. Taken together, these findings strongly support a role of relaxins in the progression of breast cancer where they foster primary tumour growth as well as metastatic colonization by direct and indirect means. PMID:23963762

  13. Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of STAT3 signaling pathway.

    Science.gov (United States)

    Cai, Qiaoyan; Lin, Jiumao; Wei, Lihui; Zhang, Ling; Wang, Lili; Zhan, Youzhi; Zeng, Jianwei; Xu, Wei; Shen, Aling; Hong, Zhenfeng; Peng, Jun

    2012-01-01

    Signal Transducer and Activator of Transcription 3 (STAT3), a common oncogenic mediator, is constitutively activated in many types of human cancers; therefore it is a major focus in the development of novel anti-cancer agents. Hedyotis diffusa Willd has been used as a major component in several Chinese medicine formulas for the clinical treatment of colorectal cancer (CRC). However, the precise mechanism of its anti-tumor activity remains largely unclear. Using a CRC mouse xenograft model, in the present study we evaluated the effect of the ethanol extract of Hedyotis diffusa Willd (EEHDW) on tumor growth in vivo and investigated the underlying molecular mechanisms. We found that EEHDW reduced tumor volume and tumor weight, but had no effect on body weight gain in CRC mice, demonstrating that EEHDW can inhibit CRC growth in vivo without apparent adverse effect. In addition, EEHDW treatment suppressed STAT3 phosphorylation in tumor tissues, which in turn resulted in the promotion of cancer cell apoptosis and inhibition of proliferation. Moreover, EEHDW treatment altered the expression pattern of several important target genes of the STAT3 signaling pathway, i.e., decreased expression of Cyclin D1, CDK4 and Bcl-2 as well as up-regulated p21 and Bax. These results suggest that suppression of the STAT3 pathway might be one of the mechanisms by which EEHDW treats colorectal cancer. PMID:22754353

  14. LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase pathways

    International Nuclear Information System (INIS)

    We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4 receptor antagonists block growth and induce apoptosis in pancreatic cancer cells both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4 stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human pancreatic cancer cells, as measured by thymidine incorporation and cell number. LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38 MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not involved

  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. The subcellular localization of IGFBP5 affects its cell growth and migration functions in breast cancer

    Directory of Open Access Journals (Sweden)

    Sahin Aysegul

    2009-04-01

    Full Text Available Abstract Background Insulin-like growth factor binding protein 5 (IGFBP5 has been shown to be associated with breast cancer metastasis in clinical marker studies. However, a major difficulty in understanding how IGFBP5 functions in this capacity is the paradoxical observation that ectopic overexpression of IGFBP5 in breast cancer cell lines results in suppressed cellular proliferation. In cancer tissues, IGFBP5 resides mainly in the cytoplasm; however, in transfected cells, IGFBP5 is mainly located in the nucleus. We hypothesized that subcellular localization of IGFBP5 affects its functions in host cells. Methods To test this hypothesis, we generated wild-type and mutant IGFBP5 expression constructs. The mutation occurs within the nuclear localization sequence (NLS of the protein and is generated by site-directed mutagenesis using the wild-type IGFBP5 expression construct as a template. Next, we transfected each expression construct into MDA-MB-435 breast cancer cells to establish stable clones overexpressing either wild-type or mutant IGFBP5. Results Functional analysis revealed that cells overexpressing wild-type IGFBP5 had significantly lower cell growth rate and motility than the vector-transfected cells, whereas cells overexpressing mutant IGFBP5 demonstrated a significantly higher ability to proliferate and migrate. To illustrate the subcellular localization of the proteins, we generated wild-type and mutant IGFBP5-pDsRed fluorescence fusion constructs. Fluorescence microscopy imaging revealed that mutation of the NLS in IGFBP5 switched the accumulation of IGFBP5 from the nucleus to the cytoplasm of the protein. Conclusion Together, these findings imply that the mutant form of IGFBP5 increases proliferation and motility of breast cancer cells and that mutation of the NLS in IGFBP5 results in localization of IGFBP5 in the cytoplasm, suggesting that subcellular localization of IGFBP5 affects its cell growth and migration functions in the

  17. 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. PMID:27371729

  18. Influences of combination of chemotherapy and autophagy inhibitor on the calreticulin expression in colon cancer cells

    OpenAIRE

    Peng, Rui-Qing; Dan-dan LI; Ding, Ya; Zhang, Xing; Zhang, Xiao-Shi; Wu, Xiao-jun

    2016-01-01

    Objective  To investigate the influence of chemotherapy combined with autophagy inhibitor on apoptosis and calreticulin (CRT) expression on colonic cancer cells. Methods  The colon cancer cells HCT116 were taken as the target in the present study. The inhibition rates (IC50) of chemotherapeutics oxaliplatin, 5-Fu and SN-38 were assessed by MTT assay. The changes in CRT expression on the membrane of HCT116 and apoptosis were determined with flow cytometry before and after treatment with chemot...

  19. Influences on pre-hospital delay in the diagnosis of colorectal cancer: a systematic review

    OpenAIRE

    Campbell, N C; MacDonald, S; Macleod, U; Mitchell, E D; Weller, D.

    2008-01-01

    Colorectal cancer is a major global health problem, with survival varying according to stage at diagnosis. Delayed diagnosis can result from patient, practitioner or hospital delay. This paper reports the results of a review of the factors influencing pre-hospital delay – the time between a patient first noticing a cancer symptom and presenting to primary care or between first presentation and referral to secondary care. A systematic methodology was applied, including extensive searches of th...

  20. PS3-16: The Influence of Travel Time on Breast Cancer Diagnosis and Treatment

    OpenAIRE

    Onega, Tracy; Cook, Andrea; Kirlin, Beth; Buist, Diana; Tuzzio, Leah

    2010-01-01

    Background and Aims: Longer travel time to health care services has been shown to be associated with more advanced stage at diagnosis and differences in surgical care for women with breast cancer. The influence of travel time on other disease characteristics at diagnosis and on use of other breast cancer treatments is not known. We examined travel time in relation to stage, nodal involvement, tumor size, primary and adjuvant treatments, and receipt of surveillance mammography to provide a mor...

  1. The Local Influence of Pioneer Investigators on Technology Adoption: Evidence from New Cancer Drugs

    OpenAIRE

    Leila Agha; David Molitor

    2015-01-01

    Local opinion leaders may play a key role in easing information frictions associated with technology adoption. This paper analyzes the influence of physician investigators who lead pivotal clinical trials for new cancer drugs. By comparing diffusion patterns across many drugs, we separate correlated regional demand for new technology from information spillovers. Using original data on clinical trial study authors for 21 new cancer drugs along with Medicare claims data from 1998-2008, we find ...

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

    International Nuclear Information System (INIS)

    Highlights: ► Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. ► Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. ► 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 μm 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.

  3. Influence of family size and birth order on risk of cancer: a population-based study

    Directory of Open Access Journals (Sweden)

    Sundquist Jan

    2011-05-01

    Full Text Available Abstract Background Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. Methods We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Results Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Conclusion Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer.

  4. Influence of family size and birth order on risk of cancer: a population-based study

    International Nuclear Information System (INIS)

    Family size and birth order are known to influence the risk of some cancers. However, it is still unknown whether these effects change from early to later adulthood. We used the data of the Swedish Family-Cancer Database to further analyze these effects. We selected over 5.7 million offspring with identified parents but no parental cancer. We estimated the effect of birth order and family size by Poisson regression adjusted for age, sex, period, region and socioeconomic status. We divided the age at diagnosis in two groups, below and over 50 years, to identify the effect of family size and birth order for different age periods. Negative associations for increasing birth order were found for endometrial, testicular, skin, thyroid and connective tissue cancers and melanoma. In contrast, we observed positive association between birth order and lung, male and female genital cancers. Family size was associated with decreasing risk for endometrial and testicular cancers, melanoma and squamous cell carcinoma; risk was increased for leukemia and nervous system cancer. The effect of birth order decreased for lung and endometrial cancer from age at diagnosis below to over 50 years. Combined effects for birth order and family size were marginally significant for thyroid gland tumors. Especially, the relative risk for follicular thyroid gland tumors was significantly decreased for increasing birth order. Our findings suggest that the effect of birth order decreases from early to late adulthood for lung and endometrial cancer

  5. 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

  6. Genetic variants in the HER2 gene: Influence on HER2 overexpression and loss of heterozygosity in breast cancer.

    Science.gov (United States)

    Cresti, Nicola; Lee, Joanne; Rourke, Emma; Televantou, Despina; Jamieson, David; Verrill, Mark; Boddy, Alan V

    2016-03-01

    Human epidermal growth factor receptor 2 (HER2) overexpression in breast cancer is an indicator of poor prognosis and is the pre-requisite for treatment with the agents targeting this member of the epidermal growth factor receptor family. In order to determine the influence of these common single-nucleotide polymorphisms (SNPs) in the HER2 gene, genomic DNA was obtained from 361 patients with breast cancer, aged between 29 and 82 years. Samples of tumour tissue were obtained from 241 (66%) patients and material for extraction of DNA is isolated from surrounding normal tissue by laser capture microdissection. Genotyping was performed using the Taqman fluorogenic 5' nuclease assay. Of the 360 patients with definitive determination of HER2 status, 49% were positive. The Ile655Val SNP had no influence on the frequency of HER2 expression. However, the proline allele of the Ala1170Pro SNP was associated with a higher frequency of HER2 overexpression (56% versus 43%, p = 0.015). Where the germline genotype was homozygous, the tumour genotype was identical in every case and for both SNPs. In HER2-positive tumours, heterozygosity was maintained in only 15% and 18% of the Ile655Val and Ala1170Pro SNPs, respectively. This was lower than in the HER2-negative tumours (46% and 43%, respectively). Normal breast tissue (n = 23) retained the germline genotype in all but one case. The underlying link between the Ala1170Pro SNP and HER2 positivity is not known, nor is the significance of HER2 overexpression and loss of heterozygosity in breast cancer. However, these results illustrate the complexity of HER2 genotype and overexpression in this disease. PMID:26773371

  7. Lack of the type III epidermal growth factor receptor mutation in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Olsen, Dorte Aalund; Nielsen, Jens Nederby;

    2007-01-01

    BACKGROUND: Epidermal growth factor receptor (EGFR) analysis by traditional immunohistochemistry does not provide clinicians with a reliable tool for the selection of patients to EGFR-targeted treatment in colorectal cancer (CRC). Alternative methods and further understanding of the EGFR signaling...... therapy. The aim of the present study was to investigate the presence of EGFRvIII in CRC by PCR and protein analysis. MATERIALS AND METHODS: The study included 79 colorectal cancer patients for PCR analysis and 50 patients for protein analysis by Western blots, in two different laboratories. RESULTS...

  8. Withaferin-A induces mitotic catastrophe and growth arrest in prostate cancer cells

    OpenAIRE

    Roy, Ram V; Suman, Suman; Das, Trinath P; Luevano, Joe; Damodaran, Chendil

    2013-01-01

    Cell cycle deregulation is strongly associated with the pathogenesis of prostate cancer (CaP). Clinical trials of cell cycle regulators that target either the G0/G1 or G2/M phase to inhibit the growth of cancers including CaP are increasing. In this study, we determined the cell-cycle regulatory potential of the herbal molecule Withaferin-A (WA) on CaP cells. WA induced irreversible G2/M arrest in both CaP cell lines (PC3 and DU145) for 48 h. The G2/M arrest was accompanied by upregulation of...

  9. 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.

  10. 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.

  11. Human mitochondrial transcription factor A functions in both nuclei and mitochondria and regulates cancer cell growth

    International Nuclear Information System (INIS)

    Highlights: → Mitochondrial transcription factor A (mtTFA) localizes in nuclei and binds tightly to the nuclear chromatin. → mtTFA contains two putative nuclear localization signals (NLS) in the HMG-boxes. → 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). → 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.

  12. Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    XU Tian-min; XIN Ying; CUI Man-hua; JIANG Xin; GU Li-ping

    2007-01-01

    Background Ginsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental tumours more effectively than conventional therapy. The effect of this combination on ovarian cancer remains to be evaluated. Therefore, we investigated the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and angiogenesis of human ovarian cancer.Methods Twenty-eight female athymic mice were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX,ginsenoside Rg3 and CTX combination and control, after being transplanted with ovarian cancer cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3 and CTX for the 10 days following inoculation of SKOV-3cells. The life quality and number of living days of mice were recorded. The size of tumour, tumour inhibitive rate, life elongation rate, proliferating cell nuclear antigen labelling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) of the tumour tissues were estimated.Results Life quality of mice in ginsenoside Rg3 and combined treatment groups were better and number of living days longer than control. Average tumour weights of each treated group were less than control and there was no significant difference among the treated groups. PCNALI of treated groups was lower than control. The MVD value and VEGF expression in treated groups were significantly lower than control and the MVD values of ginsenoside Rg3 and combined treatment groups were lower than that of CTX group.Conclusions Ginsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the antitumour effect each other and improved the living quality and survival time of mice with tumour.

  13. SL-01, an oral derivative of gemcitabine, inhibited human breast cancer growth through induction of apoptosis

    International Nuclear Information System (INIS)

    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

  14. Influence of late side-effects upon daily life after radiotherapy of laryngeal and pharyngeal cancer

    International Nuclear Information System (INIS)

    The influence on daily life from long-term side-effects was studied in patients treated more than 5 years ago with radiotherapy for laryngeal and pharyngeal cancer. Forty-six patients were asked to participate in telephone interviews and 44 participated. Only a minority (10%) states serious problems related to the treatment. Problems related to the voice and severe xerostomia were especially mentioned. Half of the patients treated for pharyngeal cancer, complained of xerostomia and had occasionally a feeling of being handicapped. Social relations were impaired in 10% of the patients and 10% had retired due to their cancer or therapy related side-effects. It is concluded that radiotherapy seems to be a well tolerated treatment with relatively little impairment of the daily life in patients with laryngeal cancer. In patients with pharyngeal cancer, xerostomia is a major problem, which often persists more than 5 years after treatment. (orig.)

  15. Desacetyl nimbinene inhibits breast cancer growth and metastasis through reactive oxygen species mediated mechanisms.

    Science.gov (United States)

    Arumugam, Arunkumar; Subramani, Ramadevi; Nandy, Sushmita; Powell, Sara; Velazquez, Marissa; Orozco, Alexis; Galvez, Adriana; Lakshmanaswamy, Rajkumar

    2016-05-01

    Accumulation of reactive oxygen species (ROS) has been implicated in induction of apoptosis and regulation of key signaling molecules in cancer cells. Phytochemicals are potent source of anticancer drugs as wells as potential inducers of ROS. Neem (Azadirachta indica) is a medicinal plant used for the treatment of various diseases. The main objective of this study is to investigate the anticancer effect of desacetyl nimbinene (DAN; an active ingredient of neem) against breast cancer. Normal and breast cancer cell lines were used for the study. The effect of DAN on cell proliferation, apoptosis, ROS generation, migration, and invasion was analyzed. Antioxidant enzymes superoxide dismutase (SOD)1 and SOD2 were overexpressed to test the effect of DAN-induced ROS generation on breast cancer growth. Key survival and apoptotic protein markers were analyzed to validate the anticancer effect of DAN. Our data demonstrated that DAN inhibited the growth of breast cancer cells by inducing ROS generation. Further investigations revealed that DAN treatment lead to the loss of mitochondrial membrane potential resulting in mitochondria-dependent apoptotic cell death. Increased phosphorylation of c-Jun-N-terminal kinase (JNK) and reduced phosphorylation of p38 were also observed in response to DAN treatment. Inhibition of ROS production by overexpressing antioxidant enzymes SOD1 and SOD2 reduced the DAN-induced cytotoxicity. Additionally, DAN significantly inhibited migration and invasion of MDA-MB-231 breast cancer cells. Overall, our data suggest that DAN exerts its anticancer effect on breast cancer by induction of mitochondria-mediated apoptosis mediated by ROS accumulation. PMID:26637227

  16. Influence of Experimental Parameters on Fatigue Crack Growth and Heat Build-Up in Rubber

    Directory of Open Access Journals (Sweden)

    Franziska Stadlbauer

    2013-11-01

    Full Text Available Loading parameters (frequency, amplitude ratio and waveform are varied to determine their influence on fatigue crack growth in rubber. Up to three different rubber blends are investigated: one actual engineering material and two model materials. Fatigue crack growth curves and strain distributions of pure shear and faint waist pure shear samples are compared for a model material. Fatigue behavior is studied for three different frequencies (1 Hz, 3 Hz and 5 Hz. Amplitude ratio appears to be another important influence factor concerning fatigue crack growth in rubber. The beneficial effect of positive amplitude ratios (tensional loading conditions is shown for different materials. However, fatigue crack growth is considerably increased for negative amplitude ratios (tensional-compressional loading conditions. Furthermore, the influence of the waveform is determined for three different waveform shapes. One is sinusoidal, and two have a square shape, including dwell periods and sinusoidal slopes. Special focus lies on heat build-up, which is substantial, especially for large loads, high frequencies and/or highly filled rubber blends. Plateau temperatures are determined for various loading conditions and rubber blends. A very simple linear relationship with dissipated energy per time and unit area is obtained. Results gathered with dynamic mechanical analyses show, likewise, a linear trend, but the heat build-up is very small, due to different sample geometries.

  17. The influence of Pt redistribution on Ni1-xPtxSi growth properties

    International Nuclear Information System (INIS)

    We have studied the influence of Pt on the growth of Ni silicide thin films by examining the Pt redistribution during silicide growth. Three different initial Pt configurations were investigated, i.e., a Pt alloy (Ni+Pt/), a Pt capping layer (Pt/Ni/) and a Pt interlayer (Ni/Pt/), all containing 7 at. % Pt relative to the Ni content. The Pt redistribution was probed using in situ real-time Rutherford backscattering spectrometry (RBS) whereas the phase sequence was monitored during the solid phase reaction (SPR) using in situ real-time x-ray diffraction. We found that the capping layer and alloy exhibit a SPR comparable to the pure Ni/ system, whereas Pt added as an interlayer has a much more drastic influence on the Ni silicide phase sequence. Nevertheless, for all initial sample configurations, Pt redistributes in an erratic way. This phenomenon can be assigned to the low solubility of Pt in Ni2Si compared to NiSi and the high mobility of Pt in Ni2Si compared to pure Ni. Real-time RBS further revealed that the crucial issue determining the growth properties of each silicide phase is the Pt concentration at the Si interface during the initial stages of phase formation. The formation of areas rich in Pt reduce the Ni silicide growth kinetics which influences the phase sequence and properties of the silicides.

  18. Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth

    International Nuclear Information System (INIS)

    Pancreatic cancer accompanied by a moderate-sized pseudocyst with extrapancreatic growth is extremely rare. Diagnosis of pancreatic cancer on preoperative imaging is difficult when the pancreatic parenchyma is compressed by a pseudocyst and becomes unclear. Despite advances in imaging techniques, accurate preoperative diagnosis of cystic lesions of the pancreas remains difficult. In this case, it was challenging to diagnose pancreatic cancer preoperatively as we could not accurately assess the pancreatic parenchyma, which had been compressed by a moderate-sized cystic lesion with extrapancreatic growth. A 63-year-old woman underwent investigations for epigastric abdominal pain. She had no history of pancreatitis. Although we suspected pancreatic ductal carcinoma with a pancreatic cyst, there was no mass lesion or low-density area suggestive of pancreatic cancer. We did not immediately suspect pancreatic cancer, as development of a moderate-sized cyst with extrapancreatic growth is extremely rare and known tumor markers were not elevated. Therefore, we initially suspected that a massive benign cyst (mucinous cyst neoplasm, serous cyst neoplasm, or intraductal papillary mucinous neoplasm) resulted in stenosis of the main pancreatic duct. We were unable to reach a definitive diagnosis prior to the operation. We had planned a pancreaticoduodenectomy to reach a definitive diagnosis. However, we could not remove the tumor because of significant invasion of the surrounding tissue (portal vein, superior mesenteric vein, etc.). The fluid content of the cyst was serous, and aspiration cytology from the pancreatic cyst was Class III (no malignancy), but the surrounding white connective tissue samples were positive for pancreatic adenocarcinoma on pathological examination during surgery. We repeated imaging (CT, MRI, endoscopic ultrasound, etc.) postoperatively, but there were neither mass lesions nor a low-density area suggestive of pancreatic cancer. In retrospect, we think

  19. Atmosphere influence on in situ ion beam analysis of thin film growth

    International Nuclear Information System (INIS)

    In situ, nondestructive surface characterization of thin-film growth processes in an environment of chemically active gas at pressures of several mTorr is required both for the understanding of growth processes in multicomponent films and layered heterostructures and for the improvement of process reproducibility and device reliability. The authors have developed a differentially pumped pulsed ion beam surface analysis system that includes ion scattering spectroscopy (ISS) and direct recoil spectroscopy (DRS), coupled to an automated ion beam sputter-deposition system (IBSD), to study film growth processes in an environment of chemically active gas, such as required for the growth of oxide, nitride, or diamond thin films. The influence of gas-phase scattering and gas-surface interactions on the ISS and DRS signal intensity and peak shape have been studied. From the intensity variation as a function of ambient gas pressure, the authors have calculated the mean free path and the scattering cross-section for a given combination of primary ion species and ambient gas. Depending on the system geometry and the combination of primary beam and background, it is shown that surface-specific data can be obtained during thin-film growth at pressures ranging from a few mtorr to approximately 1 Torr. Detailed information such as surface composition, structure, and film growth mechanism may be obtained in real-time, making ion beam analysis an ideal nondestructive, in situ probe of thin-film growth processes

  20. Influence of native silicon oxides on the growth of GaN nanorods on Si(001)

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Shigehiko; Seo, Jong-Uk; Uchida, Kanae; Tambo, Hiroyuki; Kameoka, Hisashi; Ishimaru, Manabu; Asahi, Hajime [Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan)

    2009-06-15

    Influence of native Si oxides on the growth of GaN nanorods on Si(001) substrates have been investigated. At the initial stage of GaN growth on clean Si(001) substrates at 450 C, (2 x 1) reflection high-energy electron diffraction patterns immediately change into halo patterns, indicating growth of amorphous materials. The cross-sectional transmission microscopy observation and secondary ion mass spectroscopy measurement reveal that there exists an amorphous Si{sub x}N{sub y} layer at the GaN/Si interface. This provides the evidence that during the initial growth of GaN on clean Si substrates with out native oxides, nitridation of Si takes place to form amorphous Si{sub x}N{sub y} as well as GaN. The structural properties and surface morphologies of these interfacial layers affect GaN nanorod growth. By contrast, native oxides act as a mask against nitridation of Si substrates. Since plasma-activated nitrogen mainly reacts with Ga to form GaN, GaN growth always proceeds under a desired N-rich growth condition. As a result, GaN nanorods are uniformly grown on Si(001) with native oxides. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  1. 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...

  2. Can cancer influence the pain agenda in Oncology Outpatient Consultations?

    OpenAIRE

    Rogers, MS. Tood, C.

    2010-01-01

    Pain in cancer patients is common, yet it is often inadequately managed. Although poor assessment has been implicated, how patients contribute to this process has not been explicated. This study aims to uncover patients' contributions to discussions about pain during oncology outpatient consultations. Seventy-four medical encounters were observed and audiotaped. Verbatim transcriptions of pain talk were examined using conversational analysis. Thirty-nine of 74 patients talked about pain with ...

  3. 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. PMID:25851203

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

    Science.gov (United States)

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

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene. PMID:25419360

  5. Impact of age on epidermal growth factor receptor mutation in lung cancer.

    Science.gov (United States)

    Ueno, Tsuyoshi; Toyooka, Shinichi; Suda, Kenichi; Soh, Junichi; Yatabe, Yasushi; Miyoshi, Shinichiro; Matsuo, Keitaro; Mitsudomi, Tetsuya

    2012-12-01

    Aging is one of the best, but rarely referred, risk factors for various types of cancer including lung cancer, because age could be a surrogate for accumulation of genetic events in cancers. Smoking inversely associates with the presence of epidermal growth factor receptor (EGFR) mutation in lung cancer, but its strong confounding with age and sex makes it difficult to evaluate sole impact of age. To clarify an impact of age on EGFR mutation, we conducted a cross-sectional study based on data of 1262 lung cancer patients. The associations between EGFR mutation and age, considering sex, smoking and histology, were evaluated using logistic regression models. In multivariate analysis, we found a significant increase of EGFR mutation prevalence by increase of age (p-trend=0.0004). Consistent trend was observed among never-smoking females (p-trend=0.011) and never-smoking males also showed similar trend although not significant. These were consistently observed when we limit the subject to those with adenocarcinoma. In conclusion, age independently associates with EGFR mutation among lung cancer. Positive association between EGFR mutation and age among never-smokers regardless of sex might indicate that EGFR mutation occurs cumulatively by unidentified internal/external factors other than smoking. PMID:23036155

  6. 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.

  7. 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.

  8. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    OpenAIRE

    Shih-Chieh Chang; Jin-Yuan Shih; Cheng-Yu Chang

    2011-01-01

    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 patie...

  9. 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. PMID:23981580

  10. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

    Science.gov (United States)

    Liu, B; Lee, K-W; Anzo, M; Zhang, B; Zi, X; Tao, Y; Shiry, L; Pollak, M; Lin, S; Cohen, P

    2007-03-15

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer. PMID:16983336

  11. The influence of the pre-metastatic niche on breast cancer metastasis.

    Science.gov (United States)

    Ursini-Siegel, Josie; Siegel, Peter M

    2016-09-28

    The emergence of metastatic disease constitutes a significant life-threatening development during cancer progression. To date, intensive efforts have been focused on understanding the intrinsic properties that confer malignant potential to cancer cells, as well as the role of the primary tumour microenvironment in promoting cancer metastasis. Beyond events occurring at the primary site, the metastatic cascade is composed of numerous barriers that must be overcome in order for disseminating cancer cells to form distal metastases. The most formidable of these is the ability of cancer cells to seed and grow in a completely foreign microenvironment. Interestingly, solid malignancies often display a particular tropism for specific tissue sites. For example, breast patients with metastatic disease will often develop bone, lung, liver or brain metastases. This mini-review will explore aspects of pre-existing and induced metastatic niches and focus on how the unique composition and function of diverse niche components, within common sites of breast cancer metastasis, enable the survival and growth of disseminated cancer cells. These common supportive functions of the niche are provided by a complex array of stromal components and molecular mechanisms that are, in part, reflective of the tissue in which the metastases arise. Finally, the metastatic niche is a dynamic structure that is continually altered and sculpted by the cancer cells during progression of the metastatic lesion. PMID:26577808

  12. A Longitudinal Study of Post-Traumatic Growth and Psychological Distress in Colorectal Cancer Survivors.

    Science.gov (United States)

    Occhipinti, Stefano; Chambers, Suzanne K; Lepore, Stephen; Aitken, Joanne; Dunn, Jeff

    2015-01-01

    The stability of post-traumatic growth over time and the relationship between post-traumatic growth and traditional distress outcomes remains unclear. We tracked post-traumatic growth in a population-based sample of colorectal cancer patients from soon after diagnosis to five years subsequently to assess the heterogeneity of a post-traumatic growth response to cancer over time and describe the simultaneous and longitudinal relationships between post-traumatic growth and psychological distress. 1966 colorectal patients who were five months post diagnosis were assessed six times over a five year period. There was considerable heterogeneity associated with both psychological distress and benefit finding scores over time. However, both for benefit finding and psychological distress, the variation in individual scores suggested an underlying positive linear trend and both lagged and lagged change components. Specifically, benefit finding and psychological distress are mutual leading indicators of each other. First, benefit finding served as a leading indicator of distress, in that increases in reported benefit finding from year to year predicted higher future increases in psychological distress. As well, in an inverse relationship, psychological distress served as a leading indicator of benefit finding, such that increases in reported distress from year to year predicted lower future increases in benefit finding. Post-traumatic growth may reflect patients coping efforts to enhance perceptions of wellbeing in response to escalating cancer-related threats, acting as harbinger of increasing trajectories of psychological distress. This explanation is consistent with a cognitive dissonance response in which threats to the integrity of the self then lead to a tendency to accentuate positive aspects of the self. PMID:26418357

  13. 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.

  14. Chondromodulin-1 directly suppresses growth of human cancer cells

    International Nuclear Information System (INIS)

    Chondromodulin-1 (ChM1), an endogenous anti-angiogenic factor expressed in cartilage, has been suggested to inhibit invasion of endothelial cells into cartilage. In addition, the ectopic administration of ChM1 has been reported to suppress tumorigenesis in vivo. However, it is unclear whether the anti-tumor effect is due to not only the anti-vascularization effect of ChM1, but also its direct action against oncocytes. In the present study, we sought to determine whether ChM1 has a direct action on tumor cells. BrdU incorporation assay was performed on human umbilical vein endothelial cells (HUVECs), normal human dermal fibroblasts (NHDFs), HepG2 cells and HeLa cells in the presence or absence of recombinant human ChM1 (rhChM1). An adenovirus that expresses ChM1, Ad-ChM1, was established and applied to the tumor xenografted in vivo, and to in vitro tumor cells cultured on plates or in soft agar. Cell cycle-related proteins and the phosphorylation of Erk, Akt, and GSK3β, the downstream molecules of the extracellular matrix-integrin signaling pathways, in HepG2 cells treated with or without Ad-ChM1 were detected by western blot analysis. Luciferase reporter assays of STAT, GAS, and ISRE, which participate in another cytokine signaling pathway, ware performed in HepG2, HeLa, and HUVEC cells. ChM1 suppressed BrdU incorporation in HUVECs and in HepG2 cells dose-dependently, but did not suppress BrdU incorporation in NHDFs and HeLa cells cultured on plates. In soft agar, however, ChM1 suppressed the growth of HeLa cells, as well as HepG2 cells. Western blot analyses demonstrated that ChM1 decreased the levels of cyclin D1, cyclin D3, and cdk6 and increased those of p21cip1 without affecting the phosphorylation levels of Erk, Akt, and GSK3β in HepG2 cells. The luciferase reporter assay demonstrated that ChM1 suppressed the transcriptional activities of STAT and GAS but not of ISRE. ChM1 directly suppressed the proliferation of tumor cells in an anchorage

  15. A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer

    Directory of Open Access Journals (Sweden)

    Katherine A Bolton

    2016-06-01

    Full Text Available Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case–control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively, but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013. This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012. Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.

  16. A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer

    Science.gov (United States)

    Bolton, Katherine A; Avery-Kiejda, Kelly A; Holliday, Elizabeth G; Attia, John; Bowden, Nikola A

    2016-01-01

    Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case–control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively), but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013). This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012). Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported. PMID:27090263

  17. Specific immunotherapy generates CD8(+) CD196(+) T cells to suppress lung cancer growth in mice.

    Science.gov (United States)

    Zhang, Jian; Liu, Jing; Chen, Huiguo; Wu, Weibin; Li, Xiaojun; Wu, Yonghui; Wang, Zhigang; Zhang, Kai; Li, Yun; Weng, Yimin; Liao, Hongying; Gu, Lijia

    2016-08-01

    That specific immunotherapy can inhibit cancer growth has been recognized; its efficiency is to be improved. This study aimed to inhibit lung cancer (LC) growth in a mouse model by using an LC-specific vaccination. In this study, a LC mouse model was created by adoptive transplantation with LC cells. The tumor-bearing mice were vaccinated with LC cell extracts plus adjuvant TNBS or adoptive transplantation with specific CD8(+) CD196(+) T cells. The results showed that the vaccination with LC extracts (LCE)/TNBS markedly inhibited the LC growth and induced CD8(+) CD196(+) T cells in LC tissue and the spleen. These CD8(+) CD196(+) T cells proliferated and produce high levels of perforin upon exposure to LCE and specifically induced LC cell apoptosis. Exposure to TNBS induced RAW264.7 cells to produce macrophage inflammatory protein-3α; the latter activated signal transducer and activator of transcription 3 and further induced perforin expression in the CD8(+) CD196(+) T cells. Adoptive transfer with specific CD8(+) CD196(+) T cells suppressed LC growth in mice. In conclusion, immunization with LC extracts and TNBS can induce LC-specific CD8(+) CD196(+) T cells in LC-bearing mice and inhibit LC growth. PMID:26910585

  18. Nonconventional opioid binding sites mediate growth inhibitory effects of methadone on human lung cancer cells.

    OpenAIRE

    Maneckjee, R; Minna, J D

    1992-01-01

    Methadone was found to significantly inhibit the in vitro and in vivo growth of human lung cancer cells. The in vitro growth inhibition (occurring at 1-100 nM methadone) was associated with changes in cell morphology and viability detectable within 1 hr and was irreversible after a 24-hr exposure to the drug. These effects of methadone could be reversed in the first 6 hr by naltrexone, actinomycin D, and cycloheximide, suggesting involvement of opioid-like receptors and the requirement for de...

  19. 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.

  20. 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.

  1. Tyrosine kinase signalling in breast cancer: Fibroblast growth factors and their receptors

    International Nuclear Information System (INIS)

    The fibroblast growth factors [Fgfs (murine), FGFs (human)] constitute a large family of ligands that signal through a class of cell-surface tyrosine kinase receptors. Fgf signalling has been associated in vitro with cellular differentiation as well as mitogenic and motogenic responses. In vivo, Fgfs are critical for animal development, and some have potent angiogenic properties. Several Fgfs have been identified as oncogenes in murine mammary cancer, where their deregulation is associated with proviral insertions of the mouse mammary tumour virus (MMTV). Thus, in some mammary tumours of MMTV-infected mouse strains, integration of viral genomic DNA into the somatic DNA of mammary epithelial cells was found to have caused the inappropriate expression of members of this family of growth factors. Although examination of human breast cancers has shown an altered expression of FGFs or of their receptors in some tumours, their role in the causation of breast disease is unclear and remains controversial

  2. [Transforming growth factor beta-1: structure, function, and regulation mechanisms in cancer].

    Science.gov (United States)

    Peralta-Zaragoza, O; Lagunas-Martínez, A; Madrid-Marina, V

    2001-01-01

    Transforming growth factor beta-1 (TGF-beta 1) is produced by several cell lineages such as lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these and other cells. In general, TGF-beta 1 has pleiotropic properties on the immune response during the development of infection diseases and cancer; however, the mechanisms of action and regulation of gene expression of this cytokine are poorly understood, in this review, the biological properties and the molecular mechanisms that regulate TGF-beta 1 gene expression are described, to understand the role of this cytokine in growth and cell differentiation. The knowledge of molecular mechanisms of gene expression of TGF-beta 1 may serve to develop new cancer therapies. The English version of this paper is available at: http://www.insp.mx/salud/index.html PMID:11547595

  3. 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.

  4. 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...

  5. ML264, A Novel Small-Molecule Compound That Potently Inhibits Growth of Colorectal Cancer.

    Science.gov (United States)

    Ruiz de Sabando, Ainara; Wang, Chao; He, Yuanjun; García-Barros, Mónica; Kim, Julie; Shroyer, Kenneth R; Bannister, Thomas D; Yang, Vincent W; Bialkowska, Agnieszka B

    2016-01-01

    Colorectal cancer is one of the leading causes of cancer mortality in Western civilization. Studies have shown that colorectal cancer arises as a consequence of the modification of genes that regulate important cellular functions. Deregulation of the WNT and RAS/MAPK/PI3K signaling pathways has been shown to be important in the early stages of colorectal cancer development and progression. Krüppel-like factor 5 (KLF5) is a transcription factor that is highly expressed in the proliferating intestinal crypt epithelial cells. Previously, we showed that KLF5 is a mediator of RAS/MAPK and WNT signaling pathways under homeostatic conditions and that it promotes their tumorigenic functions during the development and progression of intestinal adenomas. Recently, using an ultrahigh-throughput screening approach we identified a number of novel small molecules that have the potential to provide therapeutic benefits for colorectal cancer by targeting KLF5 expression. In the current study, we show that an improved analogue of one of these screening hits, ML264, potently inhibits proliferation of colorectal cancer cells in vitro through modifications of the cell-cycle profile. Moreover, in an established xenograft mouse model of colon cancer, we demonstrate that ML264 efficiently inhibits growth of the tumor within 5 days of treatment. We show that this effect is caused by a significant reduction in proliferation and that ML264 potently inhibits the expression of KLF5 and EGR1, a transcriptional activator of KLF5. These findings demonstrate that ML264, or an analogue, may hold a promise as a novel therapeutic agent to curb the development and progression of colorectal cancer. PMID:26621868

  6. Environmental influence on mussel (Mytilus edulis) growth - A quantile regression approach

    Science.gov (United States)

    Bergström, Per; Lindegarth, Mats

    2016-03-01

    The need for methods for sustainable management and use of coastal ecosystems has increased in the last century. A key aspect for obtaining ecologically and economically sustainable aquaculture in threatened coastal areas is the requirement of geographic information of growth and potential production capacity. Growth varies over time and space and depends on a complex pattern of interactions between the bivalve and a diverse range of environmental factors (e.g. temperature, salinity, food availability). Understanding these processes and modelling the environmental control of bivalve growth has been central in aquaculture. In contrast to the most conventional modelling techniques, quantile regression can handle cases where not all factors are measured and provide the possibility to estimate the effect at different levels of the response distribution and give therefore a more complete picture of the relationship between environmental factors and biological response. Observation of the relationships between environmental factors and growth of the bivalve Mytilus edulis revealed relationships that varied both among level of growth rate and within the range of environmental variables along the Swedish west coast. The strongest patterns were found for water oxygen concentration level which had a negative effect on growth for all oxygen levels and growth levels. However, these patterns coincided with differences in growth among periods and very little of the remaining variability within periods could be explained indicating that interactive processes masked the importance of the individual variables. By using quantile regression and local regression (LOESS) this study was able to provide valuable information on environmental factors influencing the growth of M. edulis and important insight for the development of ecosystem based management tools of aquaculture activities, its use in mitigation efforts and successful management of human use of coastal areas.

  7. Influence of pre sowing ultraviolet radiation of wheat seeds on its growth, efficiency and activity of endogenous phytohormones

    International Nuclear Information System (INIS)

    The experimental data on influence of ultraviolet radiation on growth, efficiency and activity of endogenous phytohormones of wheat seeds was considered in this work. It was shown that short-wave ultraviolet radiation decreased the growth processes of plants. The medium-wave and long-wave ultraviolet radiation increased the the growth processes of plants.

  8. Geographic Patterns and Stand Variables Influencing Growth and Vigor of Populus tremuloides in the Sierra Nevada (USA)

    OpenAIRE

    Christa M. Dagley; John-Pascal Berrill

    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...

  9. 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.

  10. Hiwi knockdown inhibits the growth of lung cancer in nude mice.

    Science.gov (United States)

    Liang, Dong; Dong, Min; Hu, Lin-Jie; Fang, Ze-Hui; Xu, Xia; Shi, En-Hui; Yang, Yi-Ju

    2013-01-01

    Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of SSCloAldebr cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell SSCloAldebr cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers. PMID:23621188

  11. Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

    Science.gov (United States)

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

    2011-10-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. PMID:21640721

  12. 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.

  13. Opioid growth factor receptor (OGFR expression is downregulated with progression of triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Beth Worley

    2015-12-01

    Full Text Available Purpose: Triple negative breast cancer (TNBC is an aggressive form of breast cancer that accounts for approximately 15% of the newly diagnosed cancers worldwide, and disproportionately affects younger women and women of color. Although many forms of breast cancer are successfully treated, new therapies are needed for TNBC. A novel regulatory system, the opioid growth factor (OGF – opioid growth factor receptor (OGFr axis, plays a determining role in neoplasia. OGF is an endogenous peptide that binds specifically to OGFr to inhibit cell replication. As some human cancers grow, OGFr expression is diminished, thus limiting the therapeutic efficacy of OGF. The OGF-OGFr axis is present in human TNBC cell line MDA-MB-231 and OGF  inhibits cell replication in a dosage-related, receptor-mediated manner. Methods: The present study investigated whether OGFr protein expression in human breast cancer cell lines grown in vitro or transplanted into nude mice, changed with the stage of proliferation or size of tumor using western blotting, semi-quantitative immunohistochemistry, and DNA synthesis techniques. Results: Comparison of log and confluent TNBC cultures revealed that OGF expression was significantly decreased in confluent cultures relative to levels in log-phase cells. Western blot analyses confirmed that OGFr was reduced in confluent TNBC and MCF-7 breast cancer cells in comparison to corresponding log-phase cells. Moreover, BrdU labeling was reduced in confluent cells. Small (<500 mm3 and large (>1000 mm3 TNBC tumors grown in nude mice were processed for semiquantitative   measurement of OGF and OGFr. The expression of both peptide and receptor in large tumors was downregulated relative to small tumors. Conclusion: The reduced expression of the inhibitory peptide and receptor diminishes the efficacy of the OGF-OGFr axis as a biotherapy. These data suggest that the OGF-OGFr pathway is altered with cancer progression and one or more elements of

  14. Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

    International Nuclear Information System (INIS)

    KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it

  15. Health behaviour and posttraumatic growth in parents of childhood cancer survivors

    Czech Academy of Sciences Publication Activity Database

    Slezáčková, Alena; Blatný, Marek; Jelínek, Martin; Kepák, T.; Vlčková, I.; Pilát, M.

    2009-01-01

    Roč. 24, č. 1 (2009), s. 366-367. ISSN 0887-0446. [Annual Conference of the European Health Psychology Society /23./. 23.09.2009-26.09.2009, Pisa] R&D Projects: GA ČR GA406/07/1384 Institutional research plan: CEZ:AV0Z70250504 Keywords : health behaviour * posttraumatic growth * childhood cancer survivors Subject RIV: AN - Psychology

  16. Frondoside A Suppressive Effects on Lung Cancer Survival, Tumor Growth, Angiogenesis, Invasion, and Metastasis

    OpenAIRE

    Samir Attoub; Kholoud Arafat; An Gélaude; Mahmood Ahmed Al Sultan; Marc Bracke; Peter Collin; Takashi Takahashi; Thomas E Adrian; Olivier De Wever

    2013-01-01

    A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration...

  17. 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.

  18. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia.

    OpenAIRE

    Mantzoros, C S; Tzonou, A.; Signorello, L B; Stampfer, M.; Trichopoulos, D; Adami, H. O.

    1997-01-01

    Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were...

  19. Epidermal Growth Factor Increases LRF/Pokemon Expression in Human Prostate Cancer Cells

    OpenAIRE

    Aggarwal, Himanshu; Aggarwal, Anshu; Devendra K Agrawal

    2011-01-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that reg...

  20. Signal interaction of Hedgehog/GLI and epidermal growth factor receptor signaling in cancer development

    International Nuclear Information System (INIS)

    The subject of this PhD thesis is based on the cooperation of Hedgehog (HH)/GLI with epidermal growth factor receptor (EGFR) signaling synergistically promoting oncogenic transformation and cancer growth. In previous studies we have demonstrated that the HH/GLI and EGFR signaling pathways interact synergistically resulting not only in selective induction of HH/GLI-EGFR target genes, but also in the onset of oncogenic transformation and tumor formation (Kasper, Schnidar et al. 2006; Schnidar, Eberl et al. 2009). However, the molecular key mediators acting downstream of HH/GLI and EGFR signal cooperation were largely unknown and the in vivo evidence for the therapeutic relevance of HH/GLI and EGFR signal cooperation in HH-associated cancers was lacking. During my PhD thesis I could demonstrate that the integration of EGFR and HH/GLI signaling involves activation of RAS/MEK/ERK and JUN/AP1 signaling in response to EGFR activation. Furthermore I succeeded in identifying genes, including stem cell- (SOX2, SOX9), tumor growth- (JUN, TGFA, FGF19) and metastasis-associated genes (SPP1/osteopontin, CXCR4) that showed synergistic transcriptional activation by HH/GLI-EGFR signal integration. Importantly, I could demonstrate that these genes arrange themselves within a stable interdependent signaling network, which is required for in vivo growth of basal cell carcinoma (BCC) and tumor-initiating pancreatic cancer cells. These data validate EGFR signaling as additional drug target in HH/GLI driven cancers and provide new therapeutic strategies based on combined targeting of cooperative HH/GLI-EGFR signaling and selected downstream target genes (Eberl, Klingler et al. 2012). (author)

  1. Contributions of the Epidermal Growth Factor Receptor to Acquisition of Platinum Resistance in Ovarian Cancer Cells

    OpenAIRE

    Granados, Michaela L.; Hudson, Laurie G.; Samudio-Ruiz, Sabrina L.

    2015-01-01

    Acquisition of platinum resistance following first line platinum/taxane therapy is commonly observed in ovarian cancer patients and prevents clinical effectiveness. There are few options to prevent platinum resistance; however, demethylating agents have been shown to resensitize patients to platinum therapy thereby demonstrating that DNA methylation is a critical contributor to the development of platinum resistance. We previously reported the Epidermal Growth Factor Receptor (EGFR) is a nove...

  2. 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.

  3. A sulfated polysaccharide of Ecklonia cava inhibits the growth of colon cancer cells by inducing apoptosis

    OpenAIRE

    Ahna, Ginnae; Lee, WonWoo; Kim, Kil-Nam; Lee, Ji-Hyeok; Heo, Soo-Jin; Kang, Nalae; Lee, Seung-Hong; Ahnf, Chang-Bum; Jeon, You-Jin

    2015-01-01

    We investigated anticancer effects of the crude polysaccharides (CPs) isolated from Ecklonia cava enzymatic extracts using AMG, Viscozyme, Protamex, and Alcalase enzyme against a colon cancer cell line, CT26 cells. Among them, the CP of Protamex extract (PCP) contained the highest fucose and sulfated group contents and showed the highest growth inhibitory effect against CT-26 cells. In addition, PCP dose-dependently increased the formation of apoptotic body and the percentage of Sub-G1 DNA co...

  4. ING1 and 5-Azacytidine Act Synergistically to Block Breast Cancer Cell Growth

    OpenAIRE

    Satbir Thakur; Xiaolan Feng; Zhong Qiao Shi; Amudha Ganapathy; Manoj Kumar Mishra; Peter Atadja; Don Morris; Karl Riabowol

    2012-01-01

    BACKGROUND: Inhibitor of Growth (ING) proteins are epigenetic "readers" that recognize trimethylated lysine 4 of histone H3 (H3K4Me3) and target histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes to chromatin. METHODS AND PRINCIPAL FINDINGS: Here we asked whether dysregulating two epigenetic pathways with chemical inhibitors showed synergistic effects on breast cancer cell line killing. We also tested whether ING1 could synergize better with chemotherapeutics that targe...

  5. The Effectiveness of Enteral Nutrition Support in the Growth of Children Patients with Cancer

    OpenAIRE

    Can Acipayam

    2014-01-01

    Aim: The purpose of this study was to assess, through anthropometric and biochemical parameters, the positive effect on growth of enteral nutrition support in children with cancer receiving chemotherapy. Material and Method: Forty-three consecutive patients newly diagnosed with pediatric malignant disease and receiving intensive chemotherapy were included. Twenty-six patients received an enteral nutrition formula. Seventeen control patients did not receive enteral nutrition formula. Anthropom...

  6. Anti-tissue factor short hairpin RNA inhibits breast cancer growth in vivo

    OpenAIRE

    Bluff, J. E.; Amarzguioui, M.; Slattery, J; Reed, M.W.R.; Brown, N J; Staton, C A

    2010-01-01

    Abstract In breast cancer, there is a correlation between tissue factor (TF) expression, angiogenesis and disease progression. TF stimulates tumour angiogenesis, in part, through up-regulation of vascular endothelial growth factor (VEGF). Therefore, this study aimed to establish whether TF stimulates angiogenesis and tumour progression directly and independent of VEGF up-regulation. Initially, the effects of TF and VEGF were assessed on endothelial cell migration (Boyden chamber) a...

  7. The time-evolution of DCIS size distributions with applications to breast cancer growth and progression

    OpenAIRE

    Dowty, James G.; Byrnes, Graham B; Gertig, Dorota M

    2013-01-01

    Ductal carcinoma {\\em in situ} (DCIS) lesions are non-invasive tumours of the breast which are thought to precede most invasive breast cancers (IBC). As individual DCIS lesions are initiated, grow and invade (i.e. become IBC) the size distribution of the DCIS lesions present in a given human population will evolve. We derive a differential equation governing this evolution and show, for given assumptions about growth and invasion, that there is a unique distribution which does not vary with t...

  8. Factors influencing consultation to discuss family history of cancer by asymptomatic patients in primary care.

    Science.gov (United States)

    Lim, Jennifer N W; Hewison, Jenny; Chu, Carol E; Al-Habsi, Hamdan

    2011-03-01

    Patient self-initiated consultations to discuss family history of cancer in primary care and the factors leading to these consultations have not been investigated. Seventy-one out of 150 asymptomatic patients with a family history of cancer at the Yorkshire Cancer Genetics Service participated in this study. A semi-structured questionnaire was administered. The results show that (1) family cancer events, doctors' advice and reaching the age of cancer-affected relatives were more salient in raising awareness of the added cancer risk due to family history than media and publicity, and knowledge of the genetics services; (2) knowledge of family medical history and its clinical value is not easy to ascertain; (3) the inter-relationships with other causal beliefs are of interest and could provide insights to understand the factors motivating patients to discuss family history or cancer risk; (4) the belief that 'cancer runs in the family' or is 'a family thing' may not be sufficient to heighten perceived cancer risk and motivate patients to seek medical advice; and (5) understanding of the medical concept and clinical value of family history is poor even in this group of patients who initiated the GP consultations. In conclusion, because most primary care practitioners are likely to rely on patient initiated discussion to identify individuals at an increased risk of cancer because of their family history, these findings are therefore important to help doctors and health providers understand the reasons influencing asymptomatic patients to self-refer themselves in primary care and discuss cancer risk in order to provide appropriate care. PMID:22109720

  9. 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. PMID:26985739

  10. Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth.

    Science.gov (United States)

    Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M; Yang, Jun; Starbuck, Michael W; Ravoori, Murali K; Kundra, Vikas; Vazquez, Elba; Navone, Nora M

    2012-03-01

    Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with X-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1-induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p<0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor-bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth

  11. 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.

  12. Dietary intake of a plant phospholipid/lipid conjugate reduces lung cancer growth and tumor angiogenesis.

    Science.gov (United States)

    Shuman Moss, Laurie A; Jensen-Taubman, Sandra; Rubinstein, Danielle; Viole, Gary; Stetler-Stevenson, William G

    2014-07-01

    It is well recognized that early detection and cancer prevention are significant armaments in the 'war against cancer'. Changes in lifestyle and diet have significant impact on the global incidence of cancer. For over 30 years, many investigators have studied the concept of chemoprevention. More recently, with the demonstration that antiangiogenic activity reduces tumor growth, the concept of angioprevention has emerged as a novel strategy in the deterrence of cancer development (carcinogenesis). In this study, we utilized a fast growing, highly aggressive murine Lewis lung cancer model to examine the in vivo antitumor effects of a novel, dietary supplement, known as plant phospholipid/lipid conjugate (pPLC). Our goal was to determine if pPLC possessed direct antitumor activity with relatively little toxicity that could be developed as a chemoprevention therapy. We used pPLC directly in this in vivo model due to the lack of aqueous solubility of this novel formulation, which precludes in vitro experimentation. pPLC contains known antioxidants, ferulic acid and lipoic acid, as well as soy sterols, formulated in a unique aqueous-insoluble matrix. The pPLC dietary supplement was shown to suppress in vivo growth of this tumor model by 30%. We also demonstrated a significant decrease in tumor angiogenesis accompanied by increased apoptosis and present preliminary evidence of enhanced expression of the hypoxia-related genes pentraxin-3 and metallothionein-3, by 24.9-fold and 10.9-fold, respectively, compared with vehicle control. These findings lead us to propose using this plant phosolipid/lipid conjugate as a dietary supplement that may be useful in cancer prevention. PMID:24510111

  13. Stepwise Progress in Epidermal Growth Factor Receptor/Radiation Studies for Head and Neck Cancer

    International Nuclear Information System (INIS)

    The U.S. Food and Drug Administration approval of four new epidermal growth factor receptor (EGFR) inhibitors for cancer therapy (cetuximab, panitumumab, gefitinib, and erlotinib) over the last 3 years is a remarkable milestone in oncology. Indeed, molecular inhibition of EGFR signaling represents one of the most promising current arenas for the development of molecular-targeted cancer therapies. Epidermal growth factor receptor inhibitors from both the monoclonal antibody and tyrosine kinase inhibitor class have demonstrated clinical activity in the treatment of a broad spectrum of common human malignancies. For the discipline of radiation oncology, the 2006 report of a phase III trial demonstrating a survival advantage for advanced head and neck cancer patients with the addition of weekly cetuximab during a 7-week course of radiation is particularly gratifying. Indeed, this is the first phase III trial to confirm a survival advantage with the addition of a molecular-targeted agent to radiation. Furthermore, this result seems to have been achieved with only a modest increment in overall treatment toxicity and with very high compliance to the prescribed treatment regimen. Nevertheless, much remains to be learned regarding the rational integration of EGFR inhibitors into cancer treatment regimens, as well as methods to optimize the selection of patients most likely to benefit from EGFR inhibitor strategies

  14. Wwox suppresses breast cancer cell growth through modulation of the hedgehog–GLI1 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Anwen [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Wei, Li [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Department of Oncology, NO. 401 hospital of PLA, Qingdao, Shandong (China); Ying, Mingzhen; Wu, Hongmei; Hua, Jin [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China); Wang, Yajie, E-mail: yajiewang@live.com [Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2014-01-24

    Highlights: • We investigated Gli1 as a novel partner of Wwox. • We observed a physical association between Wwox and the Gli1. • Wwox–Gli1 interaction affects Gli1 intracellular localization. • Gli1 Blocks Wwox-induced growth inhibition and apoptosis in T47D cells. - Abstract: Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog–GLI1 signaling pathway in tumorigenesis.

  15. Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth.

    Science.gov (United States)

    Barbie, Thanh U; Alexe, Gabriela; Aref, Amir R; Li, Shunqiang; Zhu, Zehua; Zhang, Xiuli; Imamura, Yu; Thai, Tran C; Huang, Ying; Bowden, Michaela; Herndon, John; Cohoon, Travis J; Fleming, Timothy; Tamayo, Pablo; Mesirov, Jill P; Ogino, Shuji; Wong, Kwok-Kin; Ellis, Matthew J; Hahn, William C; Barbie, David A; Gillanders, William E

    2014-12-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-κB and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds. PMID:25365225

  16. Factors influencing crystal growth rates from undercooled liquids of pharmaceutical compounds.

    Science.gov (United States)

    Trasi, Niraj S; Baird, Jared A; Kestur, Umesh S; Taylor, Lynne S

    2014-08-21

    Amorphous forms of drugs are increasingly being used to deliver poorly water-soluble compounds. Therefore, understanding the magnitude and origin of differences in crystallization kinetics is highly important. The goal of this study was to better understand the factors that influence crystal growth rates from pharmaceutically relevant undercooled liquids and to evaluate the range of growth rates observed. The crystal growth rates of 31 drugs were determined using an optical microscope in the temperature region between the glass transition temperature (Tg) and the melting temperature (Tm). Thermodynamic parameters such as Tm, melting enthalpy, and Tg were determined using a differential scanning calorimeter (DSC). Selected viscosity values for the undercooled liquid were taken from the literature. The growth rates of the different compounds were found to be very different from each other with a variation of about 5 orders of magnitude between the fastest growing compounds and the slowest growing compounds. A comparison of the physicochemical properties showed that compounds that had fast crystal growth rates had smaller molecular weights, higher melting temperatures, lower melt entropies, lower melt viscosities, and higher crystal densities. Variations in the growth rates of the compounds could be rationalized to a large extent by considering the thermodynamic driving force for crystallization, the viscosity, and the entropy difference between the melt and undercooled liquid. This study therefore provides important insight into factors that may compromise the stability of amorphous pharmaceuticals. PMID:25076138

  17. 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.

  18. TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression

    OpenAIRE

    Qing-Qing Liu; Feng-Feng Zhang; Fang Wang; Jing-Hua Qiu; Chun-Hua Luo; Guo-Yong Zhu; Ying-Fu Liu

    2015-01-01

    Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung can...

  19. Insulin-like growth factor-1 enhances mortality risk in women with breast cancer through epithelial-mesenchymal transition initiation

    Directory of Open Access Journals (Sweden)

    Ala-Eddin Al Moustafa

    2013-01-01

    Full Text Available The metastatic disease which leads to cancer patients′ mortality results from a multi-step process of tumor progression caused by gene alteration and cooperation. Accordingly, it was recently demonstrated that alteration level of insulin-like growth factor-1 (IGF-1 and IGF binding protein-3 (IGFBP-3 are associated with the risk of cancer related death in several human malignancies including breast cancer. On the other hand, epithelial-mesenchymal transition (EMT is described as a crucial event in cancer progression and metastasis. Herein, we discuss the association between IGF-1, IGF-1/IGFBP-3 ratio, EMT, and breast cancer mortality.

  20. 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. PMID:25895126

  1. TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer.

    Science.gov (United States)

    Liang, Fang; Li, Qiao; Li, Xiayu; Li, Zheng; Gong, Zhaojian; Deng, Hao; Xiang, Bo; Zhou, Ming; Li, Xiaoling; Li, Guiyuan; Zeng, Zhaoyang; Xiong, Wei

    2016-09-01

    We previously identified TSC22D2 (transforming growth factor β-stimulated clone 22 domain family, member 2) as a novel cancer-associated gene in a rare multi-cancer family. However, its role in tumor development remains completely unknown. In this study, we found that TSC22D2 was significantly downregulated in colorectal cancer (CRC) and that TSC22D2 overexpression inhibited cell growth. Using a co-immunoprecipitation (co-IP) assay combined with mass spectrometry analysis to identify TSC22D2-interacting proteins, we demonstrated that TSC22D2 interacts with pyruvate kinase isoform M2 (PKM2). These findings were confirmed by the results of immunoprecipitation and immunofluorescence assays. Moreover, overexpression of TSC22D2 reduced the level of nuclear PKM2 and suppressed cyclin D1 expression. Collectively, our study reveals a growth suppressor function of TSC22D2 that is at least partially dependent on the TSC22D2-PKM2-cyclinD1 regulatory axis. In addition, our data provide important clues that might contribute to future studies evaluating the role of TSC22D2. PMID:27573352

  2. Vascular Endothelial Growth Factor A Regulates the Secretion of Different Angiogenic Factors in Lung Cancer Cells.

    Science.gov (United States)

    Frezzetti, Daniela; Gallo, Marianna; Roma, Cristin; D'Alessio, Amelia; Maiello, Monica R; Bevilacqua, Simona; Normanno, Nicola; De Luca, Antonella

    2016-07-01

    Vascular endothelial growth factor A (VEGFA) is one of the main mediators of angiogenesis in non-small cell lung cancer (NSCLC). Recently, it has been described an autocrine feed-forward loop in NSCLC cells in which tumor-derived VEGFA promoted the secretion of VEGFA itself, amplifying the proangiogenic signal. In order to investigate the role of VEGFA in lung cancer progression, we assessed the effects of recombinant VEGFA on proliferation, migration, and secretion of other angiogenic factors in A549, H1975, and HCC827 NSCLC cell lines. We found that VEGFA did not affect NSCLC cell proliferation and migration. On the other hand, we demonstrated that VEGFA not only produced a strong and persistent increase of VEGFA itself but also significantly induced the secretion of a variety of angiogenic factors, including follistatin (FST), hepatocyte growth factor (HGF), angiopoietin-2 (ANGPT2), granulocyte-colony stimulating factor (G-CSF), interleukin (IL)-8, leptin (LEP), platelet/endothelial cell adhesion molecule 1 (PECAM-1), and platelet-derived growth factor bb (PDGF-BB). PI3K/AKT, RAS/ERK, and STAT3 signalling pathways were found to mediate the effects of VEGFA in NSCLC cell lines. We also observed that VEGFA regulation mainly occurred at post-transcriptional level and that NSCLC cells expressed different isoforms of VEGFA. Collectively, our data suggested that VEGFA contributes to lung cancer progression by inducing a network of angiogenic factors, which might offer potential for therapeutic intervention. PMID:26542886

  3. Enhanced Expression of Keratinocyte Growth Factor and Its Receptor Correlates with Venous Invasion in Pancreatic Cancer

    Science.gov (United States)

    Cho, Kazumitsu; Ishiwata, Toshiyuki; Uchida, Eiji; Nakazawa, Nando; Korc, Murray; Naito, Zenya; Tajiri, Takashi

    2007-01-01

    Keratinocyte growth factor (KGF) and KGF receptor (KGFR) have been implicated in cancer growth as well as tissue development and repair. In this study, we examined whether KGF and KGFR have a role in human pancreatic ductal adenocarcinoma (PDAC). KGFR mRNA was expressed in eight pancreatic cancer cell lines, whereas the KGF mRNA was detected in seven of the cell lines and was absent in MIA PaCa-2 cells. KGFR and KGF immunoreactivity were localized in the cancer cells in 41.5 and 34.0% of patients, respectively. There was a significant correlation between KGFR or KGF immunoreactivity and venous invasion and a significant correlation between the presence of both markers and venous invasion, vascular endothelial growth factor (VEGF)-A expression, and poor prognosis. Exogenous KGF increased VEGF-A expression and release in MIA PaCa-2 cells, and PANC-1 cells stably transfected to overexpress KGF-exhibited increased VEGF-A expression. Moreover, short hairpin-KGFR transfection in MIA PaCa-2 cells reduced the stimulatory effect of exogenous KGF on VEGF-A expression. Short hairpin-KGF transfection in KLM-1 cells reduced VEGF-A expression in the cells. KGFR and KGF may act to promote venous invasion and tumor angiogenesis in PDAC, raising the possibility that they may serve as novel therapeutic targets in anti-angiogenic strategies in PDAC. PMID:17525264

  4. 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.

  5. Supply- and demand-side developments influencing growth in the debit market

    OpenAIRE

    Julia S. Cheney

    2006-01-01

    On August 3, 2006, the Payment Cards Center of the Federal Reserve Bank of Philadelphia hosted a workshop led by Ronald Congemi, senior vice president of strategic industry relations for First Data Corporation, to examine developments on both the supply side and demand side that are influencing growth in the debit card market. On the supply side, Congemi addressed banks’ increasing recognition of the importance of payments-related revenues in their institutional profit and loss statements, th...

  6. Influence of biostimulators on germination parameters and early growth of sunflower seedling

    OpenAIRE

    Miladinov Zlatica J.; Balalić Igor M.; Radić Velimir B.; Crnobarac Jovan Ž.; Jocković Milan Đ.; Jokić Goran O.; Miklič Vladimir J.

    2015-01-01

    The aim of this paper was to examine the influence of biostimulators, with or without the use of fungicides, on seed quality parameters and early growth of sunflower seedling. Testing was conducted at the Institute of Field and Vegetable Crops in Novi Sad on cytoplasmic male sterile sunflower line HA-26-PR. The experiment included six treatments: Slavol S (25%), Slavol S (25%) + fungicide (a.m. metalaxyl-M), Bioplant Flora (2%), Bioplant Flora (2%) + fungic...

  7. The influence of different forms of government spending on distribution and growth

    OpenAIRE

    Commendatore, Pasquale; Panico, Carlo; Pinto, Antonio

    2009-01-01

    This paper deals with the influence of different types of government expenditure on growth. It widens that proposed by the literature which follows the lines set by Barro (1990) because it adds the changes working through the demand side, generated by the variations in the distribution of the net income of the economy, to those working through the supply side, generated by the variations in factor productivity. The analysis considers a government sector with a balanced budget and an autonomou...

  8. Changes in Climatic Factors Influencing the Growth Period of Corn in Fengjie County

    OpenAIRE

    Mao, Xiaozhen; Mou, Xinli; Ma, Chen; Huang, Jiang; Yuan, Lin

    2014-01-01

    Under the background of global climate change, we analyze the change tendency of average temperature and amount of precipitation influencing the corn's growth period. The results show that from March to August, the monthly temperatures show an upward trend, but the rise is different in different months, and the maximum temperature rise is in May. Precipitation in different months has different trends. Climate change brings about favorable conditions at high altitudes in Fengjie, reduces produ...

  9. Influence of the growth process on some laws deduced from percolation theory

    International Nuclear Information System (INIS)

    A brutal application of the percolation theory to some physical problems can lead to erroneous interpretation of the experimental results. Among these problems, the influence of the growth process on the percolation laws is studied. The behaviour of nsub(s)(t), the number of clusters of size s, at time t, is analyzed and linked to a macroscopic property of the system for a comparison to experimental laws. (author)

  10. Is Sentiment Analysis in Social Media Influence the Business Growth of Tamilnadu Tourism?

    OpenAIRE

    Senthil, V.

    2015-01-01

    This paper is an exploratory study of how Social Media Sentiments influence the business growth of Tamilnadu Tourism. Sentiment Analysis deals with the analysis of emotions, opinions, facts and sentiments in the sentences which are expressed by the people. The objectives of this paper are: First, social media interactions on the state tourism web portals managed by the Destination Management Organizations (DMOs) are gathered and analyzed. Secondly this paper presents an approach to extract se...

  11. The Role of Epidermal Growth Factor Receptor Mutations and Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in the Treatment of Lung Cancer

    International Nuclear Information System (INIS)

    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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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. PMID:26976217

  17. 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

  18. Influence of diagnostic radiography on the incidence of breast cancer and leukemia

    International Nuclear Information System (INIS)

    Little accurate information is available on the influence of diagnostic radiography on the incidence of cancer in the general population, largely because of a lack of knowledge of the numbers and the age distributions of patients undergoing radiographic examinations. We used such information from a closed population in Maine that was followed for a year, along with data from the literature on the absorbed dose from typical examinations and a mathematical model linking dose to the incidence rate of cancer, to estimate the numbers of cases of radiologically induced cancer of the bone marrow and breast. Our data indicate that about 1 percent of all cases of leukemia and less than 1 percent of all cases of breast cancer result from diagnostic radiography. In addition, such tumors generally occur late in life; the incidence of radiation-induced leukemia was highest at 69 years, and the incidence of radiation-induced breast cancer was highest at 76 years. Thus, diagnostic radiography has only a small influence on the occurrence of leukemia and breast cancer

  19. INFLUENCE OF SEED CRYSTAL DIMENSION ON CRYSTAL GROWTH FROM SOLUTION UNDER MICROGRAVITY

    Institute of Scientific and Technical Information of China (English)

    ZHU ZHEN-HE; GE PEI-WEN; XU ZHENG-YI

    2000-01-01

    The influence of the dimension of seed crystal on the characteristics of crystal growth from solution under microgravity is studied. The dimensionless average velocity of fluid Vav, the dimensionless maximum velocity of fluid Vmax, the temperature distribution index Sθ, the concentration distribution index Sφ and the dimensionless average growth rate of crystal Vcg are calculated by only taking into account the variation of the solution density caused by the temperature change, that caused by the concentration change being neglected. In certain regions of the parameter (Ra, Pr, Sc andμ) space, some scaling laws are generated: the scales of Sφ and Vcg are given by power functions ofμwith negative exponents. It is shown that the characteristics of crystal growth for small seed crystal are different from those for large seed crystal.

  20. The influence of p H during growth of bacteria in toluene

    International Nuclear Information System (INIS)

    Five toluene tolerant species were isolated from the activated sludge of a wastewater treatment plant (Dublin). The isolate were investigated for influence of pH on the growth in toluene. Four of the bacteria have been identified as Pseudomonas putida and one as an Aeromonas caviae. When these bacteria were grown with toluene as the sole source of carbon and energy, the pH of the culture medium became acidic and dropped. 0.5 M sodium phosphate buffer was selected to investigate the optimum pH for growth in the presence of 500 mu l of toluene. In general, the growth was optimum between pH 5.8 and 7.4. (author)

  1. 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.

  2. Influence of sediment organic enrichment and water alkalinity on growth of aquatic isoetid and elodeid plants

    DEFF Research Database (Denmark)

    Raun, Ane-Marie Løvendahl; Borum, Jens; Jensen, Kaj Sand

    2010-01-01

    ) increasing alkalinity (from 0.17 to 3.20 meq. L-1) enhances growth and reduces inhibition of organic sediment enrichment for elodeids but not for isoetids. 2. In low organic sediments, higher oxygen release from roots of isoetids than elodeids generated oxic conditions to greater sediment depth for Lobelia...... two elodeids (Potamogeton crispus and P. perfoliatus), we test whether organic enrichment of lake sediments has a long-lasting influence by: (i) reducing plant growth because of oxygen stress on plant roots and (ii) inhibiting growth more for isoetids than elodeids. We also test whether (iii...... because of greater CO2 supply from sediments being their main CO2 source. At higher organic enrichment, isoetid biomass was reduced, leaf chlorophyll declined up to 10-fold, root length declined from 7 to <2 cm and mortality rose (up to 50%) signalling high plant stress. 4. Lobelia was not affected by HCO...

  3. Influence of oxygen partial pressure on growth morphologies in unidirectionally solidified YBCO-Ag superconducting composites

    International Nuclear Information System (INIS)

    YBCO/Ag superconducting composites were fabricated by the unidirectional solidification method under various oxygen partial pressures. The effect of oxygen partial pressure on the growth interface stability and the morphology of Y1Ba2Cu3Ox (Y123)-Ag composite was investigated. The growth interface changed from planar to not planar with decreasing oxygen partial pressure. This phenomenon indicated that the interface stability was dominantly affected by the slope of liquidus, which is a significant function of the oxygen partial pressure. The morphology of the Y123-Ag composite was also strongly influenced by the oxygen partial pressure. In the case of 0.21 atm oxygen partial pressure (Po2), rod-like silver particles elongated along the growth direction were formed around the bottom of the facet crystal. On the other hand, spherical silver droplets were entrapped at the grain boundaries in the case of Po2 = 1atm. (author)

  4. 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.

  5. The influence of growth chemistry on the MOVPE growth of GaAs and Al(x)Ga(1-x)As layers and heterostructures

    Science.gov (United States)

    Kuech, T. F.; Veuhoff, E.; Kuan, T. S.; Deline, V.; Potemski, R.

    1986-09-01

    Various combinations of triethylgallium, triethylaluminum, trimethylgallium, and trimethylaluminum have been used during the metalorganic vapor phase epitaxy (MOVPE) growth of Al(x)Ga(1-x)As in order to ascertain the influence of their growth chemistry on the properties of the resulting semiconductor layers and quantum well structures. Substantial reductions in carbon incorporation can be achieved using the ethyl-based growth chemistry. Narrow quantum well structures were demonstrated using both ethyl- and methyl-based precursors.

  6. Influence of growth ambient on the surface and structural properties of vanadium oxide nanorods

    Science.gov (United States)

    Tien, Li-Chia; Chen, Yu-Jyun

    2013-06-01

    The influence of growth ambient on the surface and structural properties of vanadium oxide nanorods have been studied by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy (RS). The vanadium oxide nanorods, which were synthesized through an ambient controlled vapor transport process, exhibit different surface electronic properties depending upon the growth ambient. The Raman data indicates that the as-grown samples are orthorhombic V2O5 phase with a small variation of stoichiometry. Under highly oxidative conditions, nearly stoichiometry sample can be grown. If the samples were grown under less oxidizing conditions, an increase of structural disorder was observed. The observed V 2p core level spectra of both samples showed a single peak with chemical shifts corresponding to the V5+ and V4+. XPS results suggested that the highly oxidized vanadium ions (V5+) are gradually reduced to lower oxidation state (V4+) with the decreases of ambient oxygen levels during growth. The results clearly show that surface non-stoichiometry may be correlated with structural disorder of V2O5 nanorods. The growth ambient and post-annealing may influence the vanadium oxidation state and subsequent surface reactivity significantly.

  7. 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

  8. Influence of biomass burning during recent fluctuations in the slow growth of global tropospheric methane

    Science.gov (United States)

    Simpson, Isobel J.; Rowland, F. Sherwood; Meinardi, Simone; Blake, Donald R.

    2006-11-01

    During the past 15 years the annual growth rate of tropospheric methane (CH4) has shown striking changes over 2-3 year periods, varying from +1% yr-1 to slightly negative values (-0.2% yr-1). These fluctuations are superimposed on an overall slowdown of the CH4 growth rate since the 1980s. Here we use our complementary measurement of other compounds (ethane, tetrachloroethene) to confirm the influence of biomass burning on large global CH4 pulses in 1998 and 2002-2003. Methane growth rate fluctuations also track ENSO indices, most likely via the influence of ENSO activity on large-scale biomass burning. We also report the seventh year of near-zero growth of global CH4 levels (Dec. 1998-Dec. 2005). The global CH4 mixing ratio was 1772 +/- 1 ppbv in 2005, and CH4 increases of 118-376 ppbv between 2000-2020 (ten scenarios in the 2001 IPCC report, to levels around 1900+ ppbv by 2020, now appear quite unlikely.

  9. The Role of Morphine in Animal Models of Human Cancer: Does Morphine Promote or Inhibit the Tumor Growth?

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2013-01-01

    Full Text Available Morphine, a highly potent analgesic agent, is widely used to relieve pain and suffering of patients with cancer. Additionally, it has been reported that morphine is important in the regulation of cancerous tissue. Morphine relieves pain by acting directly on the central nervous system, although its activities on peripheral tissues are responsible for many adverse side effects. For these reasons, it is very important also to understand the role of morphine in cancer treatment. The published literature reporting the effect of morphine on tumor growth presents some discrepancies, with reports suggesting that morphine may either promote or inhibit the tumor growth. It has been also demonstrated that morphine modulates angiogenesis which is important for primary tumour growth, invasiveness, and the development of metastasis. This review will focus on the latest findings on the role of morphine in the regulation of cancer cell growth and angiogenesis.

  10. Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

    OpenAIRE

    2013-01-01

    AIM: To investigate human epidermal growth factor receptor 2 (HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.

  11. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    OpenAIRE

    Wu, Kun; ZHAO Yan; Liu, Bai-He; Li, Yao; Liu, Fang; Guo, Jian; Yu, Wei-Ping

    2002-01-01

    AIM: To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-α-tocopheryl succinate (VES), a derivative of natural Vitamin E, via inducing apoptosis and DNA synthesis arrest.

  12. The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer

    DEFF Research Database (Denmark)

    Roura, Esther; Travier, Noémie; Waterboer, Tim; de Sanjosé, Silvia; Bosch, F Xavier; Pawlita, Michael; Pala, Valeria; Weiderpass, Elisabete; Margall, Núria; Dillner, Joakim; Gram, Inger T; Tjønneland, Anne; Munk, Christian; Palli, Domenico; Khaw, Kay-Tee; Overvad, Kim; Clavel-Chapelon, Françoise; Mesrine, Sylvie; Fournier, Agnès; Fortner, Renée T; Ose, Jennifer; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Orfanos, Philippos; Masala, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Polidoro, Silvia; Mattiello, Amalia; Lund, Eiliv; Peeters, Petra H; Bueno-de-Mesquita, H B As; Quirós, J Ramón; Sánchez, María-José; Navarro, Carmen; Barricarte, Aurelio; Larrañaga, Nerea; Ekström, Johanna; Lindquist, David; Idahl, Annika; Travis, Ruth C; Merritt, Melissa A; Gunter, Marc J; Rinaldi, Sabina; Tommasino, Massimo; Franceschi, Silvia; Riboli, Elio; Castellsagué, Xavier

    2016-01-01

    BACKGROUND: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of...... developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants.......7). CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors....

  13. 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.

  14. 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

  15. Psychosocially Influenced Cancer: Diverse Early-Life Stress Experiences and Links to Breast Cancer

    OpenAIRE

    Schuler, Linda A.; Auger, Anthony P

    2010-01-01

    This perspective on Boyd et al. (beginning on page XXX in this issue of the journal) discusses recent published research examining the interplay between social stress and breast cancer. Cross-disciplinary studies using genetically defined mouse models and established neonatal and peripubertal paradigms of social stress are illuminating biological programming by diverse early-life experiences for the risk of breast cancer. Understanding the mechanisms underlying this programming can lead to id...

  16. Polymorphisms in the epidermal growth factor receptor gene and the risk of primary lung cancer: a case-control study

    Directory of Open Access Journals (Sweden)

    Kim Young-Chul

    2007-10-01

    Full Text Available Abstract Background Polymorphisms in Epidermal Growth Factor Receptor (EGFR gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population. Methods We first examined the frequencies of 39 candidate polymorphisms in the EGFR gene in 27 healthy Korean individuals. After then, we genotyped five polymorphisms (127378C>T, 142285G>A, 162093G>A, 181946C>T and 187114T>C that have variant allele frequencies greater than 10%, in 582 lung cancer patients and in 582 healthy controls. Results Of the 5 polymorphisms, the 181946C>T genotype distribution was significantly different between the cases and controls (P = 0.04. Compared with the 181946 CC + CT genotype, the 181946 TT genotype was associated with a significantly decreased risk of lung cancer (adjusted OR = 0.63, 95% CI = 0.45–0.88, P = 0.007. When the analyses were stratified by smoking status, the protective effect of the TT genotype was statistically significant in ever-smokers (adjusted OR = 0.59, 95% CI = 0.41–0.86, P = 0.007, but not in never-smokers (adjusted OR = 0.89, 95% CI = 0.45–1.75, P = 0.73; P = 0.08, test for homogeneity. Consistent with the results of the genotyping analysis, the CGGCT haplotype with the 181946C allele was associated with a significantly increased risk of lung cancer compared to the CGGTT haplotype carrying the 181946T allele (adjusted OR = 1.50, 95% CI = 1.09–2.07, P = 0.012 and Bonferroni corrected P-value = 0.048. Conclusion These results suggest that the EGFR polymorphisms, particularly the 181945C>T polymorphism, could be used as markers for the genetic susceptibility to lung cancer.

  17. A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy

    Science.gov (United States)

    Portz, Travis; Kuang, Yang; Nagy, John D.

    2012-03-01

    Prostate cancer is commonly treated by a form of hormone therapy called androgen suppression. This form of treatment, while successful at reducing the cancer cell population, adversely affects quality of life and typically leads to a recurrence of the cancer in an androgen-independent form. Intermittent androgen suppression aims to alleviate some of these adverse affects by cycling the patient on and off treatment. Clinical studies have suggested that intermittent therapy is capable of maintaining androgen dependence over multiple treatment cycles while increasing quality of life during off-treatment periods. This paper presents a mathematical model of prostate cancer to study the dynamics of androgen suppression therapy and the production of prostate-specific antigen (PSA), a clinical marker for prostate cancer. Preliminary models were based on the assumption of an androgen-independent (AI) cell population with constant net growth rate. These models gave poor accuracy when fitting clinical data during simulation. The final model presented hypothesizes an AI population with increased sensitivity to low levels of androgen. It also hypothesizes that PSA production is heavily dependent on androgen. The high level of accuracy in fitting clinical data with this model appears to confirm these hypotheses, which are also consistent with biological evidence.

  18. Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.

    Science.gov (United States)

    Jang, S; Yu, X-M; Odorico, S; Clark, M; Jaskula-Sztul, R; Schienebeck, C M; Kupcho, K R; Harrison, A D; Winston-McPherson, G N; Tang, W; Chen, H

    2015-08-01

    To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy. PMID:26251030

  19. 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.

  20. 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.

  1. Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling

    OpenAIRE

    Sliva, D; Jedinak, A; Kawasaki, J.; Harvey, K; Slivova, V

    2008-01-01

    The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer ce...

  2. Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer

    International Nuclear Information System (INIS)

    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

  3. 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

  4. Genetic alterations and expression of inhibitor of growth 1 in human sporadic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Li-Sheng Chen; Jian-Bao Wei; Yong-Chun Zhou; Sen Zhang; Jun-Lin Liang; Yun-Fei Cao; Zong-Jiang Tang; Xiao-Long Zhang; Feng Gao

    2005-01-01

    AIM: To explore the effect and significance of inhibitor of growth 1 (ING1) gene in carcinogenesis and progression of human sporadic colorectal cancer.METHODS: mRNA expression, mutation, and loss of heterozygosity (LOH) of ING1 gene in 35 specimens of sporadic colorectal cancer tissues and the matched normal mucous membrane tissues were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR),PCR-single strain conformation polymorphism (PCR-SSCP)and PCR-simple sequence length polymorphism (PCR-SSLP)using microsatellite markers, respectively.RESULTS: The average ratios of light intensities of p33ING1b and p47ING1a mRNA expression in the cancerous tissues were significantly lower than those in normal tissues.The difference between the two mRNA splices was not significant in the matched tissues. In addition, the ratios of light intensities of p33INB1b and p47ING1a mRNA expression in the cancerous tissues of Dukes' stages C and D were significantly lower than those in cancerous tissues of Dukes'stages A and B. However, no mutation of ING1 gene was detected in all 35 cases; only 4 cases of LOH (11.4%)were found.CONCLUSION: p33ING1b and p47ING1a mRNA expressions are closely related with the carcinogenesis and progression of human sporadic colorectal cancer. No mutation of ING1gene is found, and there are only few LOH in sporadic colorectal cancers. These might not be the main reasons for the down regulation of ING1 expression. Its low expression may happen in transcription or post-transcription.

  5. Novel STAT3 phosphorylation inhibitors exhibit potent growth suppressive activity in pancreatic and breast cancer cells

    Science.gov (United States)

    Lin, Li; Hutzen, Brian; Zuo, Mingxin; Ball, Sarah; Deangelis, Stephanie; Foust, Elizabeth; Pandit, Bulbul; Ihnat, Michael A.; Shenoy, Satyendra S.; Kulp, Samuel; Li, Pui-Kai; Li, Chenglong; Fuchs, James; Lin, Jiayuh

    2010-01-01

    The constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) is frequently detected in most types of human cancer where it plays important roles in survival, drug-resistance, angiogenesis, and other functions. Targeting constitutive STAT3 signaling is thus an attractive therapeutic approach for these cancers. We have recently developed novel small molecule STAT3 inhibitors known as FLLL31 and FLLL32, which are derived from curcumin (the primary bioactive compound of turmeric). These compounds are designed to bind selectively to Janus Kinase 2 (JAK2) and the STAT3 SH2 domain, which serves crucial roles in STAT3 dimerization and signal transduction. Here we show that FLLL31 and FLLL32 are effective inhibitors of STAT3 phosphorylation, DNA binding activity, and transactivation in vitro, leading to the impediment of multiple oncogenic processes and the induction of apoptosis in pancreatic and breast cancer cell lines. FLLL31 and FLLL32 also inhibit colony formation in soft agar, cell invasion, and exhibit synergy with the anti-cancer drug doxorubicin against breast cancer cells. In addition, we show that FLLL32 can inhibit the induction of STAT3 phosphorylation by Interferon-α (IFNα) and Interleukin-6 (IL-6) in breast cancer cells. We also demonstrate that administration of FLLL32 can inhibit tumor growth and vascularity in chicken embryo xenografts as well as substantially reduce tumor volumes in mouse xenografts. Our findings highlight the potential of these new compounds and their efficacy in targeting pancreatic and breast cancers that exhibit constitutive STAT3 signaling. PMID:20215512

  6. In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

    International Nuclear Information System (INIS)

    Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue. Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections. We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF. We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo

  7. STAT6 Mediates Interleukin-4 Growth Inhibition in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jennifer L. Gooch

    2002-01-01

    Full Text Available In addition to acting as a hematopoietic growth factor, interleukin-4 (IL-4 inhibits growth of some transformed cells in vitro and in vivo. In this study, we show that insulin receptor substrate (IRS-1, IRS-2, and signal transducer and activator of transcription 6 (STAT6 are phosphorylated following IL-4 treatment in MCF-7 breast cancer cells. STAT6 DNA binding is enhanced by IL-4 treatment. STAT6 activation occurs even after IRS-1 depletion, suggesting the two pathways are independent. To examine the role of STAT6 in IL-4-mediated growth inhibition and apoptosis, a fulllength STAT6 cDNA was transfected into MCF-7 cells. Transient overexpression of STAT6 resulted in both cytoplasmic and nuclear expression of the protein, increased DNA binding in response to IL-4, and increased transactivation of an IL-4 responsive promoter. In STAT6-transfected cells, basal proliferation was reduced whereas apoptosis was increased. Finally, stable expression of STAT6 resulted in reduced foci formation compared to vector-transfected cells alone. These results suggest STAT6 is required for IL-4mediated growth inhibition and induction of apoptosis in human breast cancer cells.

  8. Accumulation of Extracellular Hyaluronan by Hyaluronan Synthase 3 Promotes Tumor Growth and Modulates the Pancreatic Cancer Microenvironment

    OpenAIRE

    Anne Kultti; Chunmei Zhao; Netai C. Singha; Susan Zimmerman; Osgood, Ryan J.; Rebecca Symons; Ping Jiang; Xiaoming Li; Thompson, Curtis B.; Infante, Jeffrey R.; Jacobetz, Michael A.; Tuveson, David A.; Frost, Gregory I.; H. Michael Shepard; Zhongdong Huang

    2014-01-01

    Extensive accumulation of the glycosaminoglycan hyaluronan is found in pancreatic cancer. The role of hyaluronan synthases 2 and 3 (HAS2, 3) was investigated in pancreatic cancer growth and the tumor microenvironment. Overexpression of HAS3 increased hyaluronan synthesis in BxPC-3 pancreatic cancer cells. In vivo, overexpression of HAS3 led to faster growing xenograft tumors with abundant extracellular hyaluronan accumulation. Treatment with pegylated human recombinant hyaluronidase (PEGPH20)...

  9. Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107

    OpenAIRE

    Barbie, Thanh U.; Barbie, David A; MacLaughlin, David T.; Maheswaran, Shyamala; Donahoe, Patricia K.

    2003-01-01

    In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might also respond to MIS. A number of cervical cancer cell lines express the MIS type II receptor, and MIS inhibits the gro...

  10. Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluorouracil in colon cancer cell-bearing mice

    OpenAIRE

    Perboni, Simona; Bowers, Cyril; Kojima, Shinya; Asakawa, Akihiro; Inui, Akio

    2008-01-01

    The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemotherapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluorouracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BA...

  11. 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

  12. 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, J. van; Lampe, J.W.; Cats, A.; Witteman, B.J.M.; Leeuwen, F.E. van; Veer, L.J. van 't; 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

  13. In vivo quantitative phosphoproteomic profiling identifies novel regulators of castration-resistant prostate cancer growth

    DEFF Research Database (Denmark)

    Jiang, Nan; Hjorth-Jensen, Kim; Hekmat, Omid;

    2015-01-01

    Prostate cancer remains a leading cause of cancer-related mortality worldwide owing to our inability to treat effectively castration-resistant tumors. To understand the signaling mechanisms sustaining castration-resistant growth, we implemented a mass spectrometry-based quantitative proteomic app...

  14. The influence of genetic variation in thirty selected genes on the clinical characteristics of early onset breast cancer

    OpenAIRE

    Tapper, William; Hammond, Victoria; Gerty, Sue; Ennis, Sarah; Simmonds, Peter; Collins, Andrew; Eccles, Diana

    2008-01-01

    Introduction: common variants that alter breast cancer risk are being discovered. Here, we determine how these variants influence breast cancer prognosis, risk and tumour characteristics. Methods: we selected 1,001 women with early onset nonfamilial invasive breast cancer from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort and genotyped 206 single nucleotide polymorphisms (SNPs) across 30 candidate genes. After quality control, 899 cases and 13...

  15. 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.

  16. Aurora kinase inhibitors attached to iron oxide nanoparticles enhances inhibition of the growth of liver cancer cells

    International Nuclear Information System (INIS)

    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

  17. 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.

  18. A review of repeat prostate biopsies and the influence of technique on cancer detection: our experience.

    LENUS (Irish Health Repository)

    Quinlan, M R

    2012-02-01

    BACKGROUND: Follow-up of patients with an initial negative prostate biopsy, but surrounding whom a suspicion of prostate cancer persists, is difficult. In addition, debate exists as to the optimal technique for repeat prostate biopsy. AIMS: To assess the cancer detection rate on repeat prostate biopsy. METHODS: We reviewed patients who underwent prostate biopsy in our department in 2005 who had >or=1 previous biopsy within the preceding 5 years. Cancer detection rate on repeat biopsy and the influence of the number of biopsy cores were recorded. RESULTS: Cancer detection rate on repeat biopsy was 15.4%, with approximately 60% detected on the first repeat biopsy, but approximately 10% not confirmed until the fourth repeat biopsy. Gleason score was similar regardless of the time of diagnosis (6.1-6.5). Mean interval between first biopsy and cancer diagnosis (range 18-55 months) depended on the number of repeat procedures. There was an association between the number of biopsy cores and cancer detection. CONCLUSIONS: This study supports the practice of increasing the number of cores taken on initial and first repeat biopsy to maximise prostate cancer detection and reduce the overall number of biopsies needed.

  19. Factors Influencing Early Detection of Oral Cancer by Primary Health-Care Professionals.

    Science.gov (United States)

    Hassona, Y; Scully, C; Shahin, A; Maayta, W; Sawair, F

    2016-06-01

    The purposes of this study are to determine early detection practices performed by primary healthcare professionals, to compare medical and dental sub-groups, and to identify factors that influence the ability of medical and dental practitioners to recognize precancerous changes and clinical signs of oral cancer. A 28-item survey instrument was used to interview a total of 330 Jordanian primary health-care professionals (165 dental and 165 medical). An oral cancer knowledge scale (0 to 31) was generated from correct responses on oral cancer general knowledge. An early detection practice scale (0 to 24) was generated from the reported usage and frequency of procedures in oral cancer examination. Also, a diagnostic ability scale (0 to 100) was generated from correct selections of suspicious oral lesions. Only 17.8 % of the participants reported that they routinely performed oral cancer screening in practices. Their oral cancer knowledge scores ranged from 3 to 31 with a mean of 15.6. The early detection practice scores ranged from 2 to 21 with a mean of 11.6. A significant positive correlation was found between knowledge scores and early detection practice scores (r = 0.22; p oral cancer and oral mucosal lesions are needed for primary health-care professionals. PMID:25851202

  20. Growth suppression and radiosensitivity increase by HMGB1 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Hai-chao WANG; Sai-jun FAN

    2007-01-01

    Aim: HMGB 1 (high-mobility group box-1) is a nuclear protein containing a con- sensus RB (retinoblastoma)-binding LXCXE motif. In this study, we studied the potential association of HMGB 1 and RB and the in vitro and in vivo activities of HMGB 1 in human breast cancer cells. Methods: The protein-protein interaction was determined by immunoprecipitation-Western blotting and glutathione-S-trans- ferase capture assays; cell growth and radiosensitivity were examined by cell counts, MTT assay, and clonogenic assay; cell cycle progression and apoptosis were evaluated using flow cytometry; and the antitumor activity of HMGB 1 was examined with tumor xenografts in nude mice. Results: HMGB 1 was associated with RB via a LXCXE motif-dependent mechanism. HMGB 1 enhanced the ability of RB for E2F and cyclin A transcription repression. The increased expression of HMGB 1 conferred an altered phenotypes characterized by the suppression of cell growth; G12 arrest and apoptosis was induced in MCF-7 cells containing the wild- type retinoblastoma (Rb) gene, but showed no activities in BT-549 cells contain- ing the Rb gene deletion. The HMGB 1-induced apoptosis accompanied by caspase 3 activation and PARP (poly(ADP-ribose)polymerase) cleavage. HMGB 1 elevated the radiosensitivity of breast cancer cells in both the MCF-7 and BT-549 cell lines. The enhanced expression of HMGB 1 caused a suppression of growth of MCF-7 tumor xenografts in nude mice, while LXCXE-defective HMGB 1 completely lost antitumor growth activity. Conclusion: HMGB 1 functions as a tumor suppressor and radiosensitizer in breast cancer. A HMGB 1-RB interaction is critical for the HMGB1-mediated transcriptional repression, cell growth inhibition, G12 cell cycle arrest, apoptosis induction, and tumor growth suppression, but is not required for radiosensitization. Therefore, it may be possible to design new therapies for the treatment of breast cancer that exert their effects by modulating the HMGB 1 and RB regulatory